bromochloroacetic-acid and Lymphoma

Topics: Aged; Carcinoma, Medullary; Carcinoma, Squamous Cell; Diagnosis, Differential; Gastrectomy; Humans; Keratins; Lymphoma; Melanoma; Middle Aged; Neoplasm Staging; Retrospective Studies; RNA, Viral; Stomach Neoplasms

Immunohistochemistry is a strong tool in hepatopathologic diagnosis: the technique is relatively simple and inexpensive. New and very sensitive detection methods have been recently developed (e.g., the EnVision technique and the microwave antigen retrieval method). This article discusses the role of immunohistochemistry in differentiating chronic cholestatic diseases from chronic hepatitis and in characterizing infectious agents. Algorythms for the typing of lymphomas and for the differentiation of primary tumors versus metastases are proposed as well. The immunohistochemical criteria for the diagnosis of premalignant lesions are discussed.

Topics: Biliary Tract Diseases; Biopsy; Hepatitis B Surface Antigens; Hepatitis C; Humans; Immunohistochemistry; Keratin-7; Keratins; Liver; Liver Neoplasms; Lymphoma; Precancerous Conditions

Neuroendocrine bladder tumours are exceptional, and the positive diagnosis is only established when they are already large and advanced. We report an original case in view of its small dimensions. We discuss the differential diagnosis (mainly bladder metastases from lung cancer) and pathological specificities, particularly the value of epithelial immunolabelling allowing exclusion of lymphoma. Because of the similarities with bronchial neuroendocrine tumours, the potential value of serum NSE assay should be emphasized. Combined surgery-cisplatin-based adjuvant chemotherapy is recommended.

Topics: Aged; Antineoplastic Agents; Carcinoembryonic Antigen; Carcinoma, Neuroendocrine; Chemotherapy, Adjuvant; Cisplatin; Diagnosis, Differential; Female; Humans; Keratins; Lung Neoplasms; Lymphoma; Mucin-1; Neoplasm Staging; Phosphopyruvate Hydratase; Synaptophysin; Urinary Bladder Neoplasms

Topics: Adenocarcinoma; Carcinoma; Diagnosis, Differential; Endocrine System Diseases; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Melanoma; Neoplasm Invasiveness; Neoplasms, Germ Cell and Embryonal; Skin Neoplasms; Sweat Gland Neoplasms

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

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

Topics: Animals; Cell Differentiation; DNA Nucleotidylexotransferase; Guinea Pigs; Humans; Keratins; Lymphoma; Mice; Mice, Inbred C3H; Mice, Nude; Skin; Skin Neoplasms; T-Lymphocytes

Topics: Adult; Antigens, CD20; Carcinoma; Diagnosis, Differential; DNA Nucleotidylexotransferase; Female; Follow-Up Studies; Humans; Keratins; Lymphoma; Male; Middle Aged; Necrosis; Seminoma; Thymoma; Thymus Neoplasms; Tuberculosis

To study the clinicopathologic features and histologic differential diagnosis of small cell neuroendocrine carcinoma (SmCC) of kidney.. The clinicopathologic features of 12 cases of SmCC of kidney encountered during the period from 1999 to 2010 were retrospectively reviewed.. Six cases of primary and 6 cases of metastatic SmCC involving kidney were identified. Amongst the primary renal SmCC, 2 were located in renal parenchyma and 4 in renal pelvis. Chest X-ray showed negative findings. Five of them underwent radical nephrectomy. On gross examination, the tumor was located centrally around the renal pelvis in 4 cases and peripherally in renal parenchyma in 1 case. On the other hand, 4 of the 6 cases of metastatic SmCC were discovered during therapy for pulmonary SmCC. Two of these patients presented with abdominal pain and gross hematuria, with lung and renal tumor masses identified simultaneously. The diagnosis of all the 6 cases of metastatic SmCC was confirmed by fine needle aspiration biopsy. Microscopically, pure SmCC was demonstrated in the 2 cases of primary renal parenchymal SmCC and 6 cases of metastatic SmCC. The 4 primary renal pelvic SmCC coexisted with urothelial carcinoma component. On immunohistochemical study, all cases were positive for cytokeratin, synaptophysin and CD56. All metastatic cases and 4 primary cases were also positive for TTF-1. Of six patients with primary SmCC two died 4 and 9 months after operation, and two were alive with a follow-up of 25 and 138 months, respectively. Five of six cases with metastatic SmCC died 3 - 8 months after diagnosis. The other 3 cases were failed to follow-up.. Both primary and metastatic SmCC can be found in the kidney. Although rare, primary SmCC is located either in renal parenchyma or in pelvis. The diagnosis of SmCC relies on morphologic examination and immunohistochemical study. TTF-1 immunostaining cannot reliably distinguish primary from metastatic SmCC in kidney. Correlation with clinicoradiologic findings and demonstration of coexisting urothelial carcinoma component (if any) is helpful in delineation of the tumor origin.

Topics: Adult; Aged; Carcinoma, Neuroendocrine; Carcinoma, Renal Cell; Carcinoma, Small Cell; CD56 Antigen; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Keratins; Kidney Neoplasms; Lung Neoplasms; Lymphoma; Male; Middle Aged; Nephrectomy; Nuclear Proteins; Retrospective Studies; Sarcoma, Ewing; Synaptophysin; Thyroid Nuclear Factor 1; Transcription Factors; Treatment Outcome; Wilms Tumor

The observation of cytokeratins (CK's) in mass spectrometry based studies raises the question of whether the identified CK is a true endogenous protein from the sample or simply represents a contaminant. This issue is especially important in proteomic studies of the corneal epithelium where several CK's have previously been reported to mark the stages of differentiation from corneal epithelial stem cell to the differentiated cell.. Here we describe a method to distinguish very likely endogenous from uncertain endogenous CK's in a mass spectrometry based proteomic study. In this study the CK identifications from 102 human corneal samples were compared with the number of human CK identifications found in 102 murine thymic lymphoma samples.. It was anticipated that the CK's that were identified with a frequency of <5%, i.e. in less than one spot for every 20 spots analysed, are very likely to be endogenous and thereby represent a 'biologically significant' identification. CK's observed with a frequency >5% are uncertain endogenous since they may represent true endogenous CK's but the probability of contamination is high and therefore needs careful consideration. This was confirmed by comparison with a study of mouse samples where all identified human CK's are contaminants.. CK's 3, 4, 7, 8, 11, 12, 13, 15, 17, 18, 19, 20 and 23 are very likely to be endogenous proteins if identified in a corneal study, whilst CK's 1, 2e, 5, 6A, 9, 10, 14 and 16 may be endogenous although some are likely to be contaminants in a proteomic study. Further immunohistochemical analysis and a search of the current literature largely supported the distinction.

Topics: Animals; Cornea; Electrophoresis, Gel, Two-Dimensional; Humans; Immunohistochemistry; Keratins; Lymphoma; Mass Spectrometry; Mice; Mice, Inbred C57BL; Proteomics; Sequence Analysis, Protein; Thymus Neoplasms

Topics: Adenocarcinoma; Carcinoid Tumor; Child; Chromogranin A; Common Bile Duct; Common Bile Duct Neoplasms; Diagnosis, Differential; Duodenum; Gallbladder; Humans; Keratins; Lymphoma; Male; Mucin-1; Neoplasm Invasiveness; Rhabdomyosarcoma; Stomach; Synaptophysin

Topics: Abdominal Neoplasms; Adolescent; Diagnosis, Differential; Fibroblasts; Groin; Histiocytoma, Malignant Fibrous; Humans; Keratins; Lymph Nodes; Lymphoma; Male; Melanoma; Vimentin

Topics: Breast Neoplasms; Cadherins; Carcinoma, Lobular; Catenins; Delta Catenin; Diagnosis, Differential; Female; Humans; Keratins; Lymphoma; Mastitis; Plasmacytoma

Aberrant expression of cytokeratins (CK) is known to occasionally occur in malignant lymphomas. The monoclonal mouse-anti-human CK cocktail CK22 recognizes keratin polypeptides with a wide range of molecular weights and can be applied in diagnostic panels for tumors of unknown origin. Using tissue microarray technology, we tested 1059 lymphoma and acute leukemia cases, covering the most common disease entities, for aberrant CK expression, using CK22. In total, 866 of the arrayed cases were evaluable (80%), and 13 positive cases (1.5%) were found: 1 out of 230 Hodgkin lymphomas (0.4%), 1 plasma cell myeloma, 2 out of 326 diffuse large B-cell lymphomas (0.6%), 5 out of 18 mantle cell lymphomas (26%), 3 out of 70 small cell lymphomas/chronic lymphocytic leukemias (4%) and 1 out of 27 peripheral T-cell lymphomas, not otherwise specified (4%). Immunostaining was finely granular in most cases, and the total amount of positively staining cells exceeded 10% only in the cases of Hodgkin lymphoma and plasmocytoma. All CK22-positive cases, except for one mantle cell lymphoma, expressed the specific simple epithelial CK8 but not the basal/stratified epithelial CK5/6. Aberrant CK expression can be encountered in a small subset of otherwise characteristic B- and T-cell lymphomas, but not in acute leukemias, which should be considered in difficult differential diagnostic settings.

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Europe; Female; Humans; Immunohistochemistry; Keratins; Leukemia; Lymphoma; Male; Middle Aged; Tissue Array Analysis

Non-sebaceous lymphadenoma (NSL) is a rare, recently described, benign salivary gland tumor characterized by a dense lymphoid infiltrate and absence of sebaceous differentiation. To our knowledge, only seven previous cases have been reported. In this paper, we describe an additional example of NSL along with an extensive analysis of its keratin (CK) profile. The patient was a 50-year-old woman presenting with a slowly growing painless mass in the right parotid gland. The tumor was encapsulated and measured 3 x 2 x 2 cm. Microscopically, the tumor comprised islands of epithelial cells with centrally located duct-like structures within a dense lymphoid stroma. Immunohistochemically, the tumor regularly expressed CKs 7, 8/18, and 19, which are typical for columnar differentiation and CKs 17 and 5/6, which are most typically expressed in basal cells of complex epithelia. CK14 was only expressed in rare scattered cells and eventually in groups of cells. The expression of CK10/13, which correlates with squamous differentiation, was negative. Additionally, immunostaining for smooth muscle actin, vimentin, and S-100 was also performed. The immunohistochemical findings in the neoplastic epithelial component of our case suggest a differentiation of "intercalated duct phenotype" without myoepithelial cell participation.

Topics: Biomarkers, Tumor; Female; Humans; Keratins; Lymphoma; Middle Aged; Parotid Gland; Parotid Neoplasms; Treatment Outcome

Topics: Aged; Biopsy; Calbindin 2; Diagnosis, Differential; Epithelium; Gene Expression Regulation; Humans; Hyperplasia; Incidental Findings; Keratins; Lymph Nodes; Lymphoma; Male; S100 Calcium Binding Protein G

Topics: Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chromosome Aberrations; Diagnosis, Differential; Humans; Keratins; Lymphoma; Mucin-1; Urinary Bladder; Urinary Bladder Neoplasms

This study was designed to consider the cytomorphological spectrum, differential diagnosis, and the role of ancillary studies in small-cell tumors of the liver. Three independent pathologists reviewed cytological slides from 91 cases of small-cell tumors of the liver. The results were compared with the findings of three recently published studies (Cytopathology 11 (2000) 262-267; Diagn Cytopathol 19 (1998) 29-32; and Acta Cytol 40 (1996) 937-947). The role of immunohistochemistry in reaching timely and specific diagnoses was also examined. The diagnostic categories included 44 cases of metastatic small-cell undifferentiated carcinoma, 15 cases of metastatic neuroendocrine carcinoma, 10 cases of metastatic adenocarcinoma, 7 cases of malignant lymphoma, 4 cases of hepatocellular carcinoma with small-cell features, 2 cases of cholangiocarcinoma, 1 case of poorly differentiated carcinoma, and 8 cases of rare tumors including granulosa cell tumor (2 cases), sarcoma (4 cases), malignant melanoma with small-cell features (1 case), and meningioma with small-cell features (1 case). Metastatic granulosa cell-tumor, metastatic melanoma, and metastatic meningioma should be included in the differential diagnoses of small-cell malignancies found in the liver.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Carcinoma, Hepatocellular; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Cholangiocarcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Liver; Liver Neoplasms; Lymphoma; Male; Middle Aged; Mucin-1; Review Literature as Topic; S100 Proteins; Vimentin

To assess the diagnostic accuracy and to study the histologic typing of mediastinal lesions using core needle biopsies.. The histopathology and immunophenotype of 65 mediastinal core needle biopsy specimens were studied retrospectively by light microscopy and immunohistochemical staining (ABC method). Gene rearrangement studies were performed in some of the non-Hodgkin's lymphomas cases using PCR. Follow-up records were also analyzed.. Morphologically, all specimens showed a combination of epithelioid cells, lymphoid cells and fibrous tissue in different proportions. The pathologic diagnoses included lymphoma (21 cases), pulmonary carcinoma (20 cases), thymoma (14 cases), thymic carcinoma (4 cases), seminoma (3 cases) and chronic inflammation (1 case). Definitive diagnosis was not possible in 2 cases due to insufficient material. The tumor cells in lymphoma (21 cases) expressed CD20, CD3, TDT, CD30, CD15 or EMA, depending on their histologic subtypes. Tumor cells in the 17 pulmonary carcinoma cases expressed cytokeratin (CK), except 3 cases of small cell carcinoma of lung. Synaptophysin, chromogranin A and neuron-specific enolase were all positive in the 10 cases of small cell carcinoma of lung and 1 case of thymic small cell carcinoma (which was also CD5 negative). The 3 cases of adenocarcinoma of lung showed positivity for thyroid transcription factor-1 (TTF-1) and they were negative for CD5. The 14 thymoma cases expressed CK, CD3 or CD20. The 3 thymic carcinoma cases expressed CK and CD5. Placental-like alkaline phosphatase (PLAP) was positive in 3 seminoma cases which were CK-negative. Immunoglobulin heavy chain gene was rearranged in the 3 cases of diffuse large B-cell lymphoma and 1 B-cell anaplastic large cell lymphoma case. T-cell receptor beta gene was rearranged in 5 T-cell lymphoblastic lymphoma cases.. Microscopic assessment of tissue samples from mediastinal core needle biopsies should be made in combination with clinical and radiologic information. Ancillary investigations, including immunohistochemical staining and/or gene rearrangement studie, are needed in both non-lymphoma and lymphoma cases of mediastinum.

Topics: Adolescent; Adult; Aged; Biopsy, Needle; CD5 Antigens; Child; Child, Preschool; Diagnosis, Differential; Female; Follow-Up Studies; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Humans; Keratins; Lung Neoplasms; Lymphoma; Male; Mediastinal Diseases; Mediastinum; Middle Aged; Retrospective Studies; Thymus Neoplasms

Only 10 cases of lymphoepithelioma-like carcinoma of the breast have been reported in the literature. This report adds one more case to the published literature. A 62-year-old woman presented with a mass in her left breast on physical examination. The mammographic images showed a 3.0 cm, poorly defined mass in the upper outer quadrant. A biopsy was recommended. The gross specimen consisted of a 5 cm portion of breast parenchyma with no discrete tumor. On microscopic examination, the tumor was composed of sheets of epithelioid cells arranged as single cells or in cords partially obscured by a dense lymphocytic infiltrate. The epitheliod cells extensively expressed cytokeratin stain, but did not express E-cadherin. The lymphoid cells expressed L26 stain in the germinal centers, and CD3 stain in the T lymphocytes surrounding the germinal centers and in between tumor cells. In situ hybridization showed no evidence of Epstein-Barr virus infection in the tumor cells. An overall review of 11 cases shows that the disease is usually seen in older patients. In situ and invasive lobular component was reported in 36% of the cases. Eight of 11 were negative for E-cadherin, 36% were estrogen receptor-positive, 18% were progesterone receptor-positive, and all of them were HER2/neu negative. None of the reported cases have been associated with Epstein-Barr virus infection. Only two of the cases showed lymph node metastasis, and long-term follow-up in one of them showed good prognosis. In summary, lymphoepithelioma-like carcinoma of the breast is a tumor with a good prognosis that should be considered as a possible diagnosis in breast tumors with an intense lymphocytic infiltrate.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Squamous Cell; CD3 Complex; Diagnosis, Differential; Epithelioid Cells; Female; Humans; Keratins; Lymphoma; Middle Aged

Topics: Adult; Antigens, CD20; Biopsy, Fine-Needle; Breast; Breast Neoplasms; CD3 Complex; Cytodiagnosis; Female; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma

Tumours of dendritic/accessory cell origin are rare neoplasms arising in lymph nodes. Among these, tumours derived from cytokeratin-positive interstitial reticulum cells (CIRCs), a subset of fibroblastic reticulum cells, are reported even less frequently. The International Lymphoma Study Group (ILSG) has recently proposed a classification for tumours of histiocytes and accessory dendritic cells in which CIRC tumours are not included. We report a case of a CIRC tumour arising in a submandibular lymph node of a 66-year-old male.. The neoplasm was composed of spindle cells with elongated or round nuclei, prominent nucleoli and abundant cytoplasm. These cells were arranged in a diffuse fascicular and vaguely whorled pattern. The tumour cells stained diffusely for S100, vimentin, desmin, lysozyme, and focally for CD68 and cytokeratins 7, 8, 18, CK-AE1 and CK-pool. Electron microscopy was performed for further evaluation on samples taken from the paraffin block; this revealed cytoplasmic projections and rudimentary cell junctions.. Histopathologist should be aware of the existence of tumours deriving from CIRCs, as these cases may be misdiagnosed as metastatic carcinoma. Careful clinical and pathological evaluation is necessary to exclude this possibility.

Topics: Aged; Dendritic Cells; Diagnosis, Differential; Humans; Keratins; Lymph Nodes; Lymphoma; Male; Microscopy, Electron; Submandibular Gland Neoplasms; Ultrasonography

The purpose of this article is to highlight an unusual form of breast carcinoma and discuss its differential diagnosis. A 50-year-old woman underwent wide local excision of a breast lump. Microscopic examination revealed features of a lymphoepithelioma-like carcinoma. Individual tumor cells were present within an abundant lymphoid stroma. Immunohistochemistry revealed the epithelial nature of the cells and excluded a diagnosis of lymphoma. In addition, surrounding nontumorous breast tissue displayed the histologic features of sclerosing lymphocytic lobulitis or lymphocytic mastopathy. This is the second report of a lymphoepithelioma-like carcinoma of the breast, but to the best of our knowledge, it is the first description of coexistent sclerosing lymphocytic lobulitis.

Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Keratins; Lymphoma; Mastitis; Middle Aged; Sclerosis

Primary effusion lymphoma (PEL) has been recognized as a body-cavity-based lymphoma that was originally reported to be associated with human herpes virus 8 (HHV8) infection, and was frequently found in human immunodeficiency virus-positive (HIV) patients. Here we describe an autopsy case of PEL of the peritoneal cavity in an immunocompetent patient. Cytological analysis of tumor cells within ascites revealed immunocytochemical features of keratin positivity and CD45 negativity. At autopsy, the presence of a massive volume of ascites as well as diffuse tumor cell infiltrates within the serosa of the intestine and mesenterium were observed. Tumor cells were morphologically similar to anaplastic large-cell lymphoma, but were immunohistochemically positive for keratin and epithelial membrane antigen (EMA). They also showed no reactivity to representative lymphocyte surface markers including CD45, in addition to being negative for CD30 and p80NPM/ALK. Molecular analysis of the tumor cells revealed monoclonality of the immunoglobulin heavy-chain gene rearrangement which demonstrated a lymphoma of the B-cell lineage. Furthermore, HHV8 was not detected by immunohistochemical analysis, PCR or nested PCR technique. Based on these results, we consider the present case to be an HHV8-negative PEL with keratin and EMA positivity.

Topics: Adult; Ascites; Ascitic Fluid; Female; Herpesvirus 8, Human; Humans; Immunohistochemistry; Keratins; Lymphoma; Mucin-1; Peritoneal Neoplasms; Phenotype

We present the first report of bladder carcinoma that demonstrates a mixture of two distinct histological patterns resembling malignant lymphoma. The patient was a 79-year-old man. One of the histological patterns was a diffuse growth of monomorphic carcinoma cells, and the other was a dense lymphoplasmacytic infiltrate, obscuring the carcinoma. The tumor cells showing both patterns expressed cytokeratin and epithelial membrane antigen, but not lymphoid markers. Careful immunohistochemical evaluation should be done when diagnosing urinary bladder carcinomas resembling lymphomas (other than primary lymphomas).

Topics: Aged; Carcinoma; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Male; Mucin-1; Urinary Bladder Neoplasms

We report a case of cytokeratin-positive, CD45-negative primary polymorphic centroblastic lymphoma of the adrenal gland. Additional immunostaining, which demonstrated positivity for CD20 and kappa light chain, as well as detection of the monoclonal rearrangement of the immunoglobulin heavy chain gene, helped to establish the diagnosis of lymphoma and to rule out an initially favored diagnosis of poorly differentiated carcinoma.

Topics: Adrenal Gland Neoplasms; Aged; Antigens, CD20; Cell Nucleolus; Cell Nucleus; Chromatin; Cytoplasm; Gene Rearrangement; Humans; Immunoglobulin Heavy Chains; Immunoglobulin kappa-Chains; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Male; Tomography, X-Ray Computed

Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Squamous Cell; Cholangiocarcinoma; Diagnosis, Differential; Epstein-Barr Virus Infections; Germinoma; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Lymphoma; Male; Melanoma; Middle Aged; Mucin-1; Skin Neoplasms

Three cases of lympho-histiocytoid mesothelioma, a rare variant of pleural sarcomatoid malignant mesothelioma, are described. Histologically, the neoplasms were characterized by a diffuse discohesive proliferation of atypical histiocytoid cells intermixed with a marked lymphocytic and lesser plasmacytic infiltrate. One case initially was misdiagnosed as a ganglioneuroma, a second case was misinterpreted as malignant lymphoma, and a third case was sent in consultation with the differential diagnosis of inflammatory pseudotumor vs mesothelioma. Immunohistochemical studies showed strong and generalized expression of cytokeratins and vimentin by the neoplastic histiocytoid cells in all 3 cases. Two cases were positive for calretinin, one of which also was positive for HBME-1, thrombomodulin, and LeuM1. None of the cases stained with the epithelial glycoprotein markers carcinoembryonic antigen, B72.3, and Ber-EP4, or the blood group antigen, BG-8. The immunophenotype of the lymphoplasmacytic infiltrate revealed predominantly reactive, mature T cells, with fewer polytypic plasma cells, histiocytes, and B cells. In lymphohistiocytoid mesothelioma, as in the usual examples of sarcomatoid mesothelioma, the demonstration of cytokeratin expression by the neoplastic cells is the most useful diagnostic finding that allows exclusion of other neoplasms with which this entity may be confused.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Calbindin 2; Diagnosis, Differential; Ganglioneuroma; Granuloma, Plasma Cell; Histiocytes; Humans; Immunohistochemistry; Keratins; Lymphocytes; Lymphoma; Mesothelioma; Middle Aged; Plasma Cells; S100 Calcium Binding Protein G; Thrombomodulin; Vimentin

A 53-year-old woman had an orbital mass composed of a neoplastic small round cell infiltrate and no apparent extraorbital primary tumor. Although the initial diagnosis was primary orbital lymphoma, a combination of mucin histochemistry and immunohistochemical staining for cytokeratin and estrogen receptors led to the discovery of an impalpable lobular carcinoma of the breast. We discuss how detailed histopathological assessment can lead to beneficial therapy.

Topics: Biopsy, Needle; Breast Neoplasms; Carcinoma, Lobular; Combined Modality Therapy; Diagnosis, Differential; Female; Humans; Keratins; Lymphoma; Magnetic Resonance Imaging; Middle Aged; Orbital Neoplasms; Receptors, Estrogen

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

Leukocyte common antigen (CD45/LCA) and keratin expression are generally mutually exclusive in diagnostic surgical pathology. CD45 reactivity is a reliable indicator of the hematolymphoid nature of a tumor, whereas keratin reactivity is typical of epithelial differentiation (carcinomas and some sarcomas). Some lymphomas, however, might lack detectable CD45 expression, whereas occasional ones might express keratins. CD45 immunoreactivity has been considered exquisitely specific for hematopoietic cells. We report three undifferentiated or neuroendocrine carcinomas that showed membrane-associated immunoreactivity for CD45 in addition to showing distinctive keratin cocktail (AE1/AE3) and epithelial membrane antigen reactivity (all cases); also, keratin 7 was demonstrated in one case and keratin 19 in another. Two cases were lymph node metastases of undifferentiated carcinomas, one of them from the lungs and the other of an unknown origin; the former case showed neuroendocrine features. The third case represented a pulmonary large-cell undifferentiated carcinoma. These cases were negative for lineage-specific leukocyte antigens and did not show clonal immunoglobulin heavy-chain gene rearrangements. Electron microscopic studies demonstrated desmosomes and keratin-like tonofilaments in all three cases, thus confirming the epithelial nature of these tumors. The exceptional membrane staining for CD45 seen in these undifferentiated carcinomas might be comparable to experimentally detected incorporation of leukocyte antigens into the cell membranes of nonleukocytic cells in a leukocyte-rich environment. This rare diagnostic pitfall should be considered in the diagnostic surgical pathology of undifferentiated tumors. It is best avoided by employing a panel of leukocyte and epithelial antigens and by use of electron microscopy, if possible.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Desmosomes; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Leukocyte Common Antigens; Lung Neoplasms; Lymphatic Metastasis; Lymphoma; Male; Middle Aged; Neoplasms, Unknown Primary

The cytologic diagnosis of primary mediastinal lesions is challenging due to the large number of lesions which may arise (i.e., lymphoma, thymoma, germ cell tumor), often with overlapping cytomorphologic features. We present an instructive case of primary mediastinal non-Hodgkin's large-cell lymphoma with sclerosis, entrapping thymic epithelium. Preoperative fine-needle aspiration yielded predominantly epithelial fragments and few lymphoid cells leading to the cytologic misdiagnosis of thymoma. The entity of primary mediastinal large-cell lymphoma (LCL) is discussed and correlated with the cytologic features seen. In addition, histologic sections from 15 additional cases of primary mediastinal LCL were evaluated to determine the frequency with which significant numbers of epithelial fragments may be observed.

Topics: B-Lymphocytes; Biopsy, Needle; Cytodiagnosis; Diagnosis, Differential; Epithelium; Humans; Immunohistochemistry; Keratins; Lymphoma; Male; Mediastinal Neoplasms; Middle Aged; Thymoma; Thymus Gland

We report a cutaneous tumor characterized by follicular differentiation and adamantinoid features that we consider to be part of the histopathologic spectrum of trichoblastoma. Previously, similar lesions have been reported in the medical literature as cutaneous lymphadenoma or lymphoepithelial tumor of the skin.

Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Cell Differentiation; Facial Neoplasms; Humans; Keratins; Lymphoma; Male; Middle Aged; Mucin-1; Neoplasms, Basal Cell; Neoplasms, Glandular and Epithelial; Skin Neoplasms

An 82-year-old Caucasian man developed an ulcerated mass on the anterior mandibular gingiva. Five years previously he had been treated for a Merkel cell carcinoma (MCC) on his right cheek. Histopathologic examination showed small tumor cells with scanty cytoplasm, suggestive of malignancy. Immunohistochemical studies were performed with the use of nine antibodies. S-100 protein and leukocyte common antigen were helpful in ruling out melanoma and lymphoma. Pronounced reaction was shown for cytokeratin 20, a new histodiagnostic marker whose expression is almost entirely confined to Merkel cells, the gastric epithelium, and urothelium. The tentative diagnosis of metastasis of MCC was confirmed. Immunohistochemical studies are useful diagnostic aids in the establishment of the diagnosis of Merkel cell carcinoma.

Topics: Aged; Aged, 80 and over; Carcinoma, Merkel Cell; Cheek; Cytoplasm; Diagnosis, Differential; Facial Neoplasms; Gingival Neoplasms; Humans; Keratins; Lymphoma; Male; Mandibular Neoplasms; Melanoma; Skin Neoplasms

A total of 291 enlarged lymph nodes showing a range of reactive-inflammatory processes, primary and metastatic neoplasms were studied to determine the distribution and immunoprofile of their cytokeratin-positive interstitial reticulum cells (CIRC) in comparison with normal nodes. In 258/291 nodes (89%), CIRC numbers were distinctly increased in the subcapsular, paracortical and, occasionally, in the medullary zones; often, these increased CIRC formed networks around follicles, sinuses and vessels. CIRC had comparatively small, irregularly shaped bodies and dendritic processes; occasionally, giant forms were noted. CIRC contained cytokeratins (CK) 8 and 18 but not 19, as shown by immunohistochemistry, and by gel electrophoresis with subsequent immunoblotting. They co-expressed vimentin consistently, alpha-smooth-muscle actin frequently, and desmin less frequently. They did not contain desmoplakins, Factor VIII, S-100, LCA, B and T lymphocyte- and macrophage-associated antigens, chromogranin A, synaptophysin or the A-80 glycoprotein. We found no clear correlation between the increased CIRC and given nodal disease processes. However, CIRC were most abundant in nodes free of but draining malignant tumours; bizarre CIRC assemblies were noted in HIV lymphadenopathy. CIRC appear to represent a subset of the so-called "fibroblastic reticulum cells" of lymph nodes. Their function remains undetermined; their increase in diverse lymphadenopathies suggests that they partake in nodal reactions to injury. It remains unclear whether the increase in CIRC relative number is due to proliferation or to CK gene induction processes but their presence and potential capability to undergo hyperplasia with dysplastic forms should alert pathologists to possible diagnostic pitfalls. In addition, we discuss that CIRC may undergo transformation and represent the "cell of origin" of certain CK-positive tumours restricted to lymph nodes.

Topics: Cytoskeletal Proteins; Dendritic Cells; Humans; Hyperplasia; Immunohistochemistry; Keratins; Lymph Nodes; Lymphangitis; Lymphatic Diseases; Lymphoma; Microscopy, Fluorescence; Neoplasms

This report presents a case of common acute lymphoblastic leukaemia-lymphoma expressing low molecular weight cytokeratin but no leukocyte common antigen (CD45) in a 57-year-old man. The unusual morphology and clinical course together with the aberrant immunohistochemical results suggested a diagnosis of undifferentiated carcinoma. A detailed immunohistochemistry study on frozen and paraffin sections and molecular analysis prevented a diagnostic mistake.

Topics: Antibodies, Monoclonal; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Male; Middle Aged; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

Seventy-nine cases of small round cell tumors involving bone were studied in an attempt to learn whether the immunohistochemical features of the lesions might allow distinction of small cell osteosarcoma from other potential differential diagnostic considerations, including Ewing's sarcoma, atypical Ewing's sarcoma, primitive neuroectodermal tumor, mesenchymal chondrosarcoma, lymphoma, and the Askin tumor. The tissues studied were all formalin-fixed, decalcified, paraffin sections from patients between the ages of 16 and 48 years. With one exception (a small cell osteosarcoma), none of the lesions was cytokeratin positive. Moreover, none of the lesions was epithelial membrane antigen, desmin, factor VIII-related antigen, synaptophysin, or Leu-M1 positive. Accordingly, strong positivity for these antibodies in a majority of tumor cells should prompt inclusion of tumor types other than those listed above in the differential diagnosis. Vimentin positivity was seen in a majority of the tumors studied irrespective of histologic type. Scattered tumor cells (< 25%) showed positivity with antibodies to muscle-specific actin and smooth muscle actin in several of the different tumor types studied. No lesions other than lymphoma were leukocyte-common antigen (LCA) positive; all but two lymphomas were LCA positive, while all but one lymphoma were L26 positive. One (lymphoblastic) lymphoma was LCA and L26 negative. S-100, neuron-specific enolase, and Leu-7 did not prove to be specific for "neural-associated" tumors, but rather appeared in some small cell osteosarcomas, Ewing's sarcomas, atypical Ewing's sarcomas, primitive neuroectodermal tumors, mesenchymal chondrosarcomas, lymphomas, and Askin tumors. Antibody to cell surface antigen HBA71 was positive in three Ewing's sarcomas (two typical and one atypical) and negative in small cell osteosarcoma (three cases), mesenchymal chondrosarcoma (two cases), and lymphoma (one case). While some guidance may be derived from analysis of immunohistochemical staining patterns in a given lesion, the results reported in the present study do not suggest that routine immunohistochemistry alone will permit distinction of these small cell tumors of bone from one another. The value of immunohistochemical studies appears to lie particularly in the use of antibodies to LCA and S-100 protein to distinguish lymphoma and mesenchymal chondrosarcoma, and perhaps antibody to HBA71 to distinguish neural family lesions (such as Ewing's sarcoma)

Topics: Adolescent; Adult; Antigens, Differentiation; Bone Neoplasms; Chondrosarcoma, Mesenchymal; Desmin; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Membrane Glycoproteins; Middle Aged; Mucin-1; Osteosarcoma; S100 Proteins; Sarcoma, Ewing; Sarcoma, Small Cell; Synaptophysin; von Willebrand Factor

Two additional cases of cutaneous lymphadenoma (CL) are reported. The lesions presented as single nodules of many years' duration on the face. Histologically, the neoplasms consisted of irregularly shaped lobules immersed in a dense fibroblastic stroma involving the whole dermis and extending into the subcutaneous fat. Duct-like structures suggesting an eccrine differentiation were recognized. The lobules were composed of a rim of basaloid cells surrounding large epithelioid cells and lymphocytes. In some areas the basaloid lobules were only partly replaced by the inflammatory cells. Immunohistochemically, the intralobular inflammatory component was composed of a mixed B- and T-cell population and S-100-positive dendritic cells. The observation of these cases suggests that CL is not a distinct entity but may represent a basal cell carcinoma, possibly with pilar or eccrine differentiation, in which an immune host reaction pattern is exceedingly unusual.

Topics: B-Lymphocytes; Carcinoma, Basal Cell; Cheek; Diagnosis, Differential; Epithelium; Facial Neoplasms; Female; Fibroblasts; Humans; Keratins; Lymphoma; Male; Middle Aged; S100 Proteins; Skin Neoplasms; T-Lymphocytes

Two cases of cutaneous herpesvirus infection are described that clinically masqueraded as pseudolymphoma. Light microscopy demonstrated typical viral changes involving pilosebaceous complexes with sparing of the surface epithelium. Dermal changes consisted of a dense perivascular and perifollicular inflammatory infiltrate. Multinucleated lymphoid cells were found in the dermis in one case and viral inclusions in fibroblasts were present in the other case. Immunoperoxidase stains with antisera to herpes simplex virus types I and II were positive in one case and negative in the other case. Ultrastructural examination demonstrated viral particles consistent with herpesvirus in both cases. Recognition of typical histologicl features of herpesvirus folliculitis will lead to an accurate diagnosis in these types of clinically unsuspected cases.

Topics: Adult; Folliculitis; Herpesviridae; Herpesviridae Infections; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Male; Microscopy, Electron; Middle Aged; Necrosis; Skin Neoplasms

NK/Ly mouse lymphoma ascites cells were explanted and established in culture. The cells grew in monolayer and showed fibroblast-like morphology. The original NK/Ly cells contained one large metacentric marker chromosome, while the in vitro growing cells had two metacentrics in the early passages. These so-called bi-armed chromosomes were growing in number, up to seven, along with the number of subcultures. No tumour "take" was observed when the cells were given into mice intraperitoneally. However, a solid tumour developed following injection of cells into the leg muscle. The histological picture of this solid tumour was anaplastic sarcoma. It is concluded that the accumulation of bi-armed chromosomes, which were formed either by anaphase bridges, or by centric fusion of telocentric chromosomes, led to a profound alteration of lymphoma resulting a phenotype of anaplastic sarcoma.

Topics: Animals; Ascitic Fluid; Cell Division; Chromosome Aberrations; Chromosomes; Genotype; Keratins; Lymphoma; Mice; Microscopy, Electron, Scanning; Neoplasm Transplantation; Phenotype; Sarcoma, Experimental; Tumor Cells, Cultured; Vimentin

Monoclonal antibodies (mAbs) directed against the leucocyte common (CD45) antigen have been proposed as a useful tool for the differential diagnosis between malignant lymphomas (CD45+) and poorly differentiated nonhemopoietic tumors (CD45-). Thanks to the availability of mAbs directed against fixative-resistant epitopes of the CD45 molecule, this distinction can now easily be made even in routinely processed tissues. However, a small percentage of morphologically poorly defined neoplasms are difficult to diagnose even with the help of immunohistochemistry. The investigators report that 63 out of 165 anaplastic large-cell (ALC) lymphomas did not show any reactivity for the CD45 antigen in paraffin sections. In routine biopsies, the lymphomatous nature of these cases, most of which had been sent for consultation, could be always unequivocally established by demonstrating negativity for cytokeratins (mAb KL1) and clear dot-like and/or surface reactivity with the Ber-H2 mAb, which is directed against a fixative-resistant epitope of the lymphoid cell activation antigen CD30. Strikingly, 54% of the CD45-cases reacted with mAbs directed against fixative-resistant epitopes of the T cell-restricted CD45RO antigen (mAb UCHL1) or the B-restricted molecules CD45RA (mAb 4KB5) and L26 (unclustered). In order to avoid confusion of ALC lymphomas with anaplastic nonlymphoid tumors, pathologists must be aware of the existence of CD30+/CD45- ALC lymphomas, as they can mimic the above-mentioned malignancies both morphologically (due to the sinusoidal growth pattern) and phenotypically (due to the expression of EMA). The investigators conclude that the combined use of mAbs directed against fixative-resistant epitopes of the CD30, CD45RO, CD45RA, and L26 antigens and cytokeratins is essential for the correct diagnosis and treatment of these equivocal cases.

Topics: Antibodies, Monoclonal; Antigens, Differentiation; Antigens, Neoplasm; Diagnosis, Differential; Epitopes; Histocompatibility Antigens; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Leukemia, Lymphocytic, Chronic, B-Cell; Leukocyte Common Antigens; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Paraffin

Routinely-fixed and Papanicolaou stained smears with the cytologic diagnosis of undifferentiated malignant neoplasm that had been prepared with cells obtained by fine needle aspiration biopsy (n = 7), pulmonary lavage (n = 5), or thoracentesis (n = 3) from 15 unselected patients were stained by an immunocytochemical technique to evaluate the presence of keratin proteins and the leukocyte common antigen (LCA). Commercially available, well-characterized monoclonal antibodies with specificities for keratin proteins and the leukocyte common antigen, and a streptavidin-biotin-horseradish peroxidase labelling method were used. Evaluation of the stained smears revealed the presence of one of the two antigens in material obtained from each patient, thus indicating the probable cell-lineage of the neoplastic cells. The specificity of the monoclonal antibody reagents used was further evaluated in routinely-fixed and stained cytologic material from 24 histologically confirmed carcinomas and 12 lymphomas. In conclusion, immunocytochemical techniques may be successfully applied to routinely processed archival cytologic smears to determine the antigenic profile of morphologically undifferentiated cells and therefore aid in the differential diagnosis of undifferentiated malignant neoplasms.

Topics: Adult; Aged; Antigens, CD; Antigens, Neoplasm; Carcinoma, Small Cell; Cell Membrane; Cytoplasm; Diagnosis, Differential; Female; Histological Techniques; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphoma; Male; Middle Aged; Staining and Labeling

A case of undifferentiated malignant tumor of the stomach is reported. The immunohistochemistry of biopsy specimens pointed to a diagnosis of carcinoma, the tumor cells being cytokeratin positive and leukocyte common antigen (LCA) negative. After resection, however, histopathologic results showed that the tumor was a large cell lymphoma with plasmablastic differentiation. A new immunohistologic study confirmed, on the one hand, the diagnosis of lymphoma with its monotypic character IgA kappa and, on the other, positivity with three different cytokeratins of the lymphoma cells and their negativity with LCA. The aberrant immunophenotyping of this lymphoma is exceptional and must not undermine the recognized usefulness of LCA and cytokeratin, which both are basic antibody markers of immunohistochemistry in undifferentiated malignant neoplasms.

Topics: Antigens, Differentiation; Biomarkers, Tumor; Carcinoma; Diagnostic Errors; Female; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Lymphoma; Middle Aged; Stomach Neoplasms

Fourteen plasma cell tumours, including examples of solitary plasmacytoma and multiple myeloma, were studied with a panel of antibodies reactive in formalin-fixed, paraffin wax-embedded tissue. Each case showed immunoglobulin light chain restriction. Five tumours were reactive with antibodies to cytokeratin. Of these five cases, four were negative with antibodies to leucocyte common antigen and only one was weakly positive. Anti-cytokeratin reactivity by plasma cell tumours is more common than was originally anticipated and represents an important diagnostic pitfall.

Topics: Humans; Immunohistochemistry; Keratins; Lymphoma; Multiple Myeloma; Plasmacytoma

Keratinocyte expression of the monocyte/macrophage surface antigens defined by OKM1 and OKM5 antibodies (Ortho Diagnostics) was examined using the peroxidase anti-peroxidase immunohistochemical technique. A range of inflammatory cutaneous disorders were investigated, including lichen planus, psoriasis and atopic dermatitis. Positive suprabasal keratinocyte expression of OKM5 antigen was observed in all disorders, while keratinocyte staining with OKMI antibody was consistently negative. These results provide further evidence that keratinocytes may play an important role in cutaneous immune responses. Furthermore, they are consistent with the recent observation that HLA-DR positive keratinocytes may modulate cutaneous immunological reactions by inducing T-cell unresponsiveness.

Topics: Adult; Antigens, Differentiation; CD36 Antigens; Dermatitis, Atopic; Epidermis; Humans; Keratins; Lichen Planus; Lupus Erythematosus, Discoid; Lymphoma; Monocytes; Psoriasis; Skin Diseases; Skin Neoplasms

We report a case of gastric carcinoma with an unusual histologic appearance and type of cellular differentiation. The tumor was resected from an 85-yr-old man who presented with epigastric pain and monoclonal gammopathy. The tumor was antral in location and transmurally infiltrated the stomach wall. Histologically, the tumor closely resembled a lymphoma with diffuse poorly cohesive sheets of tumor cells interspersed with histiocytes. Immunohistochemical study, however, clearly demonstrated the epithelial nature of this tumor. Electron microscopy also revealed evidence of epithelial differentiation and features of parietal cell differentiation. In this report, we describe the light and electron microscopic findings, immunohistochemical staining properties, and DNA flow cytometric findings of this tumor and briefly review the literature on parietal cell carcinomas.

Topics: Aged; Aged, 80 and over; Carcinoma; Diagnosis, Differential; Follow-Up Studies; Humans; Keratins; Lymphoma; Male; Parietal Cells, Gastric; Stomach Neoplasms

Topics: Antigens, Differentiation; Diagnosis, Differential; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Lymphoma; Stomach Neoplasms

Topics: Antigens, Differentiation; Gene Expression; Histocompatibility Antigens; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Stomach Neoplasms

Formalin fixed paraffin sections of previously resected surgical specimens and ethanol fixed stamped samples of newly obtained specimens from patients with thyroid neoplastic lesions were investigated for the presence of cytokeratin by the help of avidin-biotin peroxidase complex (ABC) method using anticytokeratin monoclonal antibody PKK-1. The result showed that PKK-1 reacted only to a large cell variant of anaplastic carcinoma of the thyroid and not to a small cell type. Therefore this method appears not to be useful for differentiation between small cell carcinoma and lymphoma. The differentiation between papillary carcinoma and follicularly growing tumor was possible by this method because the former reacted to PKK-1 at a high rate, whereas most of the latter were negative to it. Freshly prepared stamped samples showed a better reaction to the monoclonal antibody, and thus this technique appears to be applicable to an aspiration biopsy cytology.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Small Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lymphoma; Thyroid Neoplasms

Among the monoclonal antibodies capable of detecting epithelial lineage, some recognize keratin and others identify antigens of epithelial membranes. Of the latter, the most commonly used is directed against an antigen present in cell membranes derived from milk fat globules, epithelial membrane antigen (EMA). To determine their relative sensitivity and specificity and hence their diagnostic value, we compared four commercially available monoclonal antibodies to low-molecular-weight keratins--AE1, CAM 5.2, PKK1, and 35 beta H11--with the monoclonal antibody to EMA (anti-EMA). We studied 383 samples of human neoplasms of diverse histogenetic types and degrees of differentiation. Anti-EMA was found to be less sensitive than the monoclonal antibodies to keratin in several epithelial tumors, including tumors of the prostate (11 of 13 negative), gastrointestinal tract (13 of 34 negative), and thymus (seven of eight negative). Anti-EMA was also less sensitive in mesotheliomas (nine of 24 negative). Of the embryonal carcinomas, all stained with the monoclonal antibodies to keratin, whereas none stained with anti-EMA. False-positive staining with anti-EMA was seen in two of 14 T-cell lymphomas. We conclude that the monoclonal antibodies to low-molecular-weight keratins are more sensitive and specific for the identification of epithelial origin of neoplasms than is monoclonal anti-EMA. Anti-EMA should not be used as the sole marker of epithelial differentiation in tumor diagnosis.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Colonic Neoplasms; False Positive Reactions; Histocytochemistry; Humans; Keratins; Lymphoma; Male; Membrane Proteins; Mucin-1; Neoplasms; Prostatic Neoplasms

The purpose of this study was to determine whether keratinocytes in certain disease states such as cutaneous T-cell lymphoma and lichen planus, express HLA-DR antigens (corresponding to the murine I-E antigens) only or whether they are also capable of expressing HLA-DQ antigens (analogues of the murine I-A antigens). Cryostat sections from 11 biopsies from cutaneous T-cell lymphoma and from 11 lichen planus biopsy specimens were submitted to indirect immunofluorescence and a 4-step immunoperoxidase method. This consists of applying monoclonal antibodies recognizing HLA-DR and HLA-DQ molecules and the intracytoplasmic invariant chain of the class II molecules. In 8 of the 11 cutaneous T-cell lymphoma specimens and in 3 of the 11 lichen planus biopsies concomitant expression of HLA-DR and HLA-DQ molecules by keratinocytes was detectable with the immunoperoxidase method. However, with the indirect immunofluorescence technique HLA-DQ antigens on keratinocytes could not be detected. The simultaneous expression of surface-bound HLA-DR antigens and intracytoplasmic gamma-chains was demonstrable in all cases investigated and with both the immunohistologic methods applied.

Topics: Epidermis; Histocytochemistry; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunochemistry; Isoantigens; Keratins; Lichen Planus; Lymphoma; Skin Neoplasms; T-Lymphocytes

A battery of polyclonal and monoclonal antibodies directed against cytokeratins, desmin, vimentin, glial fibrillary acidic protein and neurofilament proteins of mammalian species was used to demonstrate intermediate filament (IF) expression in normal and lymphoma tissues of northern pike by indirect immunofluorescence microscopy. Frozen sections of pike intestine, skin, skeletal muscle, heart, liver, testis, head-, mid-, and posterior kidney and brain demonstrated IF in a manner which strengthens the idea that they are evolutionarily highly conserved. The results also confirm the IF-subclass specificities for different types of tissues, as noted by others in other species. Pike lymphoma cells showed morphological resemblance to head kidney cells; immunofluorescence microscopy and immunoblotting revealed vimentin expression, suggesting that the Aland pike lymphoma is a true mesenchymal neoplasm and is derived from haemic cells. The significance of these studies in relation to similar work with other species and to the possible use of IFs in the classification of normal and diseased tissues in fish is discussed.

Topics: Animals; Cytoskeleton; Desmin; Electrophoresis, Polyacrylamide Gel; Fish Diseases; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Immunologic Tests; Intermediate Filament Proteins; Intermediate Filaments; Keratins; Lymphoma; Microscopy, Fluorescence; Salmonidae; Vimentin

Definitive diagnosis of gastric large cell lymphoma and its distinction from anaplastic carcinoma in endoscopic biopsy material may be problematic. To assess the utility of immunohistochemical studies in routinely processed, paraffin-embedded tissue in this situation, we applied immunostaining for leukocyte common antigen (LCA) and cytokeratin in 17 cases diagnosed on biopsy as undifferentiated malignant tumor but proved on resection to be primary gastric large cell lymphoma. Clinical and endoscopic features failed to distinguish lymphoma from carcinoma in these cases. Immunoreactivity for LCA occurred in 15 cases (88 per cent) and was correctly and readily interpreted on blinded evaluation. Open review increased the yield to 16 cases (94 per cent). Tumor cells were uniformly negative for cytokeratin; however, staining of adjacent epithelium for cytokeratin provided additional confirmation of the lymphoid nature of the tumor. The one case in which excessive background staining precluded interpretation consisted of a single biopsy specimen of necrotic tumor. We conclude that antibodies to LCA and cytokeratin are sensitive, specific, and reliable diagnostic adjuncts that are useful in the definitive biopsy diagnosis of gastric large cell lymphoma.

Topics: Adolescent; Adult; Aged; Antibodies; Biopsy; Histocompatibility Antigens; Histocytochemistry; Humans; Immunochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Middle Aged; Stomach Neoplasms

We report T6 antigen expression on keratinocytes in 11 cutaneous T lymphomas treated by PUVA therapy. This staining was absent before treatment. T6 reactivity was strictly limited to cell membrane. The nature of this expression is discussed, and it is suggested that it could be attributed to a passive diffusion from Langerhans's cells.

Topics: Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Epidermal Cells; Epidermis; HLA-DR Antigens; Humans; Keratins; Leukocyte Count; Lymphoma; PUVA Therapy; Skin Neoplasms; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Nine primary human renal-cell tumors (RCT), one lymph-node metastasis, 4 human xenografts of a RCT in nude mice and a rat RCT line were analyzed by flow cytometry (FCM) using propidium iodide for DNA analysis and antibodies to cytokeratin and vimentin in the indirect immunofluorescence technique for labelling of specific tumor-cell populations. By means of 2-dimensional FCM analysis, vimentin- and cytokeratin-positive (tumor) cells were compared and their DNA content and proliferative fraction analyzed separately from those of cytokeratin-negative stromal and inflammatory cells. In primary human RCT, 2 subpopulations of cells were detected and analyzed separately. Small numbers of tumor cells with an abnormal DNA stemline were also detected. In addition, co-expression of intermediate filament proteins of both the cytokeratin and the vimentin types was detected in the aneuploid cell population. Comparison of 2 model systems of RCT with primary human RCT revealed a similar pattern of tumor-cell subfractions within these tumors. The 2-parameter FCM analysis permits the detection of subpopulations in complex cell suspensions and the quantification of these fractions, as well as analysis of their cellular DNA content.

Topics: Animals; Carcinoma, Renal Cell; Flow Cytometry; Fluorescent Antibody Technique; Humans; Keratins; Kidney Neoplasms; Lymphoma; Mice; Mice, Nude; Rats; Rats, Inbred Strains; Vimentin

Twenty cases of undifferentiated thyroid tumours were reviewed histologically. In seven cases the histogenesis was difficult to determine using morphological criteria. Immunohistochemical staining with a panel of antibodies to lymphoid and epithelial cells, including monoclonal antibodies directed against the leucocyte common antigen, cytokeratin, and epithelial membrane antigen confirmed that four of these cases were lymphomas and that one was a medullary carcinoma. In the remaining two cases immunohistochemistry was unhelpful. In the thirteen histologically typical tumours, the immunohistochemical profile was in keeping with their histogenesis as determined by morphological criteria. Immunohistochemical staining with a panel of selected antibodies allows the reliable diagnosis of undifferentiated thyroid neoplasms, when this cannot be reached using routine histological techniques.

Topics: Aged; Antibodies, Monoclonal; Antigens; Carcinoma; Female; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Membrane Proteins; Middle Aged; Mucin-1; Thyroid Neoplasms

Fifteen cases of non-Hodgkin's lymphoma of the anterior mediastinum are reported. In the first group of four, fresh tissue was available and immunohistochemical studies demonstrated their B-cell origin, with monotypic immunoglobulin production in two. Only fixed tissue was available in the second group of 11 patients. All stained with antibody to leucocyte common antigen (PD7/26) and three showed monotypic immunoglobulin production. If the two groups are combined seven of the 15 tumours were clearly of B-cell origin. Classification on morphological grounds was difficult, with most tumours showing mixtures of centroblasts and large centrocytes, and the original diagnoses had included Hodgkin's disease (three), thymoma (one) and undifferentiated carcinoma (two). None of the patients had evidence of extra-thoracic disease at presentation and when this developed the organs involved were liver (one), kidney (two) and thyroid (one). Direct extension within the chest led to infiltration of chest wall, sternum, lung, superior vena cava and other structures. The site of origin, lack of nodal involvement and, in one case, presence of residual thymus around the tumour indicate an origin in thymic B-cells.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, Surface; B-Lymphocytes; Female; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Immunoglobulin D; Immunoglobulin G; Immunoglobulin M; Keratins; Leukocyte Common Antigens; Lymphoma; Male; Mediastinal Neoplasms; Middle Aged; Thymus Gland

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

The reactivity of a monoclonal antibody against human T lymphotropic retrovirus (antibody 12/1-2, recognising the HTLV-1 p19 internal core viral protein) with benign and malignant cutaneous biopsy specimens was examined and compared with results obtained on normal skin, on various other human cells and tissues, and on immunoblotted extracts of tonsil squamous epithelium. In keeping with previous studies, 12/1-2 labelled a proportion of the thymic epithelial stroma and the entire layer of basal cells in stratified non-keratinized and keratinized epithelium. Furthermore, antibody 12/1-2 reacted with basal cell carcinomas and showed an essentially identical staining pattern in normal skin, cutaneous T cell lymphomas, and a range of benign dermatoses. The dot blot preparations showed that 12/1-2 recognised an antigen associated with keratin intermediate filaments. These data indicate that antibody 12/1-2 forms a useful marker for subsets of epithelial cells, which presumably participate in T cell education, and that a range of cutaneous disorders of widely different aetiology show no abnormalities in epithelial expression of this antigen.

Topics: Antibodies, Monoclonal; Antibodies, Viral; Antigens; Carcinoma, Basal Cell; Deltaretrovirus; Epithelium; Humans; Keratins; Lymphoma; Palatine Tonsil; Skin; Skin Diseases; Skin Neoplasms; T-Lymphocytes; Thymus Gland

The histologic and immunologic features of an unusual morphologic expression of nodular sclerosing Hodgkin's disease, which ahs been termed the "syncytial variant," are described. In biopsy material from 18 cases, numerous Reed-Sternberg cell variants were observed in sheets and cohesive clusters, and at least focal evidence of nodular sclerosis was present in each case. The granulocyte antibody anti-Leu M1 reacted with antigenic determinants in Reed-Sternberg cells and atypical variants thereof in 13 of the 18 cases; the lack of staining with antibodies reactive with the leukocyte common (T200) antigen (PD7/26), keratin (AE1), and S100 protein (polyclonal anti-S100) was helpful in excluding non-Hodgkin's lymphoma, carcinoma, and melanoma, respectively. This unusual form of nodular sclerosing Hodgkin's disease is important to recognize, since it may simulate metastatic neoplasms, thymoma, and non-Hodgkin's lymphoma.

Topics: Adolescent; Adult; Aged; Animals; Antibodies, Monoclonal; Diagnosis, Differential; Female; Histocompatibility Antigens; Hodgkin Disease; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Lymphoma; Male; Middle Aged; Neoplasm Metastasis; S100 Proteins

Paraffin sections of formalin-fixed tumor samples from 26 patients with neuroendocrine (Merkel cell) carcinoma of the skin (NECS) were studied immunohistochemically with three monoclonal antibodies to low molecular weight keratin (MAB-K) and with antibodies to leukocyte common antigen (LCA), neurofilament (NF), neuron-specific enolase (NSE), S100 protein (S100), and chromogranin (CGN), to investigate the relative diagnostic value of these antibodies. Samples from 20 lymphomas, 10 non-oat cell undifferentiated carcinomas, 10 oat cell carcinomas, and 10 melanomas served as controls. Keratin was found in 25 of the 26 NECS and in all undifferentiated and oat cell carcinomas. A ball-like immunostaining for keratins, resembling an inclusion body was seen only in cases of NECS and some carcinoids. Neurofilament, NSE, and CGN were expressed by fewer NECS than was keratin and all NECS were negative for LCA and S100. None of the lymphomas and melanomas contained detectable keratin, NF, NSE, or CGN. Only the lymphomas stained with LCA. Only the melanomas were S100-positive. It is concluded that keratin is the most useful single discriminating marker in the separation of neuroendocrine (Merkel cell) carcinoma of the skin from lymphoma, melanoma and, when the characteristic inclusion-like pattern is seen, from metastatic oat cell carcinoma.

Topics: Adult; Aged; Antibodies, Monoclonal; Carcinoid Tumor; Carcinoma; Carcinoma, Small Cell; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Histocytochemistry; Humans; Immunochemistry; Keratins; Lung Neoplasms; Lymphoma; Male; Melanoma; Microscopy, Electron; Middle Aged; Nerve Tissue Proteins; Skin Neoplasms

Topics: Adult; Aged; Cells, Cultured; Epidermal Cells; Female; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Interferon-gamma; Keratins; Lymphoma; Male; Middle Aged; Skin Neoplasms

Different tumours of the head and neck were analysed by immunohistochemistry. The distribution pattern of several intermediate filaments was studied. Keratin filaments were typical of carcinomas, whereas vimentin filaments were typical of mesenchymal tumours of different origin. The advances of this new technique of "tumour typing" are discussed.

Topics: Carcinoma, Basal Cell; Cytoskeleton; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Lymphoma; Melanoma; Mouth Neoplasms; Nasopharyngeal Neoplasms; Neuroma, Acoustic; Oropharyngeal Neoplasms; Tonsillar Neoplasms; Vimentin

Epithelial membrane antigen and keratin proteins represent markers of epithelial differentiation that may be detected in routine formalin-fixed, paraffin-embedded tissues. Eighty-seven neoplasms, including 48 adenocarcinomas of various types, squamous and transitional cell carcinomas, small-cell anaplastic carcinomas, carcinoid tumors, mesotheliomas, hepatomas, melanomas (metastatic), adrenal cortical carcinomas, germ cell tumors, and extramammary Paget's disease, were assessed to determine the relative effectiveness of these antigens as tumor markers. Immunoperoxidase studies were performed using monoclonal antibodies to epithelial membrane antigen and monoclonal (combined AE1 and AE3) and polyclonal (bovine muzzle keratins) antibodies to keratin proteins. In more than half the cases (50/87%), both markers yielded comparable results. However, in 29 cases (33%), keratin proteins were clearly superior to epithelial membrane antigen as a tumor cell marker. Particular discrepancies were apparent for some gastrointestinal adenocarcinomas, squamous cell carcinomas, hepatomas (hepatocellular type), spindle cell components of mesotheliomas, and carcinoid tumors. Epithelial membrane antigen represented a better marker in eight cases (9%), mainly for small-cell anaplastic carcinomas and some renal cell and pulmonary adenocarcinomas. Adrenal cortical carcinomas, melanomas, and seminomas were nonimmunoreactive for both antigens. Epithelial membrane antigen and keratin proteins represent useful complementary markers in diagnostic surgical pathology.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Carcinoma; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Membrane Proteins; Mucin-1; Neoplasms

Topics: Carcinoma, Squamous Cell; Clinical Enzyme Tests; Diagnosis, Differential; Histocytochemistry; Humans; Keratins; Lymphoma; Mouth Neoplasms

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

Immunohistochemical studies using antisera to keratin and secretory component (SC) and monoclonal antibody against leukocyte common antigen (LCA) were performed on 92 biopsy and autopsy specimens taken from 65 patients with nasopharyngeal carcinoma. Five biopsy specimens from malignant lymphoma of the nasopharynx and tonsil, and 20 biopsy specimens of nasopharyngeal epithelium were also included in the study. Keratin was positively stained in all squamous cell carcinomas and nonkeratinizing carcinomas, and 38 of 46 undifferentiated carcinomas (82.6%), but in no malignant lymphomas. LCA was intensely stained in all malignant lymphoma, but in no nasopharyngeal carcinomas. SC was positively stained in two of the 46 undifferentiated carcinomas (4.3%). Nasopharyngeal carcinoma is a definite malignant epithelial neoplasm and can be distinguished from malignant lymphoma by immunostaining for keratin and LCA. Some undifferentiated carcinoma may show cellular differentiation toward ciliated epithelium.

Topics: Adolescent; Adult; Aged; Antigens; Carcinoma; Carcinoma, Squamous Cell; Child; Female; Histocompatibility Antigens; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunoglobulin Fragments; Keratins; Leukocyte Common Antigens; Leukocytes; Lymphoma; Male; Middle Aged; Nasopharyngeal Neoplasms; Secretory Component

Forty-nine cases encompassing 16 different types of malignant lymphoma were examined for their intermediate filament protein (IFP) type by indirect immunofluorescence microscopy of cryostat sections. In all cases, vimentin was shown to be the only IFP type detectable in these tumours. Lymphomas are negative for keratin and desmin, which are characteristic for benign and malignant epithelial or muscular tissues respectively. In addition, eighteen cases are described in which antibodies to intermediate filament proteins were used successfully to distinguish between lymphoma and metastatic carcinoma where differential diagnosis was difficult or impossible on the basis of routine histology.

Topics: Adolescent; Adult; Aged; Antibodies; Carcinoma; Child; Desmin; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Lymphoma; Male; Microscopy, Fluorescence; Middle Aged; Vimentin

Five large cell malignant neoplasms were studied by immunohistochemistry and electron microscopy. Ultrastructural examination demonstrated numerous circumferential microvilli in 3 cases and a more polarized distribution in 2 cases. The tumor cells in 2 cases demonstrated the surface glycoprotein T29/33, indicative of a hematopoietic neoplasm. Two cases (including one positive for T29/33) contained intracytoplasmic IgG-kappa. Anti-keratin staining using both polyclonal and monoclonal antibodies was negative. Two patients are alive and in remission after treatment for lymphoma. One died with tumor following a progressive course, and one has been lost to follow-up. A fifth patient died of tumor and at autopsy was found to have a disseminated pancreatic tumor. Microvilli around large malignant cells have been commonly associated with epithelial tumors; however, our findings indicate that, in the absence of intercellular junctions and tonofilaments, the possibility of malignant lymphoma should be considered and pursued immunohistochemistry.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Immunoglobulins; Keratins; Lymph Nodes; Lymphoma; Male; Mesentery; Microscopy, Electron; Microvilli; Middle Aged

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

A total of 43 cases undifferentiated large cell tumours presenting in lymph nodes were stained by immunoperoxidase techniques using antibodies against keratin and a leucocyte-associated glycoprotein. In 26 cases diagnosed histologically as metastatic carcinoma, staining with the keratin antibody suggested a squamous cell origin in 11 cases. This was supported by microscopic observation of intracellular filaments in seven cases. In 15 patients in whom the original diagnosis was uncertain, a definite diagnosis was possible in all cases following immunoperoxidase staining with the two antibodies and most of these proved to be large cell lymphomas. In two cases a potentially major diagnostic error was detected. It is suggested that the staining of undifferentiated human neoplasms using combinations of antibodies reactive with epithelial and lymphoid cells should result in much greater diagnostic accuracy in the field of large cell tumours presenting in lymph nodes.

Topics: Adolescent; Adult; Aged; Antibodies; Carcinoma; Female; Humans; Immunoenzyme Techniques; Keratins; Leukocytes; Lymph Nodes; Lymphatic Metastasis; Lymphoma; Male; Middle Aged; Prospective Studies

As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells.

Topics: Epidermis; Fluorescent Antibody Technique; Graft vs Host Disease; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Keratins; Lichen Planus; Lymphoma; Skin Diseases; T-Lymphocytes

A histological review of 72 undifferentiated thyroid tumors was performed in order to discover small cell anaplastic carcinomas and Non-Hodgkin lymphomas. Cases suspected to be lymphoma were examined for the presence of Ig and keratin and lectins with a PAP-procedure. Among the 72 cases, 68 (94,5%) were anaplastic carcinomas of various types. Four cases (5,5%) were diffuse small cell tumors, which had previously been regarded as anaplastic carcinomas. All four could be identified as Non-Hodgkin lymphomas by histology, immunohistochemistry, repeat biopsy or autopsy. The findings suggest that the majority of small cell anaplastic thyroid tumors are lymphomas and that true anaplastic small cell carcinoma of the thyroid must be extremely rare. Its diagnosis requires electronmicroscopy and/or immunohistochemistry to demonstrate the epithelial nature of tumor cells.

Topics: Adenocarcinoma; Biopsy; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Immunoglobulins; Keratins; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Thyroid Gland; Thyroid Neoplasms

Immunocytochemical stains for three epithelial cell markers--keratin, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA)--have been examined on paraffin-embedded material from 14 patients with nasopharyngeal carcinoma (NPC). Tumour cells staining positively for keratin were found in all cases and for EMA in eight; two tumours contained CEA-positive cells. Seven cases of Hodgkin's disease and 24 non-Hodgkin's lymphomas were uniformly negative. Keratin is the most reliable epithelial marker for identifying NPC and excluding lymphoma. The regular finding of stainable keratin in non-keratinising and anaplastic NPC supports the view that NPC is a homogeneous group exhibiting variable degrees of squamous differentiation.

Topics: Antigens; Carcinoembryonic Antigen; Carcinoma; Cell Membrane; Diagnosis, Differential; Epithelium; Hodgkin Disease; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Nasopharyngeal Neoplasms

This paper reports three cases of lupus erythematosus (LE) associated with thymomas, all of which were discovered after the onset of LE. The diagnosis of LE was established by clinical and laboratory data. Histologically, the thymomas were of the three main types: epithelial, lympho-epithelial, and predominantly fusiform. In two cases, thymectomy did not modify the course of LE; in one vase, the absence of cytoplasmic secretory vesicles in the epithelial cells and the non-labelling of these cells by an antiserum thymic factor monoclonal antibody represented direct evidence of a functional thymus deficiency. Antikeratin antibodies were used to distinguish thymomas from lymphomas; epithelial thymomas exhibited the same keratin specificities as normal thymus, although the labelling pattern (net-like) was different. Labelling of epidermis with the same antiserum confirmed the theory of an epidermis-thymus relationship.

Topics: Aged; Animals; Antibodies, Monoclonal; Diagnosis, Differential; Epithelium; Female; Fluorescent Antibody Technique; Humans; Immune Sera; Keratins; Lupus Erythematosus, Systemic; Lymphoma; Male; Mice; Middle Aged; Rabbits; T-Lymphocytes; Thymoma; Thyroid Neoplasms

Immunoperoxidase technics were used to identify keratin and carcinoembryonic antigen (CEA) in exfoliated cells of fine-needle aspirates and body cavity fluids. Staining was evaluated in cytocentrifuge preparations from 27 malignant and 30 benign cytologic specimens. Most reactive mesothelial cell preparations were strongly positive for keratin and negative or only weakly positive for CEA. Diffuse, peripheral, and perinuclear concentration of staining for keratin was noted in exfoliated reactive mesothelial cells. Positive staining for keratin, predominantly diffuse, was noted in exfoliated cells from 56% of the adenocarcinomas. Sixty-nine per cent of adenocarcinoma preparations were strongly positive for CEA. These findings suggest that keratin proteins are not restricted to squamous cells and that keratin staining does not permit distinction between adenocarcinoma and mesothelial cells in cytologic specimens. Staining for CEA and keratin was compared in cytocentrifuge preparations and histologic sections of 12 adenocarcinomas and 7 lymphomas. In some adenocarcinomas, staining was detected only in cytologic preparations. Possible explanations for these differences are discussed. Variable staining for keratin was observed among exfoliated reactive mesothelial cells, possibly identifying different mesothelial cell populations. All reactive and neoplastic lymphoid cells were negative for keratin and CEA in cytologic and histologic preparations. Immunoperoxidase technics can be applied to rehydrated Papanicolaou-fixed and Papanicolaou-stained cytologic preparations with excellent preservation of cytologic detail.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Epithelium; Female; Formaldehyde; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Mesothelioma; Paraffin

Eight cases of primary and metastatic nasopharyngeal lymphoepithelioma and four cases of malignant lymphoma of the pharyngeal region were studied for the presence of keratin by indirect immunofluorescence microscopy. The results showed that all the cases of primary and metastatic lymphoepithelioma contained keratin-positive cells, whereas all the lymphomas were negative for keratin. Anti-keratin antibody thus seems to be a valuable aid in the differential diagnosis between lymphoepithelioma and lymphoma.

Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Fluorescent Antibody Technique; Histocytochemistry; Humans; Keratins; Lymphoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Pharyngeal Neoplasms

This paper describes the use of a panel of seven monoclonal antibodies (selected so as to include reagents reactive with both epithelial and lymphoid cells) for distinguishing between anaplastic carcinoma and high grade lymphoma. Details are given of the immunohistological reactions of these antibodies against a wide range of both normal and malignant tissues and of a number of practical instances in which use of the antibody panel enabled a diagnosis to be made when routine histological examination had been inconclusive.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Female; Histocompatibility Antigens; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Lymphoma; Male

The interactions between lymphocytes, Langerhals cells and keratinocytes, are described by electron microscopy in cutaneous lesions of malignant epidermotropic lymphomas (mycosis fungoides and Sézary's syndrome). Various contacts are observed between the different cells. During the degenerating process of keratinocytes, Langerhans cells disappear and histiocytic cells are bound to necrosing epidermal cells. The immunological process of Pautrier microabscess formation is discussed by comparison with ultrastructural aspects of cutaneous lecions of G.V.H. reaction in man.

Topics: Adult; Aged; Cell Nucleus; Epidermis; Female; Humans; Intercellular Junctions; Keratins; Langerhans Cells; Lymphocytes; Lymphoma; Male; Microscopy, Electron; Middle Aged; Mycosis Fungoides; Organoids; Sezary Syndrome; Skin Neoplasms

Indirect immunofluorescence staining in two thymomas, one case of thymic hyperplasia, 10 malignant lymphomas and three seminomas was done with an antibody prepared against keratins from human epidermis. Staining was observed only in the epithelial cells of the thymomas and thymic hyperplasia and correlated well with electron microscopic studies. Immunofluorescence staining of thymic tumors with antikeratin antibody provides a simple, specific, and sensitive method for distinguishing thymoma from lymphoma and seminoma. The method may also prove to be useful in other instances in the distinction between epithelial and nonepithelial tumors.

Topics: Adult; Aged; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Humans; Immune Sera; Keratins; Lymphoma; Middle Aged; Thymoma; Thymus Neoplasms