Gastrointestinal Neoplasia in Small Animals
GI neoplasia is uncommon in dogs and cats, with gastric tumors representing <1% and intestinal tumors <10% of overall neoplasia in these species. GI neoplasms tend to be malignant. The average age of dogs with GI neoplasia is 6–9 yr and of cats 10–12 yr.
Specific etiologic agents for GI neoplasia have not been identified. The increased risk of Belgian Shepherds for gastric carcinoma, and of Siamese cats for intestinal adenocarcinoma and lymphoma may reflect genetic predispositions. Feline leukemia has been suggested to be an underlying factor in development of feline GI lymphoma, even in cats with a negative retroviral status. Helicobacter infections are associated with gastric neoplasia in people, but similar direct links have not been established in dogs or cats.
Adenocarcinomas are the most common GI neoplasia in dogs and are typically found in the duodenum, colon, and rectum. Gastric adenocarcinomas are common in dogs and frequently affect the lower ⅓ of the stomach (eg, lesser curvature and pyloric region). Adenocarcinoma is commonly identified in the feline intestinal tract, especially in the jejunum and ileum. Adenocarcinomas are very aggressive and frequently metastasize to regional lymph nodes, liver, and lung. At the time of diagnosis in dogs, as many as 44% of intestinal and as many as 95% of gastric adenocarcinomas have metastasized. Adenomas and carcinomas in situ are uncommonly found in the GI tract of dogs or cats. These polyp-like masses are usually solitary and located in the colon or rectum in dogs.
Lymphoma is the most common feline GI neoplasia, and it is also common in dogs. GI lymphoma most commonly affects the small intestine as well as extra-gastrointestinal organs such as the liver. Two subtypes of feline GI lymphoma have been reported: a low-grade, small-cell lymphocytic lymphoma and a more aggressive, poorly differentiated, large-cell, lymphoblastic lymphoma. Canine GI lymphoma is usually poorly differentiated and aggressive, similar to lymphoblastic lymphoma in cats.
GI stromal tumors (GISTs) are mesenchymal in origin in dogs; they are rarely seen in cats. One of the major diagnostic criteria for GISTs include positive c-kit (CD117) reaction on immunohistochemistry. Before the recognition of GISTs, many of these tumors were likely classified as leiomyosarcomas. GISTs typically are found in the cecum and large intestine. In contrast, leiomyosarcomas are most common in the stomach and small intestine. The metastatic rate is as high as 30% with leiomyosarcomas and likely lower with GISTs. Uncommon GI tumors of dogs and cats include mast cell tumors, leiomyomas and leiomyosarcomas, fibrosarcomas, and plasmacytomas.
Clinical signs of GI neoplasia depend on the location and extent of the tumor and its possible metastases or paraneoplastic syndromes (eg, hypercalcemia, hypoglycemia). The most common clinical signs associated with GI neoplasia include vomiting (with or without blood), anorexia, weight loss, diarrhea, and lethargy. Signs of constipation or tenesmus may accompany colonic and rectal tumors. An abdominal mass or organomegaly may be palpable on physical examination. Abdominal pain and ascites may reflect peritonitis secondary to a ruptured portion of neoplastic bowel.
Routine laboratory studies and plain radiographs do not show specific changes associated with GI neoplasia. Hypoglycemia is often associated with leiomyomas/leiomyosarcomas. Hypercholesterolemia and increased alkaline phosphatase activity has been seen in some nonlymphomatous neoplasia. Microcytic anemia with or without hypoproteinemia is a common finding with ulcerated masses and chronic blood loss. Electrolyte and acid-base disturbances may reflect ongoing vomiting and can include hypochloremia, hypokalemia, and metabolic alkalosis or acidosis. Paraneoplastic hypercalcemia has been associated with lymphoma and intestinal adenocarcinoma.
Contrast abdominal radiographs may reveal mass lesions in the GI tract or areas of ulceration. Abdominal ultrasonography may reveal focal or diffuse thickening of the GI tract and loss of normal layering. Regional lymph nodes may be enlarged, and splenomegaly and/or hepatomegaly may accompany some cases of GI lymphoma. Ultrasound can facilitate fine-needle aspirates or needle biopsy sample collection for cytologic or histologic analysis.
Endoscopy of the upper and lower GI tract can facilitate identification and partial-thickness biopsy of GI neoplasia. However, endoscopic biopsy collection is limited by the small size and superficial nature of the biopsy, because some GI tumors are submucosal and this technique may only collect superficial mucosa. A false diagnosis of gastritis or enteritis may reflect inflammation of the mucosa overlying a neoplastic process. In one study, endoscopic biopsies were adequate to detect feline gastric lymphoma but not adequate to differentiate inflammatory bowel disease from lymphoma in the GI tract. Recent studies suggest that endoscopic ileal biopsies aid in the diagnosis of lymphoma and other GI diseases, compared with endoscopic duodenal biopsies. Full-thickness surgical biopsies collected via laparoscopy or laparotomy may more suitably establish a diagnosis and will allow for biopsy of regional lymph nodes and liver to evaluate for metastasis. Immunohistochemistry may be required to differentiate between types of neoplasia for GI biopsies. PCR for antigen receptor rearrangement detects clonality of a population of lymphocytes and can aid in the diagnosis of GI lymphoma when performed on inconclusive biopsy sections, especially in cats.
Surgical excision of the tumor is recommended for nonmetastatic, nonlymphomatous neoplasia. Curative resection, with margins of ≥4 cm, should be attempted.
The median survival time for GI adenocarcinoma in dogs is 10–15 mo if the tumor was focal and completely resected but only 3 mo if metastasis is present at diagnosis. Adjuvant chemotherapy (eg, carboplatin) may be prescribed; optimized chemotherapy protocols for treatment of GI adenocarcinoma have not been reported. GI lymphoma is typically treated with chemotherapy. Phenotypic variations of feline GI lymphoma warrant different treatment strategies.
Small-cell (well-differentiated, low-grade) lymphoma is treated with prednisone (2 mg/kg/day, PO) and chlorambucil (either 2 mg PO every other day or 15 mg/m2 daily for 4 days, every 3 wk). The prognosis associated with small-cell GI lymphoma is good, with a median survival time of 765 days. Poorly differentiated GI lymphoma in dogs and cats is poorly responsive to chemotherapy. If treatment is attempted, a multidrug chemotherapy protocol (eg, Wisconsin-Madison) is recommended, but complete remission rates are low, and median survival times are usually <3 mo. Focal lymphoma may be surgically excised, and follow-up chemotherapy may be recommended. GISTs and leiomyosarcomas are slow-growing and slow to metastasize. In a study of dogs with a diagnosis of either leiomyosarcoma or GIST, median survival time was 37 mo after complete resection, although another report suggests that GISTs are associated with a better survival rate than leiomyosarcomas. Malignant GI neoplasia usually has a poor prognosis (survival <6 mo), even with surgical and medical therapy. Benign lesions, such as leiomyomas and colorectal adenomas, have a good prognosis with surgical excision.