bromochloroacetic-acid and Sarcoma

Epithelioid sarcoma (ES) is a distinctive malignant mesenchymal neoplasm with atypical epithelioid cells palisading around a central zone of necrosis. ES is a rare entity even in soft tissue pathology. Immunohistochemically, tumors usually show diffuse epithelial membrane antigen and cytokeratin expression and loss of nuclear INI1 (SMARCB1) expression. Here, we report a case of a 64-year-old man with ES arising in the left conchal bowl. Given the clinical presentation including patient's age, sun-exposed area of skin, and slow-growing, asymptomatic, small pink pearly papule, this patient was initially misdiagnosed with basal cell carcinoma clinically and treated with topical imiquimod at an outside facility. The lesion continued to grow and eventually became symptomatic despite the treatment after which biopsy was obtained. Despite the unusual anatomic site and the patient's age, the microscopic and immunohistochemical findings were characteristic of conventional-type ES. Our case shows that ES can arise in rare locations and in older adults where it may be more easily misdiagnosed clinically and pathologically as a nonmelanoma skin cancer.

Topics: Aged; Biomarkers, Tumor; Biopsy; Humans; Keratins; Male; Middle Aged; Sarcoma; Skin Neoplasms; SMARCB1 Protein

Topics: Cell Dedifferentiation; Chordoma; Diagnosis, Differential; Female; Fibrosarcoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Sacrococcygeal Region; Sarcoma; Spinal Neoplasms; Vimentin

Topics: Chromosomal Proteins, Non-Histone; Diagnosis, Differential; DNA-Binding Proteins; Follow-Up Studies; Humans; Infant; Infant, Newborn; Keratins; Male; Mucin-1; Phosphopyruvate Hydratase; Rhabdoid Tumor; Rhabdomyosarcoma; S100 Proteins; Sarcoma; Sarcoma, Clear Cell; Skin Neoplasms; SMARCB1 Protein; Transcription Factors; Vimentin

Eccrine porocarcinoma is an uncommon sweat gland malignancy. To the best of our knowledge, there has been no report in the English literature of porocarcinoma with predominantly undifferentiated sarcomatous change. We present two cases of sarcomatoid eccrine porocarcinoma associated with a benign poroma. Case 1 pertained to an 82-year-old woman with an ulcerated chest wall tumor, and Case 2 was that of a 74-year-old woman who presented with an ulcerated plaque in the lower leg. Case 1 showed an unusual pseudo-angiosarcomatous morphology with spindle cells dissecting through collagen bundles and forming vascular like channels. Case 2 revealed high-grade malignant spindle cells with focal evidence of ductal differentiation. In both the cases, benign poromatous elements were histologically evident. Immunohistochemistry performed showed pancytokeratin positivity in spindle cells of both lesions. Epithelial membrane antigen and carcino-embryonic antigen positivity in the malignant ductal elements and focal smooth muscle actin staining of the spindle cells were demonstrated in Case 2. A brief review of relevant literature is presented.

Topics: Acrospiroma; Actins; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Leg; Mucin-1; Muscle, Smooth; Sarcoma; Staining and Labeling; Sweat Gland Neoplasms; Thoracic Wall

Miscellaneous primary tumors of the uterine cervix are rare. Markers which can be utilized to detect these tumors are very few and in most cases, have not been clinically validated. The information provided in this article will help in developing strategies to discover novel markers and initiate translational research in this ignored area. Based on the reported studies, cytokeratin markers are common in many tumors and few of these rare cancers demonstrate human papilloma-virus (HPV) and Epstein Bar virus (EBV) infection. Due to the very low prevalence of these tumors, epidemiological studies have not been conducted and the etiology of these tumors is largely unknown.

Topics: Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Female; Humans; Immunohistochemistry; Keratins; Lipoma; Melanoma; Neurilemmoma; Rare Diseases; Sarcoma; Uterine Cervical Neoplasms

Sarcomatoid carcinoma of the small bowel is rare; to our knowledge, 19 cases have been reported to date in the English literature under several names. We report an additional case occurring in the jejunum of a 55-year-old man. The tumor was a polypoid 7.5-cm mass, which infiltrated the full thickness of the intestinal wall and the serosa of an adhesed loop of small bowel. On microscopic examination, the neoplasm was composed of sheets of spindle cells; focally, an anaplastic component was present, including tumor giant cells with bizarre nuclei. On immunohistochemical stains, tumor cells were positive for cytokeratin 7, cytokeratin AE1/AE3, vimentin, and focally, epithelial membrane antigen. No staining for cytokeratin 20 was found. Sarcomatoid carcinoma must be kept in mind in the differential diagnosis of malignant spindle cell tumors of the small bowel. As consensus regarding the terminology of these rare tumors is being reached, immunohistochemical stains are essential for accurate diagnosis.

Topics: Carcinoma; Cell Nucleus; Diagnosis, Differential; Fatal Outcome; Humans; Jejunal Neoplasms; Keratin-7; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Proteins; Sarcoma; Vimentin

Malignant breast neoplasms consisting of mixtures of epithelial and mesenchymal elements, are a rarity. Pathogenesis of such diverse elements within obviously infiltrating carcinomas has been the subject of much controversy. After the advent of immunohistochemistry, it is now generally accepted that metaplasia of the epithelial elements of a carcinoma gives these lesions their pseudosarcomatous appearance. Hence the name metaplastic carcinoma is given to malignant breast neoplasms which show Cytokeratin positivity in both epithelial and mesenchymal elements. We recently encountered such a case, which is being presented here along with relevant review of literature.

Topics: Adult; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Humans; Keratins; Metaplasia; Sarcoma

A 4-year-old boy presented with a 6-month history of a red papule on the nasal septum. Physical examination was otherwise unremarkable. A biopsy specimen showed an epithelioid sarcoma characterized by nodular collections of epithelioid tumor cells with central, tumor cell necrosis. By immunohistochemistry the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and CD34, but negative for S-100, CD31, factor VIII-related antigen, CD68, actin, desmin and myoglobin. Epithelioid sarcoma is an uncommon tumor of uncertain histogenesis that typically arises in the extremities of young adults. Both the age of our patient and the location of his tumor are unusual, emphasizing the spectrum of presentations that may occur with epithelioid sarcoma. Epithelioid sarcoma should be considered in the differential diagnosis of granulomatous diseases and epithelioid tumors of children, even in unusual locations.

Topics: Antigens, CD34; Biomarkers, Tumor; Child, Preschool; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Neoplasm Proteins; Nose; Sarcoma; Skin Neoplasms; Vimentin

A 57-year-old woman presented with a 10 x 10 cm anterior mediastinal mass. The tumor had invaded the pericardium, both lungs and the left brachiocephalic vein, and was treated by partial resection and postoperative radiation therapy. Pathological examination of the tumor revealed squamous cell carcinoma with a spindle cell sarcomatous component. Immunohistochemically, keratin and epithelial membrane antigen were positive in both the spindle cell sarcomatous areas and the squamous cell carcinomatous area and thus, a diagnosis of thymic carcinoma of sarcomatoid type was made. The patient died of recurrent disease 1 year after surgery. This case is the seventh reported in the English literature. Because of the poor outcome, adjuvant therapy is recommended.

Topics: Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; Neoplasm Invasiveness; Sarcoma; Thymus Neoplasms

A case of carcinosarcoma arising in the skin of the left arm of a 69-year-old woman is reported with a review of the literature. The tumor was composed of low-differentiated squamous cell carcinoma, which was intermingled with a pleomorphic sarcoma. The carcinomatous component had keratin and lacked vimentin, whereas the phenotype of the sarcomatous portion was the reverse. The former presented additionally focal expression of S-100 protein, which was lacking in other portions of the carcinoma. The phenotypic data, supplemented by p53 immunostaining, which was present in both components, suggest their common origin in this tumor.

Topics: Aged; Arm; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Nucleus; Chromatin; Coloring Agents; Epithelium; Female; Humans; Keratins; Mitosis; Organelles; Phenotype; S100 Proteins; Sarcoma; Skin Neoplasms; Tumor Suppressor Protein p53; Vimentin

A rare case of ovarian mucinous cystadenocarcinoma with sarcoma-like mural nodules is reported. Macroscopically, nodular or granular lesions were scattered over the inner surface of a huge, multilocular tumor in the left ovary. The histopathological features were consistent with those of previously documented cases, except significant squamous metaplasia in the present case. The pleomorphic sarcoma-like cells showed a positive reaction for vimentin and alpha-antichymotrypsin but were negative for carcinoembryonic antigen and common epithelial membrane antigen by immunohistochemistry. Electron microscopically, the tumor cells had neither desmosomes nor secretory granules, but they possessed abundant intermediate filaments. Both immunostaining and ultrastructure suggested that the sarcoma-like nodules were derived from reactive proliferation of fibrohistiocytic cells. The fibrohistiocytic reaction seemed to occur in response to hemorrhage, because hemorrhage was reported to be associated with the mural nodules in most of the previous cases as well as ours.

Topics: Cystadenocarcinoma, Mucinous; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Middle Aged; Ovarian Neoplasms; Sarcoma

Herein we report the clinicopathological features of four cases of pulmonary artery sarcoma that appeared at our institution during a period of 30 years. The patients, 2 males and 2 females, were 50-62 years old. Tumour was found in the pulmonary trunk and right pulmonary artery in all cases, in the pulmonary valve and left pulmonary artery in three of the four cases, and in the right ventricular outflow tract in one case. There was direct extension or metastases to the lungs in two cases, the heart in one case, mediastinum or lymph nodes in two cases and the pleura in one case. Ultrastructural examination in one case revealed cells with features of smooth muscle cells and myofibroblasts. Immunohistochemical examination of three cases gave the following results: vimentin and smooth muscle specific actin was positive in all three cases, desmin in one case and cytokeratin in one case. No positivity was found for Factor VIII. This and other studies indicate that histologically most pulmonary artery sarcomas are leiomyosarcomas or "undifferentiated spindle cell sarcomas". Immunohistochemical and ultrastructural examinations favour an origin from myofibroblasts, probably derived from multipotent (undifferentiated) cells in the wall of the vessel. Most lesions show extensive intrathoracic growth although they rarely metastasize outside the thoracic cavity. They have a poor prognosis although some cases are currently being diagnosed during life.

Topics: Cell Membrane; Cell Nucleus; Desmin; Endoplasmic Reticulum; Female; Golgi Apparatus; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Pulmonary Artery; Sarcoma; Vimentin

Historically, antibodies to cytokeratin intermediate filaments have been models of target specificity. In most diagnostic settings, the utility of these antibodies was unquestioned; reactivity for cytokeratin was dogmatically equated with epithelial differentiation. Recently, however, the diagnostic importance of these antibodies has been challenged, prompted by the demonstration of cytokeratin reactivity in a variety of "nonepithelial" neoplasms. In this review, the evolving literature on this topic is explored, and the practical implications of these findings are discussed.

Topics: Humans; Keratins; Sarcoma; Soft Tissue Neoplasms

We report a case of vulvar epithelioid sarcoma with metastases to the scalp, an inguinal lymph node, lungs, liver, and kidneys. Epithelioid sarcoma typically involves the extremities of young men and may be confused histologically with various benign and malignant processes. Only five cases of primary vulvar epithelioid sarcoma have been previously reported. The present case represents the first report of cutaneous metastases from this primary site. We also review the literature pertaining to the clinical, pathologic, and immunohistochemical features of this rare tumor.

Topics: Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Sarcoma; Scalp; Skin Neoplasms; Vulvar Neoplasms

We describe two cases of alveolar soft part sarcoma (ASPS) that occurred as a primary lesion in the uterine cervix. In both cases, the tumor exhibited the typical histologic features of ASPS. In one case, the material for immunohistochemical staining and electron microscopy was available, and the findings of these studies were consistent with the diagnosis of ASPS. A review of the literature disclosed seven previous cases of ASPS occurring in the female genital tract. The tumor was located in the uterine cervix in only three cases. Although ASPS most commonly involves the soft tissues of the extremities and the head and neck region, it can also occur in rather unusual locations such as the female genital tract. Pathologists should be aware of these unexpected occurrences.

Topics: Actins; Adult; Desmin; Female; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; S100 Proteins; Sarcoma; Uterine Cervical Neoplasms; Vimentin

Keratin protein immunohistochemistry is a powerful diagnostic tool whose role has already been firmly established in many surgical pathology laboratories. Recent studies of the biology of keratin proteins have defined the heterogeneity of keratin protein expression among various epithelial tissues and their tumors and provide the basis for understanding the immunoreactivity of epithelial tumors with various keratin antibodies. Successful execution of the procedure requires attention to technical details such as the fixation of tissue, use of proteolytic enzymes such as trypsin for formalin-fixed tissues, and the choice of the appropriate antibody and controls. Broadly reactive polyclonal and monoclonal antibodies to keratins have been remarkably useful in identifying poorly differentiated and undifferentiated carcinomas. Monoclonal antibodies of restricted specificity and monospecific antibodies to keratin are under development and may prove helpful in defining the organ of origin of metastatic carcinomas. Keratin protein immunohistochemistry supplements existing information used by pathologists in diagnosis, and the immunohistochemical results should be interpreted in the light of the clinical findings, gross and microscopic pathology, and the results of any other special studies.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Bone Neoplasms; Carcinoid Tumor; Carcinoma; Humans; Immunoassay; Keratins; Neoplasms; Sarcoma; Soft Tissue Neoplasms

Most mammalian nucleated cells contain a cytoplasmic fibril system called intermediate filaments. Unlike other cytoskeletal proteins, the subunit proteins of intermediate filaments show a remarkable cell-type-specificity in their expression: mesenchymal, muscle, epithelial, glial and neuronal cells containing each their cell type specific filaments. In this review we discuss the possibilities to use antibodies to these filaments in the diagnosis and histogenetic analysis of human tumors. This approach is based on findings which indicate that these filaments retain their cell-type specific expression also in tumors.

Topics: Antibodies; Carcinoma; Cytoskeleton; Desmin; Glial Fibrillary Acidic Protein; Glioma; Humans; Intermediate Filaments; Keratins; Mesothelioma; Neoplasms; Rhabdomyosarcoma; Sarcoma; Vimentin

The cytoskeleton (CSK) of eukaryotic cells is composed of a complex interconnected network of filaments which is important in a wide variety of cellular functions including changes in cell shape, cell motility, mitosis, anchorage-dependent growth, and the localization of cellular organelles such as mitochondria, polyribosomes, and secretory granules. The various proteins comprising the cytoskeleton include actin in microfilaments, tubulin in microtubules, and the heterogeneous group of intermediate filament proteins that are associated with different cell types (keratin in epithelial cells, vimentin in fibroblasts, desmin in muscle cells, glial filament protein in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins are closely associated with the cytoskeleton and influence its organization. In neoplastic cells, the expression of these different CSK proteins, especially the intermediate filament proteins, reflects their morphologic and functional differentiation. The carcinomas contain keratin; identification of individual keratin components may allow further sub-classification of carcinomas which is consistent with their tissue of origin. The sarcomas of muscle origin contain desmin. Vimentin is found primarily with cells of mesenchymal origin, but may coexist with other intermediate filament proteins in other tumors. One example is the coexistence of keratin and vimentin in tumors, such as mesotheliomas, which are derived from epithelial cells of embryonic origin. Glial fibrillary acidic protein is the most specific marker for glial tumors. Tumors of neural origin are characterized by the presence of neurofilament subunits. Therefore, analysis of CSK composition would be useful in diagnosis of clinical specimens and aid in studies of lineage relationships of neoplasms. Although no consistent differences in cytoskeletal structure between neoplastic and normal cells have been identified so far, the presence of more subtle biochemical alterations in the cytoskeletal structure of neoplastic cells that contributes to malignant behavior has not been ruled out. Since the cytoskeletal network plays an important role in cell shape and cell locomotion, which in turn are thought to be involved in growth control, invasion, and metastasis, further work is directed at identifying the various alterations in cytoskeletal architecture that

Topics: Actin Cytoskeleton; Actins; Animals; Astrocytes; Carcinoma; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Cytoskeletal Proteins; Cytoskeleton; Desmin; Epithelium; Glial Fibrillary Acidic Protein; Glioma; Granulocytes; Humans; Intermediate Filament Proteins; Keratins; Leukemia; Lymphoma; Macrophages; Microtubules; Molecular Weight; Muscles; Neoplasm Metastasis; Neoplasms; Neoplasms, Nerve Tissue; Neurons; Sarcoma; Tissue Distribution; Vimentin

Immunohistochemistry of intermediate filaments (IF) is a new and important way to evaluate the epithelial, mesenchymal, muscular, glial, or neural differentiation in tumors. This is based on the stable cell-type-specific expression of IF proteins in normal and neoplastic tissues. Immunohistochemical studies with antibodies to intermediate filaments have also given new perspectives in the histogenesis and biologic nature of many tumors. This article reviews both the recent findings and the authors' experience in the use of intermediate filament antibodies in tumor diagnosis and classification.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Carcinoma, Squamous Cell; Desmin; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immunochemistry; Keratins; Melanoma; Mesothelioma; Microfilament Proteins; Microscopy, Electron; Neoplasm Proteins; Neoplasms; Nervous System Neoplasms; Sarcoma; Soft Tissue Neoplasms; Thyroid Neoplasms; Urinary Bladder Neoplasms; Vimentin

Immunofluorescence and immunoperoxidase (peroxidase-antiperoxidase, PAP) techniques for the demonstration of neural and non-neural cell markers are contributing greatly to increase the diagnostic accuracy of difficult tumors of the central nervous system. Well characterized nervous system markers include glial fibrillary acidic (GFA) protein, the three protein subunits of neurofilaments, neuron-specific enolase (NSE), myelin basic protein, and S-100 protein. The most important and reliable of these is GFA protein, which is widely in use for the immunohistochemical diagnosis of tumors of the glioma group. Its many practical applications are reviewed and illustrated. Other neural markers, in particular the specificity of NSE and S-100 protein, need to be critically evaluated. Problems related to the immunohistochemical diagnosis of central neuroepithelial tumors of putative neuroblastic origin remain complex and still need to be resolved. Non-neural markers, such as vimentin, desmin, cytokeratins, Factor VIII, alpha-fetoprotein, human chorionic gonadotropin, and immunoglobulins have well defined, although more restricted, applications in surgical neuropathology.

Topics: alpha-Fetoproteins; Antibodies, Monoclonal; Antigens; Carcinoma; Central Nervous System Diseases; Chorionic Gonadotropin; Cytoskeleton; Desmin; Factor VIII; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Immune Sera; Immunoenzyme Techniques; Immunoglobulins; Intermediate Filament Proteins; Keratins; Lymphoma; Medical Oncology; Meningeal Neoplasms; Myelin Basic Protein; Neoplasm Metastasis; Neoplasms; Neoplasms, Germ Cell and Embryonal; Neurology; Oligodendroglia; Phosphopyruvate Hydratase; S100 Proteins; Sarcoma; Vascular Diseases; Vimentin; von Willebrand Factor

In most cell types intermediate or 10-mm filaments (IF) are a major cytoskeletal organization and, thus, directly or indirectly influence the structural appearance of the cytoplasm. In line with the cell type-specific expression patterns of different IF proteins in normal animal and human tissue, IF typing distinguishes the major tumor groups, as documented by results with several hundred human tumors classified by conventional histologic methods. Carcinomas are characterized by cytokeratins, sarcomas of muscle cells by desmin, nonmuscle sarcomas by vimentin, and gliomas by glial fibrillary acidic protein. Furthermore, certain tumors originating from the sympathetic nervous system, e.g., ganglioneuroblastoma, pheochromocytoma, and at least some neuroblastomas, are characterized by the presence of neurofilaments. Carcinomas can often be further subdivided with regard to their possible derivation by examining their cytokeratin profiles. The IF type characteristic of the cell of origin seems to be kept not only in the primary tumor but usually also in solid metastases. In general, tumors do not acquire additional IF types. Therefore, IF typing can provide an unambiguous and rapid characterization in certain cases, that are difficult to diagnose by conventional techniques. Some useful examples are the small cell tumors of childhood and the discrimination between undifferentiated carcinoma and lymphoma. IF typing of a few tumors has already led to a revision or reconsideration of the original light microscopic diagnosis. The combined results indicate that at least certain carcinomas, as well as certain other tumor types, seem to arise by the selective multiplication of a particular and identifiable cell type present in the normal tissue. The procedure is not restricted to tumor material. IF typing of Mallory bodies, Alzheimer's disease tangles, certain myopathies, and the cells of the amniotic fluid offers further interesting applications. Thus, IF typing should become a valuable new tool both in histology and surgical pathology.

Topics: Amniotic Fluid; Animals; Carcinoma; Cells, Cultured; Cytoskeleton; Desmin; Embryo, Mammalian; Fluorescent Antibody Technique; Ganglioneuroma; Glial Fibrillary Acidic Protein; Glioma; Humans; Intermediate Filament Proteins; Keratins; Muscular Diseases; Neoplasm Metastasis; Neoplasms; Neuroblastoma; Pheochromocytoma; Sarcoma; Vimentin

The authors assessed a panel of immunohistochemical stains against 109 pediatric solid tumors, primarily rhabdomyosarcomas, under the auspices of the Intergroup Rhabdomyosarcoma Study. Fresh tumor tissue received from participating organizations was divided into portions that were either frozen or fixed in formalin, alcohol, or B5. Immunostaining was performed by the avidin-biotin complex method using monoclonal antibodies to desmin, neurofilaments, vimentin, cytokeratin, and leukocyte common antigen on cryostat sections. Tissue was also embedded in paraffin and stained with antimuscle-specific actin (MSA) and polyclonal antibodies to desmin, creatine kinase M subunit (CKM), myoglobin, and neuron-specific enolase (NSE). Antidesmin staining of cryostat sections was the most sensitive indicator of rhabdomyosarcoma (58 of 62 specimens positive). Results with this reagent in alcohol-fixed and formalin-fixed tissue were similar (46 of 56 positive versus 43 of 56 positive, respectively) and comparable with results with anti-MSA in formalin-fixed tissue (43 of 55 positive). However, the proportion of cells stained by antidesmin was higher in alcohol-fixed tissue than in formalin-fixed tissue. Staining with antimyoglobin and anti-CKM was much less satisfactory, with positivity rates of 17 of 37 and 11 of 57, respectively, in formalin-fixed rhabdomyosarcomas. Immunostaining of muscle markers revealed evidence of myogenesis in six undifferentiated sarcomas and in two sarcomas with inadequate histologic study on hematoxylin-eosin-stained sections. However, positivity was also noticed in samples of fibromatosis, Wilms' tumor, ectomesenchyoma, peripheral primitive neuroectodermal tumor, renal rhabdoid tumor, myositis ossificans, malignant fibrous histiocytoma, and embryonal sarcoma of the liver. The authors conclude that combined use of antidesmin and anti-MSA enhances the diagnosis of childhood sarcomas, especially when employed with other techniques such as electron microscopic study.

Topics: Actins; Biomarkers, Tumor; Child; Cytoplasm; Desmin; Fixatives; Humans; Immunoenzyme Techniques; Keratins; Myoglobin; Phosphopyruvate Hydratase; Prospective Studies; Rhabdomyosarcoma; Sarcoma; Staining and Labeling; Vimentin

RNA sequencing of unclassified soft tissue tumors has allowed for definition of multiple new entities. Antonescu et al. recently reported three case of low grade sarcoma with recurrent EWSR1/FUS::NACC1 fusion and distinctive storiform architecture that were suggestive of a novel tumor type.. Here, we present a case of an additional sarcoma with FUS::NACC1 fusion that arose in the head and neck and showed immunohistochemical evidence of epithelial differentiation.. A 41 year old woman presented with throat and inner ear pain and was found to have a nasopharyngeal mass. Biopsy highlighted a spindle cell neoplasm composed of bland cells arranged in a tight storiform pattern. On immunohistochemistry, the tumor cells were focally positive for S100 in a fibrillary pattern but were also positive for high molecular weight cytokeratin, p40, and CD34. RNA sequencing demonstrated a FUS::NACC1 fusion. The patient remains free of disease 2 years after surgical resection.. These findings confirm the previously-reported recurrent storiform histology in sarcomas with EWSR1/FUS::NACC1 fusion while simultaneously expanding the immunohistochemical spectrum of this entity to include overt epithelial differentiation. With involvement of a head and neck mucosal site, these findings also expand the differential diagnosis to include multiple mesenchymal entities including spindle cell squamous cell carcinoma. Further recognition of this emerging entity via expanded RNA sequencing panels will be necessary to determine the prevalence of these unique features.

Topics: Adult; Biomarkers, Tumor; Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Neoplasm Proteins; Repressor Proteins; RNA-Binding Protein FUS; Sarcoma; Soft Tissue Neoplasms

Extranodal follicular dendritic cell sarcomas are infrequent diagnostically challenging tumors. Because of their rarity, heterogeneous histomorphologic features and variable histologic grades a significant number of extranodal lesions are prone to be misdiagnosed. Even though they have a characteristic immunoprofile, expression of a range of nonspecific markers is well documented. Even though they are typically negative for keratins, few authors have reported lesions expressing keratin. Keratin expressing tumors are more likely to be misinterpreted by pathologists further deterring their inclusion in the differential diagnosis. We report an intraabdominal mesenteric follicular dendritic cell sarcoma in a 44-year-old male that immunophenotypically expressed keratin antigens. The lesion showed a high-grade pleomorphic epithelioid appearance and the initial differential diagnosis included lymphoma, sarcomas, melanoma, and carcinomas. Follicular dendritic cell sarcoma was not considered. Expression of epithelial membrane antigen and keratin further deterred the diagnosis which was reached only after extensive use of immunomarkers. The tumor cells expressed CD21, CD23, and D2-40. Morphologically, the tumor showed some thymoma-like features with occasional TDT-expressing background T-lymphocytes. These features were hints to reconsider our differential diagnosis to include follicular dendritic cell tumors. Awareness of this aberrant staining of epithelial immunomarkers and attention to certain clues should encourage pathologists to consider this entity. Speculative assumptions may explain this unusual keratin expression in some lesions. The histomorphologic and immunohistochemical heterogeneity may suggest different variants and grades of follicular dendritic cell sarcomas. The prevalence, importance, and histogenesis of keratin expression in follicular dendritic cell sarcomas warrant further studies.

Topics: Adult; Biomarkers, Tumor; Carcinoma; Dendritic Cell Sarcoma, Follicular; Dendritic Cells, Follicular; Diagnosis, Differential; Humans; Keratins; Male; Sarcoma

A 10-year-old peach-faced lovebird (Agapornis roseicollis) was evaluated for an ulcerated and painful mass at the location of a fracture 2 years previously. Whole body radiographs showed a humeral fracture with a presumptive neoplastic proliferation in the distal diaphysis. Right wing amputation was elected but the animal died during recovery from surgery. Histopathological examination of the amputated wing revealed an infiltrative sarcomatous neoplastic proliferation. Immunohistochemistry (IHC) was carried out to characterize the tumour using antibodies against vimentin, desmin, smooth muscle actin (SMA), S-100, ionized calcium-binding adapter molecule-1 (IBA-1), CD18, cytokeratin and epithelial membrane antigen (EMA). The mesenchymal component of the mass was immunolabelled for vimentin and SMA and sparse epithelial cells were immunopositive for cytokeratin. Very few scattered cells were immunopositive for CD18 and IBA-1. The final diagnosis was consistent with an undifferentiated sarcoma with intralesional hyperplastic epithelium. According to the location, the history of a previous fracture and the histological pattern and IHC profile, the tumour was classified as an undifferentiated sarcoma with entrapped air sac epithelium.

Topics: Agapornis; Animals; Bird Diseases; Keratins; Sarcoma; Soft Tissue Neoplasms; Vimentin

A 10-year-old female rabbit developed an unencapsulated and asymmetrical superficial dermal mass on the neck. The tumour was invasive with central ulceration and contained three different histological components, namely trichoblastomatous, basal cell carcinoma (BCC)-like and undifferentiated carcinomatous. In the trichoblastomatous component, which occupied most of the tumour, epithelial neoplastic cells formed ribbon-like cellular trabeculae with a palisaded appearance and stromal giant cells. The BCC-like component was a unique lesion composed of epithelial foci and sarcomatous stroma. The sarcomatous stroma consisted of pleomorphic mesenchymal cells with collagen fibres and frequent giant cells with one or more bizarre nuclei. In the undifferentiated carcinomatous component, neoplastic cells had a sheet-like growth pattern without trichoblastic or squamous differentiation. Immunohistochemically, neoplastic epithelial cells were positive for p63 and cytokeratin (CK) while the stromal and giant cells were immunopositive for vimentin but negative for CK and p63. This is the first report of a malignant trichoblastoma with a sarcomatous stroma in animals.

Topics: Animals; Carcinoma, Basal Cell; Epithelial Cells; Female; Keratins; Rabbits; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms

Although rare, malignant sarcomatoid breast tumours without evidence of epithelial differentiation comprise a diagnostic challenge with management implications. Earlier studies have generally considered these to be primary breast sarcomas; however, supporting evidence is lacking and management remains variable. This study aimed to provide an evidence-based approach to improve the consistency of diagnosis and management for such cases.. A large series (n = 140) of metaplastic breast carcinoma (MBC) diagnosed in Nottingham over 18 years was analysed. Only cases with available data on immunohistochemical expression of cytokeratins (CKs) were included. The prevalence and pattern of expression for various CKs were assessed and details of tumours negative for CKs were collected. A diagnostic approach based on our experience is provided. Forty-seven cases (34%) showed foci of conventional type invasive breast carcinoma or ductal carcinoma in situ (DCIS), while 93 cases (66%) were diagnosed as MBC based on morphology and/or CK expression. Ninety-seven cases (69%) were negative for one or more CKs, with 18 cases (13%) negative for five or more CKs. Eight cases (6%) lacked expression of all CKs tested. Further examination showed evidence of carcinomatous nature in five cases, and three were diagnosed as MBC following extensive diagnostic work-up and based on our experience.. This study suggests that MBC represents a spectrum of neoplasms, with some lacking CK expression. Sarcomatoid neoplasms of the breast lacking evidence of carcinomatous morphology and CK expression may represent an extreme end of differentiation that can be considered as carcinomas rather than sarcomas for management purposes (following extensive work-up).

Topics: Adult; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cohort Studies; Diagnosis, Differential; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Retrospective Studies; Sarcoma

Squamous cell carcinoma is the most common malignant tumor of the uterine cervix with a well-documented link to infection with human papillomaviruses (HPV). According to a recent classification, there are several morphological variants of cervical squamous carcinoma, without reference to sarcomatoid squamous cell carcinoma, which is well described in other organs.. In this paper, we describe an extremely rare case of a 77-year-old woman with primary malignant cervical tumor displaying biphasic histomorphology with an epithelioid and sarcomatoid part; the latter was immunohistochemistry positive for cytokeratin and vimentin. The association with a high-grade squamous intraepithelial lesion and molecular proof of HPV33 infection in the tumor tissue supported our diagnosis of carcinoma with partial sarcomatoid differentiation.. We report a rare case of a primary cervical epithelial tumor with a partial sarcomatoid phenotype, an unequivocal HPV infection, and an associated precancerous lesion in the cervical mucosa. This is the first description of an HPV33 infection underlying a biphasic epithelioid-sarcomatous tumor of the uterine cervix. The terminology overlap between sarcomatoid carcinoma and carcinosarcoma is also discussed.

Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Differentiation; Cervix Uteri; Female; Humans; Keratins; Papillomavirus Infections; Sarcoma; Uterine Cervical Neoplasms

Feline mammary tumors are usually malignant and aggressive carcinomas. Most cases are simple monophasic carcinomas (1 epithelial population), and additional phenotyping is usually not needed. In this study, we describe 10 malignant mammary tumors from 9 female cats that had unusual histomorphology: they appeared biphasic, with 2 distinct cell populations. Initially, they were morphologically diagnosed as either carcinosarcoma (1/10) or malignant pleomorphic tumor (9/10) of the mammary gland, as the latter did not match any previously described histological subtype. Immunohistochemistry (IHC) was performed for pancytokeratin, cytokeratins 8 and 18, cytokeratin 14, cytokeratins 5 and 6, vimentin, p63, calponin, alpha-smooth muscle actin, Ki-67, ERBB2, estrogen receptor alpha, and progesterone receptor. In 7 of 10 cases, the biphasic nature was confirmed and, on the basis of the IHC results, they were classified as carcinoma and malignant myoepithelioma (4/10), ductal carcinoma (1/10), and carcinosarcoma (2/10). The other 3 of 10 cases were monophasic based on IHC. In the cases of carcinoma and malignant myoepithelioma, the malignant myoepithelial cells were 100% positive for vimentin (4/4) and variably positive for p63, calponin, and cytokeratins (4/4). These findings show that, although rare, biphasic mammary carcinomas do occur in cats. In dogs and humans, tumors composed of malignant epithelial and myoepithelial cells have a less aggressive behavior than certain simple carcinomas, and therefore, their identification might also be clinically significant in the cat.

Topics: Animals; Biomarkers, Tumor; Calcium-Binding Proteins; Calponins; Carcinoma; Carcinoma, Ductal; Carcinosarcoma; Cat Diseases; Cats; Dogs; Female; Immunohistochemistry; Keratins; Mammary Neoplasms, Animal; Microfilament Proteins; Myoepithelioma; Sarcoma; Vimentin

The accumulated evidence has indicated the diagnostic role of cytokeratin (CK) and vimentin protein immunoassay in primary esophageal spindle cell carcinoma (PESC), which is a rare malignant tumor with epithelial and spindle components. However, it is largely unknown for the expression of CK and vimentin in pathological changes and prognosis of PESC.. Eighty-two PESC patients were identified from the esophageal and gastric cardia cancer database established by Henan Key Laboratory for Esophageal Cancer Research of Zhengzhou University. We retrospectively evaluated CK and vimentin protein expressions in PESC. Clinicopathological features were examined by means of univariate and multivariate survival analyses. Furthermore, the co-expression value of cytokeratin and vimentin was analyzed by receiver operating characteristic (ROC) curve.. The positive pan-cytokeratins AE1/AE3 (AE1/AE3 for short) staining was chiefly observed in cytoplasm of epithelial component tumor cells, with a positive detection rate of 85.4% (70/82). Interestingly, 19 cases showed AE1/AE3 positive staining both in epithelial and spindle components (23.2%). However, AE1/AE3 expression was not observed with any significant association with age, gender, tumor location, gross appearance, lymph node metastasis and TNM stage. Furthermore, AE1/AE3 protein expression does not show any effect on survival. Similar results were observed for vimentin immunoassay. However, in comparison with a single protein, the predictive power of AE1/AE3 and vimentin proteins signature was increased apparently than with single signature [0.75 (95% CI = 0.68-0.82) with single protein v.s. 0.89 (95% CI = 0.85-0.94) with AE1/AE3 and vimentin proteins]. The 1-, 3-, 5- and 7-year survival rates for PESC patients in this study were 79.3%, 46.3%, 28.0% and 15.9%, respectively. Multivariate analysis demonstrated age and TNM stage were independent prognostic factors for overall survival (P = 0.036 and 0.003, respectively). It is noteworthy that only 17.1% patients had a PESC accurate diagnosis by biopsy pathology before surgery (14/82). 72.4% PESC patients with biopsy pathology before surgery had been diagnosed as squamous cell carcinoma.. The present study demonstrates that cytokeratin and vimentin protein immunoassay is a useful biomarker for PESC accurate diagnosis, but not prognosis. The co-expression of cytokeratin and vimentin in both epithelial and spindle components suggest the possibility of single clone origination for PESC.

Topics: Adult; Aged; Anion Exchange Protein 1, Erythrocyte; Biomarkers, Tumor; Chloride-Bicarbonate Antiporters; Esophageal Neoplasms; Female; Gene Expression; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prognosis; ROC Curve; Sarcoma; Vimentin

Topics: Adolescent; Adult; Aged; Arm; Biomarkers, Tumor; Cell Differentiation; Child; Desmin; Diagnosis, Differential; Endothelium, Lymphatic; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Proteins; S100 Proteins; Sarcoma; Thigh; Vascular Endothelial Growth Factor Receptor-3

Topics: Gait Disorders, Neurologic; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Peripheral Nervous System Neoplasms; Peroneal Nerve; Sarcoma

Diagnosis of an epithelioid sarcoma (ES) is challenging on fine needle aspiration cytology (FNAC) smears. There are few documented series describing cytopathologic features and immunostaining results of ESs. The present study describes cytopathologic features of seven cases of ES. All seven tumors occurred in males within age-range of 22-61 years; in sites, such as forearm (n = 3), hand (n = 2), thigh (n = 1), and inguinal region (n = 1). FNAC was performed for metastatic lesions (n = 5), recurrent lesions (n = 4), as well as for a primary diagnosis (n = 1). FNAC smears in most cases were moderate to hypercellular, composed of polygonal cells(seven cases) and spindle cells(three cases), arranged in loosely cohesive groups, non-overlapping clusters, and scattered singly, containing moderate to abundant cytoplasm, defined cell borders, vesicular nuclei, and discernible nucleoli. Variable cytopathologic features identified in certain cases were "rhabdoid-like" intracytoplasmic inclusions (n = 5), giant cells (n = 3), and interspersed scanty, metachromatic stroma (n = 4). Histopathologic examination revealed two cases of conventional-type ES, three of proximal/large cell-type ES, and two cases of mixed-type ES, displaying features of conventional and proximal subtypes. By immunohistochemistry (IHC), tumor cells were positive for cytokeratin (CK)(4/5), epithelial membrane antigen (EMA) (6/6), panCK (1/1), vimentin (3/3), and CD34 (7/7). Tumor cells were completely negative for INI1/SMARCB1 (0/2) and CD31 (0/5). In our settings, FNAC was mostly performed in recurrent and/or metastatic cases of ES, and rarely for a primary diagnosis of ES. Important cytopathologic features of ESs include loosely cohesive, non-overlapping clusters of polygonal cells with variable "rhabdoid-like" and spindle cells. Optimal diagnostic IHC markers in such cases include CK, EMA, AE1AE3, CD34, and INI1/SMARCB1. Clinical correlation is imperative in all cases. Diagn. Cytopathol. 2016;44:636-642. © 2016 Wiley Periodicals, Inc.

Topics: Adult; Antigens, CD34; Arm; Biomarkers, Tumor; Biopsy, Fine-Needle; Humans; Keratins; Male; Middle Aged; Mucin-1; Platelet Endothelial Cell Adhesion Molecule-1; Sarcoma; SMARCB1 Protein; Soft Tissue Neoplasms; Thigh; Vimentin

Epithelioid sarcoma is a rare mesenchymal neoplasm, with an as yet unidentified cell of origin. Two subtypes of epithelioid sarcoma, distal/classic and proximal/large cell type, are recognized in the literature; with the proximal-type having a lower incidence amongst the two. Here, we present a case of proximal-type epithelioid sarcoma in a previously healthy young man. Fine-needle-aspiration of a large axillary mass was performed for diagnosis. The cytologic findings included a dispersed population of large epithelioid to polyhedral cells with abundant cytoplasm. Immunohistochemical staining showed coexpression of keratin and vimentin, as well as loss of INI1 staining, consistent with an epithelioid sarcoma, proximal subtype.

Topics: Adult; Axilla; Biomarkers, Tumor; Biopsy, Fine-Needle; Cytodiagnosis; Humans; Keratins; Lymph Nodes; Magnetic Resonance Imaging; Male; Sarcoma; Vimentin; Young Adult

Peritoneal mesothelioma is rare, and the sarcomatoid variant is more infrequent, with <30 cases reported to date in the literature. Several case series have described the morphologic features of sarcomatoid peritoneal mesothelioma (SPe); however, the clinicopathologic features are not well characterized. To our knowledge, this is the first large series reporting the clinicopathologic features of SPe. We reviewed our database of 3106 malignant mesothelioma cases. Of 248 peritoneal mesotheliomas, 15 (4%) were sarcomatoid variant (0.5% of all mesotheliomas). Only cases with 100% sarcomatoid morphology diagnosed by open surgical biopsy and/or autopsy were included. Thus, 4 cases were excluded leaving 11 cases of SPe. Two additional cases of SPe previously published by 1 of the authors (V.L.R.), not included in the database, are added yielding 13 cases total. The median age at diagnosis was 66 years (range=48 to 85 y), and there was a male predominance (M:F=3.25:1). Survival from date of diagnosis to date of death was 5 months (range=0 to 12 mo). The most common presenting symptom was abdominal pain, and 3 of 4 women were suspected to have cholecystitis/cholelithiasis. All cases stained positive for cytokeratins, and 2 contained heterologous elements. Seven cases had objective markers of asbestos exposure, and 2 additional cases had occupations strongly associated with mesothelioma. Two cases with alleged household contact exposures could not be confirmed to be asbestos related by lung fiber analysis. SPe is a rare variant of mesothelioma attributed to asbestos exposure in 69% of our cases.

Topics: Aged; Aged, 80 and over; Asbestos; Autopsy; Biomarkers, Tumor; Biopsy; Databases, Factual; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Incidence; Inhalation Exposure; Keratins; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Occupational Exposure; Peritoneal Neoplasms; Predictive Value of Tests; Prognosis; Risk Factors; Sarcoma; Survival Analysis

The workup of a malignant effusion usually requires immunostaining with a panel of markers. Although nuclear Wilms tumor 1 (WT1) expression is widely used to detect tumors of ovarian and mesothelial origin, it is less well known that WT1 is also expressed in the cytoplasm of melanomas and mesenchymal tumors. Because to the authors' knowledge the diagnostic utility of cytoplasmic WT1 expression has not been explored to date, the usefulness of a WT1/AE1/AE3 dual-color immunostain in the workup of malignant effusions was evaluated.. A total of 86 pleural effusions, including 17 metastatic melanomas, 31 metastatic adenocarcinomas, 10 malignant mesotheliomas, 10 lymphoproliferative disorders, 5 metastatic sarcomas, and 13 benign specimens, were immunostained using a peroxidase-based brown chromogen for WT1 and an alkaline phosphatase-based red chromogen for AE1/AE3 on cell block sections.. The majority of malignant effusions stained in 1 of 4 distinctive patterns: 1) all lung and breast adenocarcinomas demonstrated cytoplasmic AE1/AE3 expression without nuclear or cytoplasmic WT1 expression; 2) serous carcinomas of Müllerian origin, mesotheliomas, and benign mesothelial cells were positive for cytoplasmic AE1/AE3 as well as nuclear WT1; 3) melanomas, sarcomas, and a subset of plasma cell neoplasms were positive for cytoplasmic expression of WT1 but negative for AE1/AE3; and 4) large B-cell lymphomas and a subset of plasma cell neoplasms were negative for both markers.. A WT1/AE1/AE3 dual-color immunostain can reliably identify malignancy in pleural effusions and group malignant cells into discrete subsets, thereby narrowing the differential diagnosis. This simple double stain can be a cost-effective, first-line test in the workup of patients with malignant effusions.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma; Coloring Agents; Epithelium; Humans; Immunohistochemistry; Keratins; Lymphoproliferative Disorders; Melanoma; Mesothelioma; Neoplasm Metastasis; Pleural Effusion, Malignant; Sarcoma; WT1 Proteins

To study the immunophenotype and molecular genetics of epithelioid sarcoma (ES), INI1 expression and its role in differential diagnosis.. Twenty cases of ES were retrieved from the archival files and selected for immunohistochemical study, DNA sequencing and fluorescence in-situ hybridization. The clinical and pathologic features were also reviewed.. The age of patients ranged from 16 to 75 years (mean = 40.2 years). The median age of patients in classic ES and proximal-type was 37.9 years and 42.0 years, respectively. The male-to-female ratio was 1.2: 1.0. Classic ES mostly occurred in the extremities while proximal-type ES often affected the perineum and external genitalia and trunk. Histologically, granuloma-like structures, consisting of aggregates of epithelioid and spindly tumor cells with central necrosis, were observed in classic ES. The epithelioid tumor cells contained abundant eosinophilic cytoplasm, merged with spindly cells at the periphery and admixed with collagen fibers. In proximal-type ES, the tumor cells showed prominent epithelioid and/or rhabdoid features, had marked cytologic atypia and grew in multinodular or diffuse patterns. In 2 cases of proximal-type ES studied, the "rhabdoid" tumor cells demonstrated a diffuse sheet-like growth pattern, mimicking malignant rhabdoid tumor. Immunohistochemical study showed that vimentin was positive in all cases. Pan-cytokeratin, CK8, CK7, epithelial membrane antigen and CD34 were expressed in 16, 15, 1, 18 and 13 cases, respectively. The staining for S-100 protein was focal and weak in 5 cases. None of the cases studied expressed CD31 and HMB45. Loss of INI1 was demonstrated in 10 of the 13 classic ES cases and 5 of the 7 proximal-type ES cases. The mutation of INI1 gene was detected in 1 of the 6 cases. Deletion of INI1 gene including heterozygous deletion, homozygous deletion and haploid was observed in 8 of the 11 cases.. Owing to the histologic heterogeneity, pitfalls in diagnosis of ES sometimes are encountered. INI1 is lost in most cases of ES. Immunohistochemical study, including staining for INI1, provides useful clues in pathologic diagnosis. Instead of INI1 mutation, inactivation of INI1 gene related deletion is not uncommon.

Topics: Adolescent; Adult; Aged; Antigens, CD34; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Female; Gene Deletion; Humans; Immunophenotyping; In Situ Hybridization, Fluorescence; Keratins; Male; Middle Aged; Mucin-1; Mutation; Rhabdoid Tumor; Sarcoma; SMARCB1 Protein; Transcription Factors; Young Adult

The author presents a unique case of multiple cytokeratin-negative malignant tumors consisting only of rhabdoid cells in the renal pelvis. A 54-year-old man complained of hematuria. A transurethral endoscopic examination revealed multiple papillary tumors, and transurethral resection of the bladder tumors was performed. Pathologically, they were ordinary papillary urothelial transitional cell carcinomas. Imaging modalities revealed multiple tumors of the right renal pelvis, and nephrectomy was performed. Grossly, three polypoid tumors measuring 2-4 cm were present in the pelvis. Histologically, they were composed only of malignant cells with rhabdoid features. There were no elements of transitional cell carcinoma. Immunohistochemically, the pelvic tumors were positive for vimentin and Ki-67 antigen (labeling=40%). They were negative for pancytokeratins (AE1/3, CAM5.2, KL-1 and polyclonal wide), 34βE12, cytokeratin (CK) 5/6, CK7, CK8, CK14, CK18, CK19, CK20, melanosome, EMA, CEA, desmin, S100 protein, α-smooth muscle actin, myoglobin, myogenin, CD34, p53 protein, p63, CD3, CD20, CD30, CD45, CD45RO, chromograin, synaptophysin, CD56, CD68, and KIT. NSE and PDGFRA were focally present, but this appeared nonspecific. Namely, the pelvic tumors expressed only vimentin. The author speculates that the pelvic multiple malignant "rhabdoid" tumors are not sarcomas but urothelial "rhabdoid" carcinoma with complete loss of CKs.

Topics: Biomarkers, Tumor; Diagnosis, Differential; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Rhabdoid Tumor; Sarcoma; Treatment Outcome; Urothelium; Vimentin

The development of the Cre recombinase-controlled (Cre/LoxP) technique allows the manipulation of specific tumorigenic genes, temporarily and spatially. Our original intention of this study was to investigate the role of Kras and p53 in the development of urinary bladder cancer. First, to validate the effect of intravesical delivery on Cre recombination (Adeno-Cre), we examined activity and expression of β-galactosidase in the bladder of control ROSA transgenic mice. The results confirmed specific recombination as evidenced by β-galactosidase activity in the bladder urothelium of these mice. Then, we administered the same adenovirus into the bladder of double transgenic Kras(LSLG12D/+). p53(fl/fl) mice. The virus solution was held in place by a distal urethral retention suture for 2 hours. To our surprise, there was a rapid development of a spindle-cell tumor with sarcoma characteristics near the suture site, within the pelvic area but outside the urinary track. Since we did not see any detectable β-galactosidase in the area outside of the bladder in the validating (control) experiment, we interpreted that this sarcoma formation was likely due to transduction by Adeno-Cre in the soft tissue of the suture site. To avoid the loss of skin integrity associated with the retention suture, we transitioned to an alternative technique without suture to retain the Adeno-Cre into the bladder cavity. Interestingly, although multiple Adeno-Cre treatments were applied, only urothelial hyperplasia but not carcinogenesis was observed in the subsequent experiments of up to 6 months. In conclusion, we observed that the simultaneous inactivation of p53 and activation of Kras induces quick formation of spindle-cell sarcoma in the soft tissues adjacent to the bladder but slow formation of urothelial hyperplasia inside the bladder. These results strongly suggest that the effect of oncogene regulation to produce either hyperplasia or carcinogenesis greatly depends on the tissue type.

Topics: Adenoviridae; Animals; beta-Galactosidase; Breeding; Female; Fluorescent Antibody Technique; Genotype; Hyperplasia; Integrases; Keratins; Magnetic Resonance Imaging; Mice; Mice, Transgenic; Organ Specificity; Proto-Oncogene Proteins p21(ras); Reproducibility of Results; RNA, Untranslated; Sarcoma; Staining and Labeling; Tumor Suppressor Protein p53; Urinary Bladder; Urothelium

A primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an extremely rare lesion. To date, only 49 cases have been reported. The presence of mural nodules in a PRMC may indicate a worse prognosis. We report the case of a 40-year-old Japanese woman with a PRMC with mural nodules. Microscopic examination revealed that the stromal cells of the nodules were spindle-shaped and varied in size. The nodules were immunoreactive for vimentin but negative for cytokeratin and EMA, and the nuclei of the stromal cells were pleomorphic and strongly Ki-67 immunoreactive. The nodules were diagnosed as true sarcoma. To the best of our knowledge, this is 11th published case report of a PRMC with mural nodules.

Topics: Adult; Cystadenocarcinoma, Mucinous; Female; Humans; Keratins; Prognosis; Retroperitoneal Neoplasms; Sarcoma; Vimentin

The inflammatory pseudotumor is a rare lesion, having benign behavior and some histological heterogeneity that appears in the genitourinary tract. A series of urogenital inflammatory pseudotumors are reviewed with emphasis on their clinicopathological and immunohistochemical characteristics.. A retrospective study the causistics treated between January 1981 in December 2010 was performed. It identified the cases of inflammatory pseudotumor with urogenital localization. The variables age, gender, symptoms, topography, treatment and anatomopathological and immunohistochemical characteristics of each case were analyzed.. A total of 8 cases of the urogenital-located inflammatory pseudotumor are described. Of these, 6 were located in the bladder, one in the kidney and one in the epididymis. Mean age of the patients was 46.75 (± 19.84) years. Tumor presentation symptoms were macroscopic hematuria, single symptom or accompanied by symptoms of the lower urinary tract and inguinoscrotal mass. In regards to treatment in the cases of bladder localization, transuretheral ± cystectomy were performed. In the case of kidney localization, treatment was made by means of pyelotomy and exeresis, and in the case of epididymis localization, simple exeresis was performed. The anatomopathological study showed inflammatory pseudotumor in every cases, having a mesenchymal and myxoid appearance, with fusiform cells of eosinophil cytoplasm, with presence of frequent inflammatory cells. The most common immunohistochemical pattern shows positivity for the muscle-specific actin (HHF-35), vimentin and negativity for protein S-100. ALK-1 was positive and 87.5% of the cases.. The inflammatory pseudotumor is a condition having good prognosis which, when there is a good histopathological and immunohistochemical diagnosis, every urologist should recognize and distinguish in order to carry out as conservative a surgical treatment as possible.

Topics: Actins; Activin Receptors, Type II; Adolescent; Adult; Aged; Biomarkers; Cystectomy; Diagnosis, Differential; Diagnostic Imaging; Epididymis; Female; Genital Diseases, Male; Granuloma, Plasma Cell; Humans; Keratins; Kidney Diseases; Male; Middle Aged; Retrospective Studies; Sarcoma; Spain; Urinary Bladder Diseases; Vimentin

Cutaneous epithelioid and spindle cell neoplasms occasionally pose a significant diagnostic challenge on purely histologic grounds. Given the substantial clinicopathologic overlap between these lesions, especially in small biopsies, the use of immunohistochemical studies are essential. We evaluated the utility of a battery of immunohistochemical markers, including podoplanin (D2-40), CD10, p63, and wide-spectrum cytokeratin, for distinguishing cutaneous epithelioid and spindle cell tumors. A total of 81 cases, including 42 atypical fibroxanthoma (AFX), 13 spindle cell melanoma, 10 sarcomatoid carcinoma, 9 leiomyosarcoma (LMS), and 7 leiomyoma, formed the basis of our study. Immunohistochemical results were as follows-AFX: CD10 (35 of 42), p63 (1 of 42), CK (1 of 42), and podoplanin (19 of 42); spindle cell melanoma: CD10 (7 of 13), p63 (0 of 13), CK (0 of 13), and podoplanin (2 of 13); sarcomatoid carcinoma: CD10 (5 of 10), p63 (7 of 10), CK (4 of 10), and podoplanin (7 of 10); LMS: CD10 (4 of 9), p63 (0 of 9), CK (2 of 9), and podoplanin (1 of 9); and leiomyoma: CD10 (0 of 7), p63 (0 of 7), CK (0 of 7), and podoplanin (1 of 7). Our findings showed that the combination of certain immunohistochemical markers may be a useful adjunct in the evaluation of epithelioid and spindle cell tumors of the skin. In this study, we found that a combination of wide-spectrum cytokeratin and p63 are most helpful in the distinction of sarcomatoid carcinomas from other tumors; however, there remains a substantial minority of cases of sarcomatoid carcinoma that will consistently demonstrate negative staining for these markers. We also found that CD10 and podoplanin (D2-40) have limited diagnostic utility in epithelioid and spindle cell tumors of the skin; however, a strong and diffuse pattern of staining will favor the diagnosis of AFX. Caution should also be observed in the diagnosis of spindle cell malignant melanoma because some cases may express CD10, p63, and podoplanin while being nonreactive to S100 protein. Awareness of the limitations of the use of these stains and familiarity with their staining patterns in spindle and epithelioid cell tumors of the skin are extremely important because the prognostic and therapeutic implications for such neoplasms may be quite different.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Epithelioid Cells; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Neprilysin; Predictive Value of Tests; Sarcoma; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins; Wisconsin; Young Adult

To determine the frequency, pattern and distribution of stromal keratin expression in phyllodes tumours if any, which may impact diagnostic approaches.. The clinicopathological features of 109 phyllodes tumours comprising 70 (64.2%) benign, 30 (27.5%) borderline and nine (8.3%) malignant grades were evaluated, and the immunohistochemical expression of a keratin panel (MNF116, 34βE12, CK7, CK14, AE1/3, Cam5.2), p63 and CD34 in their stromal component was assessed.. There was focal and patchy cytoplasmic keratin staining in 1-5% of stromal cells in 13 (11.9%), 24 (22%), 31 (28.4%), 2 (1.8%), 9 (8.3%) and 2 (1.8%) cases for MNF116, 34βE12, CK7, CK14, AE1/3, Cam5.2, respectively. CD34 was expressed in 79 (72.5%) cases. There was no stromal staining for p63. Stromal MNF116, 34βE12 and Cam5.2 reactivity was significantly associated with phyllodes tumour grade (p=0.027, p=0.034, p=0.009 respectively), while MNF116 stromal staining was observed in tumours with increasing cellularity (p=0.036), necrosis (p=0.015) and cystic change (p=0.048). Contrary to common understanding, these findings confirm that stromal cells in phyllodes tumours can sometimes express keratins, albeit focal and in a patchy distribution. In comparison, fibromatosis and dermatofibrosarcoma were uniformly negative for the same keratin panel, while spindle cell components of eight metaplastic carcinomas expressed at least two or more keratins in a wider distribution of up to 90% of positively stained spindle cells. All eight spindle cell sarcomas were negative for keratins.. The use of keratins as an adjunctive immunohistochemical diagnostic tool in the differential work-up of spindle cell tumours of the breast has to be interpreted with caution especially on limited core biopsy material.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Breast; Breast Neoplasms; Case-Control Studies; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Phyllodes Tumor; Sarcoma; Stromal Cells; Young Adult

The behavior of atypical fibroxanthoma is benign, if strict diagnostic criteria are applied. Tumors with similar pathologic features but deep subcutaneous invasion, necrosis, and/or lymphovascular or perineural invasion are thought to be associated with adverse outcome and are better regarded as pleomorphic dermal sarcoma or undifferentiated pleomorphic sarcoma of skin. This tumor group is not well documented in the literature, and its characteristics are only poorly defined. To study the clinical and pathologic spectrum more comprehensively, we retrieved 32 pleomorphic dermal sarcomas from our departmental files. The tumors were large (median: 25 mm) and exclusively presented on sun-damaged skin with a strong predilection for the head. Typically, elderly men were affected (median age: 81 y). Histologically, these often ulcerated tumors were poorly marginated, asymmetrical, and deeply invasive into deep subcutaneous, muscular, and/or fascial tissues. The tumors were cellular and composed of pleomorphic epithelioid cells, atypical spindle cells, and multinucleated tumor giant cells in varying proportions. Mitotic count was brisk and often atypical. Tumor necrosis was observed in 53%, lymphovascular invasion in 26%, and perineural infiltration in 29%. The majority of tumors showed a predominance of atypical spindle cells in a fascicular arrangement. A sheet-like growth of pleomorphic epithelioid cells or mixed spindle and epithelioid cell features were less frequently observed. Myxoid and keloidal change, a desmoplastic stromal response, pseudoangiomatous and storiform growth patterns, and admixed osteoclast-like giant cells were additional morphologic features in some cases. No immunoreactivity was noted for multiple cytokeratins, S100, HMB-45, desmin, and CD34. Smooth muscle actin was expressed in 70%, CD31 in 48%, epithelial membrane antigen in 16%, Melan A in 6%, and p63 in 1 case. CD10 was expressed in all cases stained. Follow-up (available for 29 patients; median: 24 mo) showed local recurrence in 28% and a metastatic rate of 10%, mainly in the skin. Progressive metastatic disease was observed in 2 patients. Remission was achieved in 1 patient using systemic chemotherapy. The second patient died in the setting of advanced-stage non-Hodgkin lymphoma. No disease-related mortality was noted. Our data underscore the importance of recognizing adverse histologic features in tumors otherwise resembling atypical fibroxanthoma. Deep subcutaneous invasion, tum

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Comorbidity; Diagnosis, Differential; Female; Humans; Keratins; Male; Middle Aged; Sarcoma; Scotland; Skin Neoplasms; Xanthomatosis

Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor. ES can be classified into proximal, distal, and fibroma-like subtypes. These tumors show both mesenchymal and epithelial immunophenotypes. Microscopically, the proximal type ES is usually characterized by nodules of spindle and epithelioid cells growing in granuloma-like pattern often presenting with central necrosis. Immunohistochemically these tumors are vimentin, pancytokeratin, and usually EMA (80%) positive. CD34 (50%) and CD99 (25%) may be positive, and occasionally SMA and S-100 immunopositivity has been reported. No specific genetic alterations have been found in ES. As far as we know, this is the first case in the literature to present ES in gingival mucosa.

Topics: 12E7 Antigen; Adult; Antigens, CD; Cell Adhesion Molecules; Desmin; Diagnosis, Differential; Gingival Neoplasms; Humans; Keratins; Male; Mandible; Sarcoma; Vimentin

To study the clinicopathologic features and differential diagnosis of epithelioid sarcoma-like hemangioendothelioma (ES-H).. The clinical, radiologic and pathologic features of three cases of ES-H were analyzed.. All the 3 cases occurred in male adults. The age ranged from 44 to 53 years. The presentations included left neck mass, iliac pain and bilateral shoulder masses. Histologically, ES-H was composed of a mixture of spindle and epithelioid tumor cells. Transition between the two cell types was demonstrated. The tumor cells were arranged in compact sheets, vague nodules or intersecting fascicles, amongst a collagenous stroma. Central coagulative necrosis was identified in one case, reminiscent the morphology that seen in epithelioid sarcoma. There was no evidence of angiogenesis, though focal presence of intracytoplasmic vacuoles was seen in one case, as in classic examples of epithelioid hemangioendothelioma. Immunohistochemical study showed that the tumor cells expressed both epithelial (AE1/AE3, CAM5.2 and epithelial membrane antigen) and endothelial (CD31, Fli-1 and factor VIII-related antigen) markers. Two of the cases were also positive for CD34. All of the patients were treated by surgical resection. Two patients remain well at 14-month and 9-month follow up, respectively. The remaining patient had repeated local recurrences during a 6-year period.. ES-H represents a rare morphologic type of hemangioendothelioma. It has some overlapping histologic features with epithelioid sarcoma and epithelioid hemangioendothelioma. The endothelial nature of ES-H is difficult to be verified on the basis of morphologic examination alone. Confirmation of the diagnosis with immunohistochemistry is necessary. ES-H is likely related to epithelioid hemangioendothelioma and may represent a cellular spindle cell variant of epithelioid hemangioendothelioma.

Topics: Adult; Antigens, CD34; Biomarkers; Diagnosis, Differential; Follow-Up Studies; Hemangioendothelioma; Hemangioendothelioma, Epithelioid; Humans; Ilium; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Mucin-1; Neck; Neoplasm Recurrence, Local; Platelet Endothelial Cell Adhesion Molecule-1; Proto-Oncogene Protein c-fli-1; Reoperation; Retrospective Studies; Sarcoma; Shoulder; von Willebrand Factor

In this case report, we have described the fine needle aspiration cytology (FNAC) of epithelioid sarcoma (ES) in a 40-year-old female patient who presented with multiple nodular swellings over right forearm and single right axillary lymph node. The FNAC smear showed predominantly dispersed as well as three-dimensional clusters of malignant cells admixed with basement membrane like material. The individual cells were moderately pleomorphic with round to oval nuclei and moderate to abundant amount of cytoplasm. The neoplastic cells have well-defined cytoplasmic borders and intercellular spaces. The excision biopsy of the swelling of the forearm showed ES. The cytology features of ES are characteristic and a preoperative diagnosis is helpful for proper management of the case.

Topics: Adult; Axilla; Biomarkers, Tumor; Biopsy, Fine-Needle; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Sarcoma; Soft Tissue Neoplasms; Vimentin

The role of CD10 needs clarification in a broader immunohistochemical battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell squamous cell carcinoma (sSCC).. We retrospectively reviewed 23 cutaneous spindle cell tumors previously classified as AFX (n = 11) or as sSCC (n = 12). Each tumor was stained with CD10, S-100, p63 and two or more cytokeratin stains. Defining AFX as a diagnosis of exclusion based on multiple negative cytokeratin stains and negative p63 staining, we reclassified four squamous cell carcinomas (SCCs) as AFX. CD10 staining was reviewed and graded in all tumors.. Fifteen tumors were classified as AFX. Strongly positive CD10 staining was observed in all 15 AFXs, as well as four (50%) of the eight SCCs. Expression of p63 was seen in six sSCCs (75%).. CD10 is consistently expressed by AFX. However, CD10 is also often strongly expressed by sSCC. Positive staining with p63 favors a diagnosis of sSCC. An immunohistochemical battery useful for distinguishing AFX from sSCC may include CD10, p63 and two cytokeratin markers. However, CD10 alone should not be relied upon in the distinction of these entities.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Keratins; Membrane Proteins; Neprilysin; Retrospective Studies; Sarcoma; Skin Neoplasms; Xanthomatosis

Topics: Antigens, Neoplasm; Biomarkers; CD56 Antigen; Cell Membrane; Cell Nucleus; Child; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-3; Keratins; Liver Neoplasms; Neoplastic Stem Cells; Protein Transport; Receptors, Cell Surface; Sarcoma

Topics: Adult; Diagnosis, Differential; Female; Humans; Keratins; Lymphatic Metastasis; Mucin-1; Rectal Neoplasms; Rhabdoid Tumor; Sarcoma; Synaptophysin; Vimentin; Young Adult

Adamantinomas of the long bones are low-grade malignant tumours. They seem to be related to osteofibrous dysplasia with a mesenchymal-to-epithelial transformation. We report a case of an adamantinoma with a revertant sarcomatoid transformation that showed a complete loss of epithelial differentiation. It corresponded to a 41-year-old male presented with an 8-cm multilobated lesion in the centre of the distal tibia. On the en bloc resection specimen, areas of classic adamantinoma were found but most of the tumor corresponded to a high-grade neoplasm with 2 histologic patterns: one made up by epithelial nests with a basaloid arrangement and positive for pankeratins and so-called glandular keratins, and a second sarcomatoid component, negative for these epithelial markers. Five months after surgery the patient had a massive relapse that consisted solely of the second sarcomatous component also negative for epithelial antibodies.Three cases of adamantinomas with sarcomatoid transformation of the epithelial component have been described but the tumours still preserved an epithelial immunophenotype. However, our case represents the extreme end of the sarcomatoid dedifferentiation of a classic adamantinoma with complete sarcomatoid transformation and total loss of epithelial markers. To our knowledge this has not been described previously.

Topics: Adamantinoma; Adult; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Cell Transformation, Neoplastic; Humans; Keratins; Male; Mesoderm; Neoplasms, Second Primary; Phenotype; Sarcoma; Tibia; Treatment Outcome

Vulvar epithelioid sarcoma is a rare, undifferentiated soft-tissue sarcoma, with a high rate of local relapse, regional nodal spread and distant metastases. The aim of this study was to investigate the clinical features, diagnosis, treatment and prognosis of this malignancy.. We studied the clinicopathologic features of 20 cases of vulvar epithelioid sarcoma, of which 4 cases were admitted to our hospital from 1999 to 2009. All of the patients received radical local excision with inguinofemoral lymphadenectomy. Seven patients were treated without adjuvant therapy. Seven patients received postoperative radiotherapy only and three underwent chemotherapy. Chemotherapy plus radiotherapy were given postoperatively in three.. The patients ranged in age from 23 to 80 years (median: 36 y). The tumors ranged from 1 to 10 cm in their greatest diameter (median: 5.1 cm). All cases showed immunoreactivity for both vimentin and cytokeratin. Follow-up information on all 20 patients was available, and covered periods ranging from 3 to 104 months.11 patients were alive with no evidence of disease. 2 patients developed lymph node metastases but alive. 7 patients had died of the disease. Survival of the early stage (I-II) patients was significantly longer than those in the advanced stage (III-IV) (median, 21 vs. 6 months, P < 0.01). There was no significant difference between survival of patients with or without inguinofemoral lymphadenectomy (median, 11.5 vs. 6 months, P = 0.086).. Because of the relatively frequent misdiagnosis, a differential diagnosis combined with immunohistochemistry is needed to determine an early and accurate diagnosis. The tumor markers exhibiting immunoreactivity includ vimentin, epithelial membrane antigen (EMA) and cytokeratin (CK). Radical local excision with adequate margin (at least 2 cm) and bilateral inguinofemoral lymphadenectomy is effective for the treatment of vulvar epithelioid sarcoma. The role of adjuvant therapy, chemotherapy and radiation remains unclear but merits consideration.

Topics: Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Female; Follow-Up Studies; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Mucin-1; Neoplasm Staging; Radiotherapy, Adjuvant; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Survival Rate; Vimentin; Vulva; Vulvar Neoplasms; Young Adult

Epithelioid sarcoma of the vulva is an extremely rare neoplasm with aggressive behavior and poor outcome. Herein, we report a case of vulvar epithelioid sarcoma presenting in a 17-year-old very early in her pregnancy. The patient presented with an asymptomatic nodule of the right labia majora of 1-year duration. Computerized tomographic scans showed enlarged inguinal lymph nodes and numerous lung nodules. Positron emission tomography was performed and revealed no suspicious lesions for metastatic disease. The patient underwent local excision of her vulvar lesion. On the basis of morphology and extensive immunohistochemistry, the lesion was classified as epithelioid sarcoma. The patient was referred to radiation therapy and upon evaluation, she was found to be in her sixth week of gestation. The patient continued with her pregnancy and underwent a lymph node dissection, which was positive. We review the literature of only the well-documented cases extensively studied by immunohistochemical analysis. We summarize the clinical presentation, clinical impression, treatment modalities, and outcomes of these cases. On account of the rarity of this disease in the vulva, there is no clear consensus on treatment modalities, but it seems that early aggressive surgical resection is the treatment of choice, with the role of adjuvant therapy to be determined.

Topics: Adolescent; Antigens, CD34; Female; Humans; Keratins; Platelet Endothelial Cell Adhesion Molecule-1; Pregnancy; Pregnancy Complications, Neoplastic; Sarcoma; Vulvar Neoplasms

Atypical fibroxanthoma (AFX) (dermal pleomorphic sarcoma) remains a somewhat controversial entity. Some authors have averred that AFX is a fiction, suggesting that such lesions merely represent misclassified examples of spindled squamous cell carcinoma. In addition, the immunoperoxidase confirmation of AFX has been less than straightforward and has historically been approached as a diagnosis of exclusion because of the lack of sensitivity and specificity of available "positive" reagents. Procollagen 1 (PC1) and CD10 represent recently developed immunoperoxidase reagents that have been forwarded as useful in this setting, and we sought to characterize our experience, both to confirm the utility of these antibodies and to compare them. Our investigation included 3 separate data sets. Group 1 consisted of a retrospective review of 98 consecutive cases in which PC1 was used in the evaluation of dermatopathology specimens in routine practice during a 13-month interval. Group 2 consisted of a direct comparison of 11 AFX, 11 dermatofibroma (DF), and 7 epithelioid dermatofibroma (EDF) using the CD10 reagent on cases identified by database search. Group 3 consisted of a retrospective review of 47 cases in which CD10 was used in routine practice during a 10-month interval. Group 1 included 47 AFX, 13 carcinomas, and 6 melanomas. PC1 expression was observed in 45 of 47 AFX (96%), with a strong reaction in 78% of cases. Among a comparison group of carcinomas, 13 of 13 displayed strong keratin immunopositivity and 11 of 13 (85%) lacked PC1 expression whereas 2 showed focal weak labeling. Six of six melanomas exhibited avid S100 expression and none labeled with PC1. In group 2, strong CD10 immunoreactivity was present in 11 of 11 AFX. Similarly, 11 of 11 DFs were also positive. In contrast, 6 of 7 cases of EDF lacked CD10 expression. Group 3 included 38 AFX and 9 miscellaneous spindle cell proliferations. Of the 38 AFX, 37 (97%) labeled with CD10 and in 34 (92%) the reaction was strong. PC1 immunostaining was also completed in 34 of 38 AFX from group 3 and 27 (79%) cases showed positive labeling. Our results confirm that both PC1 and CD10 can be used as positive markers of AFX. We believe that CD10 and PC1 immunostaining can be used as a useful adjunct to supplement the diagnosis of AFX, within the context of an immunoperoxidase panel. Not surprisingly, CD10 expression is also common in DF, a benign analog of AFX, with the exception of its epithelioid variant. In direc

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Collagen Type I; Diagnosis, Differential; Epithelioid Cells; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Middle Aged; Neprilysin; Predictive Value of Tests; Procollagen; Reproducibility of Results; Retrospective Studies; S100 Proteins; Sarcoma; Skin Neoplasms; Xanthomatosis

Only a small number of malignant mesotheliomas with heterologous elements have been described. There are currently no criteria for diagnosis and little data regarding prognosis. We suggest that the term heterologous mesothelioma should be reserved for tumours that show malignant heterologous elements, notably osteosarcomatous, chondrosarcomatous, or rhabdomyoblastic elements but have immunohistochemical and clinical characteristics of mesothelioma. We identified 27 such cases and characterized the clinical and pathological characteristics of these tumours. In our series, 89% originated in the pleura, and 11% from the peritoneal cavity. The median age at diagnosis was 68 years, ranging from 27 to 85 years. Of these cases, 93% occurred in males and 7% in women. Of the 27 mesothelioma cases 16 (59%) were sarcomatoid, 10 (37%) were biphasic, and one was reported as epithelioid; 40% (11 cases) showed osteosarcomatous elements only, 19% showed areas of rhabdomyosarcoma only, 19% contained areas of chondrosarcoma only, and 22% exhibited osteochondromatous elements. Immunohistochemical labelling for cytokeratins was present in the majority of cases. Exposure to asbestos was identified in all the 17 cases for which an exposure history was available (63%). Median survival was 6 months after diagnosis, similar to the survival seen in sarcomatoid mesotheliomas. The differential diagnosis includes primary and secondary pleural sarcomas, including osteosarcomas and chondrosarcomas. Immunohistochemical labelling for cytokeratins is helpful in the distinction, but lack of labelling for cytokeratins in a spindle cell/sarcomatoid tumour does not exclude the diagnosis of mesothelioma, irrespective of the presence of heterologous elements. We suggest that if the anatomical distribution conforms to that of mesothelioma, a diagnosis of heterologous mesothelioma should be made in preference to a diagnosis of primary pleural osteosarcoma or chondrosarcoma, regardless of cytokeratin positivity, as for conventional non-heterologous sarcomatoid mesothelioma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chondrosarcoma; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Mesothelioma; Middle Aged; Osteosarcoma; Peritoneal Neoplasms; Pleural Neoplasms; Rhabdomyosarcoma; Sarcoma; Survival Rate

Topics: Carcinoma; Diagnosis, Differential; Female; Humans; Keratins; Middle Aged; Ovarian Neoplasms; Prognosis; Sarcoma

Epithelioid sarcoma (ES) is a rare, aggressive soft tissue tumor with a characteristic predilection for adolescents and young adults, and a tendency to occur on distal extremities. We report a case of ES arising in an 80-year-old woman within a burn scar that histopathologically showed unusual 'angiomatoid' features. The patient presented initially with a solitary nodule on her right wrist arising at the site of a burn scar. Histopathologically, the tumor was composed of a proliferation of relatively bland, epithelioid and spindle cells focally arranged in a nodular pattern around areas of 'geographic' necrosis. In addition, there were prominent foci of hemorrhage and blood-filled spaces as well as tumor cells with intracytoplasmic vacuoles, features suggestive of an angiomatous process. Immunohistochemistry showed positivity of tumor cells for cytokeratins and epithelial membrane antigen (EMA) whereas all vascular markers tested were negative. The overall histopathologic features were consistent with a diagnosis of ES. Follow up showed multiple recurrences arising proximally along the right upper extremity. Our case underlines the clinical and histopathological heterogeneity of ES, emphasizing the unusual occurrence of ES with 'angiomatoid' features in the elderly. In this uncommon setting, this tumor should be especially distinguished from epithelioid hemangioendothelioma and epithelioid angiosarcoma. The significance of development of ES on a healed burn scar is uncertain, but may suggest a possible causal relationship.

Topics: Aged, 80 and over; Angiomatosis; Biomarkers, Tumor; Burns; Cicatrix; Female; Humans; Keratins; Mucin-1; Neoplasm Recurrence, Local; Sarcoma; Soft Tissue Neoplasms; Wrist

The distinction between sarcomatoid carcinoma (SC) and bona fide sarcoma can be difficult using conventional immunohistochemical markers. Epithelial-mesenchymal transition (EMT) has been proposed as a histogenetic mechanism for the development of SC. Expression of selected markers of EMT (Twist and Slug) was compared with other markers of epithelial differentiation in SC and spindle cell sarcoma to determine the utility of these antigens in this differential diagnosis. Twenty-seven cases of SC (excluding those of gynecologic origin) were stained by immunohistochemistry for cytokeratins (AE1/AE3, 5D3, CK5/6, and 34betaE12), p63, claudin-1, claudin-7, epithelial cadherin, placental cadherin, epithelial cell adhesion molecule/epithelial-specific antigen, 14-3-3sigma, Twist, and Slug. A comparison group of 21 spindle or pleomorphic spindle cell sarcomas was also studied. Immunohistochemical stains were scored in a semiquantitative manner and subsequent exploratory analyses were performed using logistic regression and chi2 tests. Only cytokeratin AE1/AE3 specifically labeled SC in a statistically significant manner. Other epithelial-specific markers tested did not distinguish SC from sarcoma primarily owing to low sensitivity. However, when positive, immunostains such as CK5/6, membranous epithelial cadherin, and nuclear p63 may aid in the distinction of SC from sarcoma. EMT markers were expressed in most cases of both SC and sarcoma, and were not useful in making a differential diagnosis between these neoplasms.

Topics: Biomarkers, Tumor; Carcinoma, Transitional Cell; Cell Differentiation; Diagnosis, Differential; Epithelial Cells; Gene Expression; Humans; Immunohistochemistry; Keratins; Mesenchymal Stem Cells; Sarcoma; Snail Family Transcription Factors; Transcription Factors; Twist-Related Protein 1

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Sarcoma

We report a case of primary sarcoma of the skin with a biphasic histological pattern, being composed of areas of mixed mesenchymal-epithelial cell proliferation and areas of purely sarcomatous growth. The tumor occurred in the posterior cervical region of a 93-year-old man, and its history was marked by sudden, rapid enlargement after many years of stable duration. The excised lesion was about 4 cm in diameter, had a firm consistency and was covered by intact skin. Histological examination showed a multifocal proliferation of follicular germinative cells arranged in corymbiform and petaloid shapes with an overall retiform growth pattern. Epithelial cords and strands were composed of cytologically uniform cells with bland nuclear features and were surrounded by a prominent, fibroblast-rich stroma reminiscent of a perifollicular sheath. In many areas of the tumor the stroma showed abrupt transition into a pleomorphic proliferation of large sarcomatous cells with frequent and often atypical mitoses. Multinucleated neoplastic cells infiltrated the epithelial structures to cause their partial or total obliteration in many fields of the lesion. Immunohistochemically, the epithelial cells displayed expression of various keratins, with a particularly intense staining for 34betaE12, and were partly positive for the CD10 antigen. A strong immunostaining for this antigen was also observed in malignant-appearing stromal areas, where no expression of cytokeratins was detected. Moreover, nuclear positivity for p53 protein was seen in sarcomatous cells, whereas it resulted in total lack of epithelial elements. Our case emphasizes that high-grade sarcoma may occur in the spectrum of trichoblastic tumors and that it may share some features of other noncutaneous biphasic neoplasms, such as mammary cystosarcoma phyllodes.

Topics: Aged, 80 and over; Cell Proliferation; Cell Transformation, Neoplastic; Hair Diseases; Hair Follicle; Humans; Keratins; Male; Neprilysin; Sarcoma; Skin Neoplasms; Stromal Cells; Tumor Suppressor Protein p53

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Humans; Keratins; Kidney Neoplasms; Male; Middle Aged; Sarcoma

Poorly differentiated, spindle cell malignancies, on sun damaged skin frequently pose a diagnostic challenge for pathologists. The vast majority of these neoplasms ultimately are diagnosed as either atypical fibroxanthoma (AFX), spindle cell melanoma (SCM), and very rarely as spindle cell squamous cell carcinoma (SCSCC), leiomyosarcoma or angiosarcoma. Light microscopic clues may suggest one of these neoplasms, but subtle and overlapping characteristics often render precise diagnosis impossible based on morphological features alone. Immunohistochemistry therefore is necessary to firmly and accurately diagnose the majority of spindle cell malignancies on sun damaged skin. Aim of this case report is to highlight the practical approach to such diagnostic dilemmas.

Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Melanoma; S100 Proteins; Sarcoma; Skin Neoplasms; Vimentin; Xanthomatosis

p63 has been recently reported to be expressed in sarcomatoid/metaplastic carcinoma of the breast, in addition to its role as a myoepithelial marker. A large series of 34 metaplastic carcinomas, including cases with pure epithelial component (squamous cell and adenosquamous carcinomas), biphasic tumours with carcinomatous and sarcomatoid components and monophasic tumours with only spindle cell component, were evaluated for p63 expression with respect to the different cellular components.. All of the metaplastic carcinomas were assessed for p63 and conventional epithelial and mesenchymal markers of AE1/3, CAM5.2 and vimentin by immunohistochemistry.. All of the different categories of metaplastic carcinomas showed similar clinico-pathological features (patient age, tumour size, nuclear grade, mitotic activity, lymph node status and hormonal receptor status). For metaplastic carcinoma with epithelial component only, p63 was only expressed in the squamous cell component, but not the adenocarcinoma component. Eight of the 10 tumours were positive for p63. For the tumours with sarcomatoid component, either singly or together with carcinomatous component, p63 was positive in 14 of 24 cases. Pure sarcomas and carcinomas were all negative for p63 staining by immunohistochemistry, thus rendering p63 staining highly specific for diagnosing metaplastic carcinoma.. Using p63 for diagnosis of metaplastic carcinoma gives a sensitivity of 65%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 66% and an accuracy of 78%. p63 may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.

Topics: Adult; Aged; Anion Exchange Protein 1, Erythrocyte; Antiporters; Biomarkers; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Sarcoma; Sensitivity and Specificity; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Vimentin

Pseudosarcomatous myofibroblastic proliferation of the genitourinary tract is rare and may develop after trauma or spontaneously. The aim of this study was to characterize further the clinicopathological features of these lesions and to examine their relationship to inflammatory myofibroblastic tumour (IMT).. Twenty-seven cases of pseudosarcomatous myofibroblastic proliferation were analysed. There were seven males and 20 females; median age was 37 years (range 16-88). Most lesions were from the bladder (n = 21), while others were in the urethra, vulva, vagina, rectum and retrovesical space. Median tumour size was 30 mm (range 6-120 mm). Seven cases (25%) had a history of prior trauma or surgery. Three cases recurred locally but not destructively. The tumours had fasciitis-like features including bland spindle cells with evenly distributed chromatin, admixed inflammatory cells (mainly lymphocytes) and often a myxoid stroma. Immunohistochemistry showed positivity for smooth muscle actin in 14/20 cases, keratin in 8/19, desmin in 7/20 and anaplastic lymphoma kinase (ALK) in 10/21 cases. Fluorescent in situ hybridization was performed in six ALK+ cases; all were negative for ALK gene rearrangement.. Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract may show ALK immunopositivity but do not show consistent ALK rearrangement. Given subtle morphological differences and more consistently benign behaviour, their relationship to inflammatory myofibroblastic tumour at other sites remains uncertain.

Topics: Actins; Adolescent; Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Desmin; Female; Fibroblasts; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Male; Middle Aged; Muscle, Smooth; Myofibroma; Protein-Tyrosine Kinases; Receptor Protein-Tyrosine Kinases; Sarcoma; Urethral Neoplasms; Urinary Bladder Neoplasms

MDM2 and CDK4 immunostaining can be useful adjuncts in diagnosing liposarcoma among soft tissue neoplasms. We examined the reproducibility of MDM2 and CDK4 staining between 2 laboratories and between tissue microarrays and whole tissue sections. Sixty-two soft tissue tumors were immunostained at the Bergonié Institute, Bordeaux, France, and the Curie Institute, Paris, France. We also examined 203 soft tissue neoplasms on standard tissue sections and tissue microarrays. There was high concordance of results obtained from the 2 laboratories (with 2 different pathologists) for MDM2 (kappa, 0.93) and CDK4 (kappa, 0.8) staining. There also was excellent concordance between results on tissue microarray and on whole tissue sections for MDM2 (kappa, 0.80) and CDK4 (kappa, 0.93). Immunostaining for MDM2 and CDK4 is a reproducible technique that may be exported to different laboratories for routine use. Tissue microarray is indicated for studying large series.

Topics: Biomarkers, Tumor; Humans; Immunoenzyme Techniques; Keratins; Observer Variation; Proto-Oncogene Proteins c-mdm2; Reproducibility of Results; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Tissue Array Analysis

Topics: Adult; Diagnosis, Differential; Epithelial Cells; Forearm; Humans; Keratins; Male; Sarcoma

A 61-year-old man with a sensation of chest compression was admitted to our hospital. He had hemothorax. After drainage with a chest tube, chest CT scan revealed multiple bilateral pulmonary nodules with slight pleural thickening. Open pleural biopsy was performed and the biopsy specimens showed tumor cells with sarcomatoid proliferation, but no definite epithelial pattern. Initial immunohistochemical staining was negative for keratin and carletinin, but positive for desmin, suggesting rhabdomyosarcoma. After supportive care, he died due to progression of the disease. Autopsy revealed extensive invasion suggesting mesothelioma, so the immunohistochemical staining was repeated. Because it revealed patchy staining for keratin and carletinin, this case was diagnosed as sarcomatoid mesothelioma. Differential diagnosis of sarcomatoid mesothelioma or rhabdomyosarcoma is made by immunohistochemical staining, but it is sometimes difficult. For the selection of the best treatment strategy for mesothelioma especially in the early stage, we should be aware of this difficulty.

Topics: Autopsy; Diagnosis, Differential; Fatal Outcome; Hemothorax; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Pleura; Pleural Neoplasms; Rhabdomyosarcoma; Sarcoma

Topics: Adult; Biopsy; Cell Differentiation; Desmin; Diagnosis, Differential; Epithelium; Female; Humans; Immunophenotyping; Keratins; Myogenin; Pelvic Neoplasms; Rhabdomyosarcoma; Sarcoma

A subcutaneous mass in the perineum of a middle-aged man was excised and pathologically diagnosed at first as 'undifferentiated carcinoma' of unknown origin, which recurred 2 years later without any metastasis. Further histological evaluation ultimately established a correct diagnosis of 'proximal-type epithelioid sarcoma', a variant of rare epithelioid sarcoma. This type of tumor may confuse pathologists because its histological characteristics resemble undifferentiated carcinoma or malignant rhabdoid tumor. Frequent immunoreactivity of CD34, in addition to expression of keratins, epithelial membrane antigen and vimentin, provides strong support for the diagnosis of this rare neoplasm. Urologists should be aware that this sarcoma commonly occurs in the genital regions.

Topics: Biomarkers, Tumor; Combined Modality Therapy; Diagnosis, Differential; Follow-Up Studies; Genital Neoplasms, Male; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Perineum; Sarcoma; Tomography, X-Ray Computed; Vimentin

Pleomorphic carcinoma of the lung (PCL) is characterized by a mixture of sarcomatoid and carcinoma components, and a poor prognosis. However, no immunophenotype of tumor markers has been characterized in PCL. To characterize the immunophenotype for CD99 in PCL, we performed an immunohistochemical evaluation of PCLs for thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7 and 20, and for CD99. CD99 was found to be expressed in both carcinomatous (47%) and sarcomatous components such as spindle cells (92%) and giant cells (57%). In the case of spindle cells, CK7 was expressed in 6 cases (46%) and TTF-1 in 2 cases (15%), whereas for giant cells CK7 was expressed in 8 cases (57%) and TTF-1 in one case (7%). However, CK20 was not expressed in either the carcinomatous or sarcomatous components in any case. Thus, CD99 was found to be widely expressed in both sarcomatous and carcinoma component in PCL. A clinicopathological analysis showed no direct correlation between the expression of CD99 and the clinical indices (stage, survival rate, invasion) of PCL.

Topics: 12E7 Antigen; Adult; Aged; Aged, 80 and over; Antigens, CD; Carcinoma; Cell Adhesion Molecules; Female; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lung Neoplasms; Male; Middle Aged; Nuclear Proteins; Prognosis; Sarcoma; Thyroid Nuclear Factor 1; Time Factors; Transcription Factors

Ameloblastic fibrosarcoma (AFS) is a rare malignant tumor of the jaw. The malignant mesenchymal component of AFS has been described as 'fibroblast-like', although little is known about the immunophenotype, except for vimentin expression. Here, we present a case of AFS in a 62-year-old woman. The mesenchymal component displayed the features of either dermatofibrosarcoma protuberans or fibrosarcoma, and was positive for CD34. This is the first reported case of CD34 expressing AFS in the maxilla.

Topics: Aged; Antigens, CD34; Dermatofibrosarcoma; Diagnosis, Differential; Female; Fibrosarcoma; Humans; Keratins; Maxillary Neoplasms; Odontogenic Tumors; Sarcoma; Vimentin

Sarcomatoid carcinomas are rare malignancies which represent poorly differentiated epithelial tumors that may be difficult to recognize as such. While some cases may have obvious epithelial areas, the sarcomatoid areas are poorly distinguishable from true sarcoma at the light microscopic level and, by immunohistochemistry, often show only limited staining for traditional epithelial markers such as cytokeratin or epithelial membrane antigen. This can be particularly problematic for diagnosis on small biopsy specimens. We sought to assess the diagnostic utility of several immunohistochemical markers of epithelial differentiation including p63, MOC-31, and thyroid transcription factor-1 on sarcomatoid carcinomas of the head and neck (19 cases; 'spindle cell carcinomas'), lung (19 cases), and urinary bladder (11 cases). These results were compared to immunohistochemistry for the traditional epithelial markers pan-cytokeratin and epithelial membrane antigen. Staining for p63 showed the greatest diagnostic utility, positive in 63, 50, and 36% of head and neck, lung, and urinary bladder sarcomatoid carcinomas, respectively. p63 stains were positive in many cases where immunohistochemistry was negative for both pan-cytokeratin and epithelial membrane antigen. All three alternative markers were quite specific for epithelial differentiation, each staining less than 10% of the control group of 73 various primary and metastatic sarcomas, melanomas, and benign spindle cell lesions. In conclusion, immunostaining beyond traditional pan-cytokeratin and epithelial membrane antigen may have diagnostic utility in this context.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Melanoma; Membrane Glycoproteins; Membrane Proteins; Middle Aged; Mucin-1; Nuclear Proteins; Sarcoma; Sensitivity and Specificity; Thyroid Nuclear Factor 1; Transcription Factors; Urinary Bladder Neoplasms

More than 85% of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), or "Ewing family of tumors" (EFTs), have the translocation, t (11;22) (q24;q12), with others having variant translocations. Identification of these by cytogenetic and/or molecular genetic techniques is specific for EFT and is increasingly recognized as the "gold standard" for diagnosis. However, these techniques are not universally available. We therefore studied a large group of genetically confirmed EFTs to more completely understand the morphologic and immunophenotypic spectrum of this rare sarcoma. Sixty-six cytogenetically, FISH or RT-PCR proven-EFTs were retrieved. In 56 cases, immunohistochemistry (IHC) was performed for pan-cytokeratins (PanCK), high molecular weight cytokeratins (HMWCK), desmin (DES), CD99, CD117, and FLI1 protein using heat-induced epitope retrieval and the Dako Envision system. The cases arose chiefly in children and young adults (median 18 years; range, 3-65 years) of both sexes (male, 32; female, 31; unknown, 3) in a variety of bone (N = 39) and soft tissue (N = 27) sites. Histologically, 46 cases (73%) showed only typical features of ES, 9 cases (16%) showed features of PNET, 3 cases (5%) showed "adamantinoma-like" features, 3 cases (5%) corresponded to "atypical Ewing sarcoma," 3 cases (5%) showed principally intersecting fascicles of spindled cells, and 2 cases had abundant hyalinized matrix. IHC results were as follows: PanCK (18 of 56, 32%), HMWCK (3 of 55, 5%), DES (1 of 56, 2%), CD99 (52 of 52, 100%), CD117 (13 of 54, 24%), and FLI1 (44 of 47, 94%). HMWCK was expressed only in "adamantinoma-like" EFTs, none of which expressed DES. In conclusion, most, but not all, EFTs can be accurately diagnosed using time-honored morphologic criteria and ancillary immunohistochemistry. However, genetic confirmation remains essential for the diagnosis of unusual morphologic variants of EFT, including "adamantinoma-like," spindled, sclerosing, and clear cell/anaplastic variants. Therefore, to exclude or confirm the diagnosis of Ewing's sarcoma in round cell sarcomas having a variety of patterns but not specifically conforming to a tumor of known lineage (eg, rhabdomyosarcoma), cytogenetics, and/or molecular analysis is required.

Topics: 12E7 Antigen; Adolescent; Adult; Aged; Antigens, CD; Cell Adhesion Molecules; Child; Child, Preschool; Desmin; Female; Gelsolin; Humans; Immunophenotyping; Keratins; Male; Microfilament Proteins; Middle Aged; Proto-Oncogene Proteins c-kit; Receptors, Cytoplasmic and Nuclear; Sarcoma; Sarcoma, Ewing; Trans-Activators; Translocation, Genetic

The spindle cell variant of rhabdomyosarcoma (RMS) is uncommon and is most often encountered in the paratesticular region of children in whom it has a good prognosis. Only isolated cases in adulthood have been described. Sixteen cases of spindle cell RMS occurring in adults were retrieved from our files. Eleven patients were male and 5 were female. Patient age ranged from 18 to 79 years (median, 32 years). Tumor size varied from 1.5 to 35 cm (median, 6 cm). The head and neck region, including the oral cavity, parotid gland, nasopharynx, and nasal cavity, was the commonest affected area, accounting for >50% of the cases, followed by retroperitoneum, thigh, leg, subscapular area, hand, vulva, and paratesticular region (1 case each). Follow-up was available in 12 cases, ranging from 1 to 102 months (median, 16.5 months). Treatment modalities included surgery, chemotherapy, and radiation. Two patients died of uncontrolled local disease 13 and 27 months after diagnosis; 4 were alive without disease at 12, 17, 24, and 102 months, including 1 patient with metastasis to 10 of 50 pelvic lymph nodes at presentation; 3 are alive with localized disease at 16, 17, and 19 months; and 1 was followed for 6 months and showed persistent local disease. One patient is alive at 10 months after diagnosis with evidence of metastatic disease to bone, lungs, and breast. All the tumors showed long fascicles of spindle cells with elongated, vesicular nuclei and pale indistinct cytoplasm. Scattered spindled or polygonal rhabdomyoblasts with abundant brightly eosinophilic cytoplasm were present in all cases. In 3 cases, focal areas showed pseudovascular, sclerosing features. There were no round cell or pleomorphic areas. Positive immunohistochemical results were as follows: desmin (15 of 15 cases), myf-4 (12 of 12), fast myosin (7 of 9), myoglobin (2 of 3), HHF-35 (9 of 9), and SMA (11 of 14). One tumor was focally positive for keratins and EMA. All tumors were negative for caldesmon, S-100 protein, and GFAP. Spindle cell RMS is a rare neoplasm in adults and appears to have distinct clinicopathologic features when compared with cases occurring in the pediatric population. Specifically, it appears to be most common in the head and neck region, and although only limited follow-up is available so far, these lesions appear to have a more aggressive clinical course in adults.

Topics: Actins; Adolescent; Adult; Aged; Desmin; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Myogenic Regulatory Factors; Myoglobin; Myosins; Rhabdomyosarcoma, Embryonal; S100 Proteins; Sarcoma

A small number of human epithelioid sarcoma cell lines have been reported, but their characterization at a molecular cytogenetic level is not well known. In this study, a new permanent human cell line, FU-EPS-1, derived from a metastatic epithelioid sarcoma developing in the axillary lymph node of a 21-year-old man is described. This cell line was characterized by use of immunocytochemistry, conventional G-banding analysis, spectral karyotyping (SKY) and comparative genomic hybridization (CGH). FU-EPS-1 cells were round, polygonal or spindle shaped with an abundant cytoplasm, and have been maintained continuously in vitro for over 100 passages during more than 15 months. Histologic features of the heterotransplanted tumors in severe combined immunodeficiency mice were essentially the same as those of the original tumor, revealing a multinodular proliferation of eosinophilic epithelioid and spindle cells. Both in vitro and in vivo, the cells were immunopositive for cytokeratins (AE1/AE3 and CAM5.2), epithelial membrane antigen, vimentin and CD34, but were negative for desmin, S-100 protein, CD31 or factor VIII-related antigen. By G-banding and SKY analyses, FU-EPS-1 revealed a hyperdiploid karyotype with the following chromosomal abnormalities: +i(5)(p10), -8, +13, der(13)t(8;13)(q?;p11), +der(19)t(9;19)(?;?) and del(22)(q13). In addition, CGH analysis identified gains of 5p, 9q, 19q and 22q and a loss of 8p. This study demonstrates the value of molecular cytogenetic techniques such as SKY and CGH in defining genomic alterations in greater detail. The FU-EPS-1 cell line will be exceedingly useful for biologic and molecular pathogenetic studies of human epithelioid sarcoma.

Topics: Adult; Animals; Antigens, CD34; Biomarkers; Cell Line, Tumor; Cell Proliferation; Female; Genome, Human; Humans; Immunohistochemistry; Keratins; Male; Mice; Mice, Nude; Mice, SCID; Mucin-1; Neoplasm Transplantation; Nucleic Acid Hybridization; Sarcoma; Sarcoma, Experimental; Spectral Karyotyping; Time Factors; Transplantation, Heterologous; Vimentin

Topics: Dendritic Cells; Histiocytes; Histiocytosis, Langerhans-Cell; Humans; Keratins; Langerhans Cells; Lymphoma, Large B-Cell, Diffuse; Sarcoma

We discuss here five cases of epithelioid sarcoma (ES) with final diagnosis established after reexamination of initial findings. Problems with differential diagnosis of these neoplasms arise since their microscopic picture may simulate several other pathological conditions such as non-neoplastic granulomatous reactions, squamous cell carcinomas and adenocarcinomas, melanomas and soft tissue sarcomas with epithelioid component. Final ES diagnosis requires presence of cytokeratin, EMA and vimentin in neoplastic cells, as confirmed by immunohistochemical reactions. Differential diagnosis is also helped by concurrent cytology assessment that allows recognizing more easily such characteristic features as presence of plasmacytoid or spindle-shaped cells.

Topics: Adenocarcinoma; Adult; Aged; Antigens, CD34; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Granuloma; Humans; Immunohistochemistry; Keratins; Male; Melanoma; Middle Aged; Mucin-1; S100 Proteins; Sarcoma; Soft Tissue Neoplasms; Vimentin

Epithelioid sarcoma is a rare mesenchymal neoplasm. Recently, a more aggressive, so-called "proximal type" epithelioid sarcoma has been described.. A 40-year-old-woman presented with 5 x 4 cm, erythematous, indurated, non-movable, painful mass on the pubic area. Histopathology demonstrated diffuse tumor-cell infiltration into the subcutaneous and fascia, which was consisted of prominent epithelioid cells and scattered rhabdoid cells. A multinodular growth pattern or granulomatous appearance with central necrosis was not observed. The tumor cells showed positive reactions for vimentin, cytokeratin (AE1/AE3), and CD34. Despite the surgery, left inguinal mass with lymphadenopathy occurred one month later. We also carried out comparative genomic hybridization (CGH) with tumor cells. CGH revealed chromosomal gain of 5q32-qter, 12q24-qter, and 22q.. We report a case of proximal-type of epithelioid sarcoma, which showed the chromosomal gains of 5q32-qter, 12q24-qter, and 22q by CGH.

Topics: Adult; Antigens, CD34; Biomarkers, Tumor; Chromosome Aberrations; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 5; DNA, Neoplasm; Female; Humans; Image Processing, Computer-Assisted; Keratins; Nucleic Acid Hybridization; Sarcoma; Skin Neoplasms; Spectral Karyotyping; Vimentin

Recurrent solitary fibrous tumor of the pleura with malignant progression occurs rarely. We report a case of solitary fibrous tumor of the pleura in an 85-year-old white woman that recurred 4 times during a span of 10 years and subsequently underwent malignant transformation. The accurate diagnosis of solitary fibrous tumor is aided by ancillary techniques, such as immunohistochemical staining; however, with malignant transformation, such tools may be of limited value. Long-term clinical follow-up is recommended for all patients with solitary fibrous tumor because of the potential adverse biological behavior of this tumor, which may lead to repeated recurrences and/or malignant transformation.

Topics: Actins; Aged; Aged, 80 and over; Antigens, CD34; Biomarkers, Tumor; Diagnosis, Differential; Disease Progression; Female; Fibroma; Humans; Keratins; Mesothelioma; Mitotic Index; Neoplasm Recurrence, Local; Pleural Neoplasms; S100 Proteins; Sarcoma; Thoracic Wall

There has been no report on useful immunohistological markers for epithelioid sarcoma (ES) so far. The purpose of this study is to evaluate the positivity and specificity of CA125 as a marker for the correct diagnosis of ES.. This study was performed in 11 patients with ES (nine men and two women; distal type: 10 cases; proximal type: one case), 78 patients with other soft tissue tumors and nine with benign granulomas. The other soft tissue tumors consisted of six synovial sarcomas, six clear cell sarcomas, eight leiomyosarcomas, six rhabdomyosarcomas, five malignant peripheral nerve sheath tumors, ten malignant fibrous histiocytomas, 17 desmoid tumors, 14 liposarcomas, six squamous cell carcinomas (cutaneous SCC of the distal extremities), two rheumatoid nodules and seven foreign body granulomas. Immunohistochemical analysis for CA125 was performed for these 89 soft tissue tumors and nine granulomas using a labeled streptavidin biotin method. Immunohistochemical analysis of epithelial membrane antigen, cytokeratin, carcinoembrionic antigen, vimentin and CD34 was performed only for the 11 ES patients.. CA125 was strongly expressed in 10 out of the 11 ES patients. EMA, cytokeratin and vimentin were also positive in all the cases. CEA was positive in two of the 11 patients. Immunohistochemical study in six ES patients showed expression of CD 34. The other 78 soft tissue tumors and nine granulomas did not express CA125.. This study clearly revealed the specificity and positivity of CA125 in ES. These data indicate that CA125 may be a useful tumor marker for diagnosing ES.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, CD34; Biomarkers, Tumor; CA-125 Antigen; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Granuloma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Rhabdomyosarcoma; Sarcoma; Sarcoma, Clear Cell; Sarcoma, Synovial; Sensitivity and Specificity; Soft Tissue Neoplasms

Telomerase is a ribonucleoprotein complex mainly composed of a reverse transcriptase catalytic subunit (telomerase reverse transcriptase gene, hTERT) that copies a template region of its RNA subunit to the end of the telomere. For detecting telomerase activity in a tissue specimen the TRAP assay is a relatively sensitive and specific method, but it can be used only on fresh tissue extracts and offers no information at the single cell level. Immunohistochemistry (IHC) allows to detect hTERT protein expression at an individual cell level in human tissues. We have tested commercially available anti-hTERT antibodies in formalin-fixed and paraffin-embedded human tissues by IHC. Only one monoclonal antibody (NCL-hTERT; Novacastra) was sufficiently specific and this was applied to human tissues in which telomerase activity had been shown by TRAP assay and hTERT mRNA expression by RT-PCR. hTERT protein localized diffusely in the nucleoplasm and more intensely in the nucleoli of cancer cells and proliferating normal cells. Mitotic cells showed diffuse staining of the entire cell. Granular cytoplasmic staining was occasionally found in some tumor cells. In telomerase-positive tumors not all the tumor cells showed hTERT immunoreactivity. A significantly heterogeneous hTERT protein expression was observed in human tumor tissues. The hTERT immunostaining in fixed tissues was concordant with telomerase activity and hTERT mRNA expression in corresponding non-fixed samples. Quantitative RT-PCR of microdissected sections showed that hTERT mRNA expression was higher in cells with nuclear expression than in those with cytoplasmic expression. Double staining with the M30 antibody showed that a subpopulation of hTERT-negative cells is apoptotic. We conclude that: (1) hTERT protein can be detected by IHC in fixed human tissues, but the choice of the antibody, tissue processing, and reaction conditions are critical, (2) hTERT protein localizes in the nucleoplasm, more strongly in the nucleolus, and occasionally in the cytoplasm, (3) telomerase-positive tumors show significant heterogeneity of hTERT protein expression, and (4) a subpopulation of hTERT protein negative tumor cells is identified as apoptotic cells.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Apoptosis; Breast Neoplasms; Cell Nucleolus; Cell Nucleus; Colonic Neoplasms; Cytoplasm; DNA-Binding Proteins; Female; Gene Expression; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphocytes; Male; Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Sarcoma; Spermatogonia; Telomerase; Urinary Bladder Neoplasms

A mixed epithelial and mesenchymal tumor of the liver arising in an adult is rare and is mostly classified as sarcomatoid hepatocellular carcinoma (HCC). In this study, a case of sarcomatoid HCC in an adult with hepatoblastoma (HB)-like features, which produced difficulty in the differential diagnosis between sarcomatoid HCC and mixed HB, is presented. The epithelial component of the tumor composed of poorly differentiated HCC, Edmondson's grade III, and more primitive components, which were embryonal and small cell undifferentiated components of HB-like areas. The small undifferentiated cells surrounded HCC and the embryonal component of HB-like area, and revealed transition partly to areas of rhabdomyosarcoma. A small portion of chondrosarcoma was also noted. Immunohistochemical analysis showed that HCC and the embryonal component of HB-like areas expressed alpha-fetoprotein (AFP) and cytokeratin 8. The small undifferentiated cells were negative for AFP but stained with cytokeratin 8 as well as CD56, which is a marker of primitive cells in many sarcoma and HB. It is not certain whether small undifferentiated cells belong to hepatic progenitor cells or primitive mesenchymal cells. Polymerase chain reaction-single-strand conformation polymorphism analysis for beta-catenin mutation using microdissection revealed no mutation of any components. A review was undertaken of the cases previously reported as adult hepatoblastoma without detailed immunohistochemical study and consider many of them may be sarcomatoid HCC. These primitive and sarcomatoid components would be arising from the dedifferentiation process of HCC.

Topics: Aged; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoma, Hepatocellular; CD56 Antigen; Diagnosis, Differential; Fatal Outcome; Hepatoblastoma; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Male; Neoplasms, Complex and Mixed; Sarcoma; Tomography, X-Ray Computed

We analyzed clinical, morphological and immunohistochemical features in 5 cases of sarcomatoid or spindle cell squamous cell carcinoma of the penis.. The clinical and pathological files of all patients with penile carcinoma treated at our hospital between 1956 and 2002 were reviewed. Cases diagnosed as sarcomatoid squamous cell cancer were selected.. Five of 341 patients (1.4%) had sarcomatoid penile carcinoma. Tumor stage was T2N0 in 2 patients, T2N2 in 2 and T4N3 in 1. In all patients partial or total penectomy was eventually performed. Three patients underwent bilateral inguinal lymphadenectomy. Four of 5 patients had distant metastatic disease and died within 1 year after diagnosis. One patient had exclusive hematogenous spread without lymph node involvement. Foci of distant metastatic tumor sites were the lung, skin, bone, pericardium and pleura. In 4 patients the diagnosis was based on the expression of keratin filaments in a predominantly spindle cell penile tumor or by the identification of carcinomatous and sarcomatoid areas on hematoxylin and eosin stained slides of the primary tumor. In 1 case a squamous component in a lymph node metastasis rendered the keratin negative spindle cell primary tumor sarcomatoid squamous cell carcinoma.. Sarcomatoid squamous cell carcinoma of the penis is a subtype of squamous cell carcinoma with a poor prognosis often associated with wide hematogeneous spread. It is a rare malignancy that is often difficult to diagnose, requiring additional immunohistochemical stains.

Topics: Aged; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Penile Neoplasms; Sarcoma

Topics: Adenocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Hepatocellular; Cholangiocarcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Sarcoma; Vimentin

Epithelioid sarcoma (ES) is a rare, aggressive soft tissue tumor characterized by nodular aggregates of epithelioid and/or spindled cells that are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen. ES that arises in the dermis may cause epidermal ulceration and can resemble, clinically, morphologically and immunohistochemically, cutaneous squamous cell carcinoma. CK 5/6 has recently been found to be an excellent marker of squamous cell carcinoma, including spindled variants, but it is not known if this marker can be utilized to distinguish superficial ES from cutaneous spindled squamous cell carcinoma (SSCC).. Twenty-four cases of ES with typical histologic features and 10 cases of SSCC with ultrastructural evidence of epithelial differentiation were studied. Immunohistochemical analysis using an antibody to CK 5/6 was performed. The extent of immunoreactivity was evaluated in a semiquantitative manner using the following scale: 0, < 5% of cells staining; 1+, 6-25% of cells staining; 2+, 26-50% of cells staining; 3+, 51-75% of cells staining; 4+, > 75% of cells staining.. CK 5/6 was expressed in all 10 cases of SSCC, including one case with 3+ staining and six cases with 4+ staining. In contrast, CK 5/6 staining was found only in rare tumor cells (1+ staining) in one of 24 (4%) cases of ES.. CK 5/6 staining is useful in distinguishing superficial ES from cutaneous SSCC.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-5; Keratins; Sarcoma; Skin Neoplasms

Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor of uncertain histogenesis that arises predominantly in the extremities of young adults. Immunohistochemically, the neoplastic cells are typically positive for vimentin, low molecular weight cytokeratin (CAM5.2) and epithelial membrane antigen (EMA).. We examined eight cases of ES from seven different patients. All cases were studied with immunohistochemistry for EMA, CAM5.2 (keratin 8 and 18), 34BE12 (keratins 1, 5, 10 and 14/15), cytokeratins 7 and 20 (CK7, CK20), and CD34.. The average patient age was 53 (range 43-76) and the male:female ratio was 5:2. The location was the upper extremity in five tumors, the lower extremity, the perineum, and the paraspinal soft tissue in one tumor each. All cases contained predominantly epithelioid cells, but spindle cells were also present in three cases. All cases contained areas of geographic necrosis. CAM5.2 was strongly positive in seven tumors and focally positive in one (8/8). EMA was diffusely positive in two cases and focally positive in five cases (7/8). CD34 was diffusely positive in 3/8 cases. 34BE12 was diffusely positive in one case and focally positive in two others (3/8). CK7 was diffusely positive in one case and focally positive in another (2/8). CK20 was negative in all cases (0/8). All cases tested were positive for vimentin (6/6), 2 cases were focally positive for HHF35 (2/5), and all cases tested were negative for S-100 protein (0/7).. In addition to the known immunoreactivity for CAM5.2 and EMA, there is positivity for CK7 and 34BE12 in a small proportion of cases. None of the cases expressed CK20. This immunophenotypic profile suggests that ES is more similar to carcinoma and synovial sarcoma than to other soft tissue tumors, and may be of diagnostic utility.

Topics: Adult; Aged; Biomarkers, Tumor; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Necrosis; Sarcoma; Soft Tissue Neoplasms

Epithelioid sarcoma has a distinctive epithelioid phenotype and characteristically exhibits immunohistochemical reactivity for epithelial markers (keratins and epithelial membrane antigen) and mesenchymal markers (most notably vimentin and CD34). Antibodies to certain keratin subunits and other novel antigens now available to surgical pathologists have not been tested on a large number of cases.. To assist in the differential diagnosis of epithelioid sarcoma and to help elucidate its histogenesis through an expanded immunohistochemical profile.. Immunohistochemical testing with diverse antibodies was performed on 95 archived epithelioid sarcomas including 73 classic and 22 histologically variant subtypes retrieved from the files of the Armed Forces Institute of Pathology.. Immunohistochemical reactivity (number positive/number of cases tested [percent positive], frequency of staining) included keratin 14 (31/64 [48%], variable), gamma-catenin (35/74 [47%], variable), keratin 5/6 (10/33 [30%], focal), calretinin (8/40 [20%], focal), keratin 20 (11/71 [15%], focal), p63 (3/20 [15%], focal), whereas 9 invasive cutaneous squamous cell carcinomas showed strong p63 positivity, epithelial-specific antigen (10/74 [14%], variable), CD117/Kit (5/37 [14%], focal), keratin 15 (3/23 [13%], rare cell), mesothelin (2/64 [3%], rare cell), and CD10 (1/41 [2%], rare cell). No reactivity was observed for keratins 2, 5, and 10.. Diagnostically, p63 and keratin 5/6 distinguish cutaneous squamous cell carcinoma (positive) from epithelioid sarcoma (usually negative). No single immunomarker was able to distinguish the main 4 histologic subtypes of epithelioid sarcoma, indicating that they are all histogenetically related lesions. The limited expression of specific keratin subtypes used in our study supports the notion that epithelioid sarcoma is a mesenchymal neoplasm capable of partial epithelial transformation.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Calbindin 2; Child; Child, Preschool; Cytoskeletal Proteins; Desmoplakins; Diagnosis, Differential; Female; gamma Catenin; Humans; Immunohistochemistry; Keratin-14; Keratins; Male; Neprilysin; Proto-Oncogene Proteins c-kit; S100 Calcium Binding Protein G; Sarcoma

To detail on sequential biopsies the morphological and immunohistochemical features of a case of primary lymph nodal fibroblastic reticulum cell (FBRC) tumour which progressed into a clinically aggressive cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma.. A 70-year-old female underwent surgical excision of an enlarged submandibular lymph node. The nodal architecture was effaced by a neoplastic proliferation of medium to large cells, round to oval to spindle in shape, growing in a storiform pattern. The tumour stained for vimentin, CD68, factor XIIIa, alpha1-antitrypsin, fascin and actin. Dendritic and endothelial cell markers were negative. A diagnosis of FBRC tumour was made by combining pathological and clinical data. The patient received no therapy but 5 months later the tumour relapsed, exhibiting a deceptively pleomorphic cytology, phenotypic changes (strong cytokeratin positivity), intense p53 expression and aggressive clinical course with fatal outcome. In-situ hybridization for Epstein-Barr virus was negative.. We speculate that the morphological changes and p53 expression of the relapsing neoplasm might reflect tumour cell dedifferentiation, in keeping with the aggressive clinical course. The intense p53 expression suggests that this oncoprotein might also play a role in reticulum cell tumorigenesis.

Topics: Aged; Disease Progression; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Microscopy, Electron; Sarcoma

A case of sarcomatoid carcinoma of the bladder is reported herein. Immunohistochemical staining with human pancytokeratin antibody was negative, while vimentin staining was strongly positive, suggesting a diagnosis of sarcoma of the bladder. Further immunohistochemical analysis revealed positivity for AE1/AE3 cytokeratins, permitting a correct diagnosis of sarcomatoid carcinoma of the bladder. It can be difficult to distinguish between sarcomatoid carcinoma, undifferentiated carcinoma and sarcoma, particularly if the biopsy specimens are of small size. In rare cases, sarcomatoid tumors may express epithelial markers different from those revealed by human pancytokeratin staining.

Topics: Aged; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Sarcoma; Urinary Bladder Neoplasms

Ten mucinous cystic ovarian tumors that contained sarcoma-like mural nodules are described. The nodules were studied by conventional and immunohistochemical methods. The sarcoma-like mural nodules occurred predominantly in middle-aged women, were multiple and sharply demarcated from the adjacent mucinous tumor, had small size, and exhibited a heterogeneous cell population. Distinction of these lesions from true sarcomatous nodules and foci of anaplastic carcinoma is important because of the worse prognosis of the two latter tumors compared with the favorable behavior of the sarcoma-like mural nodules. Six of the eight patients with follow-up information were alive and clinically free of recurrence at a mean follow-up interval of 12 years. Two patients died of other causes (thyroid and breast carcinomas). The nature of the nodules is not clear. Sarcoma-like mural nodules probably represent a reactive and self-limited phenomenon within a neoplasia. Their coexpression of vimentin and cytokeratins is consistent with an origin from submesothelial mesenchymal cells, which undergo partial transformation into epithelial cells.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Combined Modality Therapy; Cystadenocarcinoma, Mucinous; Diagnosis, Differential; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Sarcoma; Vimentin

Sarcomatous transformation in chordoma is a very rare condition and has been emphasized as a distinct entity because of its more aggressive clinical course. Here we describe a case of dedifferentiated chordoma arising from the skull base region of an 11-year-old boy, with tumor recurrence within one year. This tumor showed features of pleomorphic cell sarcoma with areas more typical of chordoma. Most of tumor cells expressed cytokeratin, epithelial membrane antigen, vimentin and S-100 protein, thus confirming the diagnosis of dedifferentiated chordoma.

Topics: Biomarkers, Tumor; Cell Differentiation; Cervical Atlas; Child; Chordoma; Combined Modality Therapy; Cranial Irradiation; Disease Progression; Fatal Outcome; Humans; Keratins; Male; Mucin-1; Neoplasm Proteins; Neoplasm Recurrence, Local; Osteolysis; Prognosis; S100 Proteins; Sarcoma; Skull Base Neoplasms; Spinal Neoplasms; Torticollis; Vimentin

Sarcomatoid carcinomas involving the intestinal tract are rare and usually associated with poor prognosis. We report a case of sarcomatoid carcinoma of the ileum, diagnosed in a 61-year-old man. The patient presented with acute intestinal occlusion. Surgical resection of the ileum was performed. At macroscopic examination, two large polypoid masses were found. Frozen section examination suggested the diagnosis of malignant stromal tumor. At histological examination, both tumors were formed by pleiomorphic, large spindle cells, presenting numerous mitoses and marked nuclear atypia. Immunohistochemical examination showed that tumor cells coexpressed vimentin and epithelial markers (cytokeratins, EMA). The final diagnosis was monomorphic sarcomatoid carcinoma. The patient deceased with metastatic disease after 3 months of follow-up. This report underlines the potential diagnostic problems raised by this unusual type of carcinoma and emphasizes the role of immunohistochemistry in assessing the correct diagnosis.

Topics: Carcinoma; Fatal Outcome; Humans; Ileum; Immunohistochemistry; Intestinal Neoplasms; Keratins; Male; Middle Aged; Sarcoma; Vimentin

Epithelioid sarcoma is a rare soft tissue tumor that, due to its clinically unspecific features, is frequently mistaken for other benign and malignant entities. We report on a 63-year-old male presenting with a relapse of an epithelioid sarcoma. At clinical inspection, the tumor presented as an erythematous nodule with ulceration in the center. Despite its slow growth, epithelioid sarcoma should be regarded as an aggressive neoplasm exhibiting frequent local recurrences and subsequent lymphatic and visceral spreading in about half of the patients. Histopathological findings are the presence of large epithelioid and spindle cells with immunoreactivity for cytokeratin and vimentin.

Topics: Biomarkers, Tumor; Diagnosis, Differential; Humans; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Reoperation; Sarcoma; Scalp; Skin Neoplasms; Vimentin

Topics: Adult; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Sarcoma; Skin Neoplasms; Vimentin

We studied the clinicopathologic and immunohistochemical features of 20 cases of proximal-type epithelioid sarcoma to identify prognostic factors. The 20 patients ranged in age from 13 to 80 years (mean, 40 y); 12 patients were male and 8 were female. The tumors presented as deep soft-tissue or subcutaneous masses on the inguinal region in five, the thigh in four, the vulva in three, the axilla in three, and one each in the flank, chest wall, back, hip and perineum. The tumors ranged from 2 to 16 cm at their greatest diameter (mean: 7.8 cm). Histologically, 12 tumors (60%) were classified as the large-cell subtype, characterized by sheets of large cells with prominent nucleoli resembling poorly differentiated carcinoma, and a frequent rhabdoid phenotype, six (30%) were classified as the conventional subtype, and two (10%) as the angiomatoid subtype. The numbers of tumors exhibiting immunoreactivity for various markers were: vimentin (20 cytokeratin (20 [100%]); epithelial membrane antigen (17 [85%]); CD34 (9 [45%]); CD99 (5 [25%]); muscle markers, either desmin or alpha-smooth muscle actin (3 [15%]), other markers such as S-100 protein, neurofilament, neuron-specific enolase, synaptophysin and CD56 (12 [60%]); and p53 (16 [80%]). Fourteen lesions (70%) exhibited an MIB-1 index of 30% or more and, by a system of histologic grading using the MIB-1 score, 16 tumors (80%) were classified as high-grade (Grade 3). Thirteen patients (65%) developed local recurrence and 15 (75%) had metastases, primarily to the lymph nodes. At the last follow-up, 13 patients (65%) had died of their disease. A large tumor size and early metastasis were independently associated with a poor outcome. We conclude that proximal-type epithelioid sarcomas are rare, undifferentiated soft-tissue sarcomas of adults, with epithelioid features and a frequent rhabdoid phenotype. These tumors, when arising in proximal locations, have a much worse prognosis than those arising in distal locations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Epithelioid Cells; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Sarcoma; Survival Analysis; Vimentin

Extrarenal malignant rhabdoid tumor (MRT), which is recognized as being histologically similar to renal MRT, is characterized by the presence of "rhabdoid cell" (RC) and a highly aggressive biological behavior. Recently it has been proposed that "proximal variant" of epithelioid sarcoma (ES), whose morphology is similar to that of MRT, actually has a more aggressive clinical course than classical type ES. Detailed immunohistochemical analysis of cytokeratin (CK) subunits was performed in 3 cases of extrarenal MRT, 3 cases of renal MRT, and 11 cases of ES comprising 2 "proximal variants" and 9 classical types. Renal and extrarenal MRTs showed positive immunoreactivity for both CK8 and CK18. Classical type ESs were diffusely positive, not only for CK8 and CK18, but also for other cytokeratin subunits including CK4, 6, 10, 13, 16, 17, and "high-molecular-weight" CKs (CK1, 5, 10, and 14). On the other hand, proximal ES revealed limited immunohistochemical reactivity for cytokeratins, compared with classical ES. In conclusion, the inclusion bodies of RCs show immunoreactivity confined to CK8, CK18, and vimentin. Furthermore, ES has additional CK expressions, while proximal ES possesses characteristics intermediate between those of classical ES and those of external MRT.

Topics: Adult; Aged; Child; Child, Preschool; Female; Humans; Immunoenzyme Techniques; Inclusion Bodies; Infant; Intermediate Filaments; Keratins; Kidney Neoplasms; Male; Middle Aged; Rhabdoid Tumor; Sarcoma; Soft Tissue Neoplasms; Survival Analysis

We assessed diagnostic criteria among 38 spindle cell tumors of the urinary bladder and obtained follow-up in 36 patients. Patients comprised 28 males and 10 females aged 2.5 months to 87 years. Hematuria was the commonest presenting symptom (27 patients). After review and immunohistochemical workup, 17 patients had inflammatory pseudotumor (myofibroblastic tumor), 4 postoperative spindle cell nodule, 1 leiomyoma, 13 sarcoma (7 low-grade; 6 high-grade), and 3 carcinoma. Mean age was 38 years for pseudotumor (range 15 to 74), 65 for postoperative spindle cell nodule, 51 for sarcoma, and 76 for carcinoma. Size of pseudotumor averaged 4.4 +/- 0.7 cm (range 1.5 to 13.0), similar to sarcoma, 4.0 +/- 0.6 cm (range 0.5 to 7.0). Similar proportions of benign tumors and sarcomas had muscularis propria invasion. The criteria that best differentiated sarcoma from inflammatory pseudotumor were presence of necrosis at the tumor-detrusor muscle interface in muscle-invasive cases, and nuclear atypia. Sarcoma also had less prominent microvasculature, less variable cellularity, consistently > or =1 mitotic figure per 10 high-power fields, and predominant acute inflammation without plasma cells. p53 protein nuclear immunostaining was moderate, unlike the rare to absent staining in pseudotumors. Because all 12 sarcomas were desmin-negative, we did not call them leiomyosarcoma; they overlapped with benign tumor in epithelial, mesenchymal, and actin immunostaining. Among 12 sarcoma patients, 2 died of tumor (at 3 months). Two of four experienced tumor recurrence after partial cystectomy (2 and 26 months). No pseudotumors recurred after transurethral resection or partial cystectomy, although one patient, 5 months after transurethral resection, had histologically identical pseudotumor that the surgeon considered residual. Another patient with pseudotumor, not a candidate for tumor ablation after transurethral resection, had continued tumor growth and he died of urosepsis. In conclusion, inflammatory pseudotumor, although overlapping with sarcoma in presentation, age range, and size, does not metastasize and remains histologically distinct from low-grade sarcoma.

Topics: Actins; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cystectomy; Desmin; Diagnosis, Differential; Female; Follow-Up Studies; Granuloma, Plasma Cell; Humans; Immunohistochemistry; Infant; Keratins; Male; Middle Aged; Mucin-1; Muscle, Smooth; S100 Proteins; Sarcoma; Treatment Outcome; Tumor Suppressor Protein p53; Urinary Bladder; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Vimentin

We report on the crush preparation findings of a case of "sarcomatoid" chordoma occurring in the sacral region of a 78-yr-old Chinese male. The smears showed clumps and small cords of polygonal tumor cells containing bubbly cytoplasm and round to oval nuclei. Focally, there were also aggregates of long filamentous spindle cells and stellate bizarre cells with marked nuclear pleomorphism. Occasional tumor cells were seen in association with dense amorphous material. Histologic examination of the excised specimen showed features of the so-called "sarcomatoid" chordoma which consisted of prominent foci of mitotically inactive spindle and pleomorphic cells, in addition to the conventional chordoma areas. An osteosarcoma-like pattern of probably metaplastic nature was also seen within the tumor. Immunohistochemical study showed that most tumor cells expressed cytokeratins. Ultrastructural examination revealed the characteristic rough endoplasmic reticulum-mitochondria complexes. While there are many spindle and pleomorphic cells seen in crush preparations, the distinction from other true high-grade malignancies is important. Recognition of these "pseudoanaplastic" cytologic features also helps to expand the morphologic spectrum of chordoma.

Topics: Aged; Biomarkers, Tumor; Chordoma; Cytodiagnosis; Histological Techniques; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Organelles; Sacrum; Sarcoma; Spinal Neoplasms

Topics: Adult; Fingers; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; Necrosis; Sarcoma; Soft Tissue Neoplasms

Salivary duct carcinoma (SDC) is a high-grade neoplasm known to histologically resemble high-grade ductal carcinoma in situ of the breast. We describe 3 cases of sarcomatoid salivary duct carcinoma, a heretofore unreported variant of SDC. Each case was a composite of SDC and sarcomatoid carcinoma and histologically similar to reported cases arising in the breast. The clinicopathologic features, including immunohistochemistry, of 3 cases were investigated. In the 3 men, ages 56, 68, and 70 years, the resected parotid tumors measured 1.5, 3.5, and 1.5 cm, respectively. Only the 3.5-cm tumor extended beyond the parotid gland into soft tissue. This patient died at 3 years with pulmonary metastases. The other patients were free of disease at 6 and 12 months. Histologically, each case was a composite of usual-type SDC and sarcomatoid carcinoma. SDC showed typical cribriform architecture, whereas anaplastic, spindled cells constituted the sarcomatoid areas. Immunohistochemically, epithelial elements stained as follows: cytokeratin (AE1/AE3 & CAM 5.2) positive in 3 of 3 cases, EMA positive in 3 of 3 cases, vimentin negative in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 positive in 1 of 2 cases. Sarcomatoid elements stained as follows: AE1/AE3 negative in 3 of 3 cases, CAM 5.2 rare positive cell in 1 of 3 cases, EMA focally positive in 3 of 3 cases, vimentin positive in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 negative in 2 of 2 cases. Electron microscopy, performed in one case, showed scattered junctional complexes congruent with epithelial differentiation. Immunohistochemical results, EMA and CAM 5.2 positivity, and ultrastructural findings supported our belief that these unique biphasic tumors represented SDC with sarcomatoid carcinoma. We conclude an element of sarcomatoid carcinoma rarely may arise in association with SDC, and it is erroneous to diagnose such tumors as "carcinosarcoma."

Topics: Aged; Biomarkers; Desmin; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mucin-1; Parotid Neoplasms; Salivary Ducts; Sarcoma; Vimentin

Fine-needle aspiration of prostatic carcinoma usually yields an acinar carcinoma that is immunoreactive for prostatic-specific antigen (PSA) and prostatic acid phosphatase (PAP). We report on two FNAs of metastatic sarcomatoid prostatic carcinoma that were PSA- and PAP-negative. Our methods included a review of the medical records and pathology results. Both cases presented with elevated serum PSA levels and prostate needle biopsies with Gleason score 8 and 9 tumors, respectively. Both cases developed retroperitoneal/pelvic lymphadenopathy, and fine-needle aspirations were performed. These showed high-grade, sarcomatoid tumors with marked anisonucleosis. Immunocytochemical staining for PSA and PAP was negative in both cases. Clinical and radiologic evaluation failed to reveal any other potential primary sites. Metastatic, sarcomatoid, PSA- and PAP-negative prostatic carcinoma is a rare diagnosis of exclusion that should be considered in the characteristic clinical setting.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoembryonic Antigen; Flutamide; Humans; Immunohistochemistry; Keratins; Leuprolide; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Sarcoma

To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms.. Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified.. Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.

Topics: Biomarkers, Tumor; Calbindin 2; Carcinoma; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lung Neoplasms; Mesothelioma; S100 Calcium Binding Protein G; Sarcoma; Thrombomodulin

Synovial sarcoma is a mesenchymal neoplasm of unknown histogenesis that shows various degrees of epithelial differentiation. It is known to contain simple epithelial keratins, and the possibility of complex epithelial keratin expression has been suggested. In this study, we immunohistochemically examined 110 well-documented synovial sarcomas including 44 biphasic, 48 monophasic, and 18 poorly differentiated (undifferentiated, highly mitotically active) tumors for 11 different keratin (K) polypeptides of the Moll catalogue. The epithelia of biphasic synovial sarcomas showed consistent, extensive reactivity for K7, K8, K14, K18, and K19. Other keratins seen in the epithelia of biphasic tumors included K17 (variable, in 77%), K13 (25%), K16 (23%), and K6 (24%) in the minority of biphasic tumors, predominantly in stratified-appearing epithelia. K10 was detected only focally in one case that showed keratinizing squamous differentiation. Focal expression of K20 was seen in 27% of cases. Monophasic synovial sarcomas had a more limited keratin repertory. Simple epithelial keratin positivity was detected, usually focally for K7 (79%), K19 (60%), K8 (45%), and K18 (46%). Two cases showed more extensive keratin positivity in the spindle cells. The monophasic tumors showed limited positivity for complex epithelial keratins: K14 (28%) and K17 (10%). K20 was detected focally in 6% of the monophasic tumors; other keratins were not detected. The poorly differentiated synovial sarcomas showed limited simple epithelial keratin reactivity, usually limited to scattered cells: K19 (61%), K7 (50%), K18 (47%), K8 (33%), but five cases showed more extensive positivity. Complex epithelial keratins were scant: K14 in one case and K17 in two cases. The immunoreactivity of capillary endothelia seen for K7 and K18 (but not for K8 and K19 with the antibodies used) is a potential diagnostic pitfall, and may cause overdiagnosis of synovial sarcoma if not properly recognized. In summary, we show complex patterns of keratins in synovial sarcoma, especially in the biphasic tumors. Such patterns establish a baseline in differential diagnostic considerations, and give an insight into the complex epithelial differentiation of this enigmatic mesenchymal tumor.

Topics: Adolescent; Adult; Aged; Child; Female; Humans; Immunohistochemistry; Keratins; Male; Mesothelioma; Middle Aged; Sarcoma; Synovial Membrane

A case of a metachronous epithelioid sarcoma and pleomorphic liposarcoma in a young woman is described. The first tumor was an epithelioid sarcoma (ES) with focal rhabdoid features localised in the left calf while the second lesion developed seven years later in the same region was diagnosed as pleomorphic liposarcoma resembling myxofibrosarcoma ( myxoid variant of malignant fibrous histiocytoma ) predominantly composed of moderately differentiated spindle cells. Multiple foci of uni- and plurivacuolated lipoblasts were seen. Following the resection of ES the patient received 57 Gy radiation to the region, therefore we regarded the second tumor as a radiation induced liposarcoma. A further interesting feature of this case is that the development of pleomorphic liposarcoma preceded by 6 months the solitary right parabronchial metastasis of ES and after 4 months of metastasectomy a third tumor developed at the site of the first lesion. This tumor showed dedifferentiation toward pleomorphic malignant fibrous histiocytoma. Our case represents a unique case of postirradiation liposarcoma developed on the base of ES.

Topics: Adolescent; Female; Humans; Immunohistochemistry; Keratins; Leg; Liposarcoma; Lymphatic Metastasis; Mucin-1; Neoplasm Metastasis; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Radiotherapy; Sarcoma; Vimentin

A case of proximal-type epithelioid sarcoma arising in the pelvic soft tissues of a 46-year-old man is presented. The tumor showed a predominantly epithelioid component with rhabdoid features, cord-like arrangement, small nests, abundant eosinophilic cytoplasm containing intracytoplasmic, paranuclear, hyaline-like globules, large vesicular nuclei, and prominent nucleoli. There were foci with alveolar arrangement and a spindle-cell proliferation. The tumor cells were positive for cytokeratin CAM5.2, vimentin, epithelial membrane antigen, and CD34. Flow cytometry showed a diploid DNA content with high S-phase fraction. The patient had pelvic lymph-node metastases. He died of the disease 5 months after diagnosis. It is important to include proximal-type epithelioid sarcoma in the differential diagnosis of pelvic tumors.

Topics: Antigens, CD34; Diagnosis, Differential; DNA, Neoplasm; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Pelvic Neoplasms; S Phase; Sarcoma; Vimentin

Epithelioid sarcoma (ES) is a distinctive soft tissue neoplasm with a predilection for the distal extremities of young adults. This tumor typically contains nodular aggregates of epithelioid and spindle cells with zonal necrosis. The neoplastic cells are generally reported to coexpress keratin and vimentin and are often stated to be positive for CD34. However, there is no large series with extensive immunohistochemical data, there are few data with regard to expression of different keratin subtypes, and there are no large series discussing the epithelioid sarcoma subtypes. In the current study, we immunohistochemically evaluated 88 typical and 24 variant (8 angiomatoid, 9 large cell/rhabdoid, and 7 "fibroma-like") ESs. Nearly all ESs with typical histology (94%) were positive for keratin 8 (K8), whereas 72% were positive for K19, 48% for intermediate- and high-molecular-weight keratins (34betaEH12), and 22% for K7; reactivity with the latter two antibodies was usually seen in only a minority of tumor cells. Vimentin reactivity was present in all cases, EMA in 96% of cases and muscle-specific actin and CD34 were noted in 41% and 52% of the cases, respectively. A few ESs (7%) showed focal cytoplasmic CD31 reactivity, but none exhibited a distinctive membrane staining pattern, and examples tested for FVIIIRAg were negative. The angiomatoid, fibroma-like, and large cell-rhabdoid ES variants had immunohistochemical profiles similar to the classic cases, supporting a common pathogenesis. Although not consistently expressed in ES, the presence of CD34 is helpful in distinguishing this entity from primary and metastatic carcinomas and other sarcomas such as malignant rhabdoid tumor.

Topics: Adolescent; Adult; Aged; Antigens, CD; Child; Child, Preschool; Cytoskeletal Proteins; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucin-1; Neoplasm Recurrence, Local; S100 Proteins; Sarcoma

Epithelioid sarcoma (ES) is an aggressive soft-tissue malignant tumor generally arising in the distal extremities of young adults. The microscopic diagnosis of ES is often difficult because of its rarity and its possible confusion with other malignant tumors or even with benign granulomatous processes. Two cases of ES and a recurrence of one of these tumors, diagnosed by fine-needle aspiration biopsy (FNAB), are reported. Cytologic smears were quite similar in both cases including the relapse, showing single or loosely arranged groups of medium to large atypical cells. Single cells had well-defined eosinophilic cytoplasms and one or more atypical, eccentrically located nuclei, resulting in a plasmacytoid appearance. Nuclei had fine granular chromatin and one or two large nucleoli. The cells sometimes palisaded along the edges of necrotic material. The immunocytochemical stains showed diffuse cytoplasmic positivity for cytokeratins (CAM 5.2) and both cytoplasmic and cell membrane positivity for vimentin, while S-100 protein and HMB 45 immunostaining were negative, thus supporting the cytological diagnosis of ES, which was subsequently proven on the surgical samples. Diagn. Cytopathol. 1999;21:405-408.

Topics: Adult; Biopsy, Needle; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Sarcoma; Soft Tissue Neoplasms

We report 51 cases of a previously undescribed tumor of the distal extremities that is often mistaken for an inflammatory or infectious process, Hodgkin's disease, or various sarcomas. These lesions developed in patients of all ages (range, 4-81 yr; median, 40 yr) and affected the sexes nearly equally (27 men, 24 women). They presented as a painless mass of the fingers (14 cases), hand (11 cases), wrist or arm (10 cases), toe or foot (8 cases), or lower leg (5 cases), usually within the subcutaneous tissues. Grossly, they were infiltrative, multinodular masses characterized by a dense chronic inflammatory infiltrate that merged with a stroma, which varied from densely hyaline to focally myxoid and contained sheets of short spindled to rounded epithelioid cells. Focally, the epithelioid cells were extremely large with bizarre, vesicular nuclei and macronucleoli resembling Reed-Sternberg cells or virocytes. Despite the level of atypia, mitotic activity was low. The tumor cells consistently expressed vimentin but lacked a variety of other mesenchymal, epithelial markers, e.g., S100 protein, desmin, actin, neuron-specific endolase, epithelial membrane antigen, HMB-45, CD34) and leukocyte markers (CD15, CD30, CD45). Keratin was noted focally and weakly in four cases and CD68 focally in six cases, the latter suggesting that the cells had acquired phagocytic properties. Immunostains for cytomegalovirus were negative. Polymerase chain reaction for Epstein-Barr virus showed amplification levels consistent with latent infection in 4 of 10 cases, but no cases showed levels consistent with active infection. All of the bacterial and viral cultures were negative. Follow-up information was available in 27 cases. Recurrences developed in six patients (interval, 15 mo-10 yr), but there were no metastases or tumor-related deaths. In one patient, progressive proximal extension up the arm was noted. Although the most common submitting diagnosis was that of an inflammatory or infectious process, the negative studies for infectious agents, clinical behavior with local recurrences, immunophenotypic profile, and cytologic atypia support the idea that these are unusual mesenchymal neoplasms with at least the potential for local recurrence. It remains to be investigated whether with time these lesions will prove to have metastatic potential.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD; Biomarkers, Tumor; Child; Child, Preschool; Diagnosis, Differential; DNA, Viral; Extremities; Female; Follow-Up Studies; Granuloma, Plasma Cell; Herpesvirus 4, Human; Hodgkin Disease; Humans; Keratins; Male; Middle Aged; Reed-Sternberg Cells; Sarcoma; Vimentin

Immunohistochemistry occasionally is used to determine the lineage of entirely necrotic tumors. However, the sensitivity and specificity of antibodies on necrotic tissue are unknown. To determine the usefulness of immunohistochemistry with necrotic lesions, a series of 24 known tumors consisting of 14 carcinomas, 2 lymphomas, 2 melanomas, and 6 sarcomas (all with extensive necrosis) was examined for reactivity with 6 cytokeratin antibodies, S100, and LCA. Carcinomas stained positively with at least 1 cytokeratin antibody in 78% of the cases. The cytokeratin antibodies with the highest sensitivity were AE1, AE1/3, S903, and PANCK. These antibodies also retained specificity for epithelial differentiation; no reactivity was observed in the 10 necrotic nonepithelial tumors. LCA retained its reactivity with necrotic lymphoma, but S100 reacted with only one third of the necrotic lesions. Unexpectedly, reactivity for LCA and S100 occurred in some necrotic carcinomas. Keratin markers can be used on necrotic tissue to determine epithelial differentiation, but the results obtained with S100 and LCA on necrotic tissue should be interpreted with caution.

Topics: Antibodies; Antibody Specificity; Carcinoma; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Melanoma; Necrosis; Neoplasm Metastasis; Neoplasms; S100 Proteins; Sarcoma

While undergoing a repeat Caesarian section, a 21-year-old woman was found to have a subcutaneous, 3.5-cm tumor-like lesion in the abdominal wall. It had a lobulated contour and consisted of gelatinous tan nodules with intervening fibrous septa. It had a composite histology, including a solid pattern of large glassy cells with a predominant perivascular and pericystic/cisternal topography (35% surface area); a pattern of dyscohesive, vacuolated cells including physaliphorous-like forms (35% surface area); and a myxoid pattern of spindle to stellate cells showing frequent cell contact and lying within an optically clear or pale eosinophilic and bubbly extracellular matrix with a prominent capillary framework. A strong and diffuse cytoplasmic expression of vimentin (only) was present in all cytoarchitectural patterns. The extracellular matrix and intracytoplasmic vacuoles contained abundant acid mucosubstance, mostly hyaluronic acid. No distinct endometrial gland, stigma of hemorrhage, or nuclear estrogen/progesterone receptor protein expression was observed. There were variously sized and shaped cystic spaces lined by a flat to cuboidal cytokeratin-positive cell lining and focally containing neutral and acid mucosubstance. These spaces are interpreted as dilated endometrial glands rather than mechanically entrapped inclusions of mesothelial origin. In this setting, florid decidual reaction represents a potential diagnostic pitfall because it could be confused with more commonly encountered myxoid or epithelioid tumors of mesenchymal, epithelial, or melanocytic cell lineage.

Topics: Abdominal Neoplasms; Adult; Biomarkers, Tumor; Diagnosis, Differential; Embryo Implantation; Endometriosis; Female; Humans; Immunohistochemistry; Keratins; Sarcoma

We present one case of sarcomatoid chromophobe cell renal carcinoma with an indolent clinical course and assume that the carcinomatous component may affect the biologic behavior. The patient was a 61-year-old man who underwent right radical nephrectomy for a 11.2 cm tumor in the lower pole. The immunohistochemical findings demonstrate that EMA and cytokeratins 8 and 18 are useful markers for the sarcomatoid fraction, and the lectin study shows a loss of surface blood antigen. Chromophobe cell carcinoma may convert into sarcomatoid carcinoma. The existence of sarcomatoid renal cell carcinoma as a distinct entity should be re-considered.

Topics: Adenocarcinoma; Aged; Antigens, Surface; Biomarkers, Tumor; Humans; Immunohistochemistry; Keratins; Kidney Neoplasms; Lectins; Male; Mucin-1; Nephrectomy; Sarcoma

Carcinosarcoma is a rare neoplasm that displays morphological features of both an adenocarcinoma and a sarcoma. The question is whether two tumors co-exist or whether the two morphological aspects represent sequential steps in tumor progression. We report a case of carcinosarcoma of the caecum in a young female. To characterize the two tumor cell populations and to gain insight into the pathogenesis of the lesion, we conducted immunohistochemical and ultrastructural analyses of the tumor. The biphasic aspect of the tumor showed an admixture of carcinoma and spindle-cell sarcomatoid areas. Both adenocarcinoma and sarcomatous cells were positive for cytokeratins. Vimentin was undetectable in the epithelial portion, but many of the sarcomatous cells stained for vimentin. Electron microscopic analyses of the sarcomatous portion revealed budding of "retroviral particles" from the rough endoplasmic reticulum cisternae. Our data support the contention that "carcinosarcoma" is a part of a single clinicopathological continuum with "spindle-cell carcinoma", the former being the biphasic expression of the neoplasia, the latter the monophasic expression; the presence of productive retroviral infection in the sarcomatous cells could constitute one of the additional support in tumor progression from the carcinomatous to the sarcomatous phase.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Carcinosarcoma; Cell Transformation, Neoplastic; Colonic Neoplasms; Disease Progression; Endoplasmic Reticulum, Rough; Fatal Outcome; Female; Humans; Keratins; Neoplasm Proteins; Organelles; Retroviridae; Sarcoma; Vimentin

Eleven cases of sarcomatoid renal cell carcinoma were studied to determine the relative frequency of various subtypes of renal cell carcinoma that may be associated with sarcomatoid transformation. The epithelial components in these tumors were subcategorized according to established histologic criteria into chromophobe carcinoma (n = 6 cases), clear cell carcinoma (n = 3), papillary carcinoma (n = 1), and indeterminate (n = 1). In nine cases, material was available for immunohistochemical and DNA ploidy studies. The sarcomatoid component in all cases showed positivity for epithelial membrane antigen cytokeratin, indicating an epithelial derivation of these cells. Staining for mesenchymal markers was mostly negative, except for vimentin, which reacted strongly in all cases. DNA ploidy studies using flow cytometry and cell image analysis provided very similar results. Five of five chromophobe sarcomatoid carcinomas showed hypodiploid cell lines in the epithelial areas, whereas the sarcomatoid components mostly showed aneuploid peaks. In the remaining cases, DNA ploidy pattern was more variable. These findings indicate that chromophobe carcinoma may be the most frequent epithelial component associated with sarcomatoid renal cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; DNA; Female; Flow Cytometry; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratins; Kidney Neoplasms; Male; Middle Aged; Mucin-1; Ploidies; Retrospective Studies; Sarcoma; Vimentin

An 82-year-old man with microhematuria and class V cells in his urinary cytologic specimen was referred to our clinic. Cystoscopy revealed a solid, broad-based tumor of 1 cm in diameter in the bladder diverticulum. A partial cystectomy was performed. The tumor was composed of transitional cell carcinoma (TCC), sarcomatous spindle cells and the area of transition between TCC and spindle cells. The histopathological diagnosis was sarcomatoid carcinoma. Immunohistochemical examination showed that the spindle cells and the area of transition were positive for keratin, cytokeratin, vimentin and muscle actin. The histopathological and immunohistochemical transitions between the TCC and the spindle cells suggested that the sarcomatous elements originated from the TCC during tumor progression.

Topics: Actins; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Transitional Cell; Humans; Immunohistochemistry; Keratins; Male; Sarcoma; Urinary Bladder Neoplasms; Vimentin

In view of the different terminology for salivary gland tumours with giant cells, eleven cases were analysed by histopathology and immunocytochemistry. Four cases (three pleomorphic adenomas, one carcinosarcoma in a pleomorphic adenoma) were classified as having a foreign-body giant cell reaction, and five cases (two mucoepidermoid carcinomas, one acinic cell carcinoma, two carcinomas in pleomorphic adenomas) as having a sarcomatoid osteoclast-like giant cell reaction. In two further cases a giant cell tumour and a giant cell granuloma were associated with carcinomas in pleomorphic adenomas. All giant cells showed characteristic expression of CD68 as a typical marker for histiocytes and macrophages with their origin in mononuclear haematopoetic stem cells. There was no evidence for an epithelial origin of the giant cells because all those examined had a negative reaction to cytokeratin. Foreign-body cells were characterized by cytoplasmic vacuoles and irregularly dispersed nuclei. They showed a focally circumscribed reaction mostly outside the connective tissue pseudocapsule of the tumours. The sarcomatoid osteoclast-like giant cell reactions in carcinomas were distinctly intermingled with the carcinomatous patterns. In contrast, the associated osteoclast-like giant cell tumour was distinctly separate from the salivary gland tumour tissue and was composed of numerous larger osteoclast-like giant cells with a greater number of nuclei (more than 20); these giant cells were uniformly distributed throughout the tumour tissue. The giant cell granuloma was also separate from the carcinoma and was composed of nests of smaller, more irregularly distributed giant cells.

Topics: Adenoma, Pleomorphic; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Mucoepidermoid; Carcinosarcoma; Cell Lineage; Cell Nucleus; Connective Tissue; Epithelial Cells; Foreign-Body Reaction; Giant Cell Tumors; Giant Cells; Giant Cells, Foreign-Body; Granuloma, Giant Cell; Hematopoietic Stem Cells; Histiocytes; Humans; Immunohistochemistry; Keratins; Macrophages; Neoplasms, Multiple Primary; Osteoclasts; Salivary Gland Neoplasms; Sarcoma; Vacuoles

A case of epithelioid sarcoma in the tongue is reported. The patient, a 35 year old woman, presented with a non-ulcerated painful lesion of the tongue. Microscopically, the tumour was characterised by multiple coalescent nodules with central geographic necrosis infiltrating the lingual muscle. The tumour cells were epithelioid with abundant eosinophilic cytoplasm and atypical nuclei. Immunohistochemically, the tumour cells stained for vimentin, keratin, and epithelial membrane antigen. These morphological and immunohistochemical appearances led to the diagnosis of epithelioid sarcoma of the tongue. Seven years later, the patient died with metastatic dissemination to the scalp, lungs, and brain. No case of epithelioid sarcoma arising in the tongue has been described previously.

Topics: Adult; Brain Neoplasms; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Sarcoma; Scalp; Skin Neoplasms; Tongue Neoplasms

Atypical variants of liver carcinomas may represent diagnostic pitfalls when compared with classical types. We described two cases of unusual hepatocellular carcinoma with sarcomatoid pattern. Both were large tumors in elderly people. Their immunohistochemical investigation showed a coexpression of various epithelial and mesenchymal markers. There were positivities of antibodies against cytokeratin, actin and desmin in the first case, against cytokeratin, chromogranin and actin in the second case and against EMA and A1AT in both of them. Such a tumor was not found either in five year bioptic and four year necroptic archival material or in the Hlava Institute histopathological collection. The frequency of the tumor was about 4% of all hepatocellular carcinomas according to the literature.

Topics: Actins; Aged; Carcinoma, Hepatocellular; Desmin; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Sarcoma

Topics: Biopsy, Needle; Histocytological Preparation Techniques; Immunoenzyme Techniques; Keratins; Melanoma; Sarcoma

This case report illustrates a patient presenting with sciatica and diagnosed with epithelioid sarcoma involving the spine.. The treatment of this patient involved multiple mass resections and decompressions of the spinal canal. Radio- and chemotherapy were applied once a clear diagnosis was obtained.. Epithelioid sarcoma is a rare tumor mainly arising in the extremities. Confusion with a benign inflammatory process are possible. Treatment after histologic diagnosis involves wide resection. To our knowledge, this report represents the first case of epithelioid sarcoma involving the spine.. After initial discectomy, recurrent scarring and mass formation required multiple decompression procedures and fusion. The initial pathology revealed inflammatory reaction on fibrosis. In a later procedure, the histologic diagnosis of epithelioid sarcoma was made. Radiotherapy and chemotherapy were begun immediately.. Despite aggressive resections, radiotherapy, and chemotherapy, the patient died 3 months after the last surgical procedure.. Spinal epithelioid sarcoma can be mistaken for a benign inflammatory process. After a histologic diagnosis, aggressive wide resection is necessary. Multiple recurrences are documented with this tumor in other sites. Prognosis in trunk involvement is less favorable than involvement of the extremities. The role of adjuvant radio- and chemotherapy is unclear for spinal involvement.

Topics: Adult; Electromyography; Humans; Keratins; Magnetic Resonance Imaging; Male; Reoperation; Sacrum; Sarcoma; Sciatica; Spinal Neoplasms; Tomography, X-Ray Computed; White People

Cytokeratin (CK) positivity has been considered a specific marker for epithelial differentiation in cytologic specimens. After observing CK reactivity in fine-needle aspirate (FNA) specimens of melanoma and sarcoma, a retrospective study of melanomas and sarcomas was undertaken to investigate the frequency of anomalous CK staining in these neoplasms. Cell block sections and/or restained smears from 36 melanomas and sarcomas were retrospectively stained for CK. An appropriate internal positive control (HMB-45), S100 protein, or vimentin) was also used to insure antigen preservation. Of the smears from 19 melanomas, five revealed focal strong CK positivity of neoplastic cells, two cases showed faint or equivocal staining, 11 cases were negative for CK, and one could not be interpreted due to inadequate controls. Of the smears from 14 sarcomas, two showed positivity for CK (one fibrosarcoma and one condrosarcoma), 11 were negative, and one had inadequate controls. The number of CK positive cells was less than that observed with the appropriate internal positive control antibodies. Destained Papanicolaou smears were superior to Diff-Quik smears for retrospective immunocytochemical stains. Cell block sections from four of the melanomas and one sarcoma demonstrated no aberrant staining. Since cytokeratin positivity occasionally is seen in nonepithelial neoplasms, its presence alone cannot be used to make a definitive diagnosis of carcinoma. Therefore, a panel of immunocytochemical stains should be utilized in diagnosis of FNA specimens.

Topics: Biopsy, Needle; Humans; Immunohistochemistry; Keratins; Melanoma; Retrospective Studies; Sarcoma

A case of primary hepatic tumor exclusively composed of malignant cells with sarcomatous features is described and compared immunohistochemically with two cases of hepatocellular carcinoma (HCC) with a sarcomatous component. More than 30% of HCC cells were positively stained with anti-cytokeratin (CAM5.2), anti-albumin, anti-fibrinogen and anti-alpha 1-antitrypsin antibodies, and some with anti-epithelial membrane antigen. The present sarcomatoid tumor and the sarcomatous component with HCC showed similar immunohistochemistry; many tumor cells were strongly immunoreactive for vimentin and some positive for cytokeratin, albumin, fibrinogen and alpha 1-antitrypsin. Other immunohistochemical markers, indicating specific differentiations to lineage of macrophages, muscle cells, glial cells, endothelial cells and so forth, were not detected in sarcomatous tumor cells of all cases. These findings suggest that the present sarcomatoid tumor would belong to an anaplastic sarcomatous variant of HCC.

Topics: Aged; Albumins; alpha 1-Antitrypsin; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Fibrinogen; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Sarcoma; Vimentin

Three clonal sub-populations, GRU-IA, GRU-IB, and GRU-IC, isolated from the human epithelioid sarcoma cell line GRU-I, were characterized morphologically, cytogenetically and with regard to proliferation kinetics. Immunocytochemically, major differences became evident in the expression of cytokeratin 18 and neurofilament proteins, which are indicative for epithelial and neural differentiation respectively. Vimentin, a mesenchymal differentiation marker, however, could be detected in all tumor cells of each sub-population. Laminin, a major compound of basement membranes, formed abundant intercellular network-like patterns in GRU-IB and GRU-IC, whereas GRU-IA was characterized by a diffuse intracellular reaction, suggesting a disorder in laminin secretion. Cytogenetically, all sub-populations proved to be DNA-aneuploid, the DNA index ranging from 1.4 to 1.5. Proliferation analysis revealed doubling times ranging from 13 (GRU-IC) to 19 hr (GRU-IA). These strictly defined clonal sub-populations provide a valuable tool for further investigations of the biological behavior of human epithelioid sarcoma with special regard to tumor heterogeneity.

Topics: Aneuploidy; Animals; Cell Differentiation; Cell Division; Clone Cells; DNA, Neoplasm; Flow Cytometry; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Humans; Keratins; Laminin; Membrane Glycoproteins; Mice; Mice, Nude; Mucin-1; Mucins; Neurofilament Proteins; Sarcoma; Tumor Cells, Cultured; Vimentin

FNAB smears of eleven epithelioid sarcomas were reviewed and analysed. Ten cases had a very similar cytomorphologic picture composed predominantly of dissociated epithelioid-like cells with eccentrically placed nuclei. These tumors were clearly malignant but difficult to differentiate morphologically from melanoma, epithelioid leiomiosarcoma, and Schwannoma or adenocarcinoma. One case was composed of spindle cells and was reminiscent of a fibrohistiocytic tumor. Immunocytochemical reactions to vimentin and cytokeratin were performed in six cases on the Papanicolaou stained smears. The reactions to both antigens were positive in all six cases. Ultrastructural characteristics of eight of the tumors are also described. It seems that epithelioid sarcoma has a rather distinct cytomorphologic picture. Taking into consideration clinical data and using also immunocytochemistry, a definitive diagnosis of epithelioid sarcoma can probably be given from FNAB smears.

Topics: Adult; Aged; Biopsy, Needle; Cell Nucleus; Cytodiagnosis; Cytoplasm; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Sarcoma; Vimentin

Pseudosarcomatous fibromyxoid tumor of the genitourinary tract is a rare pathologic entity of hitherto unknown etiology that, because of the cellular pleomorphism and the infiltrative nature of the lesion, may be mistakenly diagnosed as sarcomatoid carcinoma or sarcoma. We retrospectively studied nine pseudosarcomatous fibromyxoid tumors involving the bladder and prostate to define characteristic parameters that may allow for accurate diagnosis. The study patients included four men and five women with a mean age of 48.7 years. Histologic analysis revealed myxoid lesions with a proliferation of spindle fibroblastic cells in a background of granulation tissue-type vascularity and inflammatory cells. Mitoses were infrequent and no atypical forms were found. Immunostaining was positive for vimentin and smooth muscle actin, and negative for S-100 protein, desmin, myoglobin, and keratin. Ultrastructurally, the lesion displayed fibroblastic and myofibroblastic cell features. Flow cytometric DNA content analysis revealed uniform DNA diploidy and a low S-phase fraction. All patients were alive and well with no evidence of disease after a mean follow-up of 4.8 years. In contrast, the sarcomatoid carcinomas and sarcomas of the urinary bladder and prostate that were used as controls occurred in older patients and had more frequent mitoses with atypical forms, tumor-type necrosis, and different immunostaining profiles; they were preponderantly aneuploid or diploid with high S-phase fraction. Awareness of the clinicopathologic and biologic characteristics of these lesions is necessary to ensure their accurate diagnosis and to prevent unnecessary radical therapy.

Topics: Actins; Adult; Carcinoma; Desmin; Diagnosis, Differential; DNA, Neoplasm; Female; Fibroma; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Myoglobin; Ploidies; Prostatic Neoplasms; Retrospective Studies; S Phase; S100 Proteins; Sarcoma; Urinary Bladder Neoplasms; Vimentin

Virtually all reported cases of epithelioid sarcoma have been vimentin rich, and the coexpression of vimentin and keratin is considered a characteristic immunophenotype in these tumors. We report three cases of soft tissue tumors with histologic and clinical features consistent with epithelioid sarcoma, all of which failed to immunoreact by standard immunohistochemistry for vimentin using two different monoclonal antibodies. Antigen retrieval demonstrated focal vimentin staining in one case, whereas the other two remained negative. An extensive panel of immunohistochemical stains revealed strong diffuse staining with keratin and epithelial membrane antigen in all three cases as well as patchy membrane staining with an antibody to CD34. CD34 positivity is commonly seen in epithelioid sarcoma, but it is very rarely found in carcinomas. We conclude that these cases represent a unique immunophenotypic variant of epithelioid sarcoma that can be immunohistochemically confirmed, despite the lack of identifiable vimentin, by their immunoreactivity for keratin and CD34.

Topics: Adult; Antigens, CD; Antigens, CD34; Cytoplasm; Diagnostic Errors; Eosinophils; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Sarcoma; Soft Tissue Neoplasms; Vimentin

An ulcerated tumour was removed by a Whipple's operation from the descending part of the duodenum of a 38-year-old male. The tumour cells were mainly spindle-shaped, arranged in nests and had very prominent nucleoli. A few cells contained melanin and melanosomes. Immunoreactivity for S-100 protein and focally for HMB-45 was observed. These features are diagnostic for clear cell sarcoma of tendons and aponeuroses. Because no other primary tumour could be found and the search for similar cases from the literature was unsuccessful, we believe that this tumour is the first reported clear cell sarcoma in a visceral location.

Topics: Adult; Desmin; Duodenal Neoplasms; Duodenum; Humans; Immunohistochemistry; Keratins; Male; Melanoma; S100 Proteins; Sarcoma; Soft Tissue Neoplasms; Tendons; Tomography, X-Ray Computed; Ultrasonography; Vimentin

Malignant spindle cell neoplasms are a diagnostic challenge regardless of their location. In the retroperitoneum a major consideration in the differential diagnosis is sarcomatoid renal cell carcinoma; if an epithelial component cannot be recognized histologically, special studies may be required to reach the correct diagnosis. In an attempt to better characterize this entity, 23 cases of sarcomatoid renal cell carcinoma (6.3%) were identified from a review of 363 renal cell carcinomas. Blocks were available for immunohistochemical analysis in 18 cases. The epithelial and sarcomatoid portions were studied with a panel of antibodies directed against cytokeratin (AE1/AE3, CAM 5.2, and 34 beta E12), epithelial membrane antigen, Leu-M1, muscle-specific actin, S100 protein, desmin, and vimentin. The epithelial nature of the spindle cell component was best demonstrated by positive reactivity with the anti-cytokeratin AE1/AE3 (in 17 [94%] of the 18 cases). The other epithelial markers stained the spindle cell component less frequently: cytokeratin CAM 5.2 in seven cases (39%); epithelial membrane antigen in nine cases (50%); and high-molecular-weight cytokeratin 34 beta E12 in no cases (0%). In 10 cases (56%) vimentin positivity and in six cases (33%) actin positivity was seen in the spindled areas. The spindle cell component stained for Leu-M1 in four cases (22%) and for S100 protein in one case (6%) and did not react for desmin in any case. From this study we conclude that in the majority of sarcomatoid renal cell carcinomas the epithelial nature of the spindle cells, as indicated by cytokeratin expression, can be documented using immunohistochemical methods.

Topics: Carcinoma, Renal Cell; Humans; Immunohistochemistry; Immunophenotyping; Intermediate Filament Proteins; Keratins; Kidney Neoplasms; Sarcoma

A new human epithelioid sarcoma cell line (ES020488) was established from a cutaneous metastasis in 26-year-old man, and was morphologically characterized in vitro and in vivo by comparison with the original tumor. The ES020488 cells showed a male karyotype ranging from 39 to 83 chromosomes, with various abnormalities but no specific pattern. The cells were round, polygonal or spindle-shaped with abundant cytoplasm and round nuclei containing prominent nucleoli; they proliferated in a sheet-like pattern. Tumors transplanted into nude mice revealed essentially the same features as the original tumor. Both in vitro and in vivo, the cells immunohistochemically expressed vimentin, cytokeratin, and EMA, but not desmin and S-100 protein. Ultrastructural study revealed irregular or round nuclei containing abundant euchromatin and prominent nucleoli, many intermediate filaments running irregularly or around the nucleus, and a number of filopodia-like processes. ES020488 cells were thus proven to retain and exhibit the unique morphological characteristics of an epithelioid sarcoma both in vitro and in vivo. These cells are possibly derived from synovioblastic mesenchyme.

Topics: Adult; Animals; Cell Division; Cell Nucleolus; Cell Nucleus; Cytoplasm; Humans; Immunohistochemistry; Karyotyping; Keratins; Male; Mice; Mice, Nude; Microscopy, Electron; Neoplasm Transplantation; Sarcoma; Skin Neoplasms; Tumor Cells, Cultured; Vimentin

Immunostaining for cytokeratin has a well-established diagnostic application in distinguishing sarcomatous mesotheliomas from sarcomas based on the premise that cytokeratin expression is common in mesotheliomas but very rare in sarcomas. However, the frequency of cytokeratin detection is highly dependent on the choice of antibody. The aim of this study was to examine the distribution of simple cytokeratins and stratified cytokeratins in 45 mesotheliomas of various types and to assess the diagnostic utility of a simple cytokeratin antibody, a stratified cytokeratin antibody, and a broad spectrum cytokeratin antibody with the aim of establishing the superiority of one for routine diagnostic use. Particular attention was paid to the potential utility of these antibodies in biopsy specimens. The broad spectrum cytokeratin antibody performed better than both the simple cytokeratin antibody (paired t-test: P < 0.01) and the stratified cytokeratin antibody (P < 0.01) as a diagnostic marker of mesothelioma and should be used in preference to the other two antibodies, particularly when considering small biopsy specimens.

Topics: Antibodies; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Mesothelioma; Sarcoma

Although there have been a few reports dealing with the sarcomatous changes of intrahepatic cholangiocarcinoma, its clinicopathologic features as well as immunohistochemical nature remain obscure.. Among 155 cases of intrahepatic cholangiocarcinoma, 7 cases of sarcomatous cholangiocarcinoma were chosen. Immunohistochemical studies using the avidin-biotin-peroxidase complex method were performed on these cases.. The tumor showed both mucin-producing adenocarcinoma areas and sarcomatous areas, the latter being predominant in three cases and focal in the other four. All the sarcomatous areas consisted of atypical spindle cells arranged in sheets or bundles. Pleomorphic giant cells were observed in some sarcomatous components in five cases. Immunohistochemical staining for keratin and epithelial membrane antigen revealed apparent positivity in the sarcomatous components of five cases. The patients with these tumors showed aggressive intrahepatic spreading and widespread metastasis of the sarcomatous cells, and demonstrated poorer prognosis than those with ordinary cholangiocarcinoma, with one exception, a patient who remained disease-free for 3 years after surgery.. These findings favor the possible epithelial origin of sarcomatous cells. Radical operation would be necessary for patients with this special type of cholangiocarcinoma.

Topics: Adenocarcinoma, Mucinous; Adenoma, Bile Duct; Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Sarcoma

Eight epithelioid sarcomas (ES) were studied by electron microscopy, immunohistochemistry, and DNA flow cytometry. Ultrastructurally, the tumour cells showed desmosome-like intercellular junctions and numerous microvilli, in addition to whorled arrangements of intermediate filaments. Tumour cells were positive for epithelial membrane antigen, cytokeratin, and vimentin, and negative for carcinoembryonic antigen and desmin. All seven cases examined by flow cytometry showed diploid or hyperploid (near diploid) DNA content. This seems to correspond to the relatively long clinical course and low-grade malignant nature of ES. Although the histogenesis of ES is still uncertain, the results of this study suggest that it is a tumour of primitive mesenchymal cells with the capacity to show epithelial differentiation.

Topics: Adult; CD4-CD8 Ratio; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunohistochemistry; Intercellular Junctions; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Microvilli; Middle Aged; Mucin-1; Ploidies; Sarcoma; Soft Tissue Neoplasms; Vimentin

In order to clarify the histogenesis and the direction of differentiation of spindle-cell and sarcomatous components of esophageal carcinosarcoma, 20 cases of the disease were reviewed histologically and immunohistochemically using the avidin-biotin-peroxidase complex method with monoclonal and polyclonal antibodies to various keratins, vimentin, desmin, muscle specific actin and S-100 protein. A gradual transition between carcinomatous and spindle cell sarcomatous components was present histologically in all 20 cases. Positive immunoreactivity for keratins was found in carcinomatous areas in all cases. Spindle cells in the transitional areas were positive for keratins in nine cases and for vimentin in five. Two cases demonstrated trace positive reactions to both keratin and vimentin in the same areas of transitional spindle cells between carcinomatous and sarcomatous components. The sarcomatous component showed an immunohistochemically positive reaction for vimentin in ten cases and for desmin in two. In one of the 20 cases, chondrosarcomatous cells were seen which showed a positive reaction to S-100 protein but were negative to keratin. The findings strongly suggested that neoplastic epithelial cells may show dedifferentiation to transforming spindle cells and also disdifferentiation to non-epithelial sarcoma like chondrosarcoma and leiomyosarcoma.

Topics: Actins; Adult; Aged; Anaplasia; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Nucleus; Cytoplasm; Desmin; Esophageal Neoplasms; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; S100 Proteins; Sarcoma; Vimentin

Pathologic findings and immunohistochemical characterizations of 18 cases of uterine sarcomas were studied. In endometrial stromal sarcoma (ESS), 5 out of 10 cases had ovarian sex cord-like pattern and 4 out of 10 cases had smooth muscle differentiation. Immunohistochemical findings showed vimentin, desmin and cytokeratin positive in 9/10, 6/10, 2/10 cases respectively which reflects that ESS may differentiate into both epithelium and muscle components morphologically. In malignant mixed Mullerian tumors (MMT), its carcinomatous structure may be positive about vimentin, and its sarcomatous structure may be positive to the epithelium markers, which indicates that both the sarcoma and carcinoma structures have possibly a common origin. It is considered to be of value for the diagnosis of MMT, if the tumor has differentiated both epithelium and mesoderm components or to be positive to myoglobin, NSE* in immunoreaction, accompanying with the morphologic characterizations of the tumor.

Topics: Desmin; Female; Humans; Immunohistochemistry; Keratins; Neoplasms, Germ Cell and Embryonal; Sarcoma; Uterine Neoplasms; Vimentin

Five cases of a previously undescribed variant of epithelioid sarcoma are presented. This variant differs from the usual lesion in its absence of the typical necrobiotic nodular epithelioid pattern. It is instead composed of deceptively bland fibrohistiocytic and myoid cells arranged in a fibroma-like or dermatofibroma-like pattern with an affinity for osseous involvement. The clinical presentation, ultrastructural features, and presence of vimentin and low molecular weight keratin within the tumor cells justifies their designation as an epithelioid sarcoma variant.

Topics: Adolescent; Adult; Bone Neoplasms; Calcaneus; Diagnosis, Differential; Female; Femoral Neoplasms; Fibroma; Fingers; Histiocytoma, Benign Fibrous; Humans; Humerus; Keratins; Male; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms; Thigh; Tibia; Toes; Ulna; Vimentin

Clear cell sarcoma of kidney (CCSK) is a rare but distinct tumor of childhood frequently confused with Wilms' tumor (nephroblastoma). It has a characteristic histology, a marked predilection for metastasis to bone, and an aggressive clinical course with a high relapse rate in spite of surgical excision, chemotherapy and radiotherapy. We report the first histologically proven CCSK in a Malaysian patient. This was an 8-mth-old Malay boy who was clinically diagnosed to have stage I Wilms' tumor. Despite treatment, he developed multiple metastases 10 mths after initial presentation and died soon after. Emphasis is placed on recognizing this entity in view of (1) its naturally aggressive behaviour and (2) the prospect of improving prognosis with currently recommended intensified chemotherapeutic regimes. Its immunohistochemical profile of vimentin-positivity and negativity for epithelial membrane antigen, cytokeratin and Factor-8 related antigen is more in favour of a mesenchymal or glomerular origin than a tubular or vascular origin.

Topics: Humans; Immunohistochemistry; Infant; Keratins; Kidney Neoplasms; Malaysia; Male; Membrane Glycoproteins; Mucin-1; Sarcoma; Vimentin; von Willebrand Factor

The presence of individual keratin polypeptides and desmoplakins was immunohistochemically studied in 25 spindle cell sarcomas of different types using acetone-fixed frozen sections. Results revealed that keratins 8 and 18 were present in a high number of tumors: 9 of 9 synovial sarcomas, 5 of 7 leiomyosarcomas, 5 of 5 malignant schwannomas, and 1 of 4 undifferentiated spindle cell sarcomas. In addition to keratins 8 and 18, the glandular component of synovial sarcoma showed prominent reactivity with antibodies to keratins 7 and 19. Also the glandular epithelial cells in synovial sarcoma showed desmoplakin immunoreactivity preferentially in a luminal distribution, but desmoplakin was absent in other spindle cell sarcomas. Furthermore keratin 13 was seen focally in 4 of 9 synovial sarcomas. In contrast, keratins 7, 13, and 19 were practically absent in leiomyosarcomas, malignant schwannomas, and undifferentiated spindle cell sarcomas. The widespread presence of keratins 8 and 18 in various spindle cell sarcomas may reflect aberrant keratin expression in mesenchymal cells, previously described in cultured transformed fibroblasts. The presence of keratins 7 and 19 and desmoplakin is highly associated with morphologically observable epithelial differentiation restricted to synovial sarcoma among spindle cell sarcomas.

Topics: Cytoskeletal Proteins; Desmoplakins; Desmosomes; Humans; Keratins; Leiomyosarcoma; Neurilemmoma; Peptides; Peripheral Nervous System Neoplasms; Sarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms

Twenty-three cases (12 low grade, 11 high grade) of endometrial stromal sarcoma were studied with monoclonal antibodies to vimentin, keratin, desmin, muscle actin, epithelial membrane antigen, and collagen type IV, using the avidin-biotin immunoperoxidase method. Tumors were highly variable in the expression of these antigens. Some tumors contained both epithelial and smooth muscle-related antigens; others were immunoreactive only for the intermediate filament vimentin. Immunoreactivity patterns for metastases or recurrences were similar to the respective primary tumor and no correlation was observed between tumor grade and antigen expression. Normal myometrium, when present, was keratin-positive and variably epithelial membrane antigen-positive. We conclude that endometrial stromal sarcoma, as well as normal myometrium, may express both epithelial and/or muscle-related antigens. These findings most likely reflect a common mesodermal-mullerian derivation and illustrate the intimate relationship of the endometrial stromal cell to the endometrial glands and myometrium. Knowledge of these immunoreactivity patterns is essential when evaluating poorly differentiated uterine tumors or spindle cell tumors presenting in extrauterine locations.

Topics: Actins; Adult; Aged; Collagen; Desmin; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Myometrium; Sarcoma; Uterine Neoplasms; Vimentin

Three cases (two ovarian and one retroperitoneal) of mucinous tumors with solid nodules are reported. The predominant picture in the three cases was that of a mucinous cystic tumor, but small nodules of solid anaplastic carcinoma were found in all three cases. In addition, one case showed microscopic foci of microcyst rupture with histiocytic response reminiscent of sarcoma-like mural nodules, one case showed several sarcoma-like nodules, and one case showed apparent transition from anaplastic carcinoma to spindle cell sarcoma. Histologic and immunohistochemical characteristics of the lesions are given, as differentiation of these nodules is important.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; Cystadenocarcinoma; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Mucins; Ovarian Neoplasms; Retroperitoneal Neoplasms; Sarcoma; Staining and Labeling; Vimentin

We report six cases of carcinoma showing sarcomatous change in the urinary tract examined by conventional histochemistry and immunohistochemistry. All of the cases were transitional cell carcinoma with or without focal squamous cell carcinoma. Sarcomatous components resembling spindle cell sarcoma with a marked myxoid stroma or chondrosarcomatous element were also observed in all cases. The sarcomatous elements were closely associated with the areas of squamous cell carcinoma in three cases. Various histochemical staining procedures demonstrated mesenchymal features in the stroma of sarcomatous areas. By immunohistochemical examination, the epithelial components showed positive reactions for keratin, epithelial membrane antigen and, focally, carcinoembryonic antigen. The sarcomatous components revealed a positive immunoreaction for keratin but lacked other epithelial markers in all cases. Chondrosarcomatous elements in two cases were positive for both keratin and S-100 protein. These findings indicate that sarcomatous elements in carcinoma may represent mesenchymal metaplasia with partial or complete loss of epithelial features. However, further study will be necessary in order to determine whether heterogeneous elements, such as chondrosarcomatous areas, are epithelial or truly mesenchymal in origin.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins; Sarcoma; Urologic Neoplasms; Vimentin

Six cases of primary hepatic carcinomas with a significant amount of sarcomatoid elements were examined by using immunohistochemical stainings. Four of the six cases were associated with ordinary hepatocellular carcinoma (HCC), one with cholangiocellular carcinoma (CCC), and one with mixed HCC and CCC. Alpha-fetoprotein and alpha-1-antitrypsin were negative in sarcomatoid cells of all cases; vimentin stained positively in sarcomatoid tumor cells in two of the six cases; and cytokeratin (CK8) was detected in five cases. The CK8 was not detected in tumor cells of two cases of hepatic angiosarcoma, two of metastatic leiomyosarcomas, and one of metastatic fibrosarcoma, although vimentin stained positively in all these true sarcomas. It was concluded that sarcomatoid dedifferentiation of liver carcinomas might derive from both HCC and CCC. In addition CK8 might be an excellent marker to make a differential diagnosis of sarcomatoid cancers from true metastatic or primary sarcomas of the liver.

Topics: Aged; alpha-Fetoproteins; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Fibrosarcoma; Hemangiosarcoma; Humans; Immunohistochemistry; Keratins; Leiomyosarcoma; Liver Neoplasms; Male; Middle Aged; Sarcoma; Vimentin

We describe an ovarian mucinous cystadenocarcinoma with several sarcoma-like mural nodules (SLMN). The distinction between these lesions and foci of anaplastic carcinoma is important because of the poor prognosis of the latter. We have studied the potential value of immunohistochemistry in the differential diagnosis of these two lesions. In contrast to an anaplastic carcinoma, which was largely composed of keratin-positive cells, SLMN were negative or only focally positive. Therefore, in distinguishing SLMN from foci of anaplastic carcinoma, keratin strains may be added to other gross and microscopical differential features, such as size, demarcation, and presence or lack of obvious carcinomatous elements.

Topics: Adult; Carcinoembryonic Antigen; Cystadenocarcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Ovarian Neoplasms; Sarcoma

Nineteen primary intracranial sarcomas out of a total of about 25,000 brain tumour biopsies are reported. Subtypes included malignant fibrous histiocytoma (6 cases), leiomyosarcoma (3), rhabdomyosarcoma (2), angiosarcoma (2), and one case each of fibrosarcoma, low-grade fibromyxoid sarcoma, malignant ectomesenchymoma, mesenchymal chondrosarcoma, differentiated chondrosarcoma and Ewing's sarcoma. Histological and immunohistochemical features corresponded to those of extracranial sarcomas. Nests of pleomorphic astrocytes mimicking glioma were detected in the five storiform-pleomorphic malignant fibrous histiocytomas. Our results indicate that intracranial sarcomas can be classified like their extracranial counterparts. The low incidence compared with earlier series is related to changes in classification and progress in histogenetic clarification.

Topics: Adult; Aged; Biomarkers, Tumor; Brain Neoplasms; Child; Child, Preschool; Desmin; Female; Glial Fibrillary Acidic Protein; Hemangiosarcoma; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Infant; Keratins; Leiomyosarcoma; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Rhabdomyosarcoma; Sarcoma; Vimentin

A case is presented of a rhabdomyosarcoma of the oesophagus with a description of the cytology, light microscopy, and immunocytochemical findings and a discussion of spindle cell tumours occurring at this site. Cytologically, large bizarre shaped pleomorphic cells were seen in which desmin was demonstrated in order to confirm the diagnosis after destaining a Papanicolaou stained slide and restaining it with antibody to desmin.

Topics: Carcinoma; Carcinosarcoma; Desmin; Diagnosis, Differential; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Rhabdomyosarcoma; Sarcoma; Staining and Labeling; Vimentin

We report an undifferentiated sweat gland carcinoma of the vulva in an 80-year-old woman. The tumor, which was located in the right labium majus, resembled an epithelioid sarcoma histologically; it had a granulomatous appearance with multiple tumor nodules containing epithelioid tumor cells. The tumor also contained rhabdoid cells; a large cluster of them showed histological features indistinguishable from those of a malignant rhabdoid tumor. Immunohistochemically, the tumor cells reacted not only for epithelial markers such as cytokeratins, EMA, and CEA, which are known to be expressed by epithelioid sarcoma, but also for CA125 and with monoclonal antibodies recognizing sweat gland structures--namely, EKH5 and EKH6. For comparison, two epithelioid sarcomas and two extrarenal malignant rhabdoid tumors were also studied. Of these tumors, only one extrarenal rhabdoid tumor reacted with EKH5, and none reacted for CA125. Electron-microscopic examination of the present tumor showed the presence of discontinuous basal laminae and tonofibril-like structures as well as primitive cell junctions and interdigitating filopodia. From these findings, we conclude that the tumor was an undifferentiated sweat gland carcinoma mimicking an epithelioid sarcoma. Findings in this case support the idea of the diverse histogenesis of extrarenal malignant rhabdoid tumors and indicate that electron microscopy is important for differentiating epithelioid sarcoma from skin adnexal carcinoma.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Carcinoma; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Sarcoma; Skin Neoplasms; Sweat Gland Neoplasms; Sweat Glands; Vulvar Neoplasms

Topics: Artifacts; Humans; Immunochemistry; Keratins; Sarcoma; Soft Tissue Neoplasms

A new permanent cell line (GRU-1) derived from the lymph-node metastasis of a human epithelioid sarcoma was established in tissue culture. Immunohistochemically, the original tumor had exhibited an intriguing potential for multidirectional differentiation with features of mesenchymal, epithelial and neural differentiation, evidenced by the co-expression of vimentin, cytokeratins and neurofilament proteins, respectively. This capability for multidirectional differentiation was fully preserved in the cultured cells. GRU-1 tumor cells proved to be uniformly positive for vimentin and a considerable proportion of the tumor cells exhibited a positive reaction for cytokeratins and neurofilament proteins. The neural markers neuron-specific enolase (NSE) and synaptophysin were observed in a small proportion of GRU-1 cells. Ultrastructurally, GRU-1 cells showed desmoplastic activity in vitro, being enmeshed by collagen fibrils. DNA distribution, as studied by flow cytophotometry, revealed DNA-diploidy (DNA index = 1) and a G0/G1-proportion of 70.5%. After heterotransplantation in nude mice, GRU-1 tumor cells expressed vimentin and cytokeratin only, whereas the neural markers could not be further demonstrated.

Topics: Adult; Animals; Cell Line; Cell Transformation, Neoplastic; DNA, Neoplasm; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Lymphatic Metastasis; Mice; Mice, Nude; Microscopy, Electron; Neoplasm Transplantation; Neurofilament Proteins; Sarcoma; Tumor Cells, Cultured; Vimentin

We studied an unusual sarcoma with morphologic features diagnostic of epithelioid sarcoma by conventional light microscopy, transmission electron microscopy, and immunohistochemistry. The primary tumor, which was located in the deep soft tissues of the buttock of a 32-year-old woman, and its metastases to lymph nodes, liver, and lung were available for investigation. The histomorphological and ultrastructural appearance of the primary tumor and its metastatic deposits were typical of epithelioid sarcoma. Immunohistochemistry revealed a strong and uniform reactivity for vimentin in both the primary tumor and its metastases. In contrast, a marked cytoskeletal heterogeneity became evident for cytokeratins and neurofilaments, which were observed exclusively in lymph node metastasis. To our knowledge, the observation of neurofilaments in epithelioid sarcoma has not previously been reported.

Topics: Adult; Buttocks; Cytoskeleton; Endoplasmic Reticulum; Female; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Microscopy, Electron; Sarcoma; Vimentin

Two hundred soft tissue sarcomas, accrued consecutively over a 4-year period, were examined by light and electronmicroscopy and by routine immunohistochemistry. The commonest tumour type was malignant fibrous histiocytoma. Fibrosarcoma, composed only of fibroblasts, was diagnosed in only one case; three others, composed also of myofibroblasts, could be regarded as fibrosarcomas or myofibrosarcomas. Immunohistochemistry was of most value in the diagnosis of rhabdomyosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumour of Schwann cell type and epithelioid sarcoma. Electronmicroscopy was of most use for the diagnosis of malignant peripheral nerve sheath tumour of perineurial cell type and marker-negative monophasic synovial sarcoma, and for confirming malignant fibrous histiocytoma. Fifteen of 19 marker-negative spindle cell tumours (79%) were diagnosable by electronmicroscopy. A combination of techniques resulted in a specific diagnosis in 193 cases (96.5%). The routine use of electronmicroscopy in sarcoma diagnosis can improve accuracy of diagnosis, establish the true frequency of marker-positivity for each ultrastructurally confirmed tumour type and minimise the number of unclassifiable cases.

Topics: Biomarkers, Tumor; Diagnostic Errors; Evaluation Studies as Topic; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Sarcoma; Soft Tissue Neoplasms

An autopsy case of high-grade endometrial stromal sarcoma (ESS) is reported. Immunohistochemical study of the ESS was done in comparison with carcinosarcoma (CS), leiomyosarcoma (LMS) and normal endometrium in the uterus in order to trace the origin of ESS, which is a point of some controversy. Co-expression of keratin and vimentin and/or desmin positivity in several elements of CS and LMS, and glandular or stromal tissues in normal endometrium made it difficult immunohistochemically to be certain of the origin of ESS.

Topics: Antigens; Antigens, Differentiation; Autopsy; Carcinosarcoma; CD57 Antigens; Desmin; Endometrium; Female; Humans; Immunohistochemistry; Keratins; Leiomyosarcoma; Middle Aged; Phosphopyruvate Hydratase; S100 Proteins; Sarcoma; Uterine Neoplasms; Vimentin

We wished to assess the antigenic expression of primary lung tumors diagnosed as either carcinosarcoma or sarcoma in order to determine whether this information would be useful in distinguishing the two. We therefore immunohistochemically analyzed six pulmonary carcinosarcomas and five primary lung sarcomas for the presence of carcinoembryonic antigen (CEA), S100 protein, cytokeratin and vimentin using commercially available monoclonal and polyclonal antibodies on formalin fixed tissues. Six of six carcinosarcomas stained positively for cytokeratin while none of the sarcomas stained. In three carcinosarcomas both the carcinomatous and sarcomatous areas were positive while in three only the carcinomatous areas were positive. CEA staining was present in five carcinosarcomas and absent in all the sarcomas. CEA positivity was strong and not confined to those tumors with obvious gland formation. Staining for S100 protein was positive in two carcinosarcomas but only in those areas showing chondroid differentiation. Immunohistochemical staining for vimentin using two different monoclonal antibodies gave inconsistent results. We conclude that in differentiating between a carcinosarcoma and a sarcoma of the lung, immunohistochemical staining for both cytokeratin and CEA are useful with cytokeratin marginally preferable. The data indicate that carcinosarcoma of the lung, like that of the upper aerodigestive tract, expresses antigens suggesting both epithelial and mesenchymal differentiation.

Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinosarcoma; Cell Transformation, Neoplastic; Diagnosis, Differential; Epithelium; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Mesoderm; S100 Proteins; Sarcoma; Vimentin

Normal and well differentiated neoplastic canine tissues were immunohistochemically stained for keratin, vimentin and desmin intermediate filament proteins using commercially available monoclonal antibodies. Keratin was detected in 56 of 57 carcinomas, vimentin in 59 of 62 sarcomas and desmin in three of four muscle cell tumors. Most normal and neoplastic tissues expressed only one type of intermediate filament; exceptions were one hemangiosarcoma and one pulmonary carcinoma in which there was coexpression of vimentin and keratin proteins. Since immunohistochemical detection of intermediate filaments has tissue-specific distribution in the majority of well differentiated canine neoplasms, these stains may be useful in the differential diagnosis of anaplastic canine tumors. However, the monoclonal antibodies to cytokeratin which were tested in this study failed to detect intermediate filaments in liver, pancreas and salivary glands which suggests that these antibodies may also be unable to detect epithelial tumors derived from these tissues. In addition, in nine neoplasms, the normal tissues adjacent to neoplastic cells failed to stain for the intermediate filament normally expressed. When this occurs, evaluation of intermediate filament expression is invalid for the determination of tissue of origin of the neoplastic cells.

Topics: Animals; Antibodies, Monoclonal; Carcinoma; Desmin; Dog Diseases; Dogs; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Sarcoma; Vimentin

A 47-year-old female was admitted for a right hypochondrial pain and was diagnosed as having a hepatic tumor with a cystic lesion. After a right and a caudal lobectomy, she died of hepatic failure due to a tumoral recurrence. At autopsy, a cystic tumoral nodule, 15 x 7 cm in size, and numerous other nodules were revealed in the liver. Metastases were seen in both lungs, the left kidney, the colon, the mesenterium, the peritoneum, the diaphragm, and the para-pancreatic lymph nodes. The hepatic tumors consisted of four types of tumor cells: spindle, round, mixed (spindle and round cells), and cells with pseudoalveolar features. All tumor cells showed a positive immunohistochemical reaction to polyclonal keratin, low molecular monoclonal keratin, alpha 1 anti-trypsin, vimentin and to actin in their cytoplasms. This is considered a very rare case.

Topics: Actins; alpha 1-Antitrypsin; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Sarcoma; Vimentin

The estrogen receptor content, determined immunohistochemically by staining with monoclonal antibodies, was studied in seven consecutive cases of endometrial stromal sarcoma. In addition, the mitotic rate and immunohistochemical patterns (vimentin, desmin, actin, cytokeratins) were determined. Five of seven cases contained estrogen receptors, three low-grade (fewer than 10 mitoses/10 high-power fields [hpf]) and two high-grade (10 or more mitoses/10 hpf), the latter having a relatively low mitotic rate. The two negative cases were high-grade with a very high number of mitoses. Tumor cells were positive only to vimentin. Based on these results, we postulate that estrogen receptors are undetectable only in highly proliferating neoplasms. Thus, immunohistochemically determined estrogen receptor levels may indicate the aggressiveness of endometrial stromal sarcoma, and might be a guideline in selecting patients for hormonal therapy. The presence of positive immunostaining to vimentin confirms the mesenchymal origin of endometrial stromal sarcoma.

Topics: Actins; Adult; Aged; Antibodies, Monoclonal; Desmin; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Mitosis; Receptors, Estrogen; Sarcoma; Uterine Neoplasms; Vimentin

The clinical and pathological features of 33 previously untreated patients with primary breast sarcoma were retrospectively analysed to evaluate the prognostic significance of histologic variables on survival. The series comprised 17 cystosarcomas phyllodes and 16 stromal sarcomas (excluding angiosarcomas). All tumors were reviewed and classified in similar fashion to extramammary soft tissue sarcomas. In addition, immunohistochemical studies were performed on paraffin sections with a panel of several antibodies directed against cytoskeletal filaments and cellular enzymes; five cases were also examined by electron microscopy. Most tumors were malignant fibrous histiocytoma (21 cases) and fibrosarcoma (6 cases) types. Surgery was the main therapy. Metastasis-free survival rate was significantly correlated only with histological grade, consisting of tumor differentiation, tumor necrosis, and mitotic activity. Courses and survivals of the cystosarcoma and stromal groups were identical, questioning the clinical value of this pathologic distinction. All local recurrence, metastasis, or death occurred within 30 months, though follow-up was much longer. Immunohistochemistry was disappointing for identification of specific histologic sub-types.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Biomarkers, Tumor; Breast Neoplasms; Desmin; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mitosis; Necrosis; Neoplasm Metastasis; Phyllodes Tumor; Prognosis; Retrospective Studies; Sarcoma

The first case of a sarcomatoid carcinoma of the adrenal gland is reported. The patient, a 68-year old woman, developed a recurrence two months after presentation and died of the disease 7 months later with multiple metastases. The differential diagnosis of this entity is discussed and its aggressive behaviour is emphasized.

Topics: Adrenal Gland Neoplasms; Aged; Carcinoma; Female; Humans; Immunochemistry; Keratins; Sarcoma; Tomography, X-Ray Computed; Vimentin

The paper presents immunofluorescence findings on the distribution of medium-sized vimentinic and cytokeratinic filaments in the cells of epithelioid sarcoma. Two morphologically different types of tumor cells have been shown to be distinguished by the pattern of their filament expression: fusiform fibroblastoid cells contain vimentin (a mesenchymal type of differentiation), but there is a coexpression of cytokeratin and vimentin (an epithelial type) in the so-called epithelioid cells. Double mesenchymal-and-epithelial differentiation of the cells makes it possible to suppose that this tumor is of mesodermal rather than mesenchymal origin as is generally accepted. The features found in the distribution of medium-sized filaments in the epithelioid sarcoma may be useful in the practical differential diagnosis of this tumor as compared to numerous morphologically similar neoplasms.

Topics: Adolescent; Adult; Child; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Middle Aged; Sarcoma; Soft Tissue Neoplasms; Vimentin

We have described clinical, histological immunohistochemical and ultrastructural features of four typical examples of epithelioid sarcoma. Smooth-muscle-type focal densities amid fine actin-like filaments in typical epithelioid cells often containing prominent rER have been observed, as well as a structure in the form of a densely granular cytoplasmic body. These features are suggestive of myofibroblastic differentiation. A tumour with light microscopy features typical of epithelioid sarcoma but of spindle-cell appearance is also described. Ultrastructurally this consists of myofibroblasts and it is suggested that this may be an unusual variant in which myofibroblastic differentiation is a major feature.

Topics: Adult; Aged; Cell Transformation, Neoplastic; Female; Fibroblasts; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Muscle, Smooth; Sarcoma; Skin Neoplasms; Vimentin

The biological nature of human sarcomatous Wilms' tumor (SWT) was studied by analyzing newly established SWT lines, both heterotransplantable in nude mice and cultured in vitro. Five lines in nude mice include two from clear cell sarcoma of the kidney (CCSK), two from malignant rhabdoid tumor of the kidney (MRTK), and one from unclassified sarcoma. Five in vitro lines include three from CCSK, one from MRTK, and one from unclassified sarcoma. All of these in vitro cell lines produced tumors when innoculated in nude mice. Most of lines, especially of MRTK and unclassified sarcoma, well maintained their original morphological characteristics. However, CCSK lines, both heterotransplantable and in vitro, often showed unique morphological changes such as the increase of cells with eosinophilic cytoplasms and the production of mucin. Ultrastructurally, clusters of intermediate filaments, twisted sheaves of filaments resembling tonofilaments, intermediate junctions, and intracellular canaliculi were found in these cells. These findings suggested that CCSK had the latent epithelial nature which became obvious in the cell lines. This was confirmed by immunohistochemical and immunoblotting analyses with anticytokeratin antibodies. The result proved that CCSK expressed cytokeratin 8 (Mr 52,000) and 19 (Mr 40,000) as well as nephroblastic Wilms' tumor and strongly indicated that there was a close relationship between CCSK and nephroblastic Wilms' tumor.

Topics: Animals; Blotting, Western; Cell Differentiation; Child, Preschool; Epithelium; Female; Humans; Infant; Intermediate Filaments; Keratins; Kidney Neoplasms; Male; Mice; Mice, Nude; Sarcoma; Tumor Cells, Cultured; Vimentin; Wilms Tumor

Epithelioid sarcoma (ES) and malignant rhabdoid tumor (MRT) have heretofore been regarded as two separate clinicopathologic entities. However, they have some histologic similarities, and both represent histogenetic and phenotypic enigmas. This study reports the pathologic and immunohistochemical findings of four vulvar neoplasms occurring in young women that represented diagnostic dilemmas because of their similarity to both ES and MRT. Only one case had the classic histologic features of ES, whereas, in our opinion, the other three cases fulfilled the histologic criteria of MRT, despite the fact that two of the three cases were reported earlier as examples of ES. Neither electron microscopy nor immunohistochemistry has been found to be helpful in separating ES from MRT, mainly because they share several ultrastructural and immunophenotypic features. The behavior of these vulvar tumors--ours and the few published examples of ES--is generally aggressive, more in keeping with MRT than classic ES. We believe that some, if not most, putative ES of the vulva are in fact MRT, a neoplasm with an unfavorable prognosis.

Topics: Adult; Cell Nucleus; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Organelles; Rhabdomyoma; Sarcoma; Vimentin; Vulvar Neoplasms

The cytoplasmic filament composition of two pure high-grade endometrial stromal sarcomas and five pure endometrial rhabdomyosarcomas was studied using the immunoperoxidase avidin-biotin method. Ultrastructural correlates were performed on the same tissues. While four of the seven tumors presented as high-grade undifferentiated neoplasms, they were readily categorized on the basis of immunocytochemical findings in which the five rhabdomyosarcomas were positive for muscle-specific actin (HHF 35) and the two stromal sarcomas were positive for vimentin only. Ultrastructure on the HHF 35-positive cases showed the presence of thick filaments and Z-band material, whereas the other tumors showed no cytoplasmic differentiation. Muscle-type actin differs stromal cells, and is useful when used in conjunction with a panel of antibodies in the categorization of undifferentiated endometrial sarcomas.

Topics: Biomarkers, Tumor; Cytoskeletal Proteins; Desmin; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Myoglobin; Rhabdomyosarcoma; Sarcoma; Uterine Neoplasms; Vimentin

Eight primary carcinomas of the lung with a prominent spindle-cell sarcomatoid component were studied by immunocytochemical staining and electron microscopy. The eight tumors were indistinguishable by conventional light microscopy, with the exception of one unusual neoplasm that followed multiple pathways of differentiation with elements of squamous cell carcinoma, rhabdomyosarcoma, chondrosarcoma, and an undifferentiated spindle-cell population. Reticulin fiber production by individual spindle cells and a sharp demarcation of the carcinomatous and sarcomatoid domains by light microscopy were not useful differentiating features. Three of the eight tumors exhibited keratin expression in both the carcinomatous and spindle-cell components. Both immunocytochemical and electron microscopic analyses were required to detect epithelial differentiation, as in one case keratin was identified only by immunocytochemical staining and in another only by ultrastructural examination. Epithelial differentiation was undetectable in the sarcomatoid component of five tumors, and in one case immunoreactive myoglobin was identified in spindle cells; skeletal muscle differentiation was confirmed ultrastructurally. We propose that pulmonary carcinomas exhibiting evidence of epithelial differentiation in a sarcomatoid component be termed spindle-cell carcinomas and that those biphasic tumors exhibiting mesenchymal differentiation into specific tissues, such as neoplastic bone, cartilage, or striated muscle, or lacking epithelial differentiation by light microscopy, immunocytochemistry, and electron microscopy be classified as carcinosarcomas. This distinction may ultimately be unnecessary, because these two tumors may represent different points along a morphologic and biologic continuum.

Topics: Carcinoembryonic Antigen; Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Microscopy, Electron; Sarcoma

Seven epithelioid sarcomas were examined by light and electron microscopy and by immunohistochemical methods for the presence of vimentin and the epithelial markers keratin and epithelial membrane antigen. All the tumors displayed vimentin and both epithelial markers. Electron microscopy showed a spectrum of cellular differentiation from primitive fibrohistiocytic cells to epithelial-type cells with junctions, microvilli, and tonofilaments. Spindle cells showed myofibroblastic and fibroblastic differentiation. Epithelioid sarcoma appears to be a tumor of primitive cells with the potential for mesenchymal and epithelial differentiation, like some embryonic tumors.

Topics: Adolescent; Adult; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Sarcoma; Vimentin

The present report is a light- and electron-microscopic and immunohistochemical study of 7 cases of epithelioid sarcoma. Formalin-fixed and paraffin-embedded material and in one case ethanol-fixed material from the tumors as well as control tissues were used for the immunohistochemical analysis. A positive reaction for cytokeratins was observed in all 7 tumors when using 3 different polyclonal antibodies and 1 of 3 monoclonal antibodies. All tumors were positively stained with monoclonal antibodies against the epithelial membrane antigen (EMA) and all except one with monoclonal antibodies against the human milk fat globule (HMFG 1 and 2). In all tumors there was a positive reaction for actin and vimentin, using monoclonal antibodies. Ultrastructurally the tumor cells were characterized by pinocytic vesicles, cytoplasmic projections surrounding lumen-like slits, desmosome-like cell junctions and abundant thin and intermediate filaments, sometimes forming condensed bundles and tonofilament-like structures. In one case there were numerous dense cytoplasmic bodies, up to 800 nm in diameter, apparently formed by condensed intermediated filaments. The tumor cells of epithelioid sarcoma share morphologic features and immunohistochemical properties with epithelial cells, which however does not exclude the possibility of a mesenchymal origin.

Topics: Actins; Adult; Antibodies, Monoclonal; Antigens; Cytoskeleton; Female; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Middle Aged; Mucin-1; Sarcoma; Soft Tissue Neoplasms; Vimentin

An adult case of combined hepatocellular-cholangiocarcinoma with variable sarcomatous changes is presented. Histologically, the tumor was composed of hepatocellular carcinoma, cholangiocarcinoma, and sarcomatous portions, including spindle-shaped, pleomorphic, and osteoplastic varieties. There was a transitional cell form between the carcinoma and sarcomatous cells. These tumor elements showed both independent and concurrent metastases. Immunohistochemical examination for keratin revealed positive staining in the tumor cells except for osteoplastic immature cells, whereas vimentin had positive results only in some sarcomatous cells. On the basis of these findings, the possibility of sarcomatous transformation of combined hepatocellular-cholangiocarcinoma was discussed.

Topics: Adenoma, Bile Duct; Aged; Carcinoma, Hepatocellular; Gastric Mucosa; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Liver Neoplasms; Lymph Nodes; Male; Neoplasm Metastasis; Sarcoma; Vimentin

Five cases of epithelioid sarcoma are reported, of which four were studied by immunohistochemistry and one by electron microscopy. Immunohistochemically, the results of cytokeratin showed that these four cases were positive to different degrees by polyclonal cytokeratin and three out of four revealed positive results with low molecular weight cytokeratin monoclonal antibody. Two cases were positive with carcinoembryonic antigen and the other two were negative. The immunohistochemical stain was helpful for differential diagnosis from other sarcomas, such as malignant fibrous histiocytoma and rhabdomyosarcoma. By electron microscopy, tumor cells could be divided into light and dark cells which possessed more or less cell organelles, intermediate microfilaments in the cytoplasm and numerous pinocytic vesicles lying along the cell membrane. The occasional presence of poorly developed desmosomes or the absence of tonofibril bundles and glandular structures can rule out the diagnosis of carcinoma. One of these cases was originally diagnosed as metastatic carcinoma to the skin by light microscopy, which was refuted by electron microscopy, and the keratin positive reaction by immunohistochemistry was helpful for the diagnosis of epithelioid sarcoma. Therefore, the authors suggest that immunohistochemical and electron microscopic studies be used for diagnosing difficult cases of epithelioid sarcoma. From our observation, we consider that the cells of epithelioid sarcoma may derive from undifferentiated mesenchymal cells possessing the potentials of differentiating into synovioblasts, histiocytes or fibroblasts.

Topics: Adult; Carcinoembryonic Antigen; Child, Preschool; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Sarcoma; Soft Tissue Neoplasms

Topics: Carcinoma, Squamous Cell; Cell Differentiation; Humans; Keratins; Sarcoma; Vimentin

A cell line (RM-HS1) derived from a human epithelioid sarcoma was established in tissue culture. Ultrastructurally, the cells show features of those found within the primary tumor. A mixed mesenchymal-epithelial phenotype, defined by reactivity with antibodies to epithelial membrane antigen and to vimentin and keratin intermediate filaments, was found in the tumor, and a similar phenotype persisted in the cultured cells. Cytogenetic analysis revealed a mode of 66 chromosomes. With the use of a variety of banding techniques together with in situ hybridization of a 3H-labeled molecular probe for 18s and 28s ribosomal RNA genes (pX1r101), the karyotypes were shown to contain extensive numerical and structural rearrangements, with up to 24 marker chromosomes.

Topics: Adult; Aneuploidy; Antigens, Neoplasm; Cell Line; Chromosome Aberrations; ErbB Receptors; Foot Diseases; Humans; Keratins; Male; Membrane Proteins; Mucin-1; Neoplasm Proteins; Sarcoma; Vimentin

Among 355 autopsy cases of hepatocellular carcinoma (HCC), 14 cases exhibited sarcomatous appearance (incidence, 3.9%). A clinicopathologic study was performed in these 14 cases, and the immunohistochemical localization of keratin (KRT), vimentin (VMT), albumin (ALB), fibrinogen (FBG) and alpha-fetoprotein (AFP) was also examined using the avidin-biotin complex method. Clinically, the HCCs with sarcomatous appearance were characterized by negative or low serum AFP levels and high incidence of extrahepatic metastasis. Grossly they were of infiltrative, mixed expansive and infiltrative, and pedunculated types. Histologically, the tumor consisted mainly of spindle-shaped cells and partly of multinucleated cells, and showed a sinusoidal growth pattern at the tumor-nontumor boundary. Immunohistochemically, tumor cells in the regions showing sarcomatous appearance were frequently found to be positive to KRT and VMT, whereas the percentage of positivity to ALB, FBG, and AFP were not significantly different from those in ordinary HCC. These results strongly suggest that the lesion showing sarcomatous appearance represents the sarcomatous change of HCC rather than being regarded as the complication of HCC and sarcoma.

Topics: Adult; Aged; Albumins; alpha-Fetoproteins; Carcinoma, Hepatocellular; Fibrinogen; Hepatitis B Surface Antigens; Histocytochemistry; Humans; Keratins; Liver Neoplasms; Middle Aged; Sarcoma; Time Factors; Vimentin

Two cases of malignant rhabdoid tumor of the kidney (MRT) and two cases of bone metastasizing renal tumor (BMRT) were studied using electron microscopy and immunohistochemistry, in an attempt to evaluate the histogenetic relation to classical Wilms' tumor (2 cases). The two cases of MRT showed ultrastructural features of intermediate filament clusters in the cytoplasm. Vimentin, keratin, laminin, and peanut (PNA) lectin were immunohistochemically demonstrated in two cases of MRT. Tissue polypeptide antigen (TPA) was detected in one case. As for BMRT, the metastatic lesion exhibited numerous rosette-like structures of tumor cells. Vimentin was immunohistochemically demonstrated in one case, but no other antibodies were stained in two cases. Two cases of classical Wilms' tumor immunohistochemically demonstrated vimentin, keratin, PNA lectin, and TPA. MRT and BMRT fall within the broad spectrum of Wilms' tumors from the histogenetic aspect, but their clinical behavior is distinct.

Topics: Bone Neoplasms; Child; Creatine Kinase; Humans; Immunoenzyme Techniques; Isoenzymes; Keratins; Kidney; Kidney Neoplasms; Laminin; Lectins; Microscopy, Electron; Myoglobin; Peanut Agglutinin; Rhabdomyosarcoma; Sarcoma; Vimentin; Wilms Tumor

Intermediate filament composition was studied in the following endometrial stromal tumors: low-grade stromal sarcoma (endolymphatic stromal myosis), high-grade stromal sarcoma with an associated adenocarcinoma (collision tumor), diffuse clear cell stromal sarcoma and a mesodermal mixed tumor (carcinosarcoma). The tumor cells of the stromal tumors as well as the mesenchymal elements of the mixed mesodermal tumor were decorated exclusively with antibodies to vimentin. Desmin was not demonstrated in these tumor cells. A biochemical study of the cytoskeletal filaments present in the low-grade stromal sarcoma revealed, in addition to vimentin, beta and gamma actin as seen in normal endometrial stroma. Cytokeratins were only identified in epithelial components which were present in some of these tumors. Intermediate filament typing in these endometrial neoplasms contributes to the elucidation of histogenetic problems, may delineate mesenchymal from epithelial elements, may separate muscle from stromal lesions and in one instance helped to define a hitherto unreported diffuse clear cell stromal sarcoma.

Topics: Actins; Adult; Aged; Desmin; Endometrium; Female; Fluorescent Antibody Technique; Histocytochemistry; Humans; Isoelectric Focusing; Keratins; Middle Aged; Myometrium; Neoplasm Metastasis; Sarcoma; Uterine Neoplasms; Vimentin

Using an avidin-biotin immunoperoxidase technic, the authors studied 29 anaplastic thyroid tumors (ATTs) to determine the frequency of hormonal (thyroglobulin--TG; calcitonin--CT), epithelial (epithelial membrane antigen, monoclonal keratin), or sarcoma (desmin; alpha-1-antichymotrypsin--ACT; vimentin) markers. Their results indicate that 27% of ATTs stain for TG and none for CT. Fifty-five percent showed epithelial markers, 48% marked for ACT, and 47% for vimentin. Coexpression of keratin and vimentin was found in 39% of cases tested. The expression of the tested antigens did not correlate significantly with histologic pattern (epithelial vs. "sarcomatous"). Of note is the fact that 30% of the ATTs the authors tested expressed none of the markers they examined, indicating total lack of differentiation.

Topics: Adult; Aged; Aged, 80 and over; Anaplasia; Calcitonin; Carcinoma; Chymotrypsin; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Mucin-1; Sarcoma; Thyroglobulin; Thyroid Neoplasms; Vimentin

In this study we examined 198 sarcomas, 38 carcinomas, 13 'tumours with a spindle cell component' and 22 malignant melanomas with a commercial monoclonal vimentin antibody. All histopathological material was formalin fixed and paraffin embedded. The results show this antibody to be a sensitive and specific marker of mesenchymal derivation or differentiation. It is a useful tool in separating sarcomas from most carcinomas, and in separating malignant melanomas from carcinomas. When used in combination with a cytokeratin antibody it identifies carcinosarcomas and synovial sarcomas.

Topics: Antibodies, Monoclonal; Carcinoma; Carcinosarcoma; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Melanoma; Neoplasms; Retrospective Studies; Sarcoma; Vimentin

The histogenesis of synovial sarcomas remains controversial. An origin from epithelium, synovium, or synovial-related cells and neural tissue has been advanced. Using a combination of a cytokeratin (epithelial marker) antibody and a vimentin (mesenchymal marker) antibody, this study suggests that a synovial sarcoma might be regarded as a carcinosarcoma. It also highlights the diagnostic utility of those antibodies in the diagnosis of synovial sarcomas.

Topics: Carcinosarcoma; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Mesoderm; Sarcoma; Sarcoma, Synovial; Vimentin

A series of 3 benign and 10 malignant smooth muscle (SM) neoplasms and of 2 malignant fibrous histiocytomas was examined by light microscopy, transmission electron microscopy, two-dimensional gel electrophoresis (2D-GE) and indirect immunofluorescence, using polyclonal monospecific or monoclonal antibodies to desmin, vimentin, cytokeratin, alpha-SM and alpha-sarcomeric (alpha-SR) actins. Benign neoplasms displayed typical light-microscopic features of SM, whereas leiomyosarcomas demonstrated variations in their histologic pattern. In 6 sarcomas, light microscopy suggested a SM differentiation, whereas in the other 4, a predominant nondistinctive spindle-cell pattern was observed. By transmission electron microscopy, all 13 neoplasms showed the minimal essential features of SM differentiation. Immunofluorescence disclosed heterogeneity of cytoskeletal protein expression: 5 neoplasms (3 benign and 2 malignant well-differentiated) expressed desmin, vimentin, and alpha-SM-actin; 2 malignant neoplasms expressed desmin and vimentin; 1 malignant neoplasm expressed desmin, vimentin and alpha-SR actin; 1 malignant neoplasm expressed vimentin and alpha-SR actin; and 4 malignant neoplasms expressed vimentin alone. By 2D-GE, 3 benign and 4 malignant SM neoplasms expressed alpha, beta, and gamma actins, and the remaining expressed only beta and gamma actins. The presence of alpha-SM actin in all benign neoplasms and in 2 well-differentiated leiomyosarcomas suggests that this actin isoform reflects a high degree of cellular differentiation. In 2 leiomyosarcomas, alpha-SR actin was detected by immunofluorescence, which suggested a skeletal muscle differentiation of these neoplasms. This study supports the assumption that leiomyosarcomas represent a heterogeneous group of neoplasms and furnishes new criteria for their characterization.

Topics: Actins; Antibodies, Monoclonal; Cell Differentiation; Desmin; Fluorescent Antibody Technique; Histiocytoma, Benign Fibrous; Humans; Intermediate Filament Proteins; Keratins; Leiomyosarcoma; Microscopy, Electron; Muscle, Smooth; Neoplasms, Muscle Tissue; Sarcoma; Vimentin

A 26-year-old woman was operated on for a bulky tumor in the sacral region; she died of massive local tumor recurrence and pulmonary metastases 3 months later. Most of the original tumor showed a highly cellular spindle-cell sarcoma compatible with a fibrosarcoma of a high grade of malignancy. In a few small areas of the tumor, a chordoma-like pattern surrounded by growth of spindle-cell sarcoma was found. The spindle-cell component exhibited vimentin positivity in all tumor cells, but many cells were also cytokeratin-positive. The chordoma-like areas showed cytokeratin in all tumor cells. The chordoma-like areas, but not the spindle-cell areas also were positive for epithelial membrane antigen and S-100 protein. This case indicates that the sarcomatous change associated with chordoma may contain keratins as a sign of epithelial differentiation, and may thus represent sarcomatous transformation of chordoma cells, rather than a coincidental soft-tissue sarcoma or collision tumor.

Topics: Adult; Chordoma; Female; Fibrosarcoma; Humans; Keratins; Lung Neoplasms; Membrane Proteins; Mucin-1; Pelvic Neoplasms; S100 Proteins; Sacrococcygeal Region; Sarcoma; Vimentin

Thirty-four cases of sarcomatoid carcinoma with minimal epithelial components (SC) and six cases of sarcomatous tumour without any epithelial component (ST) in various organs were studied by the immunoperoxidase technique for the expression of epithelial markers, cytokeratins and epithelial membrane antigen (EMA). Employing antibodies against both high and low molecular weight cytokeratins, sarcomatoid components in 30 examples of SC were stained positively. Epithelial membrane antigen was demonstrated in 19 out of 34 SC. The positive cells for epithelial markers within sarcomatoid components in some cases of SC, which were regarded as originating from squamous cell carcinoma, tended to be seen less frequently than in the tumours derived from adenocarcinoma or transitional cell carcinoma. In six cases of ST, stain for EMA was negative and stain for cytokeratins was positive in three examples. The immunohistochemical examination of epithelial markers in the tumours of these types may be of value in differentiating these tumours from true sarcomas.

Topics: Adenocarcinoma; Antigens; Carcinoma; Carcinoma, Squamous Cell; Epithelium; Histocytochemistry; Humans; Immunochemistry; Keratins; Membrane Proteins; Mucin-1; Sarcoma

Topics: Epithelium; Histocytochemistry; Humans; Keratins; Membrane Proteins; Mucin-1; Sarcoma; Soft Tissue Neoplasms

We report the occurrence of rhabdoid cells in several specified soft tissue sarcomas of round cell variety. The rhabdoid cells had an acidophilic cytoplasm containing a globular perinuclear inclusion and were characterised ultrastructurally by the presence of aggregates of 10 nm intermediate filaments. These filaments contained both cytokeratin and vimentin, as demonstrated immunohistochemically. Extensive sampling of soft tissue sarcomas revealed the presence of such cells in different types of soft tissue round cell sarcomas as follows: 12 of 13 cases of epithelioid sarcomas, 8 of 13 synovial sarcomas (composed predominantly of round cells), 6 of 20 extraskeletal myxoid chondrosarcomas and 4 of 4 round celled malignant mesotheliomas. We wish to stress that the appearance of rhabdoid cells is not a monopoly of one particular type of tumour.

Topics: Cell Aggregation; Histocytochemistry; Humans; Inclusion Bodies; Keratins; Sarcoma; Soft Tissue Neoplasms; Vimentin

Four clonal cell lines of two types were established from a heterotransplantable mixed mesodermal tumor of the human ovary. Biologic properties of these cell lines (designated CS-C1, CS-S1, CS-S2, and CS-S3) were examined. Cells of one line (CS-C1) had an epithelioid shape and grew in monolayers (C-type). The cells showed alkaline phosphatase activity, stained positively with antikeratin antiserum, and had an ultrastructure with carcinomatous characteristics. Cells of the other three cell lines (CS-S1, CS-S2, and CS-S3) had an irregular shape and grew in multilayers (S-type). Most of the cells did not show alkaline phosphatase activity. They stained, not with antikeratin antiserum, but in fibrillar array with antifibronectin antiserum. Their ultrastructure had sarcomatous characteristics. By low cell density cultures, S-type sublines arose from CS-C1 cell line, but no C-type sublines arose from CS-S1 cell line. These findings may support the theory of the combination tumor as the cytogenesis of mixed mesodermal tumor of the ovary; they also suggest the conversion of carcinomatous cells to sarcomatous cells.

Topics: Carcinoma; Cell Line; Female; Humans; Karyotyping; Keratins; Microscopy, Electron; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Sarcoma; Tumor Cells, Cultured

Primary neoplasms of the renal pelvis are rare. Most are malignant, and most of these are transitional cell carcinomas. We report the unusual occurrence of a squamous cell carcinoma with sarcomatoid stroma arising from the renal pelvic mucosa in a patient with renal lithiasis. Immunohistochemical stains for keratin intermediate filaments failed to demonstrate their presence in the spindle cell portion of the tumor. Transmission electron microscopic study did not reveal structures of an epithelial nature in these same cells. Our findings support the contention that the spindle cells of the stroma are not squamous in nature, but represent either a reactive or a neoplastic transformation of these underlying stromal elements.

Topics: Carcinoma, Squamous Cell; Epithelium; Humans; Immunohistochemistry; Keratins; Kidney Calculi; Kidney Neoplasms; Kidney Pelvis; Male; Microscopy, Electron; Middle Aged; Necrosis; Sarcoma

Mammary tumorigenesis was surveyed in retired breeding females in four sublines of the C3H strain: in standard milk-transmitted early oncogenic mouse mammary tumor virus (MMTV)-infected C3H/He and C3H/Ki mice, and in standard milk-transmitted early oncogenic MMTV free C3Hf/He and C3Hf/Ki mice. All of 58 C3H/Ki mice and 98% (306 of 309) of the C3H/He mice developed palpable mammary tumors at average ages of 276 and 284 days, respectively. Thirty-one % (47 of 152) of the C3Hf/Ki mice and 77% (168 of 218) of the C3Hf/He mice developed palpable mammary tumors at average ages of 798 and 757 days, respectively. The mammary tumors removed from C3H/He and C3H/Ki mice were all adenocarcinomas of epithelial origin, and all contained MMTV. The mammary tumors removed from C3Hf/He and C3Hf/Ki mice were either adenocarcinomas or sarcomas. The carcinomas were of epithelial origin and all expressed the late oncogenic endogenous MMTV. The sarcomas were of histiocyte or fibrocyte origin and contained neither virus particles nor MMTV antigenic markers. It is concluded that exogenous standard milk-transmitted oncogenic MMTV oncogenesis in C3H mice is not modified by host genetic factors. In contrast, late oncogenic endogenous MMTV oncogenesis is influenced both by host genetic control of the expression of the late oncogenic MMTV provirus and by the location of the proviral genes in the germline DNA.

Topics: Adenocarcinoma; Animals; Disease Models, Animal; Female; Genes, Viral; Keratins; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Mice, Inbred C3H; Sarcoma; Vimentin

Immunoperoxidase staining for human keratin proteins was performed cytologically on samples from 90 patients with malignant tumors, and histologically on samples from 164 patients with malignant tumors. At the cytological level, almost all tumor cells not only in squamous cell carcinoma but also in nonsquamous cell carcinoma were positive for keratin proteins, in contrast with the apparent abscence of keratin proteins in sarcoma. At the histological level, almost all neoplastic cells of squamous cell carcinoma were positive for keratin proteins, the same as at the cytological level. In contrast, among cases of nonsquamous cell carcinoma, the frequency of appearance of keratin proteins varied according to the organ; it tended to be low in tumors with relatively good prognosis, such as carcinomas in the digestive system or thyroid cancer, and to be high in tumor with poor prognosis, such as pulmonary cancer, gallbladder cancer and endometrial cancer. However, there was a marked difference between the frequency of appearance of keratin proteins at the cytological level and that at the histological level, particularly in the cases of gastric cancer.

Topics: Antibodies; Breast Neoplasms; Colonic Neoplasms; Female; Gallbladder Neoplasms; Histocytochemistry; Humans; Keratins; Lung Neoplasms; Neoplasms; Sarcoma; Stomach Neoplasms; Thyroid Neoplasms; Uterine Neoplasms

Tumours of uncertain tissue of origin were investigated by immunohistochemistry on formalin fixed paraffin embedded sections. Two antibodies--PD7/26, an anti common leucocyte antigen, and CAM5.2, an anticytokeratin--recognised most lymphomas and carcinomas, respectively: 88% of these tumours were identified by the two antibodies alone. These antibodies permitted the separation of the cases into groups: positive with CAM5.2, positive with PD7/26, and a third comprising those negative with both. The negative group contained other tumours and a small number of carcinomas and lymphomas; many of the lymphomas were, apparently, of histiocytic origin. Comparison of CAM5.2 with other epithelial markers showed that it was the most effective. Some further classification of the tumours was carried out with a panel of organ and cell specific antibodies: mesotheliomas were recognised by their pattern of reactivity with epithelial markers. Overall, the tumour type was determined in 90% of cases. Immunohistochemistry performed as described can be a potent aid to the diagnostic histopathology of tumours.

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Lymphoma; Mesothelioma; Neoplasms; Sarcoma; Skin Neoplasms; Thyroid Neoplasms

Three cases of clear cell sarcoma of the kidney (CCSK) and 5 cases of Wilms' tumor were investigated immunohistochemically to examine the expression of tissue-specific intermediate filaments (cytokeratin, vimentin, and desmin) and myoglobin. In CCSK, tumor cells were negative for cytokeratin, except for occasional tubular structures, and vimentin was demonstrated in only one case. In Wilms' tumor, epithelial components were positive for cytokeratin and stromal cells were positive for vimentin, while no staining was found in blastemal cells for either. Both desmin and myoglobin were negative in all tumor cells except for skeletal muscle cells in Wilms' tumor. In the current study, some neoplastic cells in CCSK were revealed to be of mesenchymal nature, but blastemal cells in Wilms' tumor were not.

Topics: Antibodies, Monoclonal; Child; Child, Preschool; Desmin; Humans; Immunoenzyme Techniques; Infant; Keratins; Kidney Neoplasms; Male; Myoglobin; Sarcoma; Staining and Labeling; Vimentin; Wilms Tumor

Nineteen synovial sarcomas, six biphasic and 13 monophasic tumors, were examined by light and electron microscopy and immunohistochemically for the presence of the epithelial markers keratin and epithelial membrane antigen (EMA). Ultrastructurally, intercellular spaces with processes are present to varying degrees in the spindle cell component of all synovial sarcomas, and junctional specializations occur in most cases. Tumors of the two types differ in their content of external (basal) lamina, which encloses the epithelial component of all biphasic tumors and is detectable in the spindle cell component of two thirds of them, but is absent from the majority of monophasic tumors. Keratin and EMA were demonstrated in both components of all six biphasic tumors. Of the 13 monophasic tumors, keratin was present in nine, EMA in eight, and at least one epithelial marker in ten. Synovial sarcoma is regarded as a distinctive soft tissue tumor with variable epithelial-like differentiation. The use of electron microscopy can increase the specificity of immunohistochemical studies of soft tissue sarcomas and allow more accurate differentiation of monophasic synovial sarcoma from other spindle cell tumors, particularly those that do not express markers.

Topics: Epithelium; Histocytochemistry; Humans; Immunochemistry; Joint Diseases; Keratins; Membrane Proteins; Microscopy, Electron; Mucin-1; Sarcoma; Soft Tissue Neoplasms; Synovial Membrane

Epithelioid sarcoma (ES) occasionally may be confused, both clinically and histologically, with isolated necrobiotic granulomas (ING), leading to misdiagnosis and potential mismanagement of these conditions. We studied 11 cases of ES and 11 of ING (6 examples of deep granuloma annulare and 5 of rheumatoid nodule) immunohistochemically, in an attempt to determine whether they could be diagnostically separated by such means. Monoclonal antibodies to cytokeratin polypeptides (CK), epithelial membrane antigen (EMA), and leukocyte common antigen (LCA) were applied to formalin-fixed, paraffin-embedded sections in each case, using the avidin-biotin-peroxidase complex technique. All ES cases stained positively for CK, and 6 expressed EMA, while examples of ING were non-reactive for these antigens. Conversely, the large epithelioid histiocytic cells in cases of ING were immunoreactive with anti-LCA, whereas no case of ES displayed this determinant in tumor cells. In the latter lesions, reactive peritumoral inflammatory cells were LCA-positive, but were readily distinguished from neoplastic cells on morphological grounds, as well as by their negativity with anti-CK and anti-EMA. Based on these data, it is concluded that immunohistologic stains for epithelial and hematopoietic antigens are valuable in the conclusive diagnostic separation of epithelioid sarcoma and necrobiotic granulomas.

Topics: Adolescent; Adult; Aged; Antigens, Surface; Child; Child, Preschool; Diagnosis, Differential; Epithelium; Female; Granuloma; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Male; Middle Aged; Sarcoma; Skin Diseases; Skin Neoplasms

Two hundred and three sarcomas, 40 carcinomas, 10 carcinomas with spindle cell features, 27 malignant melanomas and one spindle cell melanoma were examined using CAM 5.2, a monoclonal antibody to cytokeratin. This antibody which was prepared against colorectal carcinoma cells and which identifies low molecular weight intermediate filament cytokeratin proteins is suitable for use in formalin fixed, paraffin embedded material. Seventeen of the 203 sarcomas showed positive staining. These included 15/21 synovial sarcomas, 1/5 epithelioid sarcomas and 1/18 malignant neural tumours. Five carcinosarcomas showed positive staining of their epithelial components but negative staining of their spindle cell components; three out of four pure spindle cell carcinomas stained positively; a metastasis from a spindle cell renal carcinoma was negative. A spindle cell thymoma also stained positively. Thirty-seven of the 40 carcinomas stained positively; the three negative carcinomas were a squamous cell carcinoma, a renal cell carcinoma and an oat cell carcinoma. All malignant melanomas were negative. These results are compared with those of other workers and the sensitivity and specificity of CAM 5.2 as an epithelial marker is assessed.

Topics: Antibodies, Monoclonal; Carcinoma; Histocytochemistry; Humans; Keratins; Melanoma; Sarcoma; Sarcoma, Synovial; Vimentin

The undifferentiated malignant neoplasm presents a significant problem in the intelligent selection of therapy. Because of advances in chemotherapy, there are cancers that are effectively palliated, and sometimes cured if appropriately treated. Characterization of tumors by immunohistochemical stains drastically reduces the incidence of "undifferentiated" diagnoses and will optimize patient management, as illustrated by two cases of large-cell lymphoma arising in skeletal muscle.

Topics: Biopsy; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Histocytochemistry; Humans; Immunoglobulins; Immunologic Techniques; Keratins; Lymphoma; Male; Middle Aged; Muscle Proteins; Muscles; Muscular Diseases; Sarcoma

Topics: Adolescent; Adult; Antibodies, Monoclonal; Epithelium; Female; Humans; Keratins; Male; Sarcoma; Skin Neoplasms; Vimentin

Seventy cases of anaplastic thyroid carcinomas studied at the Universities of Florence (Italy) and Minnesota are presented. Three morphologic patterns were seen: spindle, giant cell, and squamoid, sometimes in combination. Ultrastructurally, evidence of epithelial differentiation was seen in most but not all cases studied. Immunohistochemically, a stain for cytokeratin using a monoclonal antibody was found the most useful adjunct to diagnosis. Unexpected positivity for carcinoembryonic antigen (CEA) was found in several squamoid tumors. The alleged frequent positivity of this tumor type for thyroglobulin and calcitonin was not confirmed. A third of the tumors were associated with a better differentiated component, of which, presumably, they represented a dedifferentiation. The extremely aggressive behavior of anaplastic thyroid carcinomas was confirmed amply in this series: all of the patients in whom follow-up information was available died of their tumor. Small cell tumors should not be included into the anaplastic category, since they invariably belong to other groups, i.e., malignant lymphoma, medullary carcinoma, and poorly differentiated ("insular") carcinoma.

Topics: Adult; Aged; Calcitonin; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Papillary; Combined Modality Therapy; Diagnosis, Differential; Female; Histocytochemistry; Humans; Immunochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Palliative Care; Sarcoma; Staining and Labeling; Thyroglobulin; Thyroid Neoplasms

For the purpose of clarifying cellular differentiation of epithelioid sarcoma, studies based on various methods were performed. Enzyme histochemical studies showed that epithelioid sarcoma tumor cells have characteristics intermediate between epithelial cells and the large plump cells of synovial sarcoma-incomplete epithelial differentiation. For alkaline phosphatase and adenosine triphosphatase particularly, positive cells and negative cells coexisted, as in the large plump cells of synovial sarcoma. Immunohistochemical studies for alpha 1-antitrypsin, alpha 1-antichymotrypsin, vimentin, and keratin also showed that epithelioid sarcoma tumor cells are very similar to the large plump cells of synovial sarcoma and have incomplete epithelial differentiation. For example, the examinations of serial sections and double staining methods revealed that keratin-positive cells are always vimentin-positive in epithelioid sarcoma and in the monophasic area of synovial sarcoma. Electron-microscopically, bundles of intermediate filaments and filopodia toward the intercellular lumen were observed, as in the monophasic area of synovial sarcoma. The results of enzyme-histochemical and immunohistochemical studies of non-neoplastic synovial lining cells, performed here for the first time, are also discussed.

Topics: Adenosine Triphosphatases; Adult; Alkaline Phosphatase; Cell Transformation, Neoplastic; Female; Fibroma; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Sarcoma; Sarcoma, Synovial; Staining and Labeling; Vimentin

Twenty-one anaplastic tumors were studied by light microscopy (LM), immunoperoxidase staining using anti-epidermal cytokeratin (ECK) and anti-Mallory body cytokeratin (MBCK) antibodies, and electron microscopy (EM), to determine whether an epithelial origin could be confirmed. The tumors were derived from lung, stomach, colon, breast, uterus, kidney, bladder, and mesothelium. By LM, the tumors consisted of either large and polygonal, spindle or small, round cells. With immunoperoxidase staining, 11 (52%) of the anaplastic tumors were positive for ECK, positivity being either absent or only weak in the main tumor mass, but marked in areas of infiltration and metastases. In contrast, all of the anaplastic tumors were positive for MBCK in the main tumor mass, infiltrating areas, and metastases. In the case of adenocarcinomas, staining was either web-like or diffuse throughout the cytoplasm with concentration occurring at the cell surface, whereas in mesotheliomas, the staining was either diffuse or showed focal perinuclear accentuation. Twelve of 13 anaplastic tumors examined by EM showed epithelial features (desmosomes, tonofilaments, lumina, and/or microvilli). As controls, 21 non-epithelial tumors (five melanomas, eight sarcomas, and eight lymphomas) showed no reactivity with either cytokeratin antibody. These studies show that the epithelial nature of undifferentiated and poorly differentiated tumors can be confirmed by immunohistochemistry using anti-cytokeratin antibodies.

Topics: Epithelium; Humans; Immunoenzyme Techniques; Keratins; Kidney Neoplasms; Lymphoma; Melanoma; Neoplasms; Sarcoma; Tissue Distribution

The presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Papillary; Chronic Disease; Epithelium; Fluorescent Antibody Technique; Goiter, Nodular; Humans; Intermediate Filament Proteins; Keratins; Lymphoma; Protein Precursors; Sarcoma; Thyroid Gland; Thyroid Neoplasms; Thyroiditis; Vimentin

Intermediate-sized filaments have been noted in epithelioid sarcoma by previous investigators, two of whom have reported that the filaments represent vimentin. We utilized polyclonal antibodies directed against keratin and immunoperoxidase techniques (PAP) to stain 32 of the more than 300 cases accumulated at the AFIP . All of our material was formalin-fixed, paraffin-embedded. Seventy-five percent of our cases (24/32) showed positive immunoreactivity, a feature that may be of diagnostic help in distinguishing epithelioid sarcoma from modular fasciitis, benign and malignant fibrous histiocytoma, malignant melanoma, and necrotizing granuloma. In these cases, the reaction was enhanced using predigestion with trypsin. The immunoreactivity varied from tumor to tumor, perhaps due to formalin fixation. Since synovial sarcoma and mesothelioma may also be cytokeratin-positive, our findings indicate that keratin immunoreactivity is not confined to epithelial tumors and may also occur in neoplasms traditionally regarded as mesenchymal.

Topics: Adolescent; Aged; Cytoskeleton; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Sarcoma; Soft Tissue Neoplasms

Twenty-four synovial sarcomas were examined for the presence of keratin proteins by an indirect immunoperoxidase method with paraffin-embedded tissues. Keratin proteins were identified in 16 of 24 cases (67 per cent). Both the pseudoglandular and spindle cell areas of all eight of the biphasic synovial sarcomas and the spindle cells of eight of the 16 monophasic synovial sarcomas contained keratin proteins. In spindle cell areas, staining was observed in single cells and small cords and clusters of cells in the absence of cleft formation or other evidence of a pseudoglandular component. The predominant cytologic staining pattern in all cases was peripheral, with localization of staining to the cell membrane or adjacent areas, but diffuse and focal cytoplasmic staining patterns were also observed. No staining for keratin proteins was seen in 101 control cases, including 52 sarcomas of various types. Carcinoembryonic antigen was also identified in four of the 24 synovial sarcomas by an indirect immunoperoxidase technique. The identification of keratin proteins may be helpful in the pathologic diagnosis of synovial sarcoma, particularly the spindle cell monophasic variant.

Topics: Adult; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Male; Middle Aged; Sarcoma; Synovial Membrane

Two cases of squamous cell carcinoma with sarcoma-like stroma of the nose and paranasal sinuses are described. To the best of our knowledge, this is the first report of such a localization for this tumour type. Keratin was localized by immunocytochemistry in the epithelial cells, as well as in occasional stromal-like elements. The importance of distinguishing these tumours from morphologically similar neoplasms is emphasized in view of their different therapeutic approach.

Topics: Aged; Carcinoma, Squamous Cell; Histocytochemistry; Humans; Immunochemistry; Keratins; Male; Nose Neoplasms; Paranasal Sinus Neoplasms; Sarcoma

Topics: Female; Humans; Joint Diseases; Keratins; Middle Aged; Neoplasms; Sarcoma; Synovial Membrane

Four cases of squamous cell carcinoma with sarcoma-like stroma located in the vulva (1), vagina (2) and cervix (1) of postmenopausal women are presented. The gross and microscopic features are very similar to those of similarly named tumors occurring in the upper respiratory and digestive tract and in the skin. Light microscopic, electron microscopic, and immunohistochemical examination provided convincing evidence that these tumors are composed solely of squamous cell carcinoma, which has undergone a spindle cell sarcoma-like transformation in the deeper portions. Follow-up revealed an aggressive clinical course in three of the four patients, who died of their tumor between 2 and 45 months after presentation. At the time of death, two of the patients had widespread metastases and the other had massive local recurrence.

Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Diagnosis, Differential; Female; Fibroma; Follow-Up Studies; Genital Neoplasms, Female; Histocytochemistry; Humans; Keratins; Middle Aged; Sarcoma; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms

We studied the expression of cytoskeletal intermediate filaments in different types of ovarian and uterine sarcomas and carcinomas. In both uterine and ovarian leiomyosarcomas, in endometrial stromal sarcomas, and also in ovarian sarcomas, most tumor cells appeared to be positive for desmin, the muscle type of intermediate filament protein. In most of the tumors, vimentin was present only in some neoplastic cells and in the vascular endothelia. Interestingly, both uterine and ovarian malignant mixed mesodermal tumors appeared to express several types of intermediate filaments, most of the stromal cells being positive for vimentin or desmin, and the epithelial component expressing keratin. The results show that most of the sarcomatous tumors of the ovary and uterus express mainly muscle type of intermediate filament protein. The results also demonstrate the ability of cells of mesodermal origin to express epithelial cytoskeleton markers--cytokeratins.

Topics: Adenocarcinoma; Cystadenocarcinoma; Desmin; Female; Histocytochemistry; Humans; Intermediate Filament Proteins; Keratins; Leiomyosarcoma; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Sarcoma; Uterine Neoplasms; Vimentin

Topics: Animals; Antibodies; Biopsy, Needle; Carcinoma; Cytoskeleton; Fluorescent Antibody Technique; Humans; Keratins; Muscle Proteins; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Sarcoma; Vimentin

Monospecific antibodies and indirect immunofluorescence microscopy were used to investigate the presence of cytoskeletal intermediate filaments of the keratin, vimentin and desmin types in 43 soft-tissue sarcomas. The results showed that vimentin was present in the neoplastic cells of all types of soft-tissue sarcomas studied, whereas keratin was absent, the only exception being the epithelial-like cells in biphasic synovial sarcoma. The presence of desmin was confined to leiomyosarcomas and rhabdomyosarcomas, which usually showed desminpositivity. In addition, malignant fibrous histiocytomas occasionally displayed some desmin-positive cells. Thus, determination of intermediate filaments is of aid in the histogenetical diagnosis of tumors, because keratin-positivity largely excludes the possibility of a sarcoma, and desmin-positivity aids in recognizing leiomyosarcomas and rhabdomyosarcomas.

Topics: Desmin; Humans; Intermediate Filament Proteins; Keratins; Sarcoma; Soft Tissue Neoplasms; Vimentin

Intermediate filaments (IF) are tissue-specific in so far that epithelial, mesenchymal, muscle and neural tissue types can be distinguished by the use of specific antibodies to keratin, vimentin, desmin and neurofilaments or glial filaments respectively. We have examined the possibility of using these sera in the differential diagnosis of human malignant tumors. Using antisera to human skin keratin and bovine lens vimentin we could differentiate between carcinomas (keratin +) and sarcomas (vimentin +). Furthermore, we could show that when cells become malignant and metastasize they retain their original IF and do not develop additional IF systems. We conclude that antibodies to IF proteins are powerful tools in the hands of a pathologist as an additional method to improve identification of tumors and their metastases.

Topics: Antibodies, Neoplasm; Carcinoma; Cytoskeleton; Diagnosis, Differential; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Sarcoma; Vimentin

Antibodies to human and bovine epidermal prekeratin and antibodies to mouse liver cytokeratin component D (Mr 49 000) have been applied in indirect immunofluorescence microscopy on sections of human tumors of mammary gland and liver. In non-neoplastic mammary gland all epithelial cells were stained with these antibodies. In pre-invasive and invasive ductal and lobular carcinomas a cell population was observed which was not significantly stained with antibodies to epidermal prekeratin but did strongly react with antibodies to liver cytokeratin D. In the liver, the antibodies to epidermal prekeratin as well as those directed against liver cytokeratin D strongly decorated bile duct epithelia. In contrast, significant staining of the hepatocytes was only achieved with antibodies to liver cytokeratin D. This different staining reaction was maintained in liver tumors of hepatocellular and cholangiocellular origin. Antibodies to vimentin stained mesenchymal cells and tumors of mesenchymal derivation but reacted not significantly with any of the epithelial and carcinoma cells examined. The difference is of practical importance for the discrimination between anaplastic carcinomas and sarcomas of unknown origin. Cytokeratin could also be detected by antibody staining using the peroxidase-antiperoxidase (PAP) technique in formaldehyde-fixed and paraffin-embedded material of skin, gastrointestinal, respiratory, urinary and genital tract as well as various glands, liver and kidney. Examples of positive reactions were shown in a squamous cell carcinoma, a basalioma and a pleomorphic adenoma of the parotis. It is concluded that the immunohistochemical analysis of intermediate filament proteins has diagnostic potential in clinical pathology and may help to elucidate histogenesis and differentiation of tumors and possibly also prognosis of tumor growth. It is further suggested to use antibodies recognizing different subsets of proteins of the cytokeratin family in order to distinguish between different types of carcinomas.

Topics: Adenoma, Pleomorphic; Breast Neoplasms; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Liver Neoplasms; Parotid Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms

Fifty primary gastrointestinal and breast carcinomas, four embryonal rhabdomyosarcomas, six nonmuscular mesenchymal malignant tumors and one mesothelioma have been studied to determine what type of intermediate filaments they express, using affinity purified antibodies to prekeratin, vimentin and desmin and FITC or peroxidase labeled second antibodies. The tissues were alcohol fixed and paraffin embedded before use. In all carcinoma cases the tumor cells are stained by antibodies to prekeratin, while the vimentin antibody only decorates the stroma. Prekeratin positive tumor cells are not only seen in well differentiated tumors, but also in signet ring cell carcinomas. In the case of rhabdomyosarcoma the tumor cells clearly were decorated by antibodies to desmin, while the vimentin antibody only stained very few tumor cells. In cases of nonmuscular mesenchymal tumors, the tumor cells could only be labeled by antibodies to vimentin and not by antibodies to prekeratin or desmin. In biphasic tumors like mesothelioma, different parts of the tumor were separated by antibodies to prekeratin and vimentin.

Topics: Adenocarcinoma, Mucinous; Breast Neoplasms; Carcinoma; Child; Cytoskeleton; Desmin; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Keratins; Mesothelioma; Neoplasms; Neoplasms, Germ Cell and Embryonal; Protein Precursors; Rhabdomyosarcoma; Sarcoma; Vimentin

Forty-three tumors were investigated by means of immunofluorescence with the use of antibodies against the following different classes of intermediate-sized (10 nm) filament proteins: 1) cytokeratins, 2) vimentin, and 3) desmin. In general, the immunologic features of tumor-cell intermediate filaments are those present in their tissue of origin. It can be seen, therefore, that, during neoplastic transformation, there are no major changes in the synthesis of the type of intermediate filament proteins when compared to normal tissues. Immunologic identification of these proteins furnishes the surgical pathologist with a quick and clear-cut way to differentiate tumors of mesenchymal origin from epithelial neoplasms, and in particular to distinguish between malignant lymphomas and lymph node metastases of undifferentiated carcinomas.

Topics: Adult; Animals; Antibodies; Breast Neoplasms; Carcinoma; Cytoskeleton; Desmin; Female; Guinea Pigs; Humans; Keratins; Male; Mice; Microtubules; Middle Aged; Muscle Proteins; Neoplasms; Protein Precursors; Sarcoma; Skin Neoplasms; Vimentin

Antibodies against constitutive proteins of different types of intermediate-sized filaments were used in immunofluorescence microscopy on frozen sections of normal rat liver and various rat liver tumors induced by treatment with nitrosamines. Antibodies to tonofilament prekeratin stained bile duct epithelia and hepatocytes of normal liver and hepatocellular carcinoma cells and ductal cells of cholangiofibromas. These cells were not significantly stained by antibodies to vimentin. By contrast, antibodies to vimentin stained mesenchymal cells of normal liver and cells of early and advanced angiosarcomas and of undifferentiated spindle cell sarcoma. These mesenchymal tumor cells were not stained with antibodies to prekeratin. The presence of intermediate-sized filaments in these tumors, often in large whorl-like aggregates, was also demonstrated by electron microscopy. The results show that immunofluorescence microscopy with antibodies to cytoskeletal proteins is a powerful tool for the classification and differential diagnosis of mesenchymal and epithelial liver tumors. We propose that staining with antibodies to proteins of different types of intermediate filaments can be used to improve the identification of tumors of other organs, including metastases, as well as non-neoplastic proliferative lesions.

Topics: Adenoma, Bile Duct; Animals; Cytoskeleton; Hemangiosarcoma; Keratins; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Muscle Proteins; Rats; Sarcoma; Vimentin

A polypoid squamous cell carcinoma with pseudosarcomatous stroma of the urinary bladder was studied electron microscopically. The epithelial component was a typical squamous carcinoma that consisted of cells with abundant bundles of tonofilaments that converged toward well-developed desmosomes; keratohyalin granules were also seen. The stroma consisted of fusiform cells with dilated rough endoplasmic-reticulum cisternae and irregular cytoplasmic projections that were suggestive of active fibroblasts. No structures suggestive of an epithelial origin or of advanced mesenchymal differentiation were recognized. These observations are consistent with the notion that the pseudosarcomatous stroma represents a reactive process that is probably related to the growth of the epithelial neoplasm. Given the differences in behavior and prognosis between carcinomas with pseudosarcomatous stroma and true carcinosarcomas, efforts at separation of these entities are warranted.

Topics: Aged; Carcinoma, Squamous Cell; Cell Nucleus; Connective Tissue; Connective Tissue Cells; Cytoplasm; Endoplasmic Reticulum; Epithelial Cells; Epithelium; Humans; Keratins; Male; Mitochondria; Sarcoma; Urinary Bladder Neoplasms; Vacuoles