Gastrointestinal Neoplasia in Dogs and Cats

In dogs, adenocarcinoma is the most common gastric and large intestinal neoplasm, whereas lymphoma occurs more frequently in the small intestine, followed by adenocarcinoma and sarcomas such as GI stromal tumor (GIST) and leiomyosarcoma. Other reported canine and feline GI neoplasms include carcinoid, adenoma, leiomyoma, fibrosarcoma, carcinoma in situ, and plasmacytoma.

In dogs, adenocarcinomas frequently affect the lower third of the stomach (eg, lesser curvature and pyloric region) and rectum. Gastric and small intestinal adenocarcinomas frequently metastasize to regional lymph nodes, liver, and lung. At the time of diagnosis, up to 77% of intestinal and up to 32% of gastric adenocarcinomas have metastasized (1).

GI lymphoma most commonly affects the small intestine as well as extra-GI organs such as the liver. Canine GI lymphoma is mostly a high-grade variant with rapid clinical progression. Colorectal lymphomas are predominantly B-cell immunophenotype (> 90–92%) (2, 3), whereas other canine GI lymphomas are more commonly T-cell immunophenotype.

Small cell, low-grade GI lymphoma, a slowly progressive indolent lymphoma, occurs less commonly in dogs but can be clinically well managed. Differentiation between high- and low-grade lymphoma requires histological and, potentially, immunohistochemical analysis, such as assessment of cellular size, mitotic index, and Ki-67 staining.

Transition of low-grade GI lymphoma into high-grade lymphoma occurs in approximately 10% of dogs.

GISTs originate from interstitial cells of Cajal, pacemaker cells that generate electrical waves in GI smooth muscles. Key diagnostic criteria for GIST are strong Kit (CD117) expression and low to absent alpha smooth muscle actin (alpha-SMA) reactivity on immunohistochemical testing.

Before the recognition of GIST, many of these tumors were likely classified as leiomyosarcomas, hence the true incidence of leiomyosarcoma may be lower than previously reported. GISTs typically occur in the cecum and large intestine. In contrast, leiomyosarcomas occur most commonly in the stomach and small intestine. Overall, GIST and leiomyosarcoma grow slowly and are slow to metastasize, with a reported metastatic rate of up to 30% in dogs. For canine GIST, c-Kit mutations are present in exon 11 most frequently (60–70%).

In cats, lymphoma is the most common GI neoplasm, followed by adenocarcinoma and mast cell tumor. Both low-grade and high-grade GI lymphomas are frequently reported, and their clinical behaviors are well characterized in cats. Low-grade GI lymphomas are mostly mucosal and T-cell immunophenotype, commonly affecting the small intestines. Small intestinal high-grade lymphoma, however, can be either T-cell or B-cell in origin. 

Adenocarcinoma is commonly identified in the feline intestinal tract, especially in the jejunum and ileum, but rarely in the stomach or large intestines. Feline adenocarcinomas are also biologically aggressive, with a high metastatic rate. Metastasis commonly occurs to regional lymph nodes (up to 52%) and lungs (up to 20%), while local invasion into the serosa is present in 85% of cases, with or without carcinomatosis (4).

Routine laboratory studies do not show specific changes associated with GI neoplasia. Abnormalities can include the following:

• Hypoglycemia may occur with leiomyomas and leiomyosarcomas due to paraneoplastic insulin-like growth factor secretion or with sepsis secondary to rupture of an intestinal mass.

• Hypercholesterolemia and increased alkaline phosphatase activity have been observed with some cases of 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.

• Azotemia may occur secondary to small intestinal hemorrhage or dehydration.

• Paraneoplastic hypercalcemia has been associated with T-cell lymphoma.

Plain radiographs do not show specific changes associated with GI neoplasia. Radiographic findings may include loss of serosal detail and, rarely, an abdominal mass effect. The radiographic impression of gastric wall thickening must be interpreted with caution because ingesta, gastric fluid, or other gastric contents can create this appearance. 

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 wall and loss of normal layering. Regional lymph nodes may be enlarged, and splenomegaly and/or hepatomegaly may accompany some cases of GI lymphoma.

Though ultrasonographically abnormal findings may suggest the presence of neoplasia, normal appearance does not rule them out, especially for the stomach. In a study of 22 gastric neoplasms in dogs and cats, abnormalities were detected in only 50% of cases with ultrasonography but in 95% with endoscopy (5).

Ultrasonography can facilitate fine-needle aspiration or needle biopsy sample collection for cytological or histological analysis. Aspirated samples are also suitable for flow cytometric immunophenotyping for lymphomas.

Abdominal CT and colonoscopy help to visualize large intestinal lesions within the pelvic cavity that are not evaluable either by ultrasonographic or digital rectal examination. Abdominal CT can also assist in distinguishing tumor types presurgically in dogs with small intestinal masses. A 2023 study described unique growth and contrast enhancement patterns with adenocarcinoma, lymphoma, and spindle cell sarcoma (6), although histological assessment remains essential for definitive diagnosis.

Though not commonly reported for canine and feline GI neoplasms, pulmonary metastasis may be revealed by thoracic imaging with 3-view radiography or CT. These staging tests are important for assessment of prognosis, especially when surgery is being considered.

Endoscopy of the 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; some GI tumors are submucosal, and this technique can collect only superficial mucosa. In one study, endoscopic biopsy samples successfully diagnosed feline gastric lymphoma in some, but in others, they were misdiagnosed as inflammatory bowel disease when compared to full thickness surgical biopsy samples (7). Compared with duodenal biopsies, endoscopic ileal biopsies may have higher yield in the diagnosis of feline lymphoma and other GI diseases.

Full-thickness surgical biopsies collected via laparoscopy or laparotomy may more suitably establish a diagnosis and will allow for concurrent biopsy of regional lymph nodes and liver to evaluate for metastasis.

In addition to histological evaluation, immunohistochemical testing of GI biopsies may be required to differentiate between types of neoplasia.

PCR for antigen receptor rearrangement (PARR) detects clonally rearranged antigen receptor genes by amplification of conserved gene segments. PARR can aid in the diagnosis of GI lymphoma when performed on inconclusive biopsy sections.

Although the sensitivity and specificity of PARR in the diagnosis of lymphoma can reach 60–90% in dogs and cats, aberrant lymphocyte antigen expression and clonal rearrangements occur in inflammatory diseases as well. Therefore, PARR results require careful interpretation, incorporating clinical, histological, and immunohistochemical assessments.

The prognosis for dogs with GI adenocarcinoma varies depending on tumor location:

• Dogs with gastric adenocarcinoma have a poor prognosis. In a 2019 study of 40 dogs with gastric adenocarcinoma, only 34 patients (85%) survived to discharge from the hospital, and the median survival time of those that were discharged was 6 months after surgery (8).

• Median survival time for canine small intestinal adenocarcinoma is reported as 4–18 months, with a 1-year survival rate of 40–60%.

• On the other hand, dogs with colorectal adenocarcinoma typically have a favorable prognosis, with a median survival time of 2–4 years after surgery.

Effective chemotherapy for treatment of GI adenocarcinoma has not been established. Use of adjuvant carboplatin, doxorubicin, and gemcitabine has been reported, although efficacy is unknown.

In contrast to that of canine carcinoma, the prognosis for feline GI adenocarcinoma is poor, regardless of tumor location. For cats that survived to discharge after surgery, reported mean survival times range from 5–15 months for small intestinal carcinomas and from 4.5–9 months for large intestinal carcinomas with or without adjuvant chemotherapy. The prognosis for cats with small intestinal carcinoma with high mitotic activity is particularly poor.

Dogs with GIST or leiomyosarcoma without gross metastasis tend to have a long remission time if the tumor is surgically resectable. In a study of leiomyosarcoma and GIST, overall median survival time was 42 months after complete resection with no difference in outcome between the diagnoses.

For cases with nonresectable or aggressive GIST, molecular targeted treatment such as tyrosine kinase inhibitors may be effective by specifically targeting aberrantly expressed Kit. A 2018 retrospective study documented measurable tumor response in 4 of 7 dogs with GIST that were treated with toceranib phosphate, a multikinase inhibitor targeting Kit and other receptors, with a median progression-free interval of 26 months (9).

High-grade large to intermediate cell size lymphoma responds to chemotherapy favorably, with a reported remission rate of up to 80% in general. 

If treatment is attempted, a multidrug chemotherapy protocol (eg, Wisconsin-Madison) may be more effective than single-agent protocols. However, the clinical responses are not durable in the majority of cases, with median survival time of 2–3 months in both dogs and cats. Canine large intestinal lymphoma is an exception, with reported median survival times of 5.5–6 years after systemic chemotherapy with or without surgical resection of the tumor.

Focal lymphomas can be surgically excised; however, adjuvant chemotherapy should still be recommended for high-grade lymphomas due to their malignant behavior in both dogs and cats. With combination of surgery and adjuvant CHOP-based chemotherapy, a 2017 retrospective study of 20 cats with a solitary GI high-grade lymphoma reported a median survival time of 14 months (10).

Small cell (well-differentiated, low-grade) lymphoma is treated with steroids and alkylating agents. Commonly used protocols include prednisolone (initial dose: 40 mg/m², PO, every 24 hours for 7 days; then 20 mg/m², every 48 hours longterm) and chlorambucil (either 2 mg, PO, every 48 hours, or 20 mg/m², PO, every 2 weeks) with reported median survival times of 1.5–3 years in cats and 14–21 months in dogs.

For treatment of refractory cases of lymphoma, rescue therapy can be attempted with other alkylators, such as cyclophosphamide (200–250 mg/m², IV or PO, administered over 2 days on days 1 and 3, every 2 weeks) or lomustine (30–60 mg/m², PO, every 4–6 weeks, unless patient is neutropenic), with some reported success in cats.

For patients with GI lymphoma confined to the abdominal cavity, radiation therapy may be an option, given the high radiosensitivity of lymphomas. A 2017 retrospective study of 11 cats described successful use of this approach in feline GI lymphoma as a rescue or consolidation therapy (11). Further studies with a larger sample size are warranted.