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1/25. A patient with preclinical Cushing's syndrome and excessive DHEA-S secretion having unilateral adrenal carcinoma and contralateral adenoma.

    We report a case of preclinical Cushing's syndrome in a 54-year-old male associated with bilateral adrenocortical tumours. Physical findings and general laboratory data were unremarkable except for mild hypertension (158/90 mmHg) and impaired glucose tolerance. Endocrinological evaluation revealed the presence of autonomous cortisol secretion including unsuppressible serum cortisol by 8 mg dexamethasone test (11 microg/dl), high serum DHEA-S (3580 ng/ml, normal: 400-3500) and increased urinary 17-KS excretion (31.0-35.8 mg/day, normal: 5.8-21.3). CT scan demonstrated the presence of tumours in both adrenals and bilateral adrenalectomy was subsequently performed. Histological examination of the resected specimens revealed an adrenocortical carcinoma on the right side and an adenoma on the left side with noticeable cortical atrophy in non-neoplastic adrenals. Immunohistochemical study of steroidogenic enzymes demonstrated that all the steroidogenic enzymes involved in cortisol biosynthesis were expressed in both right and left adrenal tumours. Enzymatic activities of 21, 17alpha, 18, 11beta-hydroxylases were detected in both right and left adrenals except for the absence of 11beta-hydroxylase activity in the left adrenal adenoma. Results of in vitro tissue steroidogenesis examined in short-term tissue culture of the specimens revealed no significant differences between carcinoma and adenoma in cortisol production, but the production of adrenal androgens in carcinoma was significantly higher than that in adenoma, which may indicate the importance of evaluating adrenal androgen levels in patients with adrenocortical neoplasms.
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2/25. Successful simultaneous operation of concomitant early gastric cancer, transverse colon cancer, and a common iliac artery aneurysm.

    In an 83-year-old Japanese man, concomitant bleeding colon cancer, early gastric cancer, and an expanding right common iliac artery aneurysm were evident. The patient underwent an artificial graft implantation, partial gastrectomy, and transverse colectomy, simultaneously. To protect against graft infection, the aneurysm was resected first, and then the retroperitoneum was tightly closed to isolate the graft from the peritoneal cavity. The postoperative course was uneventful, except for symptoms of temporary delirium. Recently, simultaneous surgery for concomitant abdominal aortic aneurysms and early gastric cancer has been commonly performed in japan because the contamination of the peritoneal cavity during a gastrectomy is thought to be less severe than that during lower abdominal surgery. However, the positive rate for bacterial culture in colorectal resections is virtually the same as that in gastrectomies. Moreover, the incidence of graft infection is substantially lower than the positive rate for bacterial culture in surgery for aneurysms. Some surgeons object to a simultaneous resection due to fear of graft infection, but even the presence of infectious organisms does not always result in graft infection. The present case illustrates the benefits of a simultaneous operation for both an aneurysm and gastrointestinal malignancy.
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3/25. Mediastinal immature teratoma with yolk sac tumor and myelomonocytic leukemia associated with Klinefelter's syndrome.

    A 14-year-old male presenting with a short history of right subclavicular chest pain was found to have a mediastinal tumor. Hematologic investigations and bone marrow examination showed features of myelomonocytic leukemia. The mediastinal tumor was excised, but the surgery was complicated by massive hemorrhage. The patient's condition deteriorated postoperatively and he died a week later. The histology of the mediastinal tumor showed the typical features of an immature teratoma with a yolk sac tumor. A prominent infiltrate of leukemic blast cells was present within blood vessels and in close proximity to the yolk sac component. The karyotypic analysis of leukemic cells isolated and cultured from the bone marrow showed 50XXY, 8, 21, iso G-group marker chromosome karyotype.
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4/25. abscess-like formation concomitant with pituitary adenoma in Cushing's disease: case report and pathological considerations.

    Pituitary abscess is a rare condition and a histological misnomer since cultures of abscess material are often negative or non-pathogenic. We report the first case of pituitary abscess-like formation concomitant with pituitary adenoma and discuss the physiopathological mechanism. A 37-year-old woman presented classic symptoms of Cushing's disease. Endocrine studies indicated the presence of adenocorticotropin (ACTH)-producing pituitary adenoma. Preoperative magnetic resonance imaging revealed two separate tumours of the pituitary. During transsphenoidal surgery, a 14-mm adenoma was removed from the right side of the gland and a pus-filled cystic tumour was opened and drained on the left. Histological diagnosis was ACTH-producing pituitary adenoma and cyst material compatible with pituitary abscess. association of separate adenoma and abscess of the pituitary gland has not been reported previously. We speculate that spontaneous adenoma infarction may provide a more comprehensible pathophysiological explanation than abscess formation.
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5/25. Intracranial malignancy in patients with bilateral retinoblastoma.

    Tumors from two patients with bilateral retinoblastoma and intracranial malignancies were studied from a clinical, histopathological, and an immunohistochemical standpoint. An antiserum derived against tissue cultured Y-79 retinoblastoma cells was utilized in order to examine the surface and cytoplasmic antigens of the two brain tumors, histopathologically diagnosed as an embryonal cell carcinoma (case 1), a pinealoblastoma (case 2), and one ocular retinoblastoma. The two brain tumors reacted with the antiserum to different degrees. In comparison, the ocular tumor reacted strongly. None of the tissues examined were found to contain retinal S- or P-antigen. The concept of retinoblastomas arising de novofrom the pineal gland and the association of intracranial malignancy occurring in retinoblastoma is stressed. The antigenic and immunologic relationships between normal retina and pineal gland and retinoblastoma, neuroblastoma, and pinealoblastomas are discussed.
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6/25. Loss of 10p material in a child with human papillomavirus-positive disseminated bilateral retinoblastoma.

    retinoblastoma (RB) is a malignant childhood tumor that results from loss or inactivation of both alleles of the RB1 gene. Human papillomavirus (HPV) dna sequences have been found in RB tissue, suggesting a role of the viral infection with RB. We here describe a child with disseminated bilateral RB without familial history, who displayed a loss of material from 10p. fluorescence in situ hybridization studies showed a somatic loss of both alleles of the RB1 gene. Moreover, sequences for HPV-6a were detected on dna extracted from eye tumor tissue and from nonstimulated peripheral blood leukocyte cultures. The eye tumor tissue was also positive for HPV L1 viral proteins. Repeated loss of the short arm of chromosome 10 in HPV-transfected keratinocytes has been reported. Loss of heterozygosity in 10p14 approximately p15 is also frequent in cervical cancers. Therefore, it seems probable that the abnormalities on 10p detected in the present case are related to the HPV infection. Thus, HPV could be a cofactor in the progression of RB by promoting nonrandom additional mutations.
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7/25. Y/6 chromosome translocation in a male with triple primary cancers involving the breast.

    Cytogenic studies were performed in a 72-year-old male patient with triple primary cancers including breast, skin and lung. Left breast cancer was diagnosed at the age of 46 and he received mastectomy and thoracic irradiation. Squamous cell carcinoma and bowen's disease were diagnosed from two separated parts of a skin lesion at the age of 70. Small-cell lung cancer was diagnosed 1 year later, and he received chemotherapy and radiotherapy. Chromosome analysis was carried out on both peripheral lymphocyte and skin fibroblast cultures at the age of 72. Out of 30 fibroblast cells karyotyped at the second passage, 7 cells (23%) consistently showed a reciprocal translocation t(Y;6)(q12;p21). The same translocation was found in one of 200 cells from lymphocyte cultures. The findings suggest that the translocation t(Y;6) might be inherent in nature, and that the patient was a mosaic of 46,XY/46,X,t(Y;6)(q12;p21). These results highlight the constitutional chromosomal abnormality as one of the possible high-risk factors for multiple primary cancers.
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8/25. Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D.

    A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled dna synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum.
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9/25. Kaposi's sarcoma in immunosuppression. Possibly the result of a dual viral infection.

    Kaposi's sarcoma of the gingiva and skin developed in an hiv-negative renal transplant patient while he was receiving cyclosporine therapy. The Kaposi's sarcoma developed shortly after the patient had an acute infection with cytomegalovirus (CMV). Electron microscopy of the tumor's established cell line showed two types of virus-like particles. CMV dna was identifiable in the cell line whereas infectious CMV could be isolated only after repeated passages (only after 3 months of culture). The other virus could not be identified, but did not appear to be either hiv or papilloma virus. The patient's tumor regressed after the discontinuation of cyclosporine therapy and the recovery from the acute CMV infection.
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10/25. Two homologous mixed mullerian tumor lines of the ovary and their characteristics.

    Two cell lines, NF and JoN, derived from human ovarian carcinosarcomas, were established in tissue culture and in nude mice. Both lines, growing in monolayers, showed morphologic features of adenocarcinoma cells (NF being aneuploid with a modal number of 53, and JoN being pseudodiploid with a modal number of 44). intermediate filaments were demonstrated immunohistochemically; the JoN line expressed keratin, but not vimentin or desmin, whereas the NF line expressed vimentin and desmin, but not keratin. plasminogen activator activity was found in both lines. It is concluded that both of these lines are potentially useful models for studying the diverse characteristics of malignant mixed Mullerian tumors.
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