History

A 10-year-old 7.8-kg castrated male Maine Coon cat was referred to the Veterinary Hospital at North Carolina State University because of a 5-month duration of vomiting, lethargy, hyporexia, and weight loss that was refractory to approximately 4 months of supportive care and treatment with an anti-inflammatory prescription of prednisolone (0.64 mg/kg, PO, q 12 h) for presumptive inflammatory bowel disease. The presumptive diagnosis was made by the primary veterinarian on the basis of the aforementioned clinical signs and results of a diagnostic workup that revealed mild proteinuria (+2), mild azotemia (BUN concentration, 24 mg/dL [reference range, 15 to 34 mg/dL]; creatinine concentration, 2.0 mg/dL [reference range, 0.7 to 1.8 mg/dL]) with a prerenal component (albumin concentration, 4.5 g/dL [reference range, 3.1 to 4.5 g/dL]; sodium concentration, 164 mEq/L [reference range, 149 to 157 mEq/L]), and hypokalemia (2.8 mEq/L; reference range, 3.7 to 5.1 mmol/L). Abdominal radiography had revealed marked gastric distention.

Clinical and Gross Findings

On physical examination, the cat was in good body condition, moderately dehydrated, reluctant to walk, and profoundly lethargic with dull mentation. A CBC and serum biochemical profile were performed and showed mild azotemia (BUN, 66 mg/dL [reference range, 15 to 34 mg/dL]; creatinine, 1.9 mg/dL [reference range, 0.7 to 1.8 mg/dL]), hypokalemia (3 mmol/L; reference range, 3.7 to 5.1 mmol/L), and a moderate hypochloremic metabolic alkalosis (bicarbonate concentration, 28 mmol/L; reference range, 15 to 23 mmol/L). Abdominal ultrasonography revealed circumferential jejunal wall thickening causing secondary mechanical obstruction and marked gastric dilation. Surgical resection of the mass was considered; however, euthanasia was elected.

Gross postmortem examination revealed a poorly demarcated, circumferential expansion of the mid jejunum by a 1.5-cm-wide X 4.5-cm-long mass. The mass caused severe narrowing of the intestinal lumen with near-complete luminal obstruction (Figure 1) and subsequent orad gas distension. On cut surface, the mass caused loss of normal intestinal wall layering and was mottled white to tan to gray, partially translucent, and gelatinous. The mesenteric lymph nodes were moderately enlarged, measuring up to 1.0 X 1.5 X 2.0 cm. The liver had a diffusely enhanced reticular pattern. Both renal pelvises were markedly roughened and gritty on cut surface.

Postmortem photograph of a transverse cut section of the mid jejunum of a 10-year-old castrated male Maine Coon cat with a history of vomiting, lethargy, hyporexia, and weight loss. There is poorly demarcated, circumferential thickening of the mid jejunum by a gelatinous to firm, mottled tan to gray intestinal wall mass (asterisk) causing narrowing of the intestinal lumen with near-complete luminal obstruction (arrow).

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.05.0244

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Postmortem photograph of a transverse cut section of the mid jejunum of a 10-year-old castrated male Maine Coon cat with a history of vomiting, lethargy, hyporexia, and weight loss. There is poorly demarcated, circumferential thickening of the mid jejunum by a gelatinous to firm, mottled tan to gray intestinal wall mass (asterisk) causing narrowing of the intestinal lumen with near-complete luminal obstruction (arrow).

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.05.0244

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Postmortem photograph of a transverse cut section of the mid jejunum of a 10-year-old castrated male Maine Coon cat with a history of vomiting, lethargy, hyporexia, and weight loss. There is poorly demarcated, circumferential thickening of the mid jejunum by a gelatinous to firm, mottled tan to gray intestinal wall mass (asterisk) causing narrowing of the intestinal lumen with near-complete luminal obstruction (arrow).

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.05.0244

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Formulate differential diagnoses, then continue reading.

Cytologic and Histopathologic Findings

Cytologic examination of postmortem touch impressions of the jejunal mass revealed a moderately cellular pleomorphic population of individualized vacuolated cells with anisocytosis and multiple prominent nucleoli, consistent with a round-cell neoplasm (Figure 2). Multiple tissue samples from the gastrointestinal tract, mesenteric lymph nodes, lungs, heart, liver, kidneys, and spleen were collected; fixed in neutral-buffered 10% formalin; and routinely processed for histologic examination. Histologically, the jejunal wall was effaced transmurally and expanded by a poorly demarcated, densely cellular neoplasm composed of round cells arranged in cords and sheets. Neoplastic cells had distinct cell borders, a mild to moderate amount of pale eosinophilic cytoplasm with poorly staining granules, and a round nucleus with finely stippled chromatin. Anisocytosis and anisokaryosis were mild; 2 mitotic figures were observed in 10 high-magnification fields (2.37 mm²). Toluidine blue staining (pH, 2.5) highlighted metachromatic granules within the neoplastic population. Scattered among the neoplastic cells were numerous eosinophils and fewer lymphocytes and plasma cells. Minimal acute hemorrhage, mild edema, occasional individual necrotic or apoptotic neoplastic cells, and fibrin exudate were present. The medullary sinuses of the mesenteric lymph nodes had moderate numbers of eosinophils. Approximately 50% of hepatocytes contained variably sized lipid-type vacuoles. The renal tubules rarely contained intraluminal basophilic granular material (mineral).

Postmortem photomicrographs of an impression smear (A) and tissue section (B) of the jejunal wall mass described in Figure 1. A—The cell population is moderately pleomorphic and individualized, with few intracytoplasmic granules. Modified Romanowsky stain; bar = 10 µm. B—The jejunal wall has been replaced by sheets of poorly granulated neoplastic mast cells. H&E stain; bar = 20 µm. Inset—The intracytoplasmic metachromatic granules are highlighted. Toluidine blue stain, pH 2.5; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.05.0244

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Postmortem photomicrographs of an impression smear (A) and tissue section (B) of the jejunal wall mass described in Figure 1. A—The cell population is moderately pleomorphic and individualized, with few intracytoplasmic granules. Modified Romanowsky stain; bar = 10 µm. B—The jejunal wall has been replaced by sheets of poorly granulated neoplastic mast cells. H&E stain; bar = 20 µm. Inset—The intracytoplasmic metachromatic granules are highlighted. Toluidine blue stain, pH 2.5; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.05.0244

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Postmortem photomicrographs of an impression smear (A) and tissue section (B) of the jejunal wall mass described in Figure 1. A—The cell population is moderately pleomorphic and individualized, with few intracytoplasmic granules. Modified Romanowsky stain; bar = 10 µm. B—The jejunal wall has been replaced by sheets of poorly granulated neoplastic mast cells. H&E stain; bar = 20 µm. Inset—The intracytoplasmic metachromatic granules are highlighted. Toluidine blue stain, pH 2.5; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.05.0244

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: transmural jejunal mast cell tumor (MST) in a cat.

Comments

The gross and microscopic findings confirmed a diagnosis of transmural jejunal MST. Mast cells originate from the bone marrow from CD34+ hematopoietic cells.¹ They function in promoting inflammatory and allergic responses and can be found in various organs such as skin, the gastrointestinal tract, and the lungs.¹ MCTs in the cat typically present as 1 of 3 entities: cutaneous, visceral (eg, spleen, liver, bone marrow/blood), and gastrointestinal, as in this case.¹ MCTs are the third most common primary intestinal neoplasm in cats, predominantly occurring in the small intestine,² and accounting for approximately 5% of all tumors at this site.³ Affected cats are usually 11 to 15 years old,³ but can be as young as 7 years old,⁴ with a mean age of 12.9 years,⁵ without breed or sex predisposition.^1,3,4 In contrast to the cutaneous form, feline intestinal MCT is often locally aggressive and has a relatively high metastatic rate.^1,2,6,7 Studies have been attempted to develop grading systems by using KIT mutation analysis as a prognostic marker, but different neoplastic nodules within the same patient can have different c-KIT (CD117) mutations. No correlation between c-KIT mutations, tumor biologic behavior, or survival time in cats has been reported to date.^1,4

Common clinical manifestations of intestinal MCT include anorexia, diarrhea, vomiting, and weight loss; occasionally, an abdominal mass can be detected on palpation.⁵ Metastasis to mesenteric lymph nodes or surrounding organs such as the liver, spleen, and, rarely, the lungs can occur.⁵ Complete staging including CBC with blood smear review, biochemical panel, bone marrow aspirate, thoracic radiography, and abdominal ultrasonography should be performed.⁸ Ultrasonography alone is not a sensitive diagnostic tool to detect metastasis; therefore, fine-needle aspirates and cytology of commonly affected organs, such as the spleen, liver, and regional lymph nodes, should be considered regardless of their ultrasonographic appearance.²

The diagnosis can be made via microscopic examination of fine-needle aspirates or biopsies of the affected gastrointestinal tract; special stains and immunohistochemistry can help in reaching the diagnosis.^1,5,7 Differential diagnoses should include other gastrointestinal neoplasms such as lymphomas (large granular lymphocytic lymphoma and T-cell lymphoma), adenocarcinomas, carcinoids, gastrointestinal stromal tumors,⁷ leiomyomas or leiomyosarcomas,² and non-neoplastic disease such as eosinophilic inflammatory bowel disease.^1,5 Special stains such as toluidine blue and Giemsa can assist in identifying metachromatic granules within the neoplastic cell population; however, the absence of these granules, as seen in cases of anaplastic mast cells or degranulation, does not exclude intestinal MCT.¹ Positive immunolabeling anti c-KIT (membranous, focal paranuclear, and diffuse cytoplasmic patterns)⁴ is only seen in a third of the cases.⁷

Feline intestinal MCT masses can be intraluminal, intramural, diffuse, solitary, or nodular.^1,4 A distinct form of intestinal MCT was also described as neoplastic cells being polygonal to spindle with fewer cytoplasmic granules.⁹ Given the presence of mast cells and stromal collagen, a sclerosing MCT variant and feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF) were initially considered in this case.^10–12 FGESF, also known as scirrhous eosinophilic gastritis, should also be considered as a differential diagnosis based on the similarities to the clinical signs of chronic vomiting and weight loss, and the histomorphology.^13,14 Masses associated with FGESF are typically firm and nonpainful on palpation, and are commonly located at the pylorus, ileocecocolic junction, and colon. On ultrasonography, FGESF can have mural thickening and loss of wall layering in the stomach, duodenum, jejunum, and colon with mixed echogenicity and hyperechoic regions; however, FGESF cannot be diagnosed based solely on results of ultrasonographic examination because of the similarities to the ultrasonographic appearance of neoplasia.¹⁵ Non-neoplastic mast cells of FGESF can be numerous; however, they are widely dispersed and embedded into dense collagen that can be often sclerotic.¹³

Patients with intestinal MCT often have advanced disease at the time of diagnosis, and treatment can be difficult. Affected cats with visceral MCT should stay on medical management with histamine blockade for a lifetime period.⁸ If surgical resection of the affected intestinal tract is to be performed, the recommended surgical margins are 5 to 10 cm, which, after formalin fixation, ideally results in margins of at least 4 cm in the oral and aboral directions.⁶ Survival times can vary. Historically, the prognosis has been considered grave, with reports describing a survival period of less than 2 to 4 months.^1,10 Cats treated with a variety of therapies, including surgical resection, chemotherapy, and/or glucocorticoids, have reported longer than expected survival times of 531 days⁵ and 538 days.⁴ Survival times exceeding 1 year have been reported in cats treated with glucocorticoids only or no treatment at all.^4,5 Systemic chemotherapy is commonly recommended because of the high metastatic rate and frequency of advanced stage or nonresectable disease at presentation. Feline MCTs that contain c-KIT mutations have been reported to be responsive to tyrosine-kinase inhibitor treatment such as toceranib phosphate.^1,16