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1/60. Histochemical investigation into the molecular mechanisms of malignant transformation in a benign glomus tumour.

    A glomangiosarcoma arose in a benign glomus tumour. The histological and immunohistochemical characteristics of the tumour were investigated. Apoptotic cells were identified by terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end labelling (TUNEL). The proportion of apoptotic cells was found to be low and TUNEL positive nuclei were present in the benign part of the tumour. Bcl-2 protein, an inhibitor of apoptosis, was strongly expressed in the glomangiosarcoma with only weak staining in the benign area. The proliferation index of the glomangiosarcoma was almost 10-fold higher than that of the benign glomus tumour. Numerous nuclei in the glomangiosarcoma were intensely stained for the tumour suppressor protein p53. The results of the this study may contribute to an understanding of the molecular basis of malignant transformation in benign glomus tumours.
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2/60. 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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keywords = prognostic
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3/60. Leptomeningeal melanomatosis with multiple cutaneous pigmented nevi: tumor cell proliferation and malignant transformation in an autopsy case.

    We experienced a rare case of leptomeningeal melanomatosis. The proliferative activity and nuclear accumulation of p53 in this tumor were examined, since the relationship between this tumor type and growth has not yet been elucidated. A 33-year-old Japanese man was shown to have leptomeningeal melanomatosis with multiple cutaneous pigmented nevi. The autopsy findings showed the presence not only of benign diffuse melanosis of the leptomeninges but also of leptomeningeal melanomatosis in the subarachnoid space and brain parenchyma. In the brain parenchyma, the direct invasion of tumor cells from the subarachnoid space and Virchow-Robin spaces filled with melanoma cells were observed. Multiple hemorrhagic areas invaded by melanoma cells were also present. Immunohistochemical staining with a monoclonal antibody to melanoma cells showed positivity in the tumor cells. Proliferation analysis using the MIB-1 antibody demonstrated that the labeling index of tumor cells invading brain parenchyma (2.54%) was higher than that in other lesions of the inner (0.89%) and outer layer (0.76%) of the subarachnoid space. Nuclear accumulation of p53 protein was rarely seen in the tumor cells. We reported a case of leptomeningeal melanomatosis. Higher proliferative activity was found in invading cells of the brain parenchyma. Malignant transformation of the tumor did not appear to be associated with p53 gene mutation.
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4/60. Malignant transformation of a dysembryoplastic neuroepithelial tumor. Case report.

    A 29-year-old man presented in 1984 with a recent onset of partial seizures marked by speech arrest. electroencephalography identified a left frontotemporal dysrhythmia. Computerized tomography (CT) scanning revealed a superficial hypodense nonenhancing lesion in the midleft frontal convexity, with some remodeling of the overlying skull. The patient was transferred to the london health Sciences Centre for subtotal resection of what was diagnosed as a "fibrillary astrocytoma (microcystic)." He received no chemotherapy or radiation therapy and remained well for 11 years. The patient presented again in late 1995 with progressive seizure activity. Both CT and magnetic resonance imaging demonstrated a recurrent enhancing partly cystic lesion. A Grade IV astrocytoma was resected, and within the malignant tumor was a superficial area reminiscent of a dysembryoplastic neuroepithelial tumor (DNT). Data on the lesion that had been resected in 1984 were reviewed, and in retrospect the lesion was identified as a DNT of the complex form. It was bordered by cortical dysplasia and contained glial nodules, in addition to the specific glioneuronal element. The glial nodules were significant for moderate pleomorphism and rare mitotic figures. The Ki67 labeling index averaged 0.3% in the glial nodules and up to 4% focally. cells were rarely Ki67 positive within the glioneuronal component. This case is the first documented example of malignant transformation of a DNT. It serves as a warning of the potential for malignant transformation in this entity, which has been traditionally accepted as benign. This warning may be especially warranted when confronted with complex forms of DNT. The completeness of resection in the benign state is of paramount importance.
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5/60. telomerase activity and the expression of telomerase components in pituitary adenoma with malignant transformation.

    BACKGROUND: telomerase activity responsible for cellular immortality may participate the development of human cancers. telomerase is a multisubunit ribonucleoprotein composed of at least three components: hTERT, hTERC, and TEP1. This is the first report showing telomerase activity and telomerase component expression in pituitary adenoma with histological malignant transformation. DESCRIPTION: A 16-year-old male with a prolactin-producing pituitary adenoma with metastasis is presented. The patient underwent three partial resections of an intra- and suprasellar lesion over a 2-year period and received focal irradiation. Eight years after the first admission, a metastatic lesion to the subarachnoid space around the medulla oblongata was detected and the lesion was resected as the fourth operation. Furthermore, the suprasellar lesion showed regrowth and partial resection was performed as the fifth operation. The last two specimens were diagnosed as pituitary carcinoma. radiotherapy with gamma knife was performed for the residual suprasellar lesion and a new lesion in the left temporal lobe after the fifth operation. telomerase activity was examined by TRAP/TRAP-HPA methods, qualitatively and quantitatively. telomere length was examined by Southern blot analysis, and the expression of telomerase components (hTERT, hTERC, and TEP1) was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The MIB1 index, telomerase activity, and hTERT expression increased according to histologic malignancy chronologically in this patient. None of the specimens showed immunoreactivity for p53, EGFR, or bc12. No telomerase activity was detected in pituitary adenomas without malignant transformation, other benign brain tumors, or normal brain tissues. CONCLUSION: We report a patient with pituitary adenoma transforming to carcinoma. The tumor cells acquired immortality and revealed malignant transformation during the course of the disease, that was proved by an increase of telomerase activity and hTERT expression.
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6/60. Melanotic differentiation in dysembryoplastic neuroepithelial tumor.

    Dysembryoplastic neuroepithelial tumor (DNT) is an uncommon intracranial tumor which is usually encountered in patients with medically intractable complex partial seizures of temporal lobe origin. Melanotic differentiation in a DNT has not been reported previously. Herewith we report a case of DNT with unique melanotic differentiation in a 23-year-old female who presented with medically intractable epilepsy. She underwent craniotomy and tumor decompression with a good outcome. We present the histopathological features of DNT with melanotic differentiation and discuss its prognostic significance.
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keywords = prognostic
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7/60. Malignant peripheral nerve sheath tumor arising in benign ancient schwannoma: a case report with an immunohistochemical study.

    A rare example of malignant transformation in an ancient schwannoma arising in the right side of the neck of a 51-year-old man without any clinical manifestations suggesting neurofibromatosis is described. The tumor, approximately 4 cm at its largest dimension, was well circumscribed and had a direct connection with the sympathetic nerve. Microscopically, the central portion of the tumor showed features of ancient schwannoma characterized by extensive hyalinization with cystic degeneration, scattered spindle cells with hyperchromatic and tapered nuclei, and some symplastic changes. However, predominantly in the outer portion, a proliferation of spindle-shaped cells with enlarged nuclei was present. The nuclei of these cells showed irregular contours, coarse granular chromatin texture, and conspicuous nucleoli. Mitotic figures and small necrotic foci with scattered apoptotic bodies were also seen. Immunohistochemically, S-100 protein was almost negative in areas consisting of overtly atypical cells where the mitotic index evaluated with MIB-1 antibody was 30.5%. In contrast, S-100-positive bland spindle cells were scattered in an extensively hyalinized area with a labeling index less than 3%. P53 protein was strongly positive in atypical spindle cells. Although it is a very uncommon event, definite nuclear atypia, frequent mitotic figures, and the existence of small necrotic foci should be recognized as indicating a diagnosis of malignant degeneration of benign schwannoma. immunohistochemistry would be useful as an ancillary technique in such a setting.
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8/60. Large cell transformation of sezary syndrome. A conventional and molecular cytogenetic study.

    Hyperdiploidy sometimes is found in mycosis fungoides-sezary syndrome, but its diagnostic significance remains undefined. We report an unusual case of sezary syndrome manifesting with leukemic large cell transformation. Conventional karyotypic analysis showed the presence of a near-tetraploid neoplastic clone. With dual-color cytometric analysis, we showed that the large Sezary cells were near-tetraploid with a dna index of 1.86, thereby demonstrating a direct relationship between cell size and ploidy. comparative genomic hybridization further showed chromosomal imbalances that were not revealed on conventional karyotyping. Our findings suggest that hyperdiploidy may be a marker of large cell transformation, so that when this karyotypic abnormality is found in mycosis fungoides-sezary syndrome, a search for such a complication is indicated.
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9/60. Slowly progressive systemic mastocytosis with high mast-cell burden and no evidence of a non-mast-cell hematologic disorder: an example of a smoldering case?

    A 43-year-old man with extensive systemic mastocytosis with poor prognostic indicators but no overt hematologic abnormality is described. This patient's clinical presentation and course are consistent with the newly proposed 'smoldering mastocytosis' category. Long-term follow-up of patients is needed to determine whether they may be at higher risk for progression into more aggressive categories.
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keywords = prognostic
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10/60. adenocarcinoma complicating Barrett's esophagus: an analysis of cell proliferation.

    In japan, cases of Barrett's esophagus with concurrent adenocarcinoma are relatively rare. We report herein a case of long-segment Barrett's esophagus-associated adenocarcinoma in a 72-year-old Japanese man. The surgical specimen showed that an ulcerating tumor, measuring 5.5 x 3.9 cm, was present in the lower esophagus adjacent to the esophagogastric junction, the background lower esophagus having an erythematous appearance. Histologically, the ulcerating tumor was a well-to-moderately differentiated tubular adenocarcinoma, with a small area of signet ring cell carcinoma invading the adventitia. In addition, the esophageal epithelium was replaced by columnar epithelium (9.5 cm in length) with multifocal dysplastic changes. Immunohistochemically, the number of Ki-67-positive cells gradually increased, moving from the normal gastric mucosa (mean Ki-67 labeling index [mKLI], 2.6%) through Barrett's epithelium (mKLI, 12.9%), low-grade dysplasia (mKLI, 16.9%), and high-grade dysplasia (mKLI. 23.7%) to invasive carcinoma, in that order, with labeling higher in the invasive tubular adenocarcinoma elements (mKLI, 40.5%) than in areas of signet ring cell carcinoma (mKLI, 20.4%). Findings in our patient suggest that increased cellular proliferation plays an integral part, in the progression of Barrett's metaplasia to adenocarcinoma. The collection of further cases for analysis will be necessary to confirm this hypothesis.
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