JPC SYSTEMIC PATHOLOGY
SIGNALMENT (JPC #2017861): 8-year-old male Irish setter
HISTORY: This dog had a well-vascularized, deep orange-brown mass at the ileocecal junction.
HISTOPATHOLOGIC DESCRIPTION: Ileocecal junction: Multifocally infiltrating the submucosa and muscular tunics and extending to cut margins is an unencapsulated, poorly circumscribed, 1.5 x 2.5 cm, multilobular neoplasm composed of polygonal cells arranged in cords, nests, packets, and more solidly cellular areas separated by variably thick, fibrovascular septa. Neoplastic cells have indistinct cell borders, moderate amounts of eosinophilic finely granular cytoplasm, round-to-oval nuclei that are vesiculate or contain coarsely clumped chromatin, and one variably distinct nucleolus. Mitoses average 1 per 10 HPF. Multifocally, neoplastic cells infiltrate the muscular tunics and are located within numerous vessels. Within the submucosa are low numbers of lymphocytes and hemosiderin-laden macrophages, and lymphatics are multifocally ectatic (edema). There are multifocal areas with hemorrhage, clear acicular clefts (cholesterol clefts) and single cell necrosis.
MORPHOLOGIC DIAGNOSIS: Ileocecal junction: Carcinoid, Irish setter, canine.
SYNONYM: Neuroendocrine carcinoma
- Carcinoids are uncommon neoplasms that arise from endocrine or paraendocrine cells in a variety of organs (gastrointestinal tract, urogenital tract, nasal cavity, tracheobronchial tree, liver and pancreas) and histologically closely resemble carcinomas of intestinal epithelial origin but have a different histogenesis
- Gastrointestinal carcinoids are rare in domestic animals; most are reported in aged dogs; they are rare in cats, cows, and horses, and very rare in other species
- Hepatic carcinoids occur in the extrahepatic and intrahepatic biliary system
- Generally considered malignant, slow growing neoplasms that metastasize similar to adenocarcinomas, via lymphatics and hematogenous routes
- May secrete vasoactive amines, including serotonin, kallikrein, insulin, gastrin, substance P, bombesin, and calcitonin
- Excessive amines usually cause no functional derangements in domestic animals
- Carcinoids that secrete gastrin (G cell tumors) are responsible for Zollinger-Ellison syndrome (gastric hypersecretion, ulcers, and diarrhea) and have been reported in cats and dogs; these are usually non-beta cell tumors of pancreatic origin rather than gastrointestinal tumors
TYPICAL CLINICAL FINDINGS:
- Intestinal obstruction, hemorrhagic diarrhea, abdominal pain, emaciation, anemia, thrombocytopenia
- Zollinger-Ellison syndrome (gastric hypersecretion, ulcers and diarrhea) from a non-beta cell tumor of pancreatic origin
- Horses: Nonspecific, chronic colic; if the nasal and maxillary sinus or retrobulbar space is involved, can see epistaxis and exophthalmos
- Cattle: Bloating, diarrhea, and weight loss
TYPICAL GROSS FINDINGS:
- Tan-yellow tumors that range from annular stenosing thickenings to nodular masses in the intestinal wall
- Rectal carcinoids may protrude from the anus
- Large tumors can cause submucosal or subserosal nodule formation and ulceration of the overlying mucosa
- There may be extensive invasion of the gut wall and vasculature
- Dogs: Primarily reported in duodenum, colon, and rectum, but also occasionally in the stomach and liver; reported in the gallbladder of 3 dogs
- Metastasis occurs to liver, spleen, kidney, lungs, regional lymph nodes, and brain
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Typical neuroendocrine appearance: Polygonal cells arranged in nests, cords, ribbons, rosettes, or diffuse sheets; small, uniform, round-to-oval cells separated by thin fibrous trabeculae or vascular channels
- May form a pseudoalveolar arrangement or palisade along stroma
- Variable distribution of mitotic figures, necrosis or mineralization
- Occasional multinucleate giant cells
- +/- Amyloid in intercellular and perivascular spaces (especially canine rectal carcinoids); amyloid is derived from polypeptides of prohormones secreted by the neoplastic cells
- May have extensive invasion of gut wall and veins with metastasis
- Numerous membrane-bound neurosecretory granules
- Plasma membrane with interdigitating processes
- Cells contain abundant rough endoplasmic reticulum
ADDITIONAL DIAGNOSTIC TESTS:
- Diagnosis is confirmed by affinity of tumor cells for silver stains, immunohistochemistry and ultrastructural examination
- Argentaffinic: Modified Fontana-Masson
- Argyrophilic: Churukian-Shenk, Grimelius
- Many carcinoids are positive with both argentaffin and argyrophilic procedures
- Positive immunohistochemistry for cytokeratin 13, synaptophysin, protein gene product 9.5, neuron-specific enolase, chromogranin A, calcitonin gene-related polypeptide, serotonin, and Leu-7
- Negative immunohistochemistry for S-100, GFAP, vasoactive intestinal peptide, galanin, methionine-enkephalin, vimentin, alpha-smooth muscle actin, somatostatin, glucagon, and gastrin
- Serum serotonin levels may be elevated
For histologic findings:
- Lymphoma: CD3 or CD79a positive
- Carcinoma: Cytokeratin positive
- Intestinal mast cell tumor: Mainly aged cats, rare in dogs; eosinophils, metachromatic granules evident with Giemsa and/or toludine blue stains
- Plasma cell tumor: +/- CD 79a, light chain positive
- Pheochromocytoma: Ultrastructurally, norepinephrine (eccentrically placed electron dense core surrounded by a wide submembranous space) or epinephrine (coarsely granular internal core and a narrow submembranous space) granules
- Adenomatous polyp (for rectal carcinoid)
- African rodent (Praomys (Mastomys) natalensis): Extremely high incidence of spontaneous gastric carcinoids (up to 50% of aged animals); animal model
- Horses: Several reports of nasal and maxillary sinus and retrobulbar carcinoids; locally malignant and expansile, with destruction of bony structures causing exophthalmos or epistaxis
- Cats: Rare
- Cattle: One recent report in an adult Holstein cow (rectal carcinoid)
- Sprague-Dawley rat, cynomolgus monkey: One report each
- Humans: “Carcinoid syndrome” is due to release of vasoactive amines resulting in flushing, diarrhea, bronchospasm, valvular heart lesions, and edema
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