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1/29. Microcystic meningioma arising in a mixed germ cell tumor of the testis: a case report.

    We report a case of a microcystic variant of meningioma arising in a mixed germ cell tumor of the testis composed predominantly of mature and immature teratoma with elements of seminoma and embryonal carcinoma. We believe this is the first such case of a meningioma arising in a teratoma within a gonadal or extragonadal site. The meningiomatous component showed positive immunohistochemical staining for epithelial membrane antigen and a lack of staining for cytokeratin, factor viii, CD31, and alpha-fetoprotein. Recognition of a non-germ cell tumor arising in the setting of a teratoma in the testis may be prognostically important depending on the nature of the non-germ cell component and whether it has spread beyond the testis.
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2/29. Establishment and characterization of a human primitive neuroectodermal tumor cell line from the cerebral hemisphere.

    The primitive neuroectodermal tumors (PNET) comprise a class of malignant nervous system neoplasms that afflict children. These tumors consist of cells that are morphologically identical to the primitive neuroepithelial cells normally seen in early stages of neural embryogenesis, supporting the notion that PNET result from a disturbance in the process of normal neuronal or glial differentiation. In the central nervous system, PNET occur most commonly in the cerebellum (medulloblastomas), but only occasionally in the cerebral hemispheres. We report here the establishment and characterization of a new human cell line (PFSK) derived from a PNET from the cerebral hemisphere of a child. The growth characteristics of PFSK cells were typical of an immortalized, transformed cell line. Cytogenetic and molecular genetic studies showed that three different sublines were present. In one of these sublines, sequences from chromosome 17 had been lost during establishment in culture. Immunocytochemical studies showed that PFSK cells expressed nestin, an intermediate filament protein normally expressed by neuroepithelial stem cells during neurulation. The PFSK cells did not express antigens typically found in terminally differentiated neurons or glia, indicating that this tumor cell line might represent neuroepithelial stem cells prior to commitment to a neuronal or glial lineage.
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3/29. Melanotic neuroectodermal tumour as a predominant component of an immature testicular teratoma. Case report with immunohistochemical investigations.

    A case of melanotic neuroectodermal tumour (MNT), or so-called retinal anlage tumour, as a predominant component of an immature testicular teratoma is presented. The patient was a 17-year-old man who furthermore had a mature mediastinal teratoma. The MNT was composed mainly of two cell types: small immature neuroblast-like cells and large columnar or cuboidal epithelial-like cells with or without melanin granules. The tumour cells were arranged in solid formations, nests, cords, alveolar and pseudoglandular structures with cleft-like or glomeruloid-like spaces. Myogenic differentiation was found in minor foci. immunohistochemistry showed both neuroepithelial and mesenchymal features with positive staining reaction for neuron-specific enolase (NSE), S-100 protein (S-100), melanoma antigen (HMB45), cytokeratin and vimentin. vimentin, desmin and actin were present in the myoid cells. To the best of our knowledge this is the first reported case of MNT originating in the testis. As this tumour component occurred in an immature teratoma, neuroectodermal differentiation of germ cell origin is considered most likely.
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4/29. A case report of mixed tumor arising in the vagina.

    We reported a case of mixed tumor arising in the vagina of a 32-year-old Japanese woman. The tumor was a finger-like polyp protruded from the lower portion of the vagina. The histologic feature of the tumor resembled that of pleomorphic adenoma of the salivary gland, consisting of stromal-type cells embedded in the myxomatous stroma, although there was no cartilagenous component. Immunohistochemical study also suggested resemblance to pleomorphic adenoma of salivary gland, being positively stained with antibodies against cytokeratin, epithelial membrane antigen, vimentin and muscle actin, but negatively with an antibody against S-100 protein. The histogenesis of the tumor is not clear, but it may be originated from myoepithelial cells.
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5/29. Desmoplastic primitive neuroectodermal tumor with divergent differentiation. Broadening the spectrum of desmoplastic infantile neuroepithelial tumors.

    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.
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6/29. Expression of CD34 antigen in testicular mixed germ cell tumor.

    The expression of CD34 was investigated in 14 cases of testicular mixed germ cell tumor to elucidate the relationship between its expression and histological patterns. Seven of 12 yolk sac tumor components were focally immunoreactive for anti-CD34 antibody. Of these, five showed focal but intense CD34 staining, while the remaining two tumors showed weak staining in small clusters or isolated tumor cells. Positive immunostaining for CD34 was seen predominantly in solid and reticular patterns of the yolk sac tumor components. seminoma, embryonal carcinoma, and choriocarcinoma components were invariably negative for CD34. If present, immunoreactivity for CD34 in yolk sac tumors is focal and variable, but useful for the distinction from other germ cell tumors.
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7/29. Pediatric embryonal tumor of the cerebellum with rhabdoid cells and novel intracytoplasmic inclusions: distinction from atypical teratoid/rhabdoid tumor.

    We report a case of embryonal tumor with novel inclusion bodies occurring in the cerebellum of a 12-year-old girl. The tumor was histopathologically composed of small undifferentiated cells intermingled with a small number of rhabdoid cells, which had an ultrastructural feature of intermediate filament whorls. Immunohistochemically, the neoplasm showed a polyphenotype, including glial fibrillary acidic protein (GFAP), S-100, synaptophysin, chromogranin a, cytokeratin, vimentin, smooth muscle actin, and desmin. However, epithelial membrane antigen (EMA) immunoreactivity was absent. The MIB-1 labeling index was high (25.6%). Ultrastructurally, there was no evidence of neuronal or myogenic differentiation. The small neoplastic cells contained numerous small intracytoplasmic inclusions stained pink by eosin and red by Masson's trichrome stain. The inclusion body was a densely packed, granulovesicular structure at the electron microscopic level, and was immunoreactive for vimentin, GFAP, desmin, and actin. reverse transcription-PCR and immunohistochemistry showed the expression of INI1 at the rna and protein levels, respectively. In conclusion, this tumor was differentiated from atypical teratoid/rhabdoid tumor by the absence of EMA and the presence of INI1 mRNA and protein, and diagnosed as an unclassified, embryonal tumor. Eosinophilic, granulovesicular inclusions of the tumor cells are novel cytoplasmic inclusions in the brain tumor.
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8/29. pulmonary blastoma with a topographic transition from blastic to more differentiated areas. An immunohistochemical assessment of its embryonic nature using stage-specific embryonic antigens.

    In order to investigate the probable embryonic nature of pulmonary blastoma, immunohistochemical studies were performed using stage-specific embryonic antigens (Ley, Lex, sialyl Lex-i) in case of pulmonary blastoma with a very wide spectrum of morphological features. The tumour presented a topographic transition from primitive blastic and embryonic areas to more differentiated areas showing diverse differentiation. Blastic areas composed of extremely immature cells were found in most peripheral parts of the tumour. Inside the blastic areas there were "embryonic" areas which morphologically resembled human embryo lungs in the pseudoglandular and canalicular stages. Most central parts of the tumour showed more differentiated features including chondrosarcomatous, leiomyosarcomatous and rhabdomyosarcomatous elements and the common type of adenocarcinomatous element. Electron microscopic observation suggested the blastic and embryonic nature of these immature cell elements. Ley was expressed in the blastic and pseudoglandular areas. Lex was expressed in the canalicular areas. These antigens were not expressed in the more differentiated areas. The topographic gradient in the tumour of morphology and antigen expression from the peripheral blastic areas to the central more differentiated areas suggests that the primitive cells gradually differentiated into more mature cells of various directions as the tumour grew in size.
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9/29. Identification of an ectopic developmental antigen that appears in malignant ascitic fluid.

    A tumor-associated antigen that shares antigenicity with a pregnancy-associated protein has been detected in ascitic fluid of patients with advanced ovarian cancer. The protein, prepared from malignant ascitic fluid by the combination of poly(ethylene glycol) 4000 fractionation, DEAE-sepharose column chromatography and preparative polyacrylamide gel electrophoresis (PAGE), was subsequently separated on sodium dodecyl sulfate-PAGE, as a single band corresponding to an approximate molecular mass of 91 kDa. Immunological analysis showed that this protein was a circulating species of an ectopic developmental antigen that markedly increases in biological fluids in tumor-bearing statuses.
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10/29. carcinosarcoma of the submandibular gland. An autopsy case.

    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.
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