Pulmonary melanoma. Primary vs metastatic.

We report one of the few cases of apparently primary pulmonary melanomas documented by both clinical and autopsy examination. The possibility of spontaneous regression of a melanoma primary in another site after metastasis has occurred may explain some of these cases.

Precocious puberty and hypothalamic hamartoma.

A 3-year-old boy with true precocious puberty and hamartoma of the hypothalamus is described. Preliminary diagnosis was established by the presence of unusually advanced puberty and skeletal age without other evidence of central nervous system dysfunction, elevated blood gonadotropin and testosterone concentrations, and positive computed tomography scans. Pneumoencephalography further delineated the tumor. Hypothalamic-pituitary-gonadal and adrenal functions were studied. Release of gonadotropins after the injection of synthetic luteinizing hormone-releasing hormone and the suppression of luteinizing hormone and of testosterone by oral fluoxymesterone were comparable to maximal responses of normal men. The diagnosis was confirmed by histologic and electron microscopic study of an excised portion of the tumor. Immunofluorescence studies indicated the presence of luteinizing hormone-releasing hormone in the hamartoma and radioimmunoassays detected thyroid-stimulating hormone-releasing hormone and somatostatin. The hamartoma resembles an autonomously functioning accessory hypothalamus. The ectopic neuroendocrine pathways, however, are responsive to hormonal stimulation and feedback. The clinical, endocrinologic, and pathologic features of published cases of precocious puberty and hypothalamic hamartoma are reviewed. Advanced or rapidly progressive true precocious puberty in the very young with elevated concentrations of blood gonadotropins and gonadal steroids and positive pneumoencephalography appear to be characteristic.

Duodenal glucagonoma: a case report.

A case of a primary carcinoid islet cell tumor of the duodenum is reported, demonstrated by histochemistry, electron microscopy, and immunofluorescence to be composed of alpha cells containing glucagon-like material. The patient was found on admission to have hyperglycemia and a diffuse skin rash. Primary duodenal glucagonoma has not been previously reported.

Vasoactive intestinal polypeptide and gastrin-producing islet cell carcinoma.

A 61-year-old woman had watery diarrhea, hypochlorhydria, hypokalemia, and elevated serum gastrin levels. She had islet cell carcinoma of the body of the pancreas with multiple metastases to the liver. Radioimmunoassay and immunofluorescence demonstrated both vasoactive intestinal polypeptide (VIP) and gastrin in the surgically removed carcinoma and in a metastatic focus. Electron microscopical findings confirmed the presence of two cell types whose secretory granules had characteristics ascribed to these two hormones. Plasma prostaglandin E levels were also elevated above normal. Serum VIP levels became elevated to the Verner-Morrison range prior to her death of a bleeding duodenal ulcer two years after initial symptoms.

IgE myeloma with osteoblastic lesions.

A 69-yr-old man with persistent anemia had multiple myeloma with an IgE-type kappa M component and Bence Jones proteinuria. Bone x-rays revealed occasional lytic lesions associated with a diffuse sclerotic reaction throughout the skeleton. Special bone histologic studies utilizing tetracycline labeling, undercalcified sections, and microradiography confirmed active osteoblastic activity. This case was compared with the four previously reported cases of IgE myeloma, one of which also had osteosclerosis.

Hypothalamic hamartoma: a source of luteinizing-hormone-releasing factor in precocious puberty.

The presence of a hypothalamic hamartoma and precocious puberty in a 19-month-old boy provided an opportunity to study their relation. Excised tissue had the ultrastructural characteristics of an independent neuroendocrine unit -- i.e., neurons containing neurosecretory granules and blood vessels with fenestrated endothelium and double basement membranes. Immunofluorescence studies using specific antibody to luteinizing-hormone-releasing factor showed antigenicity to the factor in the hamartoma. The testicular-hypothalamic-pituitary axis was tested. Clomiphene unresponsiveness suggested a lack of maturation of central-nervous-system events characteristic of normal puberty. The negative feedback system between gonad and brain was intact but partially resistant to steroid suppression. These studies suggest that hypothalamic hamartomas may cause precocious puberty by autonomous production and release of luteinizing-hormone-releasing factor into vessels that communicate with the pituitary portal blood system.

Malignant APUDoma (carcinoid) of the anterior mediastinum. Simplified methods of demonstrating biogenic amines in endocrine neoplasms.

Endocrine neoplasms of the thymus and mediastinum are uncommon. This report describes such a carcinoma and the difficulty in determining its true nature. A simple modification of the technique for formaldehyde-fume-induced fluorescence (FIF) demonstrated biogenic amines in the cells. Electron microscopy and histochemical findings confirmed the close relationship of these neoplasms with neural-crest cells capable of amine precursor uptake and decarboxylation (APUD). The FIF technique is also a more sensitive method of detecting these tumors, since it has less of the sampling problems of electron microscopy, and the fluorescent granules are more easily seen than those stained by the usual methods. The techniques are simple enough for screening all poorly differentiated carcinomas in this area to determine a more accurate incidence figure.

Chemotherapy of hydatid disease (Echinococcus granulosus) in mice with mebendazole and bithionol.

We treated female Swiss Webster mice with heavy, long standing infections of Echinococcus granulosus with mebendazole, 50 mg/kg body weight daily for 10 days and bithionol, 70 mg/kg every other day for four doses. Necropsy performed 6 weeks after completion of therapy showed no gross or histologic differences between untreated controls and bithionol-treated mice or their cysts. Mebendazole-treated mice had a significant decrease in the total number of cysts (15 vs. 100), with many of those present being ruptured. Electron microscopy of intact, mebendazole-treated cysts revealed a marked increase in vacuolization and disarray of the distal cytoplasm, dilated and degenerating microtubules, increase in the size and number of lysosomes, a decrease in the number of normal appearing golgi, and increased density of mitochondria. Several mice died shortly after the termination of mebendazole therapy, all with ruptured cysts. Due to the large volume of the cysts, the presumed cause of death was acute volume overload, but toxic or anaphylactic reactions could not be excluded. We suggest that any proposed chemotherapy of humans with hydatid disease be done cautiously, with careful monitoring.

FSH-secreting pituitary adenomas: stimulation and suppression studies in two patients.

Two patients with pituitary adenomas, partial hypopituitarism and abnormally high serum concentrations of FSH are described. In neither patient was FSH increased after the administration of LH releasing hormone and in one patient tested, there was no FSH response to clomiphene citrate. The decrease in serum FSH in response to high concentrations of testosterone (greater than 1100 ng/dl) was less than in normal men. These results indicate partial autonomy of FSH producing adenomas. Since the elevated serum FSH produced no obvious clinical symptoms, it may be undetected unless serum FSH concentrations are measured routinely in patients with pituitary tumors.

Nonfunctioning argyrophilic tumor (APUDoma) of the hepatic duct: simplified methods of detecting biogenic amines in tissue.

This report documents a foregut endocrine neoplasm in an unusual location, the main hepatic bile duct, and describes simplified methods of detecting similar endocrine tumors. Formaldehyde fume-induced fluorescence (FIF) is a quick, specific method to demonstrate biogenic amines. FIF combined with histochemical procedures showing abundant alpha-glycerol phosphate dehydrogenase and esterases indicates the neural crest origin of these and related neoplasms. Amine precursor uptake and decarboxylation (APUD) is a significant marker of these cells and gives them their name.

Unusual calcification in mixed papillary and follicular carcinoma of the thyroid gland.

An unusual egg-shell calcification was found in the thyroid gland on a routine radiograph. The 99mTc-pertechnetate thyroid image showed a cold nodule in the inferior pole of the left lobe which proved to be mixed papillary-follicular carcinoma. There was no characteristic pattern of calcification in the thyroid gland which would permit precise diagnosis of cancer; however, psammomatous calcification frequently occurs in papillary carcinoma of the thyroid.

Ewing's sarcoma of the great toe. A case report.

A case of Ewing's Sarcoma originating the great toe is reported. Because of the rarity of its appearance outside the pelvis and long tubular bones, Ewing's Sarcoma is often misdiagnosed when it occurs in the distal portion of the extremities. Ewing's Sarcoma may be difficult to distinguish from infection. Biopsy is recommended for any indolent or refractory lesions presumed to be infectious. Bone scanning with Technetium Polyphosphate is a useful tool for diagnosis and evaluation of this tumor. Vigorous integrated chemotherapy and radiotherapy had little effect in this patient with metastatic disease.

Fume-induced fluorescence in diagnosis of nasal neuroblastoma.

Nasal neuroblastoma, esthesioneuroblastoma, is frequently difficult to distinguish from the more common poorly differentiated epidermoid carcinoma of the nasal cavity and nasopharynx. We present a simple alternate method to electron microscopy, formaldehyde-fume-induced fluorescence, to demonstrate biogenic amine granules in neoplastic cells. This method is more specific and more sensitive, since it reveals the presence of biogenic amines, not merely membrane-bound granules, and it deals with larger quantities of tissue, thus avoiding some of the sampling errors inherent in electron microscopy. We also describe the histochemical relationship of this tumor to other neural crest neoplasms.

Epidermoid carcinoma of the bulbar conjuctiva in Ethiopia.

We report 26 patients with epidermoid carcinoma of the bulbar conjunctiva seen in Ethiopia, in a 29-month period. The increased frequency and aggressiveness of this neoplasm is emphasized and related to increased amount and scattering of ultraviolet radiation in the tropics.