Intestinal neoplasms in dogs and cats (Proceedings)

While not common in terms of the frequency with which they are seen in small animal practice, primary intestinal neoplasia is an important differential diagnosis for a dog or cat with vomiting, especially chronic vomiting, chronic diarrhea, anorexia and weight loss, particularly animals that are middle-aged and older. Some intestinal neoplasms have been associated with paraneoplastic syndromes such as hypoglycemia and polyuria/polydipsia, which could be additional clinical complaints.

Etiology and pathophysiology

The most common intestinal tumor in cats is lymphosarcoma; in dogs, intestinal lymphosarcoma intestinal adenocarcinoma and intestinal smooth muscle tumors are seen with around the same frequency although lymphosarcoma is reported a bit more often than the other tumor types. Other tumor types that have been described in the bowel include leiomyomas, leiomyosarcomas; gastrointestinal stromal tumors, plasma cell tumors, mast cell tumors, carcinoids (tumors of neuroendocrine origin) and extraskeletal osteosarcomas. Benign polyps can be found in the duodenum of cats or the rectum of dogs. Gastrointestinal stromal tumors (GIST) have been recently described as tumors that arise from the interstitial cells of Cajal, cells that regulate intestinal motility and peristalsis. GIST have histological features that are very similar to intestinal smooth muscle tumors, but are distinguished by positive staining for c-kit (CD117). The paraneoplastic syndromes thus described in the older literature in association with leiomyomas/leiomyosarcomas have the potential to be a result of GIST. In the report that characterizes GIST, there was a predilection for this tumor in dogs to be seen in the cecum and large intestine whereas the smooth muscle tumors were more likely to be seen in the stomach and small intestine. In this report, only the dogs with GIST had hypoglycemia. Intestinal adenocarcinomas in dogs are seen more often in the large intestine than the small intestine.

Animals with intestinal tumors are most commonly middle-aged to older. Common metastatic sites of non-lymphoid intestinal tumors include regional lymph nodes, liver, spleen, omentum/peritoneal cavity, and lung.

Intestinal tumors can disrupt normal gastrointestinal motility likely as a consequence of disruption of the intestinal smooth muscle wall and/or accompanying inflammatory changes, or cause obstructive disease. Ulceration of the intestinal mucosa is a feature of intestinal tumors in some patients, but will not be present in all. Patients with intestinal bleeding secondary to mucosal ulceration, chronic blood loss can lead to iron deficiency anemia. Iron deficiency anemia can be either regenerative or non-regenerative.

Clinical features

Patients with primary intestinal neoplasms most commonly present with a history of anorexia, weight loss, diarrhea and vomiting; melena may be seen in some and if the tumor is located in the large bowel, there may be hematochezia, tenesmus and ribbon-like stools, or frank bleeding from the anus. Animals, particularly dogs, may exhibit features of both large and small bowel diarrhea when tumors are located in the cecum or ileocecocolic region. As noted above, some patients with intestinal tumors may exhibit polyuria/polydipsia and signs of hypoglycemia (tremors, seizures).

The physical examination in patients is variable. Poor body condition will be appreciated in animals with weight loss, and an abdominal mass may be palpable in some patients. Cats with intestinal lymphoma commonly have enlarged mesenteric lymph nodes appreciated during abdominal palpation. Abdominal distension and a fluid wave are possible findings in animals with hypoalbuminemia or peritoneal carcinomatosis. Animals that have developed anemia secondary to neoplasm-associated intestinal ulceration may have pale mucous membranes. During rectal examination, rectal masses may be palpable; in the author's experience, some of these masses are very soft and friable and can be easily mistaken for a fold of mucosa, so a hurried rectal examination is not advised.

Results of routine laboratory testing (CBC, biochemical profile, urinalysis, fecal flotation) helps exclude non-gastrointestinal origins of clinical signs such as hepatic, renal or adrenal gland disease, although results are not always helpful and can, in some cases, be confusing (e.g. pre-renal azotemia and an increase in BUN disproportionate to the serum creatinine, which can reflect gastrointestinal bleeding). Hypoglycemia is a feature of occasional patients with intestinal tumors.

Anemia, which can be regenerative or non-regenerative, and may have features of iron deficiency (microcytosis, hypochromasia), may be seen in patients with bleeding intestinal tumors; anemia could also reflect chronic inflammatory disease. Erythrocytosis has been described in a dog with a cecal leiomyosarcoma (which may have been a gastrointestinal stromal tumor as alluded to below). Inflammatory leukograms (mature neutrophilia, monocytosis), thrombocytosis or thrombocytopenia are also possible on the CBC. Biochemical profile results are usually normal unless there has been large scale bleeding, in which case decreases in albumin and total protein are possible; some patients can develop hypoalbuminemia secondary to enteric protein loss. Increases in liver enzyme activities may be seen in animals with hepatic metastasis, and hyperglobulinemia secondary to monoclonal gammopathy has been occasionally described in dogs with extramedullary intestinal plasma cell tumors.

Suspicion of an intestinal tumor can be raised by plain or contrast radiographs, or abdominal ultrasonography. Radiographic findings may include a mass-like effect in the abdomen with displacement of segments of bowel if the mass is large enough; extraskeletal osteosarcomas may have a mineralized density associated with a segment of bowel. For animals with masses causing partial obstruction, dilated/distended bowel loops may also be seen. For those animals having contrast studies performed, filling defects and mucosal irregularity, and delayed passage of contrast material and mass lesions or constrictions of the affected intestinal segment may be appreciated.

Ultrasonographic features of intestinal tumors include wall thickening or masses, or in the case of intestinal lymphoma, focal or diffuse, disruption of the normal layering of the intestinal wall, and poor motility. In one study, loss or normal wall layering of the small intestine was highly associated with the presence of an intestinal tumor, but animals with severe inflammatory intestinal disease also had a loss of normal wall layering. Animals with partial small intestinal obstruction can have dilated bowel segments that exhibit hyper- or hypomotility. There may be enlargement of regional lymph nodes as a consequence of either hyperplasia secondary to inflammation or metastasis to these regional lymph nodes. Nodules in the liver or spleen may be indicative of metastatic disease. Abdominal effusion can be a consequence of peritoneal carcinomatosis or hypoalbuminemia secondary to enteric protein loss.

Endoscopic findings in animals with intestinal tumors vary with the site and tumor type. Many focal small intestinal tumors are not endoscopically visible given the working length of most endoscopes. Endoscopic findings of intestinal lymphosarcoma can include increased friability (usually manifest as increased tendency for mucosal bleeding), prominent villous tips creating a cobblestone appearance, or solitary mass like lesions. Erosions and ulceration of focal intestinal lymphoma are also possible; in the author's experience, these changes are uncommonly seen in patients with diffuse mucosal lymphoma. Large intestinal tumors may appear polypoid, or as cauliflower-like lesions; bleeding from the surface may be observed. It is possible for multiple masses to be found during colonoscopy so examination of the entire colon is important even in patients with rectal or distal colonic masses.

Definitive diagnosis of intestinal tumors is based on cytological or histological demonstration of neoplastic cells. It may be possible to obtain material for cytology from rectal scrapes in patients with rectal masses; on some occasion, the author has had pieces of tissue exfoliate onto a glove during rectal examination, and such pieces of tissue can be submitted for cytological examination, or histology if large enough. Ultrasound-guided needle aspiration cytology of an intestinal mass or enlarged mesenteric lymph node can provide a diagnosis of lymphosarcoma in dogs and cats, and occasionally be strongly suggestive of adenocarcinoma. Nodules in the liver and spleen are also candidates for aspiration and can provide cells for definitive diagnosis, and further stage the patient. Occasionally, rafts of overtly neoplastic cells can be recovered from an abdominal effusion, so it is worth performing abdominocentesis and submitting a portion of the sample to a clinical pathology laboratory for analysis. Biopsies for histopathology can be obtained by endoscopic pinch biopsy if the lesion is considered endoscopically accessible (particularly for large intestinal tumors), or during surgical exploration of the abdomen.

Patients that are suspected of intestinal tumors should be clinically staged with abdominal imaging, ideally abdominal ultrasound, and thoracic radiographs; we have seen patients at WSU that had metastatic lesions detected during abdominal computed tomographic scans that were not detected with abdominal ultrasound. Nodules observed ultrasonographically in other organs, or enlarged abdominal lymph nodes, may be aspirated as noted above for cytological examination to assess for metastasis. It is important to remember that negative results of any staging procedure do not guarantee an absence of tumor. The role of advanced cross sectional abdominal imaging (abdominal computed tomography or magnetic resonance imaging) for staging patients suspected of having intestinal tumors needs to be explored. Thoracic CT scans are more sensitive for detection of pulmonary metastasis and could be considered where available prior to taking an animal with suspected intestinal neoplasia to surgery.

Treatment

Surgical resection is the preferred treatment of dogs or cats for most all forms of intestinal neoplasia, particularly for those without overt evidence of metastatic disease; animals with evidence of intestinal obstruction and metastatic disease may need surgical resection for palliative treatment of the intestinal obstruction. Reliably effective chemotherapeutic protocols for all intestinal neoplasms save lymphoma have not been established, although many agents have been tried.

Chemotherapy is the preferred treatment approach to both dogs and cats with intestinal lymphoma. Multiple protocols have been given to dogs and cats with intestinal lymphosarcoma. The type of protocol selected is often influenced, especially in cats, by the grade of the lymphosarcoma. Cats with mature (lymphocytic) forms of intestinal lymphoma are often treated with relatively less aggressive protocols that rely on prednisone, vincristine and an alkylating agent (cyclophosphamide or chlorambucil) while lymphoblastic forms are treated with more aggressive multiagent protocols. Consultation with a veterinary oncologist can be of great value in deciding the best chemotherapeutic approach to the patient with intestinal lymphosarcoma. Plasma cell tumors of the intestinal tract have also been treated with chemotherapy (prednisone, melphalan) although there is not enough information in the literature to determine if there is any advantage to treating these dogs with chemotherapy after a clean surgical resection.

In cases in which surgery is not possible, it is reasonable to consider administration of a non-steroidal anti-inflammatory drug (NSAID), particularly for those patients that could have carcinomas. Increased cyclooxygenase-2 (COX-2) expression has been documented in dogs with colorectal polyps, and the author has seen transient (months) endoscopic resolution of colonic adenomas in a single dog following administration of an NSAID. Larger, prospective clinical studies of the role for NSAIDs in treating dogs with intestinal epithelial neoplasms, both benign and malignant, are needed.

Prognosis

The prognosis for patients with intestinal neoplasms varies with the tumor type. Cats with lymphocytic lymphosarcoma can live for many months to years; the prognosis for cats with the lymphoblastic form of intestinal lymphoma have a worse prognosis with median survivals with multi-agent protocols in the 8 month range. Dogs with intestinal lymphosarcoma are generally viewed as having a poor prognosis. Extramedullary plasma cell tumors of the intestine generally carry a good prognosis provided that surgical resection gives clean margins and there is no evidence of metastatic disease (especially to regional lymph nodes). Dogs with GIST that survive the initial perioperative period reportedly can have a good prognosis with median survivals of 37.4 months after surgical resection alone. By comparison, median survival of dogs with intestinal leiomyosarcomas treated with surgical resection was 7.8 months. In contrast to soft tissue sarcomas in other locations, there is little information regarding the prognostic value of the histological grade of intestinal leiomyosarcomas. The prognosis associated with extraskeletal osteosarcomas of the intestine has been uniformly poor (median survival times less than 2 months for the GI forms), although the author recently treated a patient with a jejunal extraskeletal osteosarcoma that lived for 7 months with surgical resection and chemotherapy before metastatic disease was detected. The prognosis associated with intestinal adenocarcinomas in cats is considered poor as most have advanced disease at the time of diagnosis; intestinal adenocarcinomas in dogs generally carry a guarded prognosis

References

Beaudry D, Knapp DW, Montgomery T, et al. Hypoglycemia in four dogs with smooth muscle tumors. J Vet Intern Med 1995; 9:415.

Cohen M, Post GS, Wright JC. Gastrointestinal leiomyosarcoma in 14 dogs. J Vet Intern Med 2003; 17:107.

Kupanoff PA, Popovitch CA, Goldschmidt MH. Colorectal plasmacytomas: a retrospective study of nine dogs. J Am Anim Hosp Assoc 2006; 42:37.

McEntee MF, Cates JM, Neilsen N. Cyclooxygenase-2 expression I spontaneous intestinal neoplasia of domestic dogs. Vet Pathol 2002; 39:428.

Pennick D, Smyers B, Webster CRL et al. Diagnostic value of ultrasonography in differentiating enteritis from intestinal neoplasia in dogs. Vet Radiol Ultrasound 2003; 44:570.

Russell KN, Mehler SJ, Skorupski KA, et al. Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990-2003). J Am Vet Med Assoc 2007; 230:1329.

Selting KA. Intestinal tumors. In: Withrow and MacEwen's Small Animal Clinical Oncology. Withrow SJ and Vail DJ, eds. Saunders Elsevier, St. Louis, 2007; pp491-503.

Takahashi T, Kadosawa T, Nagase M, et al. Visceral mast cell tumors in dogs: 10 cases (1982-1997). J Am Vet Med Assoc 2000; 216:222.