Update on Feline Gastrointestinal Neoplasia
Stanley L. Marks, BVSc, PhD, DACVIM (Internal Medicine, Oncology), DACVN
Associate Professor, University of California, Davis, School of Veterinary Medicine
Davis, CA, USA

Although gastrointestinal (GI) neoplasms account for approximately 2% of all canine and feline neoplasms, the clinical signs associated with GI neoplasms are essentially the same as those associated with inflammatory or obstructive diseases of these organs. The most common clinical signs are related to the "mass effect" of the tumor with clinical manifestations depending on the site of the tumor within the intestinal tract. Gastric tumors are typically associated with chronic vomiting, weight loss, and inappetence. Tumors of the duodenum, jejunum and ileum are associated with vomiting, diarrhea (melena) and weight loss, whereas tumors of the colon are associated with tenesmus and hematochezia. The clinical signs may result from metastatic lesions to the liver, spleen, mesenteric lymph nodes, and central nervous system producing signs such as icterus, abdominal hemorrhage, and seizures. Cats may present with pale mucous membranes and have microcytic anemia secondary to chronic blood loss. It is important to remember that not all nodular lesions of the gastrointestinal tract are neoplastic. Differentials include granulomas from inflammatory bowel disease, fungal infections, or foreign body penetration.

Gastrointestinal Lymphoma

Unlike the dog, feline gastric adenocarcinoma is rare, and the stomach is the least commonly affected gastrointestinal site in the cat. Lymphoma is the most common gastric tumor in the cat and may be solitary or one component of systemic involvement. Most cats with gastric lymphoma are negative for feline leukemia virus. Intestinal lymphoma has two morphologic forms; a diffuse type and a nodular type. Diffuse lymphoma is characterized by extensive infiltration of the lamina propria and submucosa with neoplastic lymphocytes that may cause malabsorption, steatorrhea, diarrhea, and weight loss. The nodular form causes a segmental thickening of the bowel, most often in the ileocolic region, with resultant luminal narrowing and partial intestinal obstruction. Metastasis to regional lymph nodes is common with both forms of the disease.

In a recent report of 39 cats with well differentiated gastrointestinal lymphoma, the most common clinical signs were vomiting (87%), weight loss (79%), anorexia (53%), diarrhea (53%), and lethargy (47%). Nine percent had neither vomiting nor diarrhea. An abdominal mass was palpated in 26% of cats while 32% had thickened gastrointestinal loops. Twenty-six cats were treated of which 23 received prednisone (5 mg BID) and chlorambucil (15 mg/M2 once daily for 4 consecutive days, repeated every 3 weeks). Fourteen (61%) achieved complete remission (CR). The disease free interval of those who achieved CR ranged from 5.75 to 24 months (median 15.5 months). The overall survival ranged from 0.33 to 25 months (median 12 months). There was no significant difference in disease free interval or survival due to age, sex, breed, palpable abdominal mass, retroviral status, localization of the tumor, or presence of hypoalbuminemia. Endoscopic biopsy was quite useful for obtaining a definitive diagnosis. The survival times in this study are better than those seen in cats with poorly differentiated gastrointestinal lymphoma treated with more complex and expensive protocols. Lymphoma is rarely confined to the stomach and is best treated with systemic chemotherapy. Responses of cats with gastrointestinal lymphoma to vincristine, cyclophosphamide, and prednisone are poor, with treated cats having a median survival time of less than 2 months.

A recent retrospective study of 21 cats with alimentary lymphoma treated with a more expensive multidrug protocol of prednisone, L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and methotrexate revealed an overall median duration of first remission of 20 weeks, and an overall median survival time of 40 weeks. The only factor significantly associated with duration of first remission was whether cats had a complete response following induction chemotherapy; duration of first remission was significantly associated with survival time. Cats tolerated treatment well; only 1 cat had a delay in the treatment schedule because of neutropenia. All cats were negative for FeLV and 3/19 cats were positive for FIV. Thirteen tumors were stage III, 7 were stage IV, and 1was stage V. Immunophenotyping was performed on 13 tumors; 10 were T-cell and 3 were B-cell lymphomas. This refutes the previous literature that states that almost all intestinal lymphomas are of B-cell origin.

Diagnosis

Abdominal palpation may reveal a large gastric mass (adenocarcinoma) or a diffusely thickened gastric wall (lymphoma). Plain abdominal radiographs and/or positive-contrast radiographs may reveal thickening of the gastric wall, absence of rugal folds, filling defects, or an intraluminal mass. Ultrasonographic examination of the abdominal cavity may reveal additional masses or metastases to the liver and spleen. The diagnosis is confirmed by means of a gastric biopsy procured either via endoscopy or during an exploratory laparotomy. Thoracic radiographs should be obtained to help stage the disease.

Treatment

Gastric lymphoma in cats is rarely confined to the stomach and is best treated with adjuvant systemic chemotherapy. Adjuvant chemotherapy (Table 1) is also recommended following surgical excision of a solitary lymphomatous mass.

Other Intestinal Neoplasms

Intestinal tumors occur most commonly in the rectum and colon of dogs and the small intestine of cats. Lymphoma is the most common small intestinal tumors of cats, and adenocarcinomas and mast cell tumors follow lymphoma in frequency. Adenocarcinomas are often found in the jejunum and ileum. Siamese cats are reported to have a higher frequency of small intestinal adenocarcinoma than other breeds. Mucosal ulceration is frequent and can result in melena and chronic blood loss anemia. In a recently published study evaluating malignant colonic neoplasms in 46 cats, the mean age of cats was 12.5 years (range, 6 to 18 years). Ultrasonography was useful 84% of the time in localizing the mass to the intestine. Histologic diagnosis included adenocarcinoma (21 cats), lymphoma (19), mast cell tumor (4), and neuroendocrine carcinoma (2). Other tumors affecting the intestinal tract include fibrosarcoma, undifferentiated sarcoma, leiomyomas/leiomyosarcomas, and plasmacytoma. Leiomyosarcomas of the intestine are the most common sarcoma and occur most often in the cecum and jejunum. These tumors are locally invasive malignant smooth muscle neoplasms that are slow to metastasize.

Behavior

The majority of intestinal neoplasms are malignant. Intestinal adenocarcinoma is usually in an advanced stage when diagnosed. Extension of the neoplasm beyond the bowel wall was found in 85% of dogs and 71% of cats at necropsy. The most common sites of metastases in the dog include the regional lymph nodes, liver, and lungs. In cats, the most common sites of metastases are abdominal serosa, lymph nodes, lung, and liver. Adenocarcinoma has been described as annular or intraluminal. Canine adenocarcinomas have been histologically classified into four groups that may overlap: acinar, solid, mucinous, and papillary. Papillary carcinomas tend to spread horizontally with few distant metastases. In contrast, acinar, solid, and mucinous adenocarcinomas tend to show more vertical growth and extend into bowel wall, serosa, and other organs. The clinical, gross, and morphologic types of feline intestinal adenocarcinoma are similar to that in dogs.

Primary intestinal mast cell neoplasia of the intestinal tract is the third most common feline intestinal tumor after lymphoma and adenocarcinoma. Intestinal mast cell tumors are less differentiated than cutaneous mast cell tumors. The small intestine is usually affected and lesions can be solitary or multiple, 1 to 7 cm diameter, firm segmental thickenings of the intestine. Most cats have a detectable intraabdominal mass identified by either palpation or radiographic examination. Peritoneal effusion, fever, and mild anemia may be noted. Cats frequently have concurrent hepatic and splenic involvement and peritoneal effusion can occur. Intestinal MCT is associated with widespread dissemination and carries a poor prognosis. Unlike splenic MCT's, intestinal MCT's are not associated with a peripheral mastocytosis. Metastases is common to mesenteric lymph nodes and the liver, followed by the spleen, lung, and bone marrow. Biopsy of a regional lymph node is recommended to document the presence or absence of metastatic disease. Because circulating mast cells may be observed in gastrointestinal disease, the significance of a positive buffy coat smear in this particular disease must be interpreted with caution. Most animals either die or are euthanized soon after diagnosis. If surgery is feasible, wide surgical margins, including 5 to 10 cm of normal bowel proximal and distal to the tumors are recommended. Ranitidine (1 to 2 mg/kg orally BID) should be administered following confirmation of the diagnosis of intestinal MCT. Corticosteroids should be withheld until 14 days post-surgery to ensure adequate healing of the enterectomy site.

Adenomatous polyps are benign pedunculated masses that arise from the mucosa and protrude into the lumen. Rectal polyps occur most commonly in the rectum and descending colon of dogs, whereas they occur most commonly in the small intestine of cats. Fifty percent of the reported feline cases of rectal polyps have been in cats of Asian ancestry.

Diagnosis

Physical examination may reveal an abdominal mass, thickened bowel loops, or mesenteric lymphadenopathy. Proctoscopy or colonoscopy should always be performed following digital rectal examination to identify additional tumors proximal to the rectum. Contrast radiographic studies, particularly enteroclysis, may reveal mucosal abnormalities or obstructive lesions. Ultrasonography is a valuable diagnostic tool and may reveal bowel thickening, localized ileus, or enlarged mesenteric lymph nodes. The most common abnormalities on the hemogram and serum biochemical profile are anemia and hypoproteinemia, and elevated serum hepatic enzyme concentrations.

Definitive diagnosis is usually made by intestinal biopsy via celiotomy or endoscopy. Caution must be exercised with diagnosing intestinal lymphoma via endoscopy. In some cats, the initial biopsy is interpreted as inflammatory bowel disease (lymphocytic-plasmacytic enteritis), and patients frequently show a favorable response to dietary modification and glucocorticoid therapy. These patients ultimately become refractory to therapy and necropsy reveals intestinal lymphoma. It is uncertain whether the initial lesion represented prelymphomatous change or whether it was erroneous because of sampling error.

Treatment

The most common treatment for solitary intestinal tumors is surgical resection with margins of at least 4 cm being strived for. Adjuvant chemotherapy for intestinal adenocarcinoma and leiomyosarcoma using adriamycin has been recommended although the efficacy of such treatment has not been reported in the cat. Intestinal lymphoma should be managed surgically if the tumor is associated with intestinal obstruction or perforation. Biopsies and impression smears for cytological evaluation should be performed on adjacent intestine, lymph nodes, spleen, and liver to clinically stage the disease. Diffuse intestinal lymphoma should be managed with systemic chemotherapy once the diagnosis has been confirmed. Cats with a malignant colonic mass may benefit from a subtotal colectomy.

Table 1. Chemotherapy Protocols for Cats with Gastrointestinal Lymphoma

Chlorambucil and Prednisone Protocol

Chlorambucil

2 mg (1 tablet per cat) PO every 3-4 days OR 15 mg/M2 once daily for 4 days given every 3 wks

Prednisone

5 mg BID for the rest of the cat's life

COAP Protocol

Cyclophosphamide

50 mg/m2 PO 4 days a week or every other day for 8 weeks

Vincristine

0.7 mg/m2 IV once a week for 8 weeks

Cytosine arabinoside

100 mg/m2 IV or SC BID for 4 days

Prednisone

5 mg BID for the rest of the cat's life

COP Protocol

Cyclophosphamide

50 mg/m2 PO 4 days a week or every other day for 8 weeks

Vincristine

0.7 mg/m2 IV once a week for 8 weeks

Prednisone

5 mg BID for the rest of the cat's life

Adriamycin Protocol

Adriamycin (doxorubicin)

20 mg/m2 IV every 3 weeks (do not exceed 240 mg/m2 total); or 1 mg/kg IV every 3 weeks

L-Asp-VCAP Protocol

L-asparaginase

10,000 IU/kg IP on day 1 of therapy

Vincristine

0.7 mg/m2 IV every week for 4 weeks, then every 3 weeks

Cyclophosphamide

250 mg/m2 PO on week 7, 13, 16, and 22 of therapy

Adriamycin

20 mg/m2 on week 10 and 19

Prednisone

5 mg BID for the rest of the cat's life

References

1.  Fondacaro JV, Richter KP, Carpenter JL, et al. Feline gastrointestinal well differentiated lymphocytic lymphoma: 39 cases. Abstract. Proceedings of the 17th annual ACVIM. Page 722, 1999.

2.  Zwahlen CH, Lucroy MD, Kraegel SA, Madewell BR. Results of chemotherapy for cats with alimentary malignant lymphoma: 21 cases (1993-1997). J Am Vet Med Assoc 15;213(8):1144-9, 1998.

3.  Birchard SJ, Couto CG, Johnson S. Nonlymphoid intestinal neoplasis in 32 dogs and 14 cats. J Am Anim Hosp Assoc 22:533-537, 1986.

4.  Brodey RS. Alimentary tract neoplasms in the cat: A clinicopathologic survey of 46 cases. Am J Vet Res 27:74-80, 1966.

5.  Turk MAM, Gallina AM, Russel TS. Nonhematopoeitic gastrointestinal neoplasia in cats. A retrospective study of 44 cases. Vet Pathol 18:614-620, 1981.

Speaker Information
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Stanley L. Marks, BVSc, PhD, DACVIM (IM, Oncology), DACVN
Associate Professor, University of California, Davis
School of Veterinary Medicine
Davis, CA, USA


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