Gastrointestinal stromal tumor in a horse


Gastrointestinal stromal tumor in a horse

History: A 25 year-old intact female Quarterhorse with a chronic history of difficulty eating and weight loss.

Gross findings:

This horse has severe wavemouth, serous atrophy of fat, generalized muscle wasting, and ascites.

The liver contained a 0.5 cm x 0.5 cm firm, white, irregular, nodule. There were multiple 1-2 mm white foci throughout the liver.

At the ileo-cecal junction there was a 3 cm x 2 cm x 2 cm soft mass with irregular contours in the wall of the cecum which did not occlude the lumen. When incised it was mottled yellow to red.

Histopathology:

Ileo-cecal mass:   Within the tunica muscularis is an unencapsulated, highly cellular, well demarcated neoplasm of spindle cells arranged in bundles and streams in a scant fibrovascular stroma. Neoplastic cells have variably distinct cell borders, scanty eosinophilic cytoplasm and mild anisocytosis. Nuclei are oval and elongated with finely stippled chromatin and single nucleoli. There are multifocal areas of hemorrhage within the neoplasm, and multifocal lakes of pale basophilic mucinous fluid. At the periphery of the neoplasm there is marked hemorrhage with accumulations of large numbers of macrophages containing gloden brown granular pigment (hemosiderin).

Ileo-cecal junction: The muscular tunic contains a neoplasm of fusiform spindle cells with areas of hemorrhage and mucinous extracellular matieral

Ileo-cecal mass: At the edge of the mass there are large numbers of hemosiderophages. Within the mass are small lakes of mucinous material

Ileo-cecal mass: Neoplastic cells are arranged in bundles, streams and whorls, and have multifocal areas of hemorrhage

Ileo-cecal mass: Neoplastic cells with elongated nuclei and fusiform morphology

Liver:  the liver contains multifocal mineralized granulomas characterized by central zones of degenerate, degranulated, and intact eosinophils, and bright eosinophilic debris. This area is surrounded by a layer of epithelioid macrophages which have variable amounts of eosinophilic cytoplasm and are frequently vacuolated.  There are small numbers of spindle cells at the periphery interpreted as fibroblasts.  In the larger granulomas there central zones of mineralization of necrotic debris (dystrophic mineralization), and in the largest of these there is metaplastic bone formation with trabeculae of osteoid containing osteocytes within lacunae, and lined by osteoblasts, with small areas of hematopoietic bone marrow.

Liver: Multifocal areas of degranulated eosinophils and macrophages are randomly scattered in the hepatic parenchyma

Liver: Close up view of the eosinophilic granulomas with epithelioid macrophages, and individual eosinophils in the surrounding parenchyma

Diagnosis:

Ileocecal mass: Gastro-intestinal stroma tumor

Liver: Eosinophilic, granulomatous hepatitis with mineralization and multifocal osseous metaplasia

Comment:

The poor nutritional condition of this horse is probably directly related to the poor dentition, and abnormal tooth wear making mastication difficult.  The unchewed grain and hay in the GI tract is evidence of this.  The granulomas in the liver are probably the result of nematode migration, probably Strongylus edenatus.  These were also incidental findings. The neoplasm at the ileocecal junction is an incidental finding.

Gastro-intestinal stromal tumors are uncommon low grade malignant neoplasms thought to arise from the Interstitial Cells of Cajal (ICC).  These  are pacemaker cells found in the intestinal wall between the myenteric and submucosal plexuses. Tumors derived from these cells can resemble leiomyosarcomas, fibrosarcomas, or neurofibromas, or have an undifferentiated appearance.  Immunohistochemistry will generally stain positively with antibodies for vimentin, but only rare cases will stain for muscle actin, or S-100.  Interestingly these tumors did not stain for desmin which is a common intermediate filament in the cytoplasm of other tumors with muscle (smooth or striated) differentiation.  Since they are of low-grade malignancy they have frequent local invasion into the surrounding tissues, but rarely penetrate the submucosa or metastasize. In canines, 5/50 GIST were associated with clinical signs, and 6/50 had metastasized to the liver or abdominal cavity.  Location and morphology vary widely in dogs compared to horses. The cecum or ileo0cecal junction is common in horses, but in dogs they ranged from large intestine (48%), small intestine (29%), stomach (19%), and mesentery (5%).  52% of the tumors in dogs were positive for CD 117 (KIT). 33% were positive for smooth muscle actin, but none for desmin or S-100. In a separate study some tumors were also CD34 positive (cell-cell adhesion). The negative desmin staining was common to both equine and canine GISTs, and may be a useful diagnostic feature.  The negative S-100 staining in canine tumors may suggest that the etiopathogenesis is different, but at this point we dont have enough information to make that determination. In a single case report in an F344 rat, a GIST was smooth muscle actin positive, desmin negative, and had mild scant staining for KIT and S-100.

It is interesting that these tumors express cellular molecules common to hematopoietic stem cells.  KIT (CD117) is a hematopoiteic stem cell cytokine receptor that is activated by stem cell factor. CD34 is a cellular adhesion molecule that attaches stem cells to bone marrow stroma or other tissues.  Mast cell tumors also express KIT (CD117).  To my knowledge the Interstitial Cells of Cajal are not known to proliferate or migrate during the post-natal life of the animal, only during embryological development.

References:

Del Piero F, Summers BA, Cummings JF, Mandelli G, Blomme EA. Gastrointestinal stromal tumors in equids. Vet Pathol.2001 Nov;38(6):689-97.

Frost D, Lasota J, Miettinen M. Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic, immunohistochemical, and molecular genetic study of 50 cases. Vet Pathol. 2003 Jan;40(1):42-54.

Fujimoto H, Shibutani M, Kuroiwa K, Inoue K, Woo GH, U M, Hirose M. A case report of a spontaneous gastrointestinal stromal tumor (GIST) occurring in a F344 rat. Toxicol Pathol. 2006;34(2):164-7. PubMed PMID: 16537295.

Gillespie V, Baer K, Farrelly J, Craft D, Luong R. Canine Gastrointestinal Stromal Tumors: Immunohistochemical Expression of CD34 and Examination of Prognostic Indicators Including Proliferation Markers Ki67 and AgNOR. Vet Pathol. 2010 Sep 8. [Epub ahead of print] PubMed PMID: 20826846.

Hafner S, Harmon BG, King T. Gastrointestinal stromal tumors of the equine cecum. Vet Pathol. 2001 Mar;38(2):242-6. PubMed PMID: 11280386.

LaRock RG, Ginn PE. Immunohistochemical staining characteristics of canine gastrointestinal stromal tumors. Vet Pathol. 1997 Jul;34(4):303-11. PubMed PMID: 9240839.

Lorincz A, Redelman D, Horváth VJ, Bardsley MR, Chen H, Ordög T. Progenitors of interstitial cells of cajal in the postnatal murine stomach. Gastroenterology. 2008 Apr;134(4):1083-93. Epub 2008 Jan 18. PubMed PMID: 18395089; PubMed Central PMCID: PMC2435491.

Saturday GA, Lasota J, Frost D, Brasky KB, Hubbard G, Miettinen M. KIT-positive gastrointestinal stromal tumor in a 22-year-old male chimpanzee (Pan troglodites). Vet Pathol. 2005 May;42(3):362-5. PubMed PMID: 15872385.

Sommer G, Agosti V, Ehlers I, Rossi F, Corbacioglu S, Farkas J, Moore M, Manova K, Antonescu CR, Besmer P. Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6706-11. Epub 2003 May 16. PubMed PMID: 12754375; PubMed Central PMCID: PMC164511.

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About Brian

Anatomic Pathologist, VetPath Services, Stone Ridge, NY- musculoskeletal, oral/dental, and sinonasal diseases
This entry was posted in Necropsy Cases and tagged , , , , . Bookmark the permalink.

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