[Apudoma of the prostate]. / Apudomy predstatel'noi zhelezy.

Prostatic apudomas are represented by well-, moderately- and poorly differentiated variants. Histologic differentiation determines various functional properties of tumor cells. Tumor cells of well-differentiated apudomas produce serotonin, less frequently calcitonin, poorly differentiated ones produce only ACTH. Apud cells of moderately differentiated tumors, besides their main function to synthesize biogenic amines and hormones (serotonin, ACTH) possess immunoreactivity to epithelial membrane antigen, carcinoembryonal antigen and prostatic specific antigen.

Tumor neuroendocrino de intestino / Neuroendocrine tumor of intestine

Se presentan 6 casos de tumores carcinoides de intestino, que tras una revisión de los preparados histológicos se los clasifica en 3 tumores neuroendócrinos benignos o carcinoides y 3 carcinomas neuroendócrinos. Se analiza la evolución clínica de los mismos. El empleo en la actualidad de técnicas más especificas para el diagnóstico de estos tumores ha permitido un mayor conocimiento de los mismos. Dichas técnicas, inmunomarcación enolasa neuroespecífica, grimelius, cromogranina, etc. son utilizadas por el patólogo cuando por las características macro y microscópicas sospeche un tumor de esta estirpe; (tumor amarillo brillante originado profundamente en la mucosa y que crece tanto hacia la luz como hacia la submucosa). La morfología celular, en base a las mitosis, atípicas celulares y límites del tumor, permite diferenciar a estas neoplasias en tumores de alto y bajo grado de malignidad

Metastatic pancreatic polypeptide producing tumour presenting with diabetes mellitus.

A metastatic pancreatic polypeptide tumour is described which presented clinically with diabetes mellitus. This is the first case to present this way.

[A poorly differentiated apudoma of the gallbladder]. / Nizkodifferntsirovannaia apudoma zhelchnogo puzyria.

Apudoma was found in the gall bladder removed in a 76-year-old woman because of the chronic calculous cholecystitis exacerbation. Carcinoid syndrome was absent clinically. Histologically, the tumour was a poorly differentiated carcinoid with areas of small cell and polymorphic carcinoma. Argyrophilic Pasquale reaction in the tumour cells was negative, electron microscopically small neurosecretory granules were found. Numerous ACTH-reactive cells and single serotonin-reactive cells were revealed in the tumour parenchyma by means of immunohistochemical PAP-method using antibodies against ACTH, serotonin, calcitonin, somatostatin, insulin, glucagon, P-substance. Focal hyperplasia and intestinal metaplasia of epithelium with the increase of the number of argyrophilic, ACTH-reactive cells were observed outside the tumour.

Liver transplantation for primary and secondary hepatic apudomas.

Four patients underwent liver transplantation in the Cambridge/King's College Hospital programme for malignant primary and secondary apudomas, secreting various peptide hormones and uncontrollable by standard treatment techniques. After transplantation all patients had excellent symptomatic relief and specific peptide hormone levels fell to normal ranges. Two patients remain alive and well after 38 and 22 months, the latter with recurrence of slight tumour-related symptoms and elevation of the specific secretory product. The other two patients died from chronic graft rejection 7 and 8 months after transplantation.

[Primary hepatic apudoma with serotonin syndrome]. / Pervichnaia apudoma pecheni s serotoninovym sindromom.

Primary hepatic apudoma associated with serotonin syndrome was recorded in a man of 55 followed up for 6 years. Clinically, there was a progressive enlargement of the liver with varicosis of venae subcutaneae abdominis and venae esophageae. There were also weak signs of carcinoid syndrome. The patient died of acute venous esophageal hemorrhage. The tumor, represented by white dense cystic tissue, was nearly encapsulated and involved almost the whole liver. Histologically, there were monomorphic cells with clear empty or eosinophilic cytoplasm, small central nuclei which developed into solid streaks and alveoli. Glandular formations and pseudorosettes occurred locally. Grimelius staining revealed argyrophil granules in the tumor cells cytoplasm. Metastases of the tumor were found in portal lymph nodes.

Iodine-123 MIBG imaging in a generalized pancreatic polypeptide-gastrin-serotonin secreting tumor.

The usefulness of radio-metaiodobenzylguanidine (MIBG), a specific radiopharmaceutical agent for scintigraphic imaging and treatment of phaeochromocytoma and neuroblastoma, has been extended to the location of carcinoid tumors. Scintigraphic evaluation with I-123 MIBG in a patient with a histologically proven endocrine tumor (apudoma) of unknown origin with liver and bone metastases is reported. Elevated plasma hormone levels of gastrin, pancreatic polypeptide, and serotonin were found. Tumoral content of these hormones was immunocytochemically confirmed on liver biopsy. I-123 MIBG uptake could be seen in those areas of the liver with deficient lesions in the Tc-99m colloid image with a maximal uptake in a large mass at the level of the left liver lobe. No abnormal uptake could be observed at any other level, which was in contrast with autopsy findings of generalized metastatic disease.

[A case of malignant pancreatic apudoma producer of serotonin and pancreatic polypeptide]. / Su un caso di apudoma maligno pancreatico a produzione di serotonina e polipeptide pancreatico.

Taking as their starting point the observation of a pancreatic malignant endocrine neoplasm with mixed production of serotonin and pancreatic polypeptide, the authors go on to review the literature on the diagnosis and treatment of pancreatic apudomas. The possibility of performing an extempore intraoperative histological examination makes it possible to obtain a correct diagnosis of endocrine neoplasm and thus to proceed with surgery which could not be contemplated in adenocarcinomatous forms at an equivalent stage. Chemotherapy may then provide additional therapeutic possibilities, using specific markers for malignancies of the APUD system in order to detect possible recurrences.

[Bihormonal apudoma of the pancreas]. / Bigormonal'naia apudoma podzheludochnoi zhelezy.

A pancreatic tumor that displayed bihormonal activity is described: the tumor elaborated insulin, resulting in a hyperinsulinism syndrome (spontaneous hypoglycemia) as well as a second hormone, apparently gastrin or a gastrin-like polypeptide, which led to the development of Zollinger-Ellison syndrome. The presence of these two syndromes complicated both the diagnosis and treatment of the disease. A histologic examination using an argyrophilic (Grimelius) reaction confirmed that the tumor had originated from endocrine cells of the gastrointestinal tract and was a bihormonal apudoma of the pancreas.

[Secretion of hormones by malignant tumors]. / Sekretsiia gormonov zlokachestvennymi opukholiami.

The ectopic hormone secretion by the transformed cells is analyzed. The classification of hormone-secreting tumours is suggested. Diagnostic, differential-diagnostic and prognostic values of hormone determination during neoplastic growth are estimated. Clinical and experimental criteria of tumour hormone secretion are characterized.

ACTH-producing apudoma metastatic to the liver.

A young man presented with combative psychosis and elevated levels of plasma adrenocorticotropic hormone (ACTH). A solitary vascular pancreatic mass and diffuse vascular hepatic nodules were demonstrated on selective splenic and hepatic arteriograms. These classic angiographic findings are used to emphasize the role of angiography in initial radiographic evaluation and to summarize the angiographic appearance of functioning pancreatic adenomas. Even though this is an aggressive tumor, early diagnosis and intensive treatment may allow prolonged remission, if not cure.

[Hormone production and abnormalities in gene expression in tumors].

In order to elucidate the mechanism responsible for ectopic hormone production in tumors, biosynthesis of ACHT and related peptides was studied in the pituitary and tumors at levels. In vitro biosynthesis of the ACTH/beta-LPH precursor directed by mRNA extracted from the pituitary and tumors showed no difference in translation products. It is highly likely, therefore, that different final products produced in the pituitary and tumors are caused by different posttranslational processing, such as proteolysis and glycosylation of translation products. The RNA blot analysis of tumors revealed mRNA identical to that of the pituitary. In certain tumors, however, there were larger or smaller mRNA hybridized with an ACTH/beta-LPH precursor probe, in addition to mRNA of normal size. Further studies with endonuclease S1 mapping have provided evidence suggesting that the larger one was probably produced by abnormal splicing of RNA precursor and that the smaller one was resulted possibly from aberrant transcription of the gene. The Southern blot analysis revealed no difference in restriction DNA fragments between the pituitary and tumors, indicating no evidence of gene rearrangement. From these studies, it is conceivable that ectopic ACTH production is resulted from abnormalities in the regulatory mechanism of gene expression. To further study the mechanism regulating the expression of the ACTH/beta-LPH precursor gene, human gene was transfected to mouse pituitary ACTH-producing adenoma cells (AtT-20) and fibroblasts (L-cell). The introduced human ACTH/beta-LPH precursor gene was expressed in AtT-20 cells and suppressed by glucocorticoids to an extent similar to the suppression of mouse gene. On the other hand, possible aberrant transcripts were observed in mouse L cells. It is likely, therefore, that there is a regulatory mechanism, probably "trans" acting, in the pituitary ACTH-producing producing cells and similar mechanism, though not identical, could be exerted in ectopic ACTH-producing tumors.

[Muciparous cricoid apudoma of the breast]. / Slizeobrazuiushchaia perstnevidnokletochnaia apudoma molochnoi zhelezy.

Four cases of muciparous cricoid-cell breast tumours with their cells containing endocrine granules are presented. The granules were detected with argyrophile reaction. Problems of histogenesis of the neoplasms are briefly discussed. They are defined as muciparous apudomas of the breast.

Growth hormone secretion dynamics in a patient with ectopic growth hormone-releasing factor production.

A female patient with acromegaly, hypercalcemia, and Zollinger-Ellison syndrome was found to have a very high plasma concentration (average 2,300 pmol/liter; normal less than 50 pmol/liter) of growth hormone-releasing factor as measured by a radioimmunoassay to human pituitary growth hormone-releasing factor-1-44. The plasma concentration of growth hormone averaged 25 mIU/liter (normal less than 5 mIU/liter) and there was no rise following an intravenous 100 micrograms bolus of human pituitary growth hormone-releasing factor-1-44. Plasma growth hormone and growth hormone-releasing factor levels were unaffected by bromocriptine, insulin-induced hypoglycemia, and sleep. A long-acting somatostatin analogue lowered both the growth hormone-releasing factor and the growth hormone levels. Thyrotropin-releasing hormone stimulation and oral glucose tolerance tests produced significant increases in plasma growth hormone levels whereas the growth hormone-releasing factor level remained unchanged, suggesting that when normal somatotrophs are exposed to maximal growth hormone-releasing factor stimulation, thyrotropin-releasing hormone becomes a secretagogue of growth hormone from the pituitary. It is proposed that in the absence of a radioimmunoassay for growth hormone-releasing factor, a lack of growth hormone response to growth hormone-releasing factor in a patient with acromegaly is compatible with a source of ectopic growth hormone-releasing factor production.

Doxorubicin plus cisplatin in the treatment of apudomas.

Twelve patients with advanced apudomas--six with carcinoid tumors, two with chemodectomas, two with pancreatic islet cell tumor, and one each of medullary carcinoma of the thyroid and paraganglioma of unknown primary--were treated with a combination of doxorubicin 50 mg/m2 and cisplatin 50 mg/m2 every 3 to 4 weeks. Biochemical markers were present in 8 of the 12 patients. Five of the 12 patients (3 with carcinoid and 2 with chemodectomas) responded with more than 50% regression of tumor size measured as hypothetical area. Three others (two with islet cell tumors and one with carcinoid) had clinical and/or biochemical improvements. A median duration of response was 6 months. Nausea, vomiting, and alopecia were universal. Mild or moderate leukopenia was the most frequent toxicity. No sustained nephrotoxicity was seen. The combination of doxorubicin and cisplatin provides a new palliative therapy for patients with APUD tumors.