11-year-old spayed female Japanese domestic, Felis cattus.
2008.3.25 This cat showed diarrhea lasting for one month and gradual weight loss for one year from 4.82kg to 3.76kg. Diarrhea disappeared immediately after general treatment with an anti-diarrheal drug.
2008.5.12 Repeated vomiting appeared from recent two weeks with complete loss of appetite. A mass lesion was found in the abdominal cavity by X-ray examination and echography.
2008.5.13 Intestinal obstruction was confirmed in the small intestine by barium contrast study.
2008.5.14 The mass was surgically removed. The enlargement of the mesenteric lymph node was observed during a laparotomy.
The affected part of the small intestine was a mass lesion and consisted of severely thickened intestine wall with narrowing of the lumen.
Lymphoid cells proliferated throughout the entire intestinal wall from the mucosa to the serosa and resulted in severe thickening of intestinal wall. Numerous lymphoid follicles of varying size were formed in the muscular and serosal layer among the severely infiltrated tumor cells. Some follicles had clear germinal centers and incomplete mantle zones. The tumor cells other than follicle-forming cells had small to medium-sized nuclei that are round to irregularly indented and a have thick nuclear membrane. The nuclei had dense chromatin with multiple small distinct nucleoli (or with a small distinct nucleolus). The cytoplasm was pale and abundant. Mitotic figures were observed at rate of 7 cells per 10 high power fields. Small number of eosinophils infiltrated among the tumor cells and fibrous stroma was slightly increased in some areas with proliferated tumor cell.
Immunohistochemically, the majority of tumor cells were positive for CD3 and TIA-1, negative for CD79a and CD20. In the muscular layer where the lymph follicles formed, many cells forming the follicles were positive for CD79a and CD20 and negative for CD3 and TIA-1, whereas a few cells of germinal center were positive for CD3 and TIA-1.
Based on immunohistochemical findings, tumor cells have a T-cell phenotype in this lymphoma but lymph follicles formed in the tumor mass consisted of B-cells.
Small intestine: Malignant lymphoma, T cell lymphoma.
Fine needle biopsy findings: Comparatively uniform lymphoblast-like cells were observed on the smear from needle biopsy of the mesenteric lymph node.
Hematopoietic tumors (lymphoma and mast cell tumors) are the most common type of neoplasia in the feline intestine.(7) In alimentary lymphoma, the tumors are usually of the B-cell origin, with few being T-cell origin.(4,7,11,15) B-cell lymphoma arises from the germinal center of the gut, MALT, and drainage lymph nodes.(6,7) In contrast, T-cell type of multicentric lymphoma proliferates from the paracortical area,(6,7) and T-cell lymphoma of the intestine usually involves the lamina propria with epitheliotropism to the mucosal epithelium.(2,8,15)
The present case was characterized by formation of lymph follicles in the mass of tumoral proliferation. These lymph follicles were not original lymphoid tissue, because they were formed in muscular and serosal layers where there is no lymphatic tissue in the normal condition. In addition, this lymphoma had a T-cell phenotype and the follicles were composed of B-cell phenotype. Therefore, it was likely that lymphoid follicles were formed due to the reactive response to tumor cells or immunologic stimuli by the altered environment resulting in proliferation of tumor cells. The neoplastic cell proliferation forming lymph follicles was similar to lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in morphologic growth pattern. MALT lymphoma and marginal zone lymphoma are B-cell lymphoma,(14) and the tumor cells encircle follicles outside the mantle cell layer in these types of lymphoma. Cytologically, T-cell lymphoma consists of smaller cells with low mitotic rate as in the present case. However, MALT lymphoma is usually composed of small lymphocytes with indented nuclei, or there may be a more mixed pattern with some larger lymphoid cells similar to the centrocytes and centroblasts of benign germinal centers.(14)
Intestinal T-cell lymphoma is characterized also by epitheliotropism of tumor cells.(2,8,15) Neoplastic lymphocytes usually are small round cells that resemble mature lymphocytes. However, epitheliotropism was not seen in the tumor cells of the present case. In a report of canine intestinal T-cell lymphoma, approximately 25% did not show epitheliotropic behavior.(14) In addition, in humans, MALT lymphoma usually forms lymphoepithelial lesions and tumor cells invade between mucosal epithelium. Lymphoepithelial lesions resemble epitheliotropism, but are characterized by centrocyte-like cell invasion and destruction of the epithelium. Therefore, epitheliotropism is not specific for T-cell lymphocytes and formation of lymph follicles is also not specific for B-cells.
Intestine, ileum: Lymphoma, intermediate size, low grade, transmural.
The cellular morphology and epitheliotropic behavior presented in the small intestine of a cat is distinctive for T-cell lymphoma (TCL). Intestinal lymphomas can be further classified as mucosal or transmural based on depth of invasion. Epitheliotropism can occur in both types, and occurs most commonly in the villous epithelium. Mucosal T-cell lymphoma closely matches the WHO entity enteropathy-associated T-cell lymphoma (EATCL) type II. Transmural T-cell lymphomas more often can lead to intestinal obstruction and perforation and closely match the WHO entity EATCL type I.(9)
The most common presentation of lymphoma in cats has evolved as the success of FIV/FeLV testing and vaccination programs have been realized. In the 1970s, 70% of feline lymphoma cases in the U.S. were attributed to FeLV infection which dropped to less than 15% twenty years later.(1) Interestingly, as the prevalence of these known oncogenic viruses have diminished, the incidence rate of lymphoma in cats appears to be increasing.(1,9) Retroviral-associated lymphomas commonly presented as mediastinal or multicentric forms in young cats.(3,12) The majority of lymphomas in cats now occur in the gastrointestinal tract.(9) Recent literature has also described a shift in prevalence from B-cell to T-cell lymphomas in intestinal lymphoma in cats.(9,12) Diffuse large B-cell lymphomas are considered most common in the stomach of cats.(9) Other subclassifications of significance in cats include large granular lymphocyte lymphoma which also occurs in the intestinal tract but often with more systemic involvement and is associated with a poor prognosis. T-cell rich large B-cell lymphoma is an indolent type with a mixed cell population to include bizarre giant or multinucleated cells and typically presents in a single lymph node.(3)
Conference participants were interested in the unique histologic presentation of lymphoma in this case, with the formation of multiple lymphoid follicles dispersed throughout all levels of the muscularis mucosa. Theories regarding their formation were exchanged, including immune stimulation by antigens or toxin absorption through the disrupted mucosal epithelium.
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