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• W175504397 abstract "Pheochromocytoma originates in chromaffin cells of the adrenal medulla. Its incidence is similar in both sexes and most frequent between the ages of thirty and fifty. Multiple and bilateral pheochromocytomas constitute 5 to 10 percent of all cases. Pheochromocytoma occurs sporadically or is related to family syndromes such as: syndrome of multiple endocrine neoplasia--MEN IIA and IIB, neurofibromatosis (von Recklinghausen's disease), von Hippel-Lindau's disease, Sturge-Weber's syndrome, and tuberous sclerosis. Cases in a family usually occur at a younger age and are mostly bilateral and with more aggressive biological behaviour.The aim of the study was to make histomorphological and immunohistochemical analyses of 52 pheochromocytomas. These cases are the surgical material from the Centre of Endocrine Surgery, Institute of Endocrinology, Diabetes, and Metabolic Disorders, Clinical Centre of Serbia, Belgrade, over the period from 1974 to 1997. Frozen and fixed sections, which were cut from paraffinembedded material and stained by both hematoxylin-eosin and PAS, were used in order to make pathohistological diagnoses. The expression of chromogranin A, S-100 protein and ACTH was examined using the PAP method, while neuronspecific enolase (NSE), synaptophysin and neurofilament were examined by the APAAP method with appropriate antibodies (DAKO).The patients were between 4 and 65 years of age (average age 38.5) and there were 28 females (63.64%) and 16 males (36.36%). The largest pheochromocytoma had the diameter of 12 cm, and weight of pheochromocytomas in question was from 13.5 to 370 grams, the average weight being 83.4 grams. On gross examination, the tumours proved to be well-defined, either by fibrous capsule, or by adrenocortical tissue. The cross-sections of tumours were mainly of pale red-grayish colour, and showed numerous foci of necrosis, haemorrhage and cystic softening. Histological appearance of pheochromocytomas was with significant irregularities in shapes and dimensions of the cells and their patterns. Pheochromocytes were mostly of polygonal shape (45 cases, 86.54%), whereas in 7 cases (13.46%) fusiform cells were evident. Cells were arranged, either in trabeculae intermingled with thin-walled sinusoids, or in small alveolae circumferenced by fibrovascular stroma. PAS positive hyaline globules were often present in the cell cytoplasm and also extracellularly. Cellular and nuclear pleomorphism, binuclear and multinuclear cells, as well as giant cells were evident in 35 (67.31%) pheochromocytomas. Mytotic figures were infrequent in 50 tumours (one to two on ten microscopic high power fields). Malignant pheochromocytomas (2 cases) metastasized to regional lymph nodes and liver, and lungs and bones, respectively. Pheochromocytomas were associated with MEN IIA syndrome in 6 patients (13.63%), all of whom had bilateral adrenalectomy, and in the period from two months to one year later underwent total thyroidectomy due to medullar thyroid carcinoma. Simultaneous occurrence of adrenal medullar hyperplasia and pheochromocytoma, i.e. the sequence: diffuse medullar hyperplasia--nodular medullar hyperplasia -pheochromocytoma, was found in two patients with MEN IIA syndrome (33.33%). Hyperplastic nodule (1 cm in diameter) with discrete capsule and compression of surrounding adrenal tissue was considered to be a small pheochromocytoma. All the studied pheochromocytomas showed chromogranin A, NSE, and synaptophysin immunopositivity in nearly all tumour cells. Neurofilament positivity was focal and less intense. S-100 protein positive sustentacular cells were found in 29 of 32 pheochromocytomas included in immunohistochemical examinations. Incidence frequency of S-100 protein positive sustentacular cells was high in pheochromocytomas related to family syndromes and low in malignant pheochromocytomas.Numerous features of the described pheochromocytomas appear in the already published data, namely: age of occurrence, tumour weight, histological and immunohistochemical characteristics, frequent association of bilateral pheochromocytoma and MEN IIA, as well as the occurrence of adrenal medullar hyperplasia as precursor of pheochromocytoma. Immunohistochemical analysis has confirmed the importance of pan-neuroendocrine markers (chromogranin A, NSE, and synaptophysin) in pheochromocytoma diagnosing, whereas it has been that neurofilament was of less importance. High incidence frequency of S-100 protein positive sustentacular cells in pheochromocytomas related to family syndromes was also noted by other authors.Histomorphological features of benign and malignant pheochromocytomas may be similar. Histologic criteria for aggressive biological behaviour of pheochromocytoma include: insular pattern of growth, 3-5 mytotic figures on 10 microscopic high power fields and invasion of capsular lymphatics and blood vessels. Pan-neuroendocrine markers (chromogranin A, NSE, synaptophysin) may be useful in diagnosis of pheochromocytoma. Incidence frequency of S-100 protein positive sustentacular cells is high in pheochromocytomas related to family syndromes and low in malignant sporadic pheochromocytoma." @default.
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• W175504397 title "[Pheochromocytoma--pathohistologic and immunohistochemical aspects]." @default.
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