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Can Vet J. 2010 May; 51(5): 522–524.
PMCID: PMC2857434

Language: English | French

Primary epitheliotropic intestinal T-cell lymphoma as a cause of diarrhea in a horse

Abstract

A 25-year-old Appaloosa gelding was evaluated for chronic weight loss and diarrhea. A clinical diagnosis of protein loosing enteropathy was made and the gelding was euthanized. Histology revealed neoplastic lymphocytes infiltrating the mucosa of the small and large intestine. Immunohistochemistry was positive for CD3, consistent with epitheliotropic T-cell lymphoma.

Résumé

Lymphome T intestinal épithéliotrope primaire comme cause de diarrhée chez un cheval. Un hongre appaloosa âgé de 25 ans a été évalué pour perte de poids et diarrhée chronique. Un diagnostic clinique d’entéropathie avec perte de protéine a été posé et le hongre a dû être euthanasié. L’histologie a révélé des lymphocytes néoplasiques infiltrant les muqueuses des petit et gros intestins. L’immunochimie a été positive pour CD3, qui est conforme à un lymphome T épithéliotrope.

(Traduit par Isabelle Vallières)

A 25-year-old Appaloosa gelding was examined for evaluation of weight loss of 2 mo duration and diarrhea of 1 wk duration. The gelding, which had been owned by the current owner for 8 y, was dewormed with Ivermectin and was vaccinated against eastern and western equine encephalitis, tetanus, influenza, and equine herpesvirus 30 d prior to presentation. The gelding was housed with 20 other horses in a large pen and a total of 40 horses were kept on the farm. None of the other horses were affected.

Case description

Upon arrival at the hospital, the horse had a temperature of 38°C (100.5°F), a heart rate of 50 beats per min, and a respiratory rate of 20 breaths per min. Body condition score was 3/10. Mucous membranes were pale pink and moist with a capillary refill time of < 2 s. Auscultation of the gastrointestinal tract, lungs, and heart revealed no abnormalities, and dental examination was unremarkable. Severe watery diarrhea was observed at presentation and persisted throughout hospitalization. Appetite and water intake were normal at presentation. Rectal examination revealed no abnormalities other than a firm smooth mass, approximately 8 to10 cm in diameter on the left ventral aspect of the abdomen. The mass seemed freely movable, did not compromise any other structures, and was not painful to palpation.

Blood analysis revealed hyperfibrinogenemia (7 mmol/L; reference range: 1 to 4 mmol/L), consistent with the presence of inflammation. Hypoproteinemia was characterized by hypoalbuminemia of 19 g/L (reference range: 26 to 39 g/L) and hypoglobulinemia of 20 g/L (reference range: 26 to 41 g/L). These were presumably the result of gastrointestinal protein loss. Mild increases in blood urea nitrogen (9.3 mmol/L; reference range: 3.9 to 8.9 mmol/L) and creatinine (176.8 μmol/L; reference range: 61.9 to 150.3 μmol/L) concentrations were consistent with mild dehydration. Serum electrolyte analysis revealed hypocalcemia (2.2 mmol/L; reference range: 2.6 to 3.2 mmol/L), hyponatremia (133 mmol/L; reference range: 135 to 141 mmol/L) and hypokalemia (2.0 mmol/L; reference range: 3.2–4.5 mmol/L). Hypocalcemia is consistent with hypoalbuminemia and decreased protein bound calcium. The other electroyte abnormalities were attributed to intestinal loss into the diarrheic feces. On subsequent evaluation of the serum chemistry the blood urea nitrogen and creatinine, calcium, and potassium concentration values were normal. The hypoproteinemia remained unchanged throughout hospitalization.

Abdominocentesis and urinalysis were unremarkable. The feces was negative for presence of sand and parasite ova. Fecal culture did not yield Clostridium perfringens, Clostridium difficile, or Salmonella spp. Clostridial toxin analysis was negative. Abdominal ultrasound examination was unremarkable. Abdominal radiographs revealed a small amount of sand in the cranial ventral colon. This finding was thought to be of no clinical significance.

The gelding’s condition worsened after a few days of hospitalization with a decrease in appetite and development of cool, nonpainful, pitting edema of the ventral abdomen. Forty milligrams of dexamethasone were administered intravenously and no changes in clinical signs were noted. Due to deterioration in the horse’s condition, the inconclusive clinical test results, and the age of the horse, further diagnostic tests were declined and humane euthanasia was requested by the owner.

Gross necropsy revealed severe muscle wasting with minimal subcutaneous and visceral fat, consistent with the history of chronic weight loss. A nonstrangulating lipoma was identified as the smooth, freely movable mass that had been palpable on rectal palpation. The contents of the entire intestinal tract were watery. The small intestinal mucosa and wall appeared grossly normal. All sections of the large colon had multiple, widely spaced, chronic mucosal ulcerations that were irregular and varied in size from 5 mm to 4 cm × 1 cm. The adjacent mucosal epithelium was rounded indicating fibrosis and epithelial hyperplasia. No ulcers or other abnormalities were observed in the cecum.

Histopathologic examination revealed severe infiltrative lesions present throughout all sections of the small and large intestine. The lamina propria was greatly expanded by a mixed cellular infiltrate (Figure 1). The cells often infiltrated the luminal and crypt epithelium (Figure 2) but rarely extended into the submucosa. The predominant cells were lymphocytes with scant cytoplasm and dense, occasionally cerebrate nuclei (Figure 3). Mitoses were not identified. Fewer plasma cells were present among the small intestinal infiltrate and eosinophils were mixed among the cell population in the colon. Peyer’s patches were mildly hyperplastic but otherwise normal. Ulcerated areas of the colon had cellular infiltration into the submucosa, including hemosiderin-laden macrophages. The stomach was unaffected and the duodenum was mildly affected. Other tissues examined microscopically appeared normal.

Figure 1
Low power photomicrograph of a section of intestine from a 25-year-old Appaloosa gelding with severe diarrhea. A uniform population of lymphocytes diffusely infiltrated epithelium and submucosa, with rare extension into the submucosa. Hematoxylin & ...
Figure 2
Neoplastic lymphocytes infiltrated the luminal and crypt epithelium. Hematoxylin and eosin. Bar = 50 μm.
Figure 3
Neoplastic cells were lymphocytes with scant cytoplasm and dense, often convoluted (cerebrate) nuclei. Mitoses were not identified. Hematoxylin and eosin. Bar = 20 μm.

As the mixed cellular infiltrate was suggestive of inflammatory bowel disease, but the epitheliotropism of the infiltrate suggested neoplasia, immunohistochemistry was performed. Immunohistochemical staining revealed lymphocytes that were positive for CD3 (Figure 4), a T-cell marker, consistent with a diagnosis of epitheliotropic T-cell lymphoma affecting both small and large bowel. The cells did not form a discrete mass; however, the cellular features and extensive infiltration of the mucosa supported a diagnosis of neoplasia.

Figure 4
Immunohistochemistry revealed that neoplastic cells were T-lymphocytes. Biotin-avidin immunoperoxidase stain with anti-CD3 antibody and toluidine blue counterstain. Antigen is black. Bar = 20 μm.

Discussion

An uncommon case of epitheliotropic T-cell lymphoma of the small intestine and large colon is presented. Epitheliotropic T-cell lymphoma is a distinct clinicopathologic condition, described as an unusual form of lymphoma that usually affects the small intestine. Clinical signs are associated with weight loss, anorexia, and hypoproteinemia (13) in animals and with malabsorptive syndrome in humans (4).

The term “epitheliotropism” in alimentary lymphoma refers to the characteristic homing of neoplastic T cells to the mucosal epithelium of the intestinal tract (1). This form of malignant lymphoma has been reported previously in 1 horse with chronic weight loss and protein losing enteropathy but no diarrhea (5). In a study of alimentary lymphoma in cats, only 3 out of 32 cases were classified as epitheliotropic T-cell lymphomas (6). Carreras et al (1) reported 10 cases of epitheliotropic intestinal lymphoma in cats. They all had involvement of the mucosa and lamina propia, 5 cases had neoplastic cells in the submucosa and also in the muscularis of the small intestine. The mesenteric adipose tissue was affected in only 2 cats; however, adipose tissue was only evaluated in patients that underwent full thickness biopsy (n = 4) (1). Involvement of the lamina propria and mucosa of the small intestine and the stomach without involvement of the deeper layers has been previously reported in dogs with epitheliotropic lymphoma (2,3). Similar to the epitheliotropic gastrointestinal tract lymphoma reported in other species, neoplastic lymphocytes in this case were T-cell lineage, demonstrated epitheliotropism, did not form a primary mass and were associated with severe ulceration of the mucosa of both, the small and the large intestine.

The classic alimentary form of lymphosarcoma usually affects the lymphoid tissue associated with the small intestine in horses as well as other species (13,511). Mucosal ulceration of the stomach and proximal duodenum (3,5,12) and ileum (8) have been previously reported. Various degrees of intestinal wall infiltration have been reported; from diffuse mucosal (6,8,13) to transmural intestinal thickening (7,8,12,14,15). The intestinal, splenic and hepatic lymph nodes are not commonly involved (16). Immunophenotypically, classic alimentary lymphoma is commonly composed of a heterogeneous cell population (B- and T-lymphocytes) in the horse (9,11) and in other species (6). In a study of 31 classic lymphoma cases in horses, only 6 had neoplastic lymphocytes that were T-cell in origin (9). A separate retrospective study of 37 horses with lymphoma described 26 tumors of T-cell origin and only 7 of B-cell origin (11). Most tumors classified as T-cell origin were associated with large mediastinal masses.

Chronic weight loss from malabsorption, decrease in appetite, intermittent colic, and fever are the most common clinical signs of classic alimentary lymphoma in most species (7,11,12,16). There is usually some peripheral neutrophilia with signs of toxemia due to ulceration of the intestinal mucosa (9,12). Anemia may be mild or quite severe (1,7,8,12) and hypoproteinemia is often present (3,9,12). Altered stool character may be noted, but profuse diarrhea is not common (12,16). One case of diarrhea due to classic alimentary lymphoma affecting the large colon of a horse has been reported (8) but no further cellular classification of the tumor was performed. Mitsui et al reported chronic diarrhea, hypoproteinemia and weight loss in a mare with T-cell lymphoma; however, there was no epitheliotropism observed in association with the tumor cells (13). To the author’s knowledge there is no other report of an epitheliotrophic T-cell lymphoma causing diarrhea in a horse.

Most horses with classic alimentary lymphoma die or are euthanized for humane reasons within 6 months of the onset of the clinical signs. In humans and other species including horses, T-cell epitheliotropic lymphoma warrants a poor prognosis (2,3,5,9,13,14). CVJ

Footnotes

Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ( gro.vmca-amvc@nothguorbh) for additional copies or permission to use this material elsewhere.

References

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Articles from The Canadian Veterinary Journal are provided here courtesy of Canadian Veterinary Medical Association