vasoactive-intestinal-peptide and Paraganglioma

As sensitive radioimmunoassays for the detection of polypeptide hormones are developed, the exciting discovery of a diffusely distributed system of interrelated endocrine cells has begun a new era of endocrinology. This system, although anatomically disassociated, is bound together by a number of common features such as its biosynthetic mechanism, histochemical and ultrastructural features, and embryologic origin (Table I). The most prominent feature, however, is their biosynthetic pathways for hormone production, from which the acronym APUD has been derived. These are the capacity for Amine Precursor Uptake such as DOPA and then subsequent Decarboxylation, resulting in the synthesis of bioactive amines or polypeptide hormones. Hyperplasias or neoplasms of these cells are defined as apudomas. In the last ten years a great deal of research has rapidly altered the original concepts of this system, especially in terms of its embryologic origin, physiologic interrelationships, classification, as well as the addition of many new APUD cell members. These will be reviewed, and the origin, diagnosis, and treatment of each recognized apudoma will be synthesized in light of its membership within the APUD system.

Topics: Adenoma, Islet Cell; APUD Cells; Apudoma; Carcinoid Tumor; Carcinoma; Endocrine Glands; Humans; Neural Crest; Neuroblastoma; Paraganglioma; Pheochromocytoma; Pituitary Neoplasms; Somatostatin; Thyroid Neoplasms; Vasoactive Intestinal Peptide

Gangliocytic paraganglioma (GP) is a rare neoplasm described almost exclusively in the gastrointestinal tract, especially the periampullary region. However, several examples have been reported at various sites, including the stomach, jejunum, and appendix. Herein we report a case of GP involving the nasopharynx. To our knowledge, this is the first report of GP at this site. A 44-year-old woman presented with headaches and symptoms of fullness and pressure related to mass effect. An initial endoscopic biopsy was followed by surgical excision of the nasopharyngeal mass. The triphasic tumor fulfilled the morphologic and immunohistochemical criteria for GP. The histogenesis of GP is uncertain, and the current belief is that it arises from the embryonic ventral pancreas. This concept is based largely on the location of most cases, which is along the embryologic migration route of the ventral pancreas, as well as the expression of pancreatic polypeptide by the tumor. The nasopharyngeal location of our case clearly refutes the pancreatic origin of GP. We propose that the tumor probably arises from totipotential adult stem cells, which in the right microenvironment differentiate along nonnative cell lineages.

Topics: Adult; Biopsy; Chromogranins; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Nasopharyngeal Neoplasms; Paraganglioma; S100 Proteins; Synaptophysin; Tissue Embedding; Vasoactive Intestinal Peptide

Paraffin-embedded sections of 99 human adrenal and extraadrenal paragangliomas were analyzed by the indirect immunoperoxidase technique for the presence of neuron-specific enolase (NSE) and 10 neuropeptides. Each showed diffuse staining for NSE. Most tumors were positive for [Leu5]-enkephalin (76 per cent), [Met5]-enkephalin (75 per cent), somatostatin (67 per cent), and pancreatic polypeptide (51 per cent), followed by vasoactive intestinal polypeptide (VIP) (43 per cent), substance P (31 per cent), ACTH (28 per cent), calcitonin (23 per cent), bombesin (15 per cent), and neurotensin (12 per cent). The neuropeptides paralleled to a large extent those normally found in the sympathetic nervous system. Clinically malignant paragangliomas (n = 25) with proven regional or distant metastases expressed considerably fewer neuropeptides, although the spectrum of those seen remained similar. Malignant paragangliomas contained an average of two neuropeptides per tumor, in contrast to five for the benign tumors (P less than 0.05). Logistic regression analysis of staining results revealed that the paucity of enkephalins, somatostatin, pancreatic polypeptide, and VIP along with the patient's sex was predictive of clinical malignancy. Our results show a definite relationship between expression of neuropeptides and the biologic behavior of these paragangliomas.

Topics: Adolescent; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Adult; Aged; Bombesin; Calcitonin; Child; Enkephalins; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neuropeptides; Neurotensin; Pancreatic Polypeptide; Paraganglioma; Paraganglioma, Extra-Adrenal; Phosphopyruvate Hydratase; Somatostatin; Substance P; Vasoactive Intestinal Peptide

A case of gangliocytic paraganglioma of the duodenum is reported, including light microscopic, ultrastructural, and immunohistochemical characteristics. The cytologic appearance, as might be seen in fine-needle aspiration smears, indicates a neoplasm with three cellular components (epithelioid, ganglion, and spindle cells) seen histologically by light and electron microscopy.

Topics: Duodenal Neoplasms; Female; Humans; Immunohistochemistry; Microscopy, Electron; Middle Aged; Paraganglioma; Vasoactive Intestinal Peptide

Paraganglionic tumors of the larynx are uncommon neoplasms and their secretory products have rarely been elucidated. We saw two patients whose laryngeal paragangliomas were examined with an electron microscope and by the use of immunocytochemical techniques. Both tumors manifested positive immunoreactivity against calcitonin and vasoactive intestinal polypeptide. One of the paragangliomas was immunoreactive against carcinoembryonic antigen and pursued a biologically malignant course. Our observations suggest the coexistence of amines and hormonal polypeptides in cells of paraganglionic tumors and demonstrate the multihormonal nature of these tumors.

Topics: Aged; Calcitonin; Carcinoembryonic Antigen; Female; Humans; Laryngeal Neoplasms; Male; Middle Aged; Paraganglioma; Vasoactive Intestinal Peptide

The chief cells of paraganglionic tissues have morphological and functional similarities to adrenal chromaffin cells, and both cell types are derived from the neural crest. In the present investigation cells from two glomus jugulare paragangliomas were studied in culture. Approximately 50% of the cells from one tumor, and 7% from the other spontaneously formed neurite-like processes. Numerous granular and agranular synaptic-like vesicles also appeared in the process-forming cells. In contrast to findings with normal and neoplastic adrenal chromaffin cells, addition of nerve growth factor (NGF) to the culture medium had no major effects on proportion of cells with processes. Dexamethasone caused only a small decrease in process length. Culturing of the tumors also appeared to promote production of material with VIP-like immunoreactivity. It is concluded that the phenotype of paraganglioma as well as pheochromocytoma cells may be altered in vitro. Responsiveness to specific factors such as NGF or steroids, however, may vary for related tumor cell types in different anatomic locations.

Topics: Axons; Cells, Cultured; Cytoplasmic Granules; Dexamethasone; Female; Gastrointestinal Hormones; Glomus Jugulare; Humans; Middle Aged; Nerve Growth Factors; Organoids; Paraganglia, Nonchromaffin; Paraganglioma; Synaptic Vesicles; Vasoactive Intestinal Peptide

Topics: Achlorhydria; APUD Cells; Apudoma; Carcinoid Tumor; Carcinoma; Cholecystokinin; Diarrhea; Endocrine System Diseases; Humans; Hypokalemia; Malignant Carcinoid Syndrome; Neoplasms; Pancreatic Diseases; Paraganglioma; Paraneoplastic Endocrine Syndromes; Peptides; Prostaglandins E; Somatostatin; Syndrome; Thyroid Neoplasms; Vasoactive Intestinal Peptide