Color Atlas: Feline Gastrointestinal Tumors

By Patty Ewing, DVM, MS, DACVP (Anatomic and Clinical Pathology)
angell.org/pathology
pathology@angell.org
617-541-5014

April 2024

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Introduction

Cytologic evaluation of gastrointestinal (GI) neoplasia is commonly utilized, given the widespread use of abdominal ultrasound (AUS) in both general and specialty veterinary practices. AUS allows for identifying solitary or multiple masses, which can often be sampled via fine-needle aspiration (FNA) for cytologic evaluation. In a retrospective study that evaluated the diagnostic value of cytologic examination of GI tumors in dogs and cats, there was partial or complete agreement between cytologic and histologic diagnosis for 48 of 67 (71.6%) fine needle aspirates.¹ This degree of agreement warrants using FNA for obtaining a preliminary diagnosis, especially when the owner has financial concerns or an unstable patient condition, which makes surgically obtaining a biopsy sample less desirable. Cytologic evaluation may also be helpful for surgical planning. Although ultrasound-guided FNA is less invasive and does not carry the risk associated with general anesthesia required for endoscopic and surgical biopsy, the procedure is not entirely without risk. Local hemorrhage, risk of tumor cell seeding, and leakage of intestinal content are possible complications associated with needle penetration of the GI tract. FNA should be avoided in patients with <50,000/ul platelet counts or other significant coagulopathy. Intestinal content leakage, a life-threatening complication, and tumor cell seeding can be minimized with careful selection of the needle insertion site, using a 22 gauge or smaller needle, and avoiding multiple needle insertions into the mass.^2,3 This article will review the cytologic features of the three most common types of feline GI tumors seen at Angell Animal Medical Center.

Lymphoma

Lymphoma is the most common tumor type of the feline GI tract. GI lymphoma can occur as primary GI lymphoma or, less commonly, as a component of multicentric disease. An association with feline leukemia virus (FeLV) in GI lymphoma is typically not observed. Feline GI lymphoma occurs most commonly in the small intestine, followed by the stomach, and infrequently in the large intestine. T-cell lymphoma is more common in the small intestine, and B-cell lymphoma is more common in the stomach and large intestine.⁴ The three distinct morphologic presentations of feline GI lymphoma include 1) mucosal T-cell lymphoma (enteropathy-associated T-cell lymphoma or EATL type II), which appears well-differentiated, small to intermediate size; 2) large cell lymphoma (gastric B cell lymphoma or transmural T-cell lymphoma also known as EATL type 1); large, immature cells with visible nucleoli, and 3) large granular lymphocyte (LGL) lymphoma (aka granulated lymphoma). Granular lymphoma is likely of cytotoxic T cell or natural killer cell origin. LGL lymphoma is the least common of the three morphologic types. It may exhibit an aggressive clinical course with concurrent involvement of mesenteric lymph nodes, peripheral blood, abdominal effusion, and liver. In one retrospective study, cats with LGL lymphoma who received chemotherapy had a median survival time of only 57 days.⁵ Cytologic appearance of large cell lymphoma and LGL lymphoma are shown in Figures 1 and 2, respectively. The author has found it nearly impossible to definitively differentiate EATL type II and lymphocyte-predominant inflammatory bowel disease (IBD) based on cytology alone. Thus, histopathology +/- immunohistochemistry and PCR for antigen receptor rearrangement (PARR) are recommended for diagnosis.

Figure 1. Cytologic appearance of large cell gastric lymphoma. Left: Lymphoma cells (black arrows) are intermediate to large, singly occurring round cells with a high nuclear:cytoplasmic ratio (N:C). Nuclei have dispersed chromatin, one or more large, round nucleoli, and a small amount of basophilic cytoplasm. A perinuclear clear zone is evident in most cells. Yellow arrows identify non-neoplastic small lymphocytes for size comparison. (Diff-Quik, 600x magnification.) Right: Large lymphoma cells show typical nuclear features of lymphoma, but the addition of small cytoplasmic vacuoles (clear spaces) is found in some cases of feline large-cell lymphoma. (Diff-Quik, 1000x magnification.)

Figure 2. Cytologic appearance of intestinal granular lymphoma. Left: Lymphoma cells are intermediate to large in size and have a high N:C, large round to oval nucleus, and smudged chromatin without distinct nucleoli. The basophilic cytoplasm has several magenta granules. The yellow arrow identifies a bizarre mitotic figure. (Diff-Quik, 600x magnification.) Right. Higher magnification shows a cluster of irregularly shaped magenta granules of variable size at one pole of the cytoplasm (yellow-green arrow). These round cells may be mistaken for mast cells if not carefully evaluated. The granular lymphoma cell magenta granules are round to irregular and of variable size compared to the fine metachromatic granules of uniform size evenly distributed throughout the cytoplasm of mast cells (Figure 5). Neutrophils and extracellular bacterial rods suggest ulceration of the overlying mucosa. (Diff-Quik, 750x magnification.)

Carcinoma

Adenocarcinoma is the second most common tumor type of the feline GI tract. Carcinomas are found more commonly in the feline intestine than in the stomach.⁶ Intestinal adenocarcinomas may be intraluminal or intramural and present as plaque-like lesions or masses often ulcerated. Annular or circumferential intramural lesions may lead to stenosis. Obtaining a diagnostic aspirate of carcinoma can be challenging due to necrosis, septic inflammation associated with ulceration, or the scirrhous connective tissue response that occurs with neoplastic infiltration of the intestinal wall. Cytologic findings include cohesive aggregates of epithelial cells exhibiting cytologic atypia (Figure 3, left panel), often with concurrent findings of mucus and inflammation that may be septic if the mass is ulcerated. Because benign epithelial tumors such as polyps/adenomas can exhibit considerable atypia, especially when inflamed. Likewise, some carcinomas may lack marked cytologic atypia (Figure 3, right panel), so the cytologic distinction between benign and malignant tumors must be made cautiously. For these reasons, histopathology may be required for definitive diagnosis. At the time of carcinoma diagnosis, metastasis to regional intra-abdominal lymph nodes or seeding of the peritoneum (carcinomatosis) has often already occurred.

Figure 3. Cytologic appearance of intestinal carcinoma. Left (small intestine carcinoma). Note a large cluster of carcinoma cells in a background of neutrophilic inflammation. Cells exhibit marked pleomorphism. They have large oval to irregular nuclei with large angular nucleoli and basophilic cytoplasm with cytoplasmic vacuoles. (Diff-Quik, 600x magnification.) Right (colonic carcinoma). Note the cohesive aggregate of neoplastic epithelial cells exhibiting less pleomorphism than the cells shown in the left panel. Smudgy pale blue mucus is present in the background (yellow arrows). Carcinoma diagnosis was confirmed via histopathology. (Diff-Quik, 500x magnification.)

Mast Cell Tumor

Gastrointestinal mast cell tumors generally occur as distinct extramural masses and are more common in the intestine than in cats’ stomachs.⁷ They arise from mucosal mast cells rather than connective tissue mast cells and thus are typically less well-granulated (Figure 4). Cytologically, they appear differently from other feline mast cell tumors, including visceral mast cell neoplasia (Figure 5). Special stains, including Giemsa and toluidine blue, may help identify metachromatic granules in some but not all feline intestinal mast cell tumors (Figure 4, right panel). Even immunohistochemistry with mast cell marker c-kit may not be positive in all feline intestinal mast cell tumors, which emphasizes the importance of cytopathology in identifying minimal granulation or the distinctive appearance. A variant of mast cell tumor in cats, referred to as feline sclerosing mast cell tumor, can have similar appearing poorly granulated mast cells with the addition of plump spindle cells, abundant collagen-type matrix, and numerous eosinophils. This variant of mast cell tumor can be challenging to differentiate from the entity known as feline eosinophilic sclerosing fibroplasia, and the distinction remains controversial.⁸

Figure 4. Cytologic appearance of intestinal mast cell tumor. Left (aspirate of small intestinal mast cell tumor). Note mast cells (black arrows) have a central or paracentral small oval dark nucleus with indistinct nucleoli and abundant pale cytoplasm with numerous minute vacuoles (location of non-staining granules). The yellow arrow identifies an eosinophil. (Diff-Quik, 600x magnification.) Right (histopathology of small intestinal mast cell tumor stained with toluidine blue to highlight granules). A special stain highlights fine purple granules in the cytoplasm of neoplastic mast cells. (Toluidine blue, 1000x magnification.)

Figure 5. Cytologic appearance of visceral mast cell tumor in the spleen (left) and liver (right). Note that on the left panel, neoplastic mast cells (black arrows) have more stainable granules than the distinctive intestinal mast cell tumor shown in Figure 3. The yellow arrows identify an aggregate of hepatocytes among the mast cells. (Diff-Quik, 600x magnification.)

Summary

Cytologic evaluation of GI masses sampled via ultrasound-guided FNA may be useful in obtaining a presumptive or definitive diagnosis of neoplasia. This method is less expensive and invasive than obtaining samples surgically but does not always obtain sufficient numbers of cells for diagnosis. The risk of hemorrhage and intestinal content leakage can be minimized if appropriate precautions are taken. At the MSPCA-Angell, cytologic evaluation has helped obtain a presumptive or definitive diagnosis of the following common types of feline GI neoplasia if sufficient cellular samples are obtained:  lymphoma, carcinoma, and mast cell tumor.

 References

1. Bonfanti U et al. Diagnostic value of cytologic examination of gastrointestinal tract tumors in dogs and cats: 83 cases (2001-2004). J Am Vet Med Assoc 2006 Oct 1;229(7):1130-3.
2. Penninck D and d’Anjou M. Altlas of Small Animal Ultrasonography, 2^nd Publisher:  John Wiley and Sons, 2015, p. 306.
3. Shymalak K et al. Risk of tumor cell seeding through biopsy and aspiration cytology. J Int Soc Prev Community Dent 2014 Jan-Apr 4(1):5-11.
4. Pohlman LM, et al.: Immunophenotypic and histologic classification of 50 cases of feline gastrointestinal lymphoma. Vet Pathol 46:259, 2009.
5. Krick EL, et al.: Description of clinical and pathologic findings, treatment and outcome of feline large granular lymphocyte lymphoma (1996-2004), Vet Comp Oncol 6:102, 2008.
6. Rissetto K, et al.: Recent trends in feline intestinal neoplasia: an epidemiologic study of 1,129 cases in the veterinary medical database from 1964-2004. J Am Anim Hosp Assoc 47:28-36, 2011.
7. Head KW, et al. Histologic classification of the tumors of the alimentary system of domestic animals. Series 2, Armed Forces Institute of Pathology, Washington, DC, 2003.
8. Halsey CHC, et al.: Feline intestinal sclerosing mast cell tumor: 50 cases (1997-2008). Vet Comp Oncol 8:72, 2010.