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PubMed1992

[Medullary carcinoma of the thyroid gland and the APUD system].

Medullary thyroid carcinoma, MTC, accounts for 8-10% of all thyroid malignancies. It occurs in the sporadic form (70-75%) and the familial variant (25-30%). In familial MTC the autosomal dominant type of heredity is involved. This variant is found frequently in association with other endocrine hyperplasias or tumours within the framework of the APUD system and is thus an indispensible condition of the MEN 2 syndrome, either MEN 2A (MTC and pheochromocytoma and/or hyperparathyroidism) or MEN 2B with the frequent concurrent presence of pheochromocytoma and a typical phenotype, in particular multiple neurofibromas on the lips and tongue. The type of MTC determines also to a certain extent the prognosis of the disease. MTC in the framework of MEN 2A are usually most benign, while the prognosis is poorest for MEN 2B. The sporadic variant has a poorer prognosis, as compared with differentiated thyroid carcinoma. The only effective and rational treatment of MTC is radical surgery. In all instances where we confirm the diagnosis before surgery we indicate bilateral total thyroidectomy. In the familial variant where the tumour is usually multifocal and in both lobes this indication is absolute, in sporadic forms with possible early intrathyroid dissemination of the primary tumour also to the other side, bilateral surgery is also indicated. Moreover we know that a certain ratio of assumed sporadic forms are genetically conditioned tumours and thus are familial. The histological finding of hyperplasia of the C-cells suggests the familial variant even when tumourous transformation did not occur yet.(ABSTRACT TRUNCATED AT 250 WORDS)

APUD Cells↗
PubMed1981

Mucin producing islet cell adenoma.

A well granulated beta cell adenoma of the pancreas was found incidentally at autopsy in a patient with a ruptured aortic aneurysm. The tumor was studied by histochemical an immunocytochemical methods. It consisted of a trabecular arrangement of insulin storing cells intermingled with small ducts. Both components were tightly contiguous. Goblet cells were also present within the tumor cell nests. The implication of the growth of the different types of cells is discussed in relation to the concept of an APUD system.

Adenoma↗
PubMedDate not supplied

Amyloidosis and lung cancer. A morphological and histochemical study.

A study performed on a sample of 120 subjects who died of lung carcinoma and were examined at autopsy in order to verify the presence of amyloid substance particularly localized in the tumoral tissue, is reported. In the positive cases (4 oat cell carcinomas and 1 squamous cell carcinoma), the histochemical nature of depositions was investigated to assess their belonging to the primitive or secondary type, and to the APUD or immune type. The doubtful results induced the authors to suppose an analogous behaviour of oat cell carcinoma and squamous cell carcinoma. The explanation of this phenomenon is still unclear and it should be looked for starting from two hypotheses: an analogy between oat cell carcinoma and squamous cell carcinoma both belonging to the APUD system, or simply a non-specific phenomenon (intratumoral amyloid deposition).

Adenocarcinoma↗
PubMed1976

Evidence for secretion of vasoactive intestinal peptide by tumours of pancreas, adrenal medulla, thyroid and lung: support for the unifying APUD concept.

Levels of vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay in plasma or tissue from thirty-five patients with watery diarrhoea, and in plasma of twenty-five normal controls. Plasma levels were between 0.6 and 11.0 ng/ml in thirty-one of the thirty-three patients in whom it was measured and too low to measure (less than 200 pg/ml) in the other two. Peptide levels were less than 200 pg/ml in twenty-three of the controls, but higher in the remaining two. All tissues from patients were "rich" in VIP (10 ng to 35 microgram per g). The aetiologic diagnoses included pancreatic islet-cell adenoma or adenocarcinoma, islet-cell hyperplasia, bronchogenic carcinoma, pheochromocytoma, ganglioneuroblastoma, medullary thyroid carcinoma, and retroperitoneal histiocytoma. The findings support the conclusions that: (1) VIP is a likely mediator of the water-diarrhoea syndrome; (2) the syndrome may result from a variety of tumours; (3) this or a related peptide hormone may be secreted by these tumours; and (4) these tumours may have a common embryonic origin.

APUD Cells↗
PubMed1988

A phase II trial of streptozotocin and adriamycin in advanced APUD tumors.

Thirty-three patients with advanced carcinoid tumors, islet cell carcinomas, or medullary carcinomas of the thyroid were entered into a phase II trial combining streptozotocin (STZ) and Adriamycin. Thirty-one patients are evaluable for response, and 29 are evaluable for survival. Six (19%) patients achieved objective partial responses (95% confidence limits: 5.4-33). The median duration of response for partial responders was 282 days. The median survival for responders and nonresponders was 16.2 months and 7.8 months, respectively, with an overall median survival of 10.9 months. At 10.9 months median follow-up, 4 (14%) of 29 patients are surviving. Toxicity was mild, except that nausea or vomiting occurred in 25 of 31 patients evaluable for toxicity. With this dose and schedule of administration, STZ and Adriamycin produce modest response rates with objective palliation of disease in patients with advanced amine precursor uptake and decarboxylation (APUD) tumors.

Adenoma, Islet Cell↗
PubMedDate not supplied

Clinical diagnostic application of 111In-DTPA-octreotide scintigraphy in small cell lung cancer.

Some years ago it was proved that a good percentage of small cell lung cancers, classified among cancers of the APUD system, produces somatostatin receptors that can be detected in vivo by scintigraphy with 111In-DTPA-octreotide. With the method in the whole body it is possible to identify the principal neoformation and the probable metastases. The authors present a study of 21 patients afflicted with small cell lung cancer diagnosed histologically. The study, carried out between January 1995 and December 1997, compared the radiologic iconography of the CT scan with the scintigraphic map obtained by a planar scintigraphy and in SPECT 1, 4 and 24-hr after iv injection of 110 MBq of 111In-DTPA-octreotide. The comparison was made with reference to the principal neoplasm and probable metastases. A scintigraphic study, a CT of restaging and a follow-up, done after 3 and 6 months of chemotherapy, on 15 patients with cancer that produces somatostatin receptors proved that the neoplasm sometimes regresses and sometimes progresses. In the latter case, it is possible to identify cerebral, mediastinal and hepatic metastases with the administration of 200 microg of octreotide 3 times a day for 7 days before the scintigraphy. In fact, the administration lowers background activity. The authors concluded that scintigraphy with 111In-DTPA-octreotide plays an important part in the study of patients afflicted with small cell lung cancer. Scintigraphy identifies the subgroups of patients who can be cured with somatostatin analogues together with chemotherapy. Scintigraphy presents a good sensibility in the re-staging and in the follow-up of patients who are treated, even though it is difficult to identify subdiaphragmatic metastases where liver, spleen and kidney show an increase in 111In-DTPA-octreotide.

Adult↗
PubMed1976

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.

Adult↗
PubMed1977

[Pathomorphologic studies of the endocrine cells in the gastrointestinal mucosa. Physiology, cytochemistry and ultrastructure (author's transl].

With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable electron density. According to most authors, they represent a distinct cell type and not just a variant of the G-cells. It may be very difficult, however, to separate certain forms of D1-cells from functionally altered G-cells. 5. The A-cell can be found in the gastric mucosa of certain animal species, where it has been demonstrated by immunocytochemistry with antisera to gut-glucagon. This cell type does not occur in the human gastric mucosa. 6...

Adenoma, Islet Cell↗
PubMed1989

[A rare primary small cell cancer of the esophagus].

The parvicellular carcinomas have their matrix in the neurosecretory (enterochromaffin) cells of Kultschitzky's type of the APUD-system. While in about 20% of the patients with a bronchial carcinoma a parvicellular bronchial carcinoma appears, extrapulmonary parvicellular organ carcinomas are very rarely observed. Up to 1984 altogether 72 patients with a parvicellular carcinoma of the oesophagus were world-wide registered. It is reported on an own observation of a female patient with a parvicellular carcinoma of the oesophagus and it is referred to the appearance of extrapulmonary parvicellular carcinomas. According to the present state of knowledge the extrapulmonary parvicellular carcinomas should be treated according to the therapy concepts of parvicellular bronchial carcinomas.

Aged↗
PubMed1976

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.

Adult↗
PubMedDate not supplied

[Thyroid cancer with signs of C- and A-cell differentiation].

The paper reports a case of thyroid cancer in a female patient aged 56 operated on for nodular euthyroid goiter. The tumor had a mixed histological structure of medullary-follicular cancer and resembled malignant hemangioendothelioma. Electron microscopy detected tumor cells of A- and C-cell type as well as nondifferentiated elements. The tumor contained deposits of amorphous mass deprived of tinctorial properties characteristic of APUD-amyloid and having fine-fibrillar material produced by tumor C-cells.

Adenocarcinoma, Follicular↗
PubMed1985

[Neuroendocrine tumors. Biochemical and physiopathological aspects].

Neuroendocrine tumors (secreting bioamines, peptides, hormones, prostaglandins...) represent rather homogeneous group since they correspond to a benign or malignant proliferation of cells belonging to the diffuse neuroendocrine system. This system might be considered as an extension of the concept (APUD System) proposed by Pearse to account for the common properties of these largely distributed cells. Among neuroendocrine tumors we focused since some years on apudomas and particularly carcinoïd tumors. The determination of their various secretion products in biological fluids allows the early and efficient detection of such tumors exhibiting a very slow growth. Finally the in vitro culture of carcinoïd cells appears to be of great interest in various research fields such as oncology, biochemistry and pharmacology.

Apudoma↗
PubMed1993

[Undifferentiated oat-cell tumor of the larynx. Case report].

The oat-cells tumor is a neuroendocrine growth belonging to the APUD system, sitting regularly in the lung and very rarely in the larynx. Biologically its behaviour is extremely aggressive and must be managed as a systemic disease. The up-to-date treatment is the radiotherapy associated with chemotherapy. The paper deals with one of these tumors of laryngeal site and a review of the bibliography is done.

Aged↗
PubMed1987

Merkel cell carcinoma.

Merkel cell carcinoma is a rare malignant neoplasm of the skin which is locally invasive and frequently metastasizes to lymph nodes, liver, lungs, bone, and brain. Computed tomographic and pathologic findings in an elderly woman with Merkel cell carcinoma of the buttock and regional nodal metastasis are reported. The presence of calcitonin and neuron-specific enolase within the tumor supports the theory that Merkel cell carcinoma is a neuroendocrine tumor derived from the APUD (amine precursor uptake and decarboxylase) system.

Aged↗
PubMed1999

[Mucinous breast carcinomas with neuroendocrine differentiation].

Mucinous breast carcinomas, denominated also gelatinous, mucoid and colloid (collomas), represent a heterogeneous group of neoplasms. More than half of them exhibit signs of neuroendocrine differentiation. Eighteen mucus producing carcinomas of the breast are subjected to morphological study. On the ground of demonstrating argyrophilia by the methods of Grimelius and Churukian--Shenk, and presence of secreting granules during electron microscopic study, they are assigned under the heading apudomas, i.e. tumors of the diffuse endocrine system, or the so-called APUD-system. The important practical implications of demonstrating neuroendocrine cells with a special reference to the biological patterns of this particular type of tumors are discussed.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

[Primary neuroendocrine carcinoma of the skin (Merkel cell tumor)].

Three cases of neuroendocrine carcinoma of the skin studied by light and electron microscopy and by immunohistochemical methods, are presented. It is generally accepted that these tumors originate from Merkel's cells. Some consider that they belong to the group of APUD-omas. Positive findings of epithelial (EMA, CAM 5.2) and neuroedocrine marker (NSE) in these three cases support the hypothesis of neuroendocrine differentiation in a neoplasm of epithelial origin.

Antigens, Neoplasm↗
PubMed1983

APUD system neoplasms in renal transplant patients.

Apudomas are uncommon neoplasms composed of neuroendocrine cells. They include carcinoid tumors, islet cell tumors, and small cell lung carcinoma. We found six cases of apudomas in a series of 1028 renal transplants from three medical centers (0.58%). One of these had been reported in 1976. The cases included a carcinoid tumor of a Meckel's diverticulum discovered and removed prior to transplantation, with no evidence of recurrence 9 years later. A small cell lung carcinoma was discovered 40 months after renal transplantation, with a fatal outcome 6 months later. Four clinically occult apudomas were found at autopsy, including one gastric and one bronchial carcinoid tumor, one multicentric pancreatic islet cell neoplasm, and one case of multiple ileal carcinoids. With the exception of the small cell lung cancer, none of the apudomas was clinically significant, and none was associated with carcinoid or other paraneoplastic syndrome. These cases illustrate the difficulty of diagnosis of apudomas in patients with renal failure and the usually benign nature of these tumors despite the administration of potent immunosuppressive agents.

Adenoma↗
PubMedDate not supplied

Duct-acinar-islet cell tumor of the pancreas.

Two cases of pancreatic tumor consisting of duct, acinar, and islet components are reported. Both tumors measured about 1.0 cm in diameter and were without definite fibrous encapsulation. Histologic, immunocytochemical, and electron microscopic studies revealed three distinct cell populations: duct, acinar, and islet cells. Both endocrine and exocrine components were seen within the same cell nest. Islet components predominated in both cases. Nearly all the cells in the islet component were positive for insulin. Few cells positive for glucagon, somatostatin, or pancreatic polypeptide were present within the tumor cell nests. Duct cells were the least conspicuous cellular element of the tumor; they were positive for mucin and immunoreactive for cytokeratin and carcinoembryonic antigens (CEA). The acinar component was the minor element of the tumor in both cases. Electron microscopic study also confirmed three different cell populations in the tumor: duct cells arranged in a ductal structure with intercellular attachments and microvilli, islet cells containing beta granules, and acinar cells with zymogen granules. The tumors presented herein indicate that both their endocrine and exocrine components might have been derived from a common precursor. The implication and significance of the differentiation of different cells within the same tumor is discussed in relation to the concept of an amine precursor uptake and decarboxylation (APUD) system.

Adenoma, Islet Cell↗