bromochloroacetic-acid and Neoplasms--Germ-Cell-and-Embryonal

Gonadal germ cell tumors continue to be the cause of diverse, diagnostically challenging issues for the pathologist, and their correct resolution often has major important therapeutic and prognostic implications. They are academically interesting because of the biological diversity exhibited in the two gonads and variation in frequency of certain neoplasms. The most dramatic examples of the latter are the frequency of dermoid cyst in the ovary compared to the testis and the reverse pertaining to embryonal carcinoma. Within the teratoma group, there is strong evidence that ovarian and prepubertal testicular teratomas are derived from benign germ cells, a pathogenesis that likely applies also to the rare dermoid cysts and uncommon epidermoid cysts of the testis. In contrast, postpubertal testicular teratomas derive from malignant germ cells, specifically representing differentiation within a preexistent nonteratomatous cancer. As expected, given the foregoing, teratomas in boys are clinically benign, whereas in postpubertal males they are malignant, independent of their degree of immaturity. On the other hand, immaturity is an important finding in ovarian teratomas, irrespective of age, although its significance in children has recently been challenged. It is usually recognized on the basis of embryonic-appearing neuroepithelium, which shows mitotic activity and apoptosis in contrast to differentiated neuroepithelial tissues, which may occur in mature ovarian teratomas. Rarely it is based on the presence of cellular, mitotically active glial tissue. Fetal-type tissues alone are not sufficient for a diagnosis of immature teratoma. Further differences between the teratomatous tumors in the two gonads are the relative frequency of monodermal teratomas in the ovary in contrast to the testis, where only one subset, carcinoids, is seen with any frequency. When uncommon somatic-type malignancies (usually squamous cell carcinoma) occur in mature cystic teratomas of the ovary, this is a de novo form of malignant transformation; similar tumors in the testis, a very rare event, represent overgrowth of teratomatous elements that originated from malignant, nonteratomatous germ cell tumors and, therefore, had previously undergone malignant transformation. Germinomas may have several unusual features in each gonad; these include microcystic arrangements that suggest yolk sac tumor, tubular patterns that mimic Sertoli cell tumor, apparent increased cytological atypia that

Topics: Diagnosis, Differential; Female; Germinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-1 Antigen; Male; Neoplasms, Germ Cell and Embryonal; Organic Cation Transport Proteins; Ovarian Neoplasms; Proto-Oncogene Proteins c-kit; Teratoma; Testicular 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

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: Actins; Antigens, CD34; Biomarkers, Tumor; Carcinoma; Diagnosis, Differential; Female; Humans; Keratins; Mesoderm; Myxoma; Neoplasms, Germ Cell and Embryonal; Neprilysin; Proto-Oncogene Proteins c-bcl-2; Vaginal Neoplasms; Young Adult

Undifferentiated embryonal sarcoma of the liver is rare. It is usually observed in children and adolescents. We report one case of embryonal sarcoma of the liver arising in patient without any antecedent. The only symptom was right scapular pain. The liver scan showed a multicystic lesion suspicious for infectious origin or a tumor. Serologies for ecchinococcus, schistosomiasis and brucellosis were negative. The treatment was a right hepatectomy. On gross examination, the tumor was unencapsulated, multicystic and contained large areas of necrosis admixed with gelatinous areas. Microscopically, there were epithelioid and spindle tumor cells in a myxoïd stroma. Lipoblastic-like or rhabdomyoblastic-like, giant cells and PAS positive hyaline globules in the cell cytoplasm were present. The tumor cells expressed vimentin, cytokeratin (KL1), alpha-1-antitrypsin and smooth muscle actin. This observation shows that embryonal sarcoma of the liver may develop in adult patients and should be taken into consideration in any differential diagnosis of cystic hepatic tumor.

Topics: Actins; Adult; alpha 1-Antitrypsin; Hepatectomy; Humans; Keratins; Liver Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; Vimentin

The cytological features of a rare case of undifferentiated (embryonal) sarcoma of the liver are presented. The cytology smears showed singly dispersed polygonal and spindle cells as well as loose clusters of cells held together in myxoid material. Neoplastic cells were generally large with round, oval or lobulated nuclei. The cytoplasm was variable in amount with ill-defined borders. Occasional multinucleated cells were also present. Hyaline globules were present on sections of the cell block. Immunohistochemical studies performed showed positivity for vimentin, cytokeratin and alpha-1-antitrypsin (AAT) in the tumour cells.

Topics: alpha 1-Antitrypsin; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Child; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Hepatectomy; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Neoplasms, Germ Cell and Embryonal; Treatment Outcome; Vimentin; Vincristine

Juvenile pleomorphic adenoma of the parotid gland represents an extremely rare tumour entity and is comparable to congenital tumours of the salivary glands concerning its embryonal structure. The clinical detection of the tumour in a 7-year-old girl does not exclude that the tumour had developed either earlier or immediately after the birth. The high cellularity and the evidence of primitive epithelial and myoepithelial cellular structures do not justify its classification as a malignant tumour. However the presence of embryonal tissue structures associated with the end of the third month of embryogenesis is characterized by more solid cell formations in partly verticulate arrangement. The absence of further differentiation into lobular structures and differentiated duct or acinic cell formations may be due to cell arrest. Differential diagnosis of juvenile pleomorphic adenoma must distinguished it from other congenital salivary gland tumours (e.g. congenital basal cell adenoma, hybrid basal cell adenoma-adenoid cystic carcinoma, sialoblastoma, salivary gland anlage tumour.

Topics: Adenoma, Pleomorphic; Biomarkers, Tumor; Cell Transformation, Neoplastic; Child; Diagnosis, Differential; Epithelium; Female; Humans; Keratins; Neoplasms, Germ Cell and Embryonal; Parotid Gland; Parotid Neoplasms

The marker profile of 18 samples of normal human ovarian tissues and 138 samples of their derived tumors was established using 51 monoclonal antibodies directed against intermediate filaments, ovarian carcinoma-specific antigens, general tumor-associated antigens and MHC-I/II antigens. Our data show that vimentin and keratins 7, 8, 18, and 19 were found in both epithelial and some nonepithelial ovarian tumors. Several tumor samples contained additional keratins 4, 10, 13, and 14, as well as desmin. BW 495/36 and to a lesser extent HMFG-2 were usually found in all ovarian tumors that contained simple epithelial keratins, except the absence of HMFG-2 in gonadal tumors as well as in dysgerminomas. In contrast to the keratin antibodies, these two panepithelial antibodies were negative in normal mesothelial cells and granulosa cells of the ovarian follicles. In general, the marker TAG-72 appeared useful for its discrimination between positively stained mucinous adenomas, the ovarian carcinomas as well as germ cell tumors, and the negatively stained gonadal tumors, serous adenomas, and cystomas. OV632 appeared useful in the distinction between negatively stained serous adenomas and positively stained serous carcinomas. In contrast, the monoclonal antibodies OC 125, OV-TL 3, OV-TL 16, and MOv 18 can be considered as pan-ovarian carcinoma markers, however without the discriminative capability as seen for OV632. These ovarian carcinoma-associated antigens were hardly found expressed in gonadal and germ cell tumors, except in the group of endodermal sinus tumors. HLA-I was found to be expressed in almost all nucleated cells, although loss of HLA-I expression was seen in areas of tumor cells. HLA-DR was negative in normal ovarian tissue, but heterogeneous expression was noticed in most of the epithelial tumors.

Topics: Adenoma; Antibodies, Monoclonal; Antigens, Differentiation; Biomarkers, Tumor; Cell Transformation, Neoplastic; Diagnosis, Differential; Epithelium; Female; Humans; Keratins; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Ovary

Germ cell tumors are empirically divided into seminomas and nonseminomatous germ cell tumors (NSGCT). Some authorities consider seminomas to be the precursors of NSGCT, whereas others consider them as distinct and unrelated neoplasms. Here, we report that the human NSGCT-derived stem cell line, NCCIT has hybrid features of seminoma and embryonal carcinoma, and suggest that this cell line could be useful for studying the relationship of seminoma to NSGCT.. NCCIT, a developmentally pluripotent permanent cell line derived from a mediastinal NSGCT was karyotyped and characterized morphologically, immunochemically, and biochemically. The cells were grown under standard tissue culture conditions and were also exposed to retinoic acid to induce differentiation.. The dividing NCCIT stem cell populations consist of vimentin-positive, keratin-negative cells that do not express desmoplakin or cadherin E (uvomorulin) and are not interconnected with one another. These cells have a high nucleocytoplasmic ratio and contain few cytoplasmic organelles, except for free ribosomes and a small number of mitochondria. Lacto- and globoseries oligosaccharide antigens recognized with antibodies to murine stage specific antigens 1, 3 and 4 (SSEA-1, SSEA-3 and SSEA-4), and human teratocarcinoma mucin-like antigen TRA-1-60 and TRA-1-81 are coexpressed on the cell membranes of a considerable number of stem cells. On most cells alkaline phosphatase can be detected by enzyme histochemistry. The placental isoenzyme of alkaline phosphatase was demonstrated by Western blotting in cell extracts. The liver/bone/kidney isoenzyme of alkaline phosphatase is immunochemically detected on 40% of cells. The culture supernatants also contain chorionic gonadotropin and alpha-fetoprotein, presumably derived from trophoblastic and yolk sac-like cells. The cells are hyperdiploid (chromosome range from 54 to 64) and show prominent structural chromosomal aberrations, mostly deletions and isochromosomes. Retinoic acid treatment inhibited the growth of NCCIT cells and induced stem cell differentiation into keratin, glial fibrillary acid protein, and neurofilament-positive somatic cells. The differentiation was associated with the disappearance of oligosaccharide surface antigens typical of the undifferentiated stem cells; a loss of proteins typical of undifferentiated cells and the appearance of new proteins; and the deposition of extracellular matrix.. NCCIT is a developmentally pluripotent cell line that can differentiate into derivatives of all three embryonic germ layers (i.e., ectoderm, mesoderm, and endoderm) and extraembryonic cell lineages. We suggest that this cell line could be a malignant replica of human cleavage stage embryonic cells with features intermediate between seminoma and embryonal carcinoma.

Topics: Adult; Antigens, Surface; Antigens, Tumor-Associated, Carbohydrate; Cell Differentiation; Cell Division; Chromosome Aberrations; Embryonal Carcinoma Stem Cells; Humans; Immunohistochemistry; Keratins; Male; Neoplasm Transplantation; Neoplasms, Germ Cell and Embryonal; Neoplastic Stem Cells; Transplantation, Heterologous; Tretinoin; Tumor Cells, Cultured

Malignant mixed mullerian tumors (MMMTs) are the most common sarcomatoid neoplasms of the female genital tract. The clinical, histopathological, immunohistochemical, and differential diagnostic features of MMMTs and other gynecologic mixed tumors are discussed in this article. Current concepts regarding the histogenesis and differentiation of these tumors are discussed, with emphasis on biologic and immunohistological data, and the suggestion is made that MMMTs probably represent "metaplastic" (sarcomatoid) carcinomas rather than true carcinosarcomas. Finally, clinicopathological factors that affect the survival of patients with MMMTs are reviewed.

Topics: Aged; Diagnosis, Differential; Female; Genital Neoplasms, Female; Humans; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasm Metastasis; Neoplasms, Germ Cell and Embryonal; Prognosis

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

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

Topics: Cell Nucleus; Cytoplasm; Female; Humans; Immunoenzyme Techniques; Infant; Keratins; Maxillary Neoplasms; Neoplasms, Germ Cell and Embryonal; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

We report an unusual large, multicystic, posterior fossa neuroepithelial neoplasm involving the cerebellum, brain-stem, and quadrigeminal cistern of a 9-month-old girl. The neoplasm consisted of variably sized, sharply demarcated nests of small cells with a high nuclear-cytoplasmic ratio and moderately basophilic nuclei, embedded in a desmoplastic, immature-appearing, mesenchymal stroma. The nests contained mitoses but none were seen in the stroma. Glial fibrillary acidic protein (GFAP), neurofilament protein, synaptophysin, and cytokeratin (AE-1) were expressed in the nests. Mesenchymal cells were negative for neural markers but positive for vimentin and desmin. The neoplasm was interpreted as a mixed mesenchymal and primitive neuroectodermal tumor (PNET) with histologic features reminiscent of a recently described intraabdominal desmoplastic small cell tumor. The tumor responded poorly to chemotherapy and a second operation was performed 1 year later. The second specimen bore no resemblance to the original and consisted of epithelial-like nests and clusters of neoplastic cells frequently interrupted by sinusoidal vessels. Tumor cells had medium-sized vesicular nuclei with small nucleoli, and a granular cytoplasm. Occasional less cellular islands of neuropil-like tissue contained larger cells having eccentric, vesicular nuclei with prominent nucleoli and abundant pink cytoplasm. Mitoses were not conspicuous. Many cells expressed synaptophysin, neurofilament protein, and GFAP. Neurofilament protein was strongly positive in the larger, neuron-like cells and synaptophysin stained the neuropil-like areas strongly but was less prominent in the neuronal perikarya. Unexpectedly, the neuropil-like areas expressed epithelial membrane antigen, whereas the neuronal cells were negative for chromogranin A. The peculiar histologic picture, combination of phenotypic markers, and remarkable biologic behavior of this unusual tumor defies classification according to existing nomenclature and exemplifies the broad range of phenotypes expressed by primitive neuro-epithelial neoplasms.

Topics: Brain Neoplasms; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm; Desmin; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Infant; Karyotyping; Keratins; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Phenotype; Synaptophysin; Terminology as Topic; Vimentin

Forty-seven cases of malignant mixed müllerian tumors were reviewed histologically and studied immunohistochemically with three major objectives: to analyze the histogenetic relationship between the carcinomatous and sarcomatous components of these neoplasms, to ascertain the practical role of immunohistochemical studies in diagnosis and classification, and to determine the prognostic significance of immunohistochemically verified rhabdomyoblastic and neuroendocrine differentiation. Epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) was confirmed in all carcinomatous components; within the sarcomatous areas, it was identified among individual cells (60% of cases) and within poorly formed clusters of cells (57% of cases). There was a statistically significant tendency for concordant expression of alpha-1-antichymotrypsin, Leu-M1, S-100, Leu-7, and neuron-specific enolase between the carcinomatous and sarcomatous components of individual cases. These two findings provide evidence of common origin for the sarcomatous and carcinomatous components of these neoplasms. Histologic review of metastases in 21 cases revealed a biphasic composition in the majority of metastatic lesions (62%), another feature that further supports a common origin for the two components. From a practical standpoint, immunohistochemistry may be helpful in accentuating the biphasic pattern of these neoplasms and in verifying the presence of rhabdomyoblastic differentiation. In most cases, however, careful morphologic examination and thorough sampling will suffice for correct diagnosis and subclassification. The presence of heterologous, rhabdomyoblastic, or neuroendocrine differentiation did not have a statistically significant influence on survival; the last of these was associated with a tendency for a more rapidly fatal course.

Topics: Actins; alpha 1-Antichymotrypsin; Antigens, Differentiation, Myelomonocytic; Cell Transformation, Neoplastic; Chromogranin A; Chromogranins; Desmin; Female; Genital Neoplasms, Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Myoglobin; Neoplasms, Germ Cell and Embryonal; Prognosis; S100 Proteins; Substance P; Vimentin

Two cases are reported of intra-abdominal small cell tumours expressing concomitant neural and epithelial differentiation. These features were discernible on conventional microscopy and supported immunocytochemically. Immunoreactive vimentin was also revealed in both tumours, and, in addition, one showed focal desmin positivity. Epithelial differentiation in both tumours was confirmed ultrastructurally. The tumours were interpreted to represent a variant of peripheral primitive neuroectodermal tumour, and the report serves to emphasize a potential among such tumours for complex differentiation. The neoplasms are compared with other similar tumours reported recently in children.

Topics: Abdominal Neoplasms; Adolescent; Cell Transformation, Neoplastic; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Neoplasms, Germ Cell and Embryonal; Phosphopyruvate Hydratase

We studied two cases of pigmented neuroectodermal tumor of infancy (PNTI) by routine light microscopy and immunohistochemistry on formalin fixed, paraffin embedded tissues using antibodies to HMB-45 "melanoma associated" antigen, S-100 protein, neuron specific enolase (NSE), Leu-7 antigen, chromogranin, epithelial membrane antigen, collagen Type IV, alpha-fetoprotein and muscle-specific actin and to the intermediate filaments cytokeratin (CK), vimentin, desmin and neural filaments. We found that the large epithelioid cells, many of which contained melanin pigment, were strongly positive for CK and HMB-45, and less intensively positive for vimentin and NSE. The small neuroblast-like cells revealed only focal, weak NSE positivity. Both cell types were negative for S-100 protein and for the other antigens examined. Our results suggest that: (1) the large and small cell populations in PNTI have different immunophenotypes; (2) the expression of CK and HMB-45, together with the S-100 negativity, appears unique for the pigmented cells; and (3) this profile may be helpful in the exclusion of melanoma and peripheral neuroblastoma from the differential diagnosis.

Topics: Antigens, Neoplasm; Child, Preschool; Female; Humans; Immunohistochemistry; Infant; Keratins; Male; Neoplasms, Germ Cell and Embryonal; Phosphopyruvate Hydratase; Vimentin

Eleven primitive neuroectodermal tumor (PNET) biopsies from infants under the age of 3 years were studied for the presence of various differentiation markers for neuroectodermal stem cells. Special emphasis was placed on the expression of cytokeratin proteins. The tumor cells expressed different cytokeratin proteins (CK8, CK13, CK18, CK19, KL1, AE1/AE3, MNF16) in 3 of 11 cases. These cases were furthermore characterized by a strong expression of glial fibrillary acidic protein, S-100 protein and vimentin. Vimentin and cytokeratin proteins were co-expressed; cross-reactivity between these two intermediate filaments could be excluded by immunoblotting. It is noteworthy that the three positive tumors were all from infants in their 1st year. We assume that PNETs in early infancy are characterized by a particularly wide range of differentiation patterns. The presence of cytokeratin proteins in these cases seems to be associated with the expression of vimentin and must be regarded as an indicator of an early developmental stage of the tumor cells.

Topics: Child, Preschool; Humans; Immunoblotting; Immunohistochemistry; Infant; Infant, Newborn; Keratins; Microscopy, Electron; Neoplasms, Germ Cell and Embryonal; Staining and Labeling

An asymptomatic tumor developed on the upper lip of a 63-year-old man. Histologically, the tumor contained glandular and cystic structures forming many branching lumina, and many scattered single cells in an abundant mucoid to chondroid stroma. The tumor was diagnosed as mixed tumor of the skin. Histochemically, the cells composing the tubular structures contained neutral mucopolysaccharides and the stroma, acid mucopolysaccharides. Immunohistochemically, the cells of the glandular and cystic structures showed epithelial and sweat gland differentiation (EMA-, CEA-, BRST-1- and BRST-2-positive), while the cells scattered in the stroma showed a tendency toward myoepithelial differentiation (S-100 protein- and vimentin-positive).

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Nucleus; Cytoplasm; Desmin; Glycoproteins; Humans; Immunohistochemistry; Keratins; Lip Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasms, Germ Cell and Embryonal; Neurofilament Proteins; S100 Proteins; Skin Neoplasms; Vimentin

A case of an uncommon congenital primitive neuroectodermal cerebellar tumor (PNET) in a 5-month-old child is reported. After subtotal surgical resection, the residual tumor did not respond to radiation and chemotherapy. Histologically, the tumor was composed of small, round, undifferentiated cells and several other patterns like astrocytomatous, oligodendrogliomatous, and ependymomatous structures. Immunostaining was positive for most of the cells for vimentin and S 100, fewer were positive for glial fibrillary acid protein (GFAP) and neuron-specific enolase, and only a few for synaptophysin. Surprisingly, the tumor showed strong expression of several monoclonal cytokeratins (CK) with different molecular weights, together with epithelial membrane antigen. Furthermore, we found a coexpression of the tumor cells for CK and vimentin, while CK-GFAP and CK-S 100 were negative. Ultrastructurally, intracytoplasmic intermediate filaments could be observed corresponding to immunohistochemical CK expression. The very strong CK and vimentin expression in this case was interpreted as a sign of the embryonic nature of the tumor.

Topics: Biomarkers, Tumor; Cerebellar Neoplasms; Cerebellum; Glial Fibrillary Acidic Protein; Humans; Infant; Keratins; Male; Neoplasms, Germ Cell and Embryonal; Phosphopyruvate Hydratase; Vimentin

34 cases of lacrimal epithelial tumor were studied with the anti-keratin and anti-CEA monoclonal antibody peroxidase-anti-peroxidase staining and the AB/PAS mucohistochemical staining. It was found that HK2 was positive in the gland-luminal cells and cancer cells in the squamous metaplastic portion of the tumor; K12 was positive in the mucoid, fibroid, and cartilaginoid metaplastic tumor cells, while K27 was positive in less number of the squamous cells; CEA was positive in tumor cells of the nest and glandular lumina. Mecohistochemically, the tumor cells were 100% positive. The authors were of the opinion that keratin HK2 and K12 and CEA were ideal markers for lacrimal epithelial tumors.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Cystadenocarcinoma; Eye Neoplasms; Humans; Immunohistochemistry; Keratins; Lacrimal Apparatus Diseases; Neoplasms, Germ Cell and Embryonal

Human testicular germ cell tumors were studied immunohistochemically with the monoclonal antibody to the 54-kd keratin polypeptide (keratin 7) to determine whether this antibody could be used selectively to identify trophoblastic cells. The antibody reacted with the intermediate filaments in the cytoplasm of some cells in choriocarcinoma cell lines, and in trophoblastic cells in mixed germ cell tumors and a seminoma. It did not react with classic seminoma cells, embryonal carcinoma, yolk sac carcinoma, or somatic tissues of mixed germ cell tumors. On the basis of these data we conclude that monoclonal antibody to keratin 7 is a marker for a subset of trophoblastic cells in human germ cell tumors.

Topics: Adult; Biomarkers, Tumor; Dysgerminoma; Humans; Keratins; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Trophoblasts

Six cases of hepatoblastoma (five epithelial, one mixed epithelial-mesenchymal) were studied on serially cut cryostat sections, using a panel of monoclonal antibodies directed against individual cytokeratins, vimentin, and desmin, in an indirect immunoperoxidase procedure. Embryonic and fetal-type tumor cells expressed the "hepatocellular" cytokeratins no. 8 and 18 but, surprisingly, also expressed the "bile duct type" cytokeratin no. 19. In addition, two cases had a number of tumor cells which were also positive for the "bile duct type" cytokeratin no. 7. Cells embedded in osteoid-like material were immunoreactive for vimentin but also for cytokeratins no. 7, 18, and 19. Gel electrophoresis, and Western blotting of cytoskeletal extracts, confirmed the immunohistochemical data. The implications of these findings for the histogenesis of hepatoblastoma are discussed in this report.

Topics: Adolescent; Adult; Blotting, Western; Carcinoma, Hepatocellular; Child; Child, Preschool; Desmin; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immunohistochemistry; Infant; Keratins; Liver Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; Vimentin

We are reporting the clinical and pathologic features of a primary, pulmonary, malignant germ cell tumor associated with a marked elevation of serum alpha-fetoprotein (38,427 ng/mL) and lactate dehydrogenase activity (756 U/L), in a 26-year-old female. This controversial, rare neoplasm has not been extensively discussed in the pathology literature. We emphasize the clinical importance of establishing this diagnosis in view of the favorable response to chemotherapy shown by malignant germ cell tumors.

Topics: Adult; Alkaline Phosphatase; alpha-Fetoproteins; Carcinoembryonic Antigen; Chorionic Gonadotropin; Chromogranins; Female; Humans; Immunohistochemistry; Keratins; L-Lactate Dehydrogenase; Lung Neoplasms; Membrane Glycoproteins; Mesonephroma; Microscopy, Electron; Mucin-1; Neoplasms, Germ Cell and Embryonal; S100 Proteins

We studied the immunohistopathologic features of normal lacrimal gland, benign mixed tumor, and malignant mixed tumor of the lacrimal gland. Primary antisera were to keratin, muscle-specific actin, vimentin, and glial fibrillary acid protein. Keratin stained in occasional myoepithelial cells in normal gland, ductal epithelium in normal gland and the tumors, and occasional stromal epithelioid cells in the tumors. Muscle-specific actin stained in myoepithelium and vascular smooth muscle in normal gland and the tumors, and occasional spindle-shaped and clusters of stromal cells in the tumors. Vimentin staining was nonspecific. Glial fibrillary acid protein stained in occasional myoepithelial cells in normal gland and polyhedral stromal cells in benign mixed tumor. Our findings indicate that ductal epithelium develops into the epithelial component, and some cells in the stroma and myoepithelium develop into some cells in the stroma of benign and malignant mixed tumor of the lacrimal gland.

Topics: Actins; Adolescent; Adult; Aged; Epithelium; Eye Neoplasms; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Lacrimal Apparatus; Lacrimal Apparatus Diseases; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Vimentin

We present a rare case of submandibular gland carcinosarcoma occurring in a 45-year-old male patient. His clinical history revealed that the carcinosarcoma had developed from a carcinoma ex mixed tumor in three years. In spite of repeated resection, intensive chemotherapy and irradiation, the tumor recurred and grew rapidly, and the patient died of hemothorax caused by rupture of a pulmonary metastatic tumor. The fourth recurrent tumor and autopsy specimens showed features of carcinosarcoma consisting of three tumor components, i.e., undifferentiated carcinoma, and chondrosarcomatous and osteosarcomatous growth. The metastatic nodules in both lungs and pulmonary hilar lymph nodes showed the same pattern. Immunohistochemically, the chondrosarcomatous cells were positive for vimentin and S-100 protein, and for epithelial markers such as epithelial membrane antigen (EMA) and cytokeratin (MA-902). Undifferentiated carcinoma cells, on the other hand, were partially positive for muscle actin other than cytokeratin (KL 1). Ultrastructurally, desmosome-like structures were seen in the chondrosarcomatous cells. These findings suggest that the sarcomatous lesions might have originated from epithelial cells.

Topics: Actins; Adult; Autopsy; Carcinosarcoma; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Neoplasms, Germ Cell and Embryonal; S100 Proteins; Submandibular Gland Neoplasms; Vimentin

A case of malignant mixed müllerian tumor of the ovary in a 57-year-old woman is reported along with the results of an immunohistochemical study. The tumor, measuring 16 x 10 x 9 cm, was composed predominantly of adenocarcinoma with a smaller amount of anaplastic carcinoma as an epithelial component and chondrosarcoma, liposarcoma, fibrosarcoma and rhabdomyoblasts as mesenchymal elements. Immunohistochemistry using paraffin sections demonstrated cytokeratin (CK) and epithelial membrane antigen (EMA), generally regarded as epithelial markers, not only in the epithelial component but also in chondrosarcoma cells. Vimentin and desmin, generally regarded as mesenchymal markers, were exhibited partly in carcinoma cells as well as in mesenchymal elements. Positive staining for S-100 protein was obtained not only in chondrosarcoma and liposarcoma cells, but also partly in adenocarcinoma cells. This intricate immunohistochemical picture reflected the histologic findings. It is noteworthy that both carcinoma cells and chondrosarcoma cells demonstrated simultaneous expression of CK, EMA, vimentin, desmin and S-100 protein. This somewhat unusual antigen expression by tumor cells may indicate a change in the nature of tumor cells due to microenvironmental factors.

Topics: Adenocarcinoma; alpha-Fetoproteins; Chondrosarcoma; Chorionic Gonadotropin; Desmin; Female; Fibrosarcoma; Humans; Immunohistochemistry; Keratins; Liposarcoma; Membrane Glycoproteins; Middle Aged; Mucin-1; Myoglobin; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Rhabdomyoma; S100 Proteins; Vimentin

Ten malignant myoepithelial tumors of the salivary glands and one of lacrimal gland origin were studied by light, electron microscopy and immunocytochemistry. The light microscopic appearance of the tumors varied from primarily spindle cell neoplasms (two cases), to others with predominantly epithelial components (four cases) and mixed varieties (five cases). Therefore, they can be confused with other epithelial and mesenchymal neoplasms. The electron microscopic spectrum varied from tumors with widespread and typical myoepithelial differentiation (i.e. myofilament bundles at the cell periphery, attachment plaques and intercellular junctions) to some with diffusely distributed filaments, without associated spindle densities but with attachment plaques, and others with evidence of duct formation and containing scattered cells showing intracytoplasmic tonofilaments. Often the tumors revealed mixed ultrastructural features; the relative numbers of the different cellular components was variable. The eleven neoplasms were S-100 protein, actin and keratin positive, either focally or diffusely, with varying degrees of intensity. Ten of the eleven tumors were positive for vimentin and nine of ten tested expressed carcinoembryonic antigen. Only two of nine were focally positive for glial fibrillary acidic protein. The study emphasizes the variable light microscopic appearances of these neoplasms and their immunocytochemical and ultrastructural spectrum. Accurate determination of myoepithelial differentiation sometimes requires careful evaluation of the light, ultrastructural and immunocytochemical findings. If all three diagnostic modalities are not utilized, it is likely that some of these neoplasms will be improperly classified.

Topics: Actin Cytoskeleton; Actins; Adenoma, Pleomorphic; Adult; Aged; Carcinoembryonic Antigen; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Lacrimal Apparatus; Lacrimal Apparatus Diseases; Male; Microscopy, Electron; Middle Aged; Myoepithelioma; Neoplasms, Germ Cell and Embryonal; S100 Proteins; Salivary Gland Neoplasms; Vimentin

Three cases of pulmonary blastoma (PB) were investigated microscopically with conventional stainings and immunohistochemically with monoclonal antibodies to cytokeratin, vimentin, desmin and neurofilament protein. The tumors differed in terms of morphology as well as of immunohistochemistry. Two were epithelial and mesenchymal mixed tumors, and the remaining one was a monophasic tumor of a typical blastemic character. The two mixed tumors also differed from each other. In one of them, the epithelial and mesenchymal component expressed cytokeratin and vimentin in a clear-cut manner without any transition. The other mixed tumor displayed a gradual epithelial-to-mesenchymal transition accompanied by a switch in the expression of cytokeratin and vimentin. The third tumor was of pure mesenchymal origin, expressing vimentin in the majority of cells and desmin in few cells. It is concluded that the PB is a morphologically and histogenetically heterogeneous tumor. Metaplastic changes may take place within a PB and make the recognition of embryogenesis more difficult.

Topics: Aged; Carcinoma, Squamous Cell; Desmin; Epithelium; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Vimentin

Topics: Abdominal Neoplasms; Adolescent; Adult; Antibodies, Monoclonal; Cell Transformation, Neoplastic; Child; Desmin; Diagnosis, Differential; Female; Fibroma; Humans; Keratins; Male; Neoplasms, Germ Cell and Embryonal

An 81-year-old woman was admitted to our clinic due to gross hematuria. A large bulky pedunculated mass was found in the bladder by cystoscopic examination. Subtotal cystectomy and bilateral cutaneostomy was performed on January 12, 1987. Histologically the tumor was composed of carcinomatous and sarcomatous elements. The carcinomatous element was composed fundamentally of grade 2, transitional cell carcinoma with numerous foci of squamous metaplasia. The sarcomatous element was composed of myxosarcomatous, chondro-sarcomatous pattern and non-differentiated malignant spindle cell component. Immunohistochemical examination demonstrated the presence of cytokeratin and epithelial membrane antigen in the spindle cell and more obvious carcinomatous regions, using the avidin-biotin conjugated immunoperoxidase technique. The patient died 3 months after operation. Autopsy findings showed multiple organ metastasis which were composed of carcinomatous and sarcomatous elements.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Female; Humans; Keratins; Membrane Glycoproteins; Mucin-1; Neoplasms, Germ Cell and Embryonal; Urinary Bladder Neoplasms

The clinico-pathological features of eight cases of malignant mixed müllerian tumor, a rare neoplasm composed of an admixture of epithelial and stromal elements, are reported. Four of the tumors located in the endometrium, three in the cervix and one in the ovary. Microscopically, the epithelial elements ranged from poorly to well differentiated adenocarcinoma. Homologous stromal sarcoma cells were present in six tumors and heterologous elements were also seen in the other two tumors. Immunohistochemical studies showed diffuse cytoplasmic staining of keratin in the epithelial elements of all the eight cases. Sarcomatous cells were positive focally for keratin in four spindle cell sarcoma cases. Desmin immunoreaction was moderately positive in the sarcomatous element of four neoplasms. Follow-up result was available in 7 patients of whom 3 survived and 4 died from recurrence or metastasis. Immunohistochemical findings support the stem cell origin of this tumor.

Topics: Adult; Desmin; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasms, Germ Cell and Embryonal; Uterine Cervical Neoplasms

An immunohistochemical study of keratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), vimentin, desmin, myoglobin and S-100 protein in 15 cases of uterine mixed Müllerian tumor was performed in order to analyze the expression of various antigens in different elements of this tumor. In general, the epithelial and mesenchymal components were separated easily by the presence of keratin/EMA or vimentin, respectively. However, in eight cases vimentin was expressed by epithelial cells and in four cases keratin by solid "sarcomatous" element. EMA was also identified in the "sarcomatous" areas of two cases. Specific differentiation was much easier to identify by immunohistochemical staining than by routine histologic examination. Areas with muscle differentiation were positive for desmin; myoglobin was identified in rhabdomyoblasts. S-100 protein was present in chondrosarcomatous and liposarcomatous areas. S-100 protein was also widely distributed in other elements. Quite diverse expression of various antigens revealed by immunohistochemistry reflects the histologic multiplicity of this tumor.

Topics: Antigens, Neoplasm; Carcinoembryonic Antigen; Desmin; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Neoplasms, Germ Cell and Embryonal; S100 Proteins; Uterine Neoplasms; Vimentin

The pigmented neuroectodermal tumour of infancy is a rare neoplasm of uncertain histogenesis which, in the majority of cases, arises in the maxilla and pursues a benign course. Currently, it would be classified in the group of peripheral primitive neuroectodermal tumours. Histologically it is composed of two principal cell types: neuroblast-like and melanocyte-like. Three typical cases are presented herein, which appear to be the first examined with a panel of antibodies. The neuroblast-like cells labelled positively for neurone-specific enolase but were negative for S-100, neurofilaments, glial fibrillary acidic protein, vimentin, cytokeratin, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). The melanocyte-like cells stained positively for neurone-specific enolase, vimentin and cytokeratin but were negative for S-100, neurofilaments, glial fibrillary acidic protein, EMA and CEA. The significance of these findings is discussed in the light of previous suggestions about the differentiation that these tumours show.

Topics: Cell Differentiation; Female; Humans; Immunohistochemistry; Infant; Keratins; Male; Neoplasms, Germ Cell and Embryonal; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

The immunoprofiles of 121 germ cell and trophoblastic neoplasms were defined, using a battery of antibodies against cytokeratin (CK), vimentin (VIM), epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), S-100 protein, leukocyte common antigen (LCA), UCHL-1, LN-2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), chromogranin A, Leu-7, alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), and the beta subunit of human chorionic gonadotropin (BHCG). In addition to 85 neoplasms of testicular origin, the cases included eight ovarian germ cell tumors and 28 extragonadal neoplasms. All tissues had been subjected to formalin fixation and paraffin embedding. Similar immunoreactivity patterns were seen in gonadal and extragonadal neoplasms, gestational and nongestational choriocarcinomas, components of mixed germ cell tumors and their pure counterparts, and metastatic and primary lesions. Placental alkaline phosphatase was a sensitive marker of germ cell differentiation, and expression of this marker in the absence of EMA appeared to be a staining pattern unique to germ cell tumors. Both LCA and S100 were absent in neoplastic germ cells, and thus were useful in differentiating these tumors from malignant lymphoma and malignant melanoma, respectively. Cytokeratin was helpful in distinguishing seminomas/dysgerminomas from nonseminomatous germ cell tumors, although 10% of seminomas showed focal or diffuse cytokeratin reactivity. Finally, 75% of all germ cell neoplasms displayed NSE, calling the specificity of this determinant into question.

Topics: Alkaline Phosphatase; alpha 1-Antitrypsin; alpha-Fetoproteins; Antibodies, Monoclonal; Antigens, Differentiation; Carcinoembryonic Antigen; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Histocompatibility Antigens; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Male; Membrane Glycoproteins; Mucin-1; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Peptide Fragments; Phenotype; Placenta; Pregnancy; Testicular Neoplasms; Trophoblastic Neoplasms; Vimentin

Ten cases of extrauterine malignant mixed mesodermal tumors (MMMTs), nine ovarian, and one pelvic, are presented. One patient had a purely epithelial primary ovarian tumor and MMMT in her recurrent tumors. All the other patients had MMMT in their primary and recurrent tumors. Eight patients had heterologous MMMT including cartilage, striated muscle, and adipose tissue in one case. Two patients had homologous MMMT. All cases presented with metastases involving abdominal organs that were either MMMT or epithelial neoplasms and MMMT. Five patients had recurrent tumors, one extensively involving the spleen. In all recurrent tumors, the mesenchymal components were considerably more abundant than in the primary tumors. Immunohistologic studies of intermediate filaments were performed in seven cases, revealing cytokeratin-positive epithelial structures, vimentin-positive mesenchymal (including cartilaginous) structures, as well as coexpression of cytokeratin and vimentin in anaplastic and giant tumor cells in some cases. Some anaplastic spindle cells, which on routine stains were suggestive of stromal cells, stained positive for cytokeratin, thus identifying their epithelial nature. Desmin staining performed in five cases showed positive staining of rhabdomyoblasts in only one case. Myoglobin staining performed in seven cases was positive in four. The histogenesis from primitive müllerian structures and the natural history of these uncommon neoplasms are discussed in light of the pathological and immunohistochemical data presented.

Topics: Aged; Aged, 80 and over; Carcinoma, Papillary; Desmin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Myoglobin; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Pelvic Neoplasms; Vimentin

In the female genital tract, malignant mixed müllerian tumors (MMTs) are uncommon neoplasms of uncertain histogenesis. We have examined 11 MMTs by both electron microscopy (EM) and immunoperoxidase techniques (IPX). Eight were of endometrial, two were of ovarian, and one of tubal origins. The IPX analysis included monoclonal antibodies to keratin (k) and vimentin (v) and a polyclonal antibody to myoglobin. Carcinomatous elements were always keratin positive (K+) and were focally positive for vimentin in six tumors. Homologous stromal sarcoma cells were vimentin positive (V+) and in three tumors were focally K+. Ultrastructurally, the epithelial cells were not highly differentiated and the sarcomatous elements generally resembled normal proliferative-phase stromal cells. The epithelial and stromal elements were separated by a thin basal lamina that only rarely and focally had discontinuities. No transitional cellular forms were identified. A definite positive myoglobin reaction was seen in two of the four neoplasms in which rhabdomyoblasts were identified by light microscopy. Myofilaments were identified by electron microscope in three neoplasms.

Topics: Aged; Epithelium; Female; Genital Neoplasms, Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Middle Aged; Myoglobin; Neoplasms, Germ Cell and Embryonal; Vimentin

Based on the study of two clonal cell lines, 2102Ep and TERA-2, isolated from human germ cell tumours, we have identified several properties that are commonly expressed by human embryonal carcinoma (EC) cells, the stem cells of teratocarcinomas. These properties include the expression of surface antigens SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81, and the presence of cytokeratin in the cytoplasm. However, some human EC cells lack expression of SSEA-3 and -4, although glycolipids containing these epitopes can be extracted from such variant cells. Analysis of the glycolipid composition of TERA-2 cells suggests that the switching of oligosaccharide core structure synthesis from globo-series to lacto- and ganglio-series is a key event during the differentiation of these cells. Variant, SSEA-3 and -4-negative EC cells may have already initiated these changes while retaining other features of the EC phenotype. Other studies have indicated that human EC cells variably express class I MHC antigens. We have shown that interferon induces expression of these surface molecules in EC cells without inhibiting their growth or inducing their differentiation or resistance to viral infection.

Topics: Antigens, Surface; Cell Differentiation; Cell Line; Epitopes; Glycolipids; HLA Antigens; Humans; Interferons; Keratins; Major Histocompatibility Complex; Neoplasms, Germ Cell and Embryonal

A panel of monoclonal antibodies against different keratin polypeptides, epithelial glycoproteins, placental alkaline phosphatase and collagen type IV was used to evaluate immunohistochemically the expression of the target antigens in 30 different human testicular germ-cell tumours of various types. Antikeratin antibodies detecting markers of different routes of epithelial differentiation revealed remarkable similarity of differential expression of various keratins in epithelial structures of teratomas and combined tumours as compared with normal human epithelial tissues. A considerable proportion of embryonal carcinoma cells stained positively for keratins 8, 18 and 19, while a minor subpopulation of tumour cells in embryonal carcinomas, some seminomas and many atypical intratubular cells expressed keratins 8 and 18 but usually lacked keratin 19. Antibody RICEO-MFG-06.3, specific for epithelial glycoproteins, gave negative results with seminomas as opposed to positivity in all but two nonseminomatous tumours. All but two neoplasms showed positivity for placental alkaline phosphatase, thus supporting its reliability as a marker of germ-cell tumours. It is concluded that the monoclonal antibody RICEO-MFG-06.3 and especially the keratin-19-specific antibodies BA16 and BA17 can be helpful in distinguishing embryonal carcinoma from seminoma and, together with antibodies to other keratins, in the study of the origin and histogenesis of testicular germ-cell tumours.

Topics: Alkaline Phosphatase; Antibodies, Monoclonal; Cell Differentiation; Collagen; GPI-Linked Proteins; Humans; Immunoenzyme Techniques; Isoenzymes; Keratins; Male; Membrane Proteins; Mucin-1; Neoplasms, Germ Cell and Embryonal; Placenta; Teratoma; Testicular Neoplasms

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

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

170 germ cell tumours of childhood and adolescence were studied by light microscopy and immunohistochemistry. The male-to-female ratio was 1:1.3. 52 (30.6%) tumours were benign (mature teratoma), 30 (17.6%) potentially malignant (immature teratoma), and 88 (51.8%) unequivocally malignant. The main locations were ovary, testis and sacrococcygeal region. 92 tumours were located in a gonad, 78 tumours in extragonadal sites (ratio: 1.2:1). Of the frankly malignant tumours 40 were yolk-sac tumours (YST) and an additional 19 tumours of more than one histological type contained a YST component. Therefore, 67% of the malignant tumours had a YST component. Children with immature teratoma and pure YST showed the lowest median age (5 and 24 months, respectively), while children with germinomas of various locations had the highest median age (153 months). A festoon pattern was the predominant histological feature in all YST and in the YST component of mixed germ cell tumours. Hyaline globules were found in 33/37 YST and in 16/17 YST components. Immunohistochemically, alpha 1-fetoprotein (AFP) was demonstrated in 18/22 YST and in 6/7 YST components of mixed germ cell tumours. Hyaline globules were mostly AFP-negative (only 5 cases with AFP-positive globules in addition to many AFP-negative globules). In 3 cases beta-HCG-positive giant cells were seen. In most YST prekeratin intermediate filaments could be demonstrated in the epithelial cells. Follow-up data, available from 51 cases of YST and tumours with YST components showed disease-free survival in 37 cases (72.5%). 10 patients (19.6%) died of disease, and 4 patients (7.8%) are living with disease. The comparably high rate of survivors reflects the effectiveness of modern therapy, particularly polychemotherapy, in addition to surgery.

Topics: Adolescent; alpha-Fetoproteins; Child; Child, Preschool; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Dysgerminoma; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Infant; Keratins; Male; Mesonephroma; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Peptide Fragments; Protein Precursors; Sacrococcygeal Region; Teratoma; Testicular Neoplasms

We performed studies on the lectin-binding pattern in epithelial tumor cell components of 4 cases of mixed tumor of the skin developing on the face in addition to identification of keratin and carcinoembryonic antigen (CEA), compared with those of normal sweat glands. Normal eccrine glands showed specific labelling with Dolichos biflorus agglutinin (DBA) and soybean agglutinin (SBA), whereas none of the studied lectins reacted specifically with normal apocrine glands. In mixed tumors the dark cells, which form the inner layer of the tubuloalveolar and ductal structure, showed the presence of keratin and CEA, as well as of specific sugar structures that bind to DBA and SBA. On the other hand the light cells that form the outer layer of the tubular structures or the solid epithelial cell nests gave only a faint to moderate staining of keratin, and no staining of CEA or lectins. It is probable that the inner dark cells differentiate toward the cells that have the same sugar structures on the cell surface as those of the normal eccrine gland cells, while the outer light cells appear to be immature or in a less differentiated state.

Topics: Adult; Aged; Carcinoembryonic Antigen; Epithelium; Facial Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lectins; Male; Neoplasms, Germ Cell and Embryonal; Skin Neoplasms

Topics: Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Myosins; Neoplasms, Germ Cell and Embryonal; S100 Proteins; Secretory Component; Skin Neoplasms

Normal testicular tissue and 76 testicular germ-cell tumors of various types were immunohistochemically evaluated for the expression of intermediate filament proteins of different types. In normal testes, the rete testis epithelium was positive to cytokeratin, and the Sertoli cells, stromal cells, and Leydig cells were positive for vimentin. Cytokeratin-positive cells were also found lining atrophic seminiferous tubules and were occasionally seen within nonatrophic seminiferous tubules. The classical seminomas showed vimentin positivity, but this was usually observed in a small number of tumor cells. In addition, nearly half the seminomas contained single cytokeratin-positive cells, some of which were multinucleated and appeared to represent syncytiotrophoblastic giant cells. The tumor cells in embryonal carcinomas, endodermal sinus tumors, and choriocarcinomas displayed cytokeratin positivity. In some embryonal carcinomas vimentin-positive tumor cells were also found, probably representing attempts at further differentiation of the tumor cells. In immature teratomas, both the immature and the mature epithelial structures showed cytokeratin positivity. The stromal components, including cartilage, contained vimentin, and the smooth-muscle elements, desmin. Neural tissue positive for neurofilaments and glial tissue positive for glial fibrillary acidic protein, were observed in 5 and 3 of 15 cases, respectively. It is considered that antibodies to intermediate filaments are suitable tools to characterize the differentiation patterns of testicular germ-cell tumors and have the potential to aid in the differential diagnosis especially between seminoma and embryonal carcinoma.

Topics: Antibodies, Monoclonal; Choriocarcinoma; Desmin; Dysgerminoma; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Male; Mesonephroma; Neoplasms, Germ Cell and Embryonal; Teratoma; Testicular Neoplasms; Testis; Vimentin

We have examined 18 primary malignant lung tumours categorized as either carcinosarcoma, blastoma or spindle-cell carcinoma according to accepted criteria. Two monoclonal antibodies to keratins, CAM 5.2 and LP 34, were used to determine whether the non-epithelial or spindle-cell components of each tumour showed evidence of keratin expression. By this means the epithelial nature of the five tumours classified as spindle-cell carcinomas was confirmed. In all four pulmonary blastomas and in five of nine carcinosarcomas, the sarcomatous elements failed to stain for keratin but in the remaining four carcinosarcomas there was focal staining. The histogenesis of these tumours is discussed and it is suggested that the sarcomatous component of a carcinosarcoma may be derived from malignant epithelial cells by a process of mesenchymal metaplasia with a switch in intermediate filament type. It remains uncertain whether blastomas are derived from both endoderm and mesoderm, or from either one of these tissues, with one component representing complete metaplastic transformation.

Topics: Aged; Antibodies, Monoclonal; Carcinoma; Carcinosarcoma; Cell Transformation, Neoplastic; Female; Humans; Intermediate Filaments; Keratins; Lung Neoplasms; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal

Primary cultures of 9 benign human pleomorphic adenomas were analyzed by immunofluorescence and antibodies against the different intermediate filaments and microfilaments. The cultured cells were also cytogenetically characterized by G- and C-banding techniques. The adenoma cells expressed at least three different classes of intermediate filaments, viz. prekeratin, vimentin and glial fibrillary acidic protein (GFA). No correlation between chromosomal pattern and intermediate filament expression was found. The frequency of cells stained for each of the different antibodies varied considerably among the tumours. Prolonged culturing appeared to induce a reduction of cells positive for prekeratin. This was probably a true loss of antigens and not an effect of overgrowth of stromal cells. It is concluded that the cells studied, on the basis of several criteria, are of neoplastic origin. This in vitro system appears to be well suited for further histogenetic studies on pleomorphic adenomas.

Topics: Actin Cytoskeleton; Cells, Cultured; Chromosome Aberrations; Cytoskeleton; Glial Fibrillary Acidic Protein; Histocytochemistry; Humans; Intermediate Filaments; Keratins; Neoplasms, Germ Cell and Embryonal; Protein Precursors; S100 Proteins; Vimentin

The ultrastructural features of a chondroid syringoma (mixed tumor of skin) are presented. The tumor consisted of groups of epithelial cells, ductal structures, and cells lying individually within a cartilaginous matrix. Many of these latter cells were indistinguishable morphologically from true chondrocytes. Some of these chondroid cells showed positive staining for cytokeratin using the immunoperoxidase technique. Transitional cells with characteristics intermediate between epithelial and chondroid cells are noted.

Topics: Biopsy; Cytoskeleton; Facial Neoplasms; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasms, Germ Cell and Embryonal; Skin; Skin Neoplasms

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

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

Epithelial cells can be distinguished from various non-epithelial cells by the presence of keratin-type intermediate-sized filaments, which can be detected by immunofluorescence microscopy, using antibodies to alpha-keratin. In the present study, two types of antibodies were obtained. One of them was specific for alpha-keratin (mol. wt. 49,000 to 69,000 daltons) in whole epidermis, and the other for alpha-keratin (mol. wt. 62,000 and 69,000 daltons) in prickle and granular cells but not in basal cells. Four cases of so-called mixed tumour of the skin were studied by immunofluorescence microscopy using these antibodies. Tumour cells nests of cuboidal and polygonal cells, tubular structures and keratinous cysts reacted with these antibodies, as did individually-dispersed tumour cells within the myxoid and chondroid matrix. These results indicate that all the tumour cells of the so-called mixed tumour of the skin are of epithelial origin. Differences in staining intensity between these tumor cells and their specificity for these two antibodies are discussed with reference to keratin differentiation in tumour cells.

Topics: Adult; Cytoskeleton; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Microscopy, Fluorescence; Middle Aged; Neoplasms, Germ Cell and Embryonal; Skin; Skin Neoplasms

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

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

Topics: Dermoid Cyst; Female; Granuloma; Humans; Keratins; Laparoscopy; Medical Records; Neoplasms; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Peritoneum; Teratoma