History
A 12-year-old 9.1-kg (20-lb) neutered male Scottish Terrier was evaluated because of a 3-month history of vomiting, anorexia, and lethargy. Four weeks prior, the dog underwent exploratory laparotomy, during which diffuse thickening of the gastric wall and splenomegaly were noted. A splenectomy was performed, and pancreatic, hepatic, gastric, and intestinal biopsy specimens were obtained. Splenic extramedullary hematopoiesis was diagnosed; no other abnormalities were detected in the remaining organs and no clinical improvement was noticed after provision of supportive care (subcutaneous fluid therapy and administration of glucocorticoids).
Clinical and Gross Findings
At the referral evaluation, the dog had signs of depression and a body condition score of 2 on a scale of 1 to 5. A CBC revealed no abnormalities. Serum biochemical analyses revealed high alkaline phosphatase activity (600 U/L; reference range, 10 to 119 U/L), low concentrations of BUN (5 mg/dL; reference range, 8.5 to 28.5 mg/dL) and chloride (105 mmol/L; reference range, 108 to 126 mmol/L), and high total CO2 concentration (28 mmol/L; reference range, 14 to 24 mmol/L). A canine pancreatic lipase immunoreactivity test was performed and serum pancreatic lipase activity was high (573 μg/L; reference range, 0 to 200 μg/L). Owing to the dog's severe lethargy and to exclude a possible neurologic disorder, MRI of the brain and cervical spinal cord and CSF fluid sample analysis were performed but no abnormalities were evident. Abdominal ultrasonography and MRI revealed a hyperechoic and hyperattenuating cranial mesenteric area consistent with peritonitis and diffuse thickening of the gastric wall and right pancreatic lobe. The dog was anesthetized, and an esophageal feeding tube was placed to facilitate feeding; however, the dog continued to vomit when tube-fed despite aggressive gastroprotectant and antiemetic treatments. Euthanasia (by means of IV injection of pentobarbital solution) was elected 9 days after the referral evaluation because of the rapid deterioration of the dog's condition and lack of improvement following supportive treatment.
Necropsy findings included diffuse thickening and firmness of the gastric wall (Figure 1). The gastric mucosal surface was diffusely covered by strands of clear mucus. In general, the thickness of cross sections of the gastric wall was 1.3 cm. The surrounding omentum and mesentery had nodular and firm areas that were adhered to the liver, pancreas, and duodenum. There were a few pale red to tan, 1- to 2-cm-diameter, poorly demarcated nodules in the liver (hepatic nodular hyperplasia) and multifocal, white, 5-mm-diameter, well-demarcated nodules throughout the pancreas (pancreatic nodular hyperplasia).
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Photograph of the partially opened stomach (A) and gastric wall (B) of a Scottish Terrier that was evaluated because of a 3-month history of vomiting, anorexia, and lethargy. The stomach has a diffusely thickened wall and thickened mucosal folds that are covered by strands of mucus. A closer view of the gastric wall (B) shows the thickened mucosa (arrow) and muscle layers (asterisk).
Citation: Journal of the American Veterinary Medical Association 248, 8; 10.2460/javma.248.8.893
Photograph of the partially opened stomach (A) and gastric wall (B) of a Scottish Terrier that was evaluated because of a 3-month history of vomiting, anorexia, and lethargy. The stomach has a diffusely thickened wall and thickened mucosal folds that are covered by strands of mucus. A closer view of the gastric wall (B) shows the thickened mucosa (arrow) and muscle layers (asterisk).
Citation: Journal of the American Veterinary Medical Association 248, 8; 10.2460/javma.248.8.893
Photograph of the partially opened stomach (A) and gastric wall (B) of a Scottish Terrier that was evaluated because of a 3-month history of vomiting, anorexia, and lethargy. The stomach has a diffusely thickened wall and thickened mucosal folds that are covered by strands of mucus. A closer view of the gastric wall (B) shows the thickened mucosa (arrow) and muscle layers (asterisk).
Citation: Journal of the American Veterinary Medical Association 248, 8; 10.2460/javma.248.8.893
Histologic, Histochemical, and Immunohistochemical Findings
Histologic examination of the stomach wall revealed a highly infiltrative and malignant epithelial neoplasm that expanded the gastric submucosa, muscle layers, serosal surface, and adjacent omentum and mesentery (Figure 2). Small groups of neoplastic cells that originated from the deep gastric mucosa and infiltrated the underlying tissues were occasionally observed. Neoplastic cells were multifocally arranged in small nests or cords and were supported by preexisting tissue and abundant collagenous stroma. Individual neoplastic cells were moderately pleomorphic and polygonal with eosinophilic, homogeneous, or vacuolated cytoplasm with indistinct borders. Approximately 30% of the neoplastic cells had faintly basophilic, fibrillar, Alcian blue stain–positive cytoplasmic material. Nuclei were round to oval and had finely stippled chromatin with 1 or 2 nucleoli and moderate anisokaryosis. Bi- or multinucleate neoplastic cells were scattered throughout the examined samples. The number of mitotic figures in 10 hpfs (400X) was 21. Groups of neoplastic cells were often located within veins and lymphatic vessels throughout the gastric submucosa, muscle layers, and omentum. The gastric mucosa contained small foci of epithelial cell dysplasia and scattered dilated glands. A small, well-demarcated metastatic focus was observed within the colonic external muscle layer. Neoplastic cells had finely granular cytoplasmic material that was immunopositive for pancytokeratin Lu-5, and rare neoplastic cells were immunopositive for cytokeratin 20. Other findings during necropsy were hepatic nodular hyperplasia and pancreatic nodular hyperplasia.
Photomicrographs of a section of the gastric muscle layer from the dog in Figure 1. A—Neoplastic cells have diffusely infiltrated the muscle layers and are arranged in nests and cords throughout the section. H&E stain; bar = 100 μm. B—A higher-magnification view of the same image as in panel A to illustrate the neoplastic cell morphology and supporting collagenous stroma. H&E stain; bar = 50 μm. C—Groups of neoplastic cells have cytoplasmic Alcian blue stain–positive material. Alcian blue stain; bar = 50 μm. D—Immunohistochemical analysis reveals that neoplastic cells have granular, cytoplasmic immunoreactivity for pancytokeratin Lu-5. 3,3′-diaminobenzidine and hematoxylin stain; bar = 25 μm.
Citation: Journal of the American Veterinary Medical Association 248, 8; 10.2460/javma.248.8.893
Photomicrographs of a section of the gastric muscle layer from the dog in Figure 1. A—Neoplastic cells have diffusely infiltrated the muscle layers and are arranged in nests and cords throughout the section. H&E stain; bar = 100 μm. B—A higher-magnification view of the same image as in panel A to illustrate the neoplastic cell morphology and supporting collagenous stroma. H&E stain; bar = 50 μm. C—Groups of neoplastic cells have cytoplasmic Alcian blue stain–positive material. Alcian blue stain; bar = 50 μm. D—Immunohistochemical analysis reveals that neoplastic cells have granular, cytoplasmic immunoreactivity for pancytokeratin Lu-5. 3,3′-diaminobenzidine and hematoxylin stain; bar = 25 μm.
Citation: Journal of the American Veterinary Medical Association 248, 8; 10.2460/javma.248.8.893
Photomicrographs of a section of the gastric muscle layer from the dog in Figure 1. A—Neoplastic cells have diffusely infiltrated the muscle layers and are arranged in nests and cords throughout the section. H&E stain; bar = 100 μm. B—A higher-magnification view of the same image as in panel A to illustrate the neoplastic cell morphology and supporting collagenous stroma. H&E stain; bar = 50 μm. C—Groups of neoplastic cells have cytoplasmic Alcian blue stain–positive material. Alcian blue stain; bar = 50 μm. D—Immunohistochemical analysis reveals that neoplastic cells have granular, cytoplasmic immunoreactivity for pancytokeratin Lu-5. 3,3′-diaminobenzidine and hematoxylin stain; bar = 25 μm.
Citation: Journal of the American Veterinary Medical Association 248, 8; 10.2460/javma.248.8.893
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: diffuse, invasive, undifferentiated gastric carcinoma with extension to the omentum and mesentery and metastasis to the colon.
Case summary: diffuse, invasive, undifferentiated gastric carcinoma in a dog.
Comments
Given the clinical signs and results of MRI and gross necropsy, differential diagnoses for the case described in the present report included gastric carcinoma, Ménétrier disease, and hypertrophic gastropathy.1 Lymphoma, gastric neuroendocrine tumor, gastrointestinal stromal tumor, and leiomyoma were considered less likely possibilities because these neoplasms usually develop as nodules and not as diffuse mural lesions in the stomach.1 Because MRI findings of diffuse gastric wall thickening may be similar in cases of diffuse gastric carcinoma, Ménétrier disease, and hypertrophic gastropathy, histologic evaluation of stomach wall sections is usually necessary to derive a definitive diagnosis.1 Histologic examination of full-thickness gastric biopsy specimens may reveal marked mucous cell hyperplasia or epithelial hyperplasia, and these findings are indicative of Ménétrier disease and hypertrophic gastropathy, respectively.1,2 A gastric biopsy specimen obtained from the dog of this report was examined, but findings were inconclusive (possibly because epithelial neoplastic cells were admixed with abundant amounts of collagenous stroma and were very scant in some areas). However, histologic, histochemical, and immunohistochemical findings were consistent with diffuse, invasive, undifferentiated gastric carcinoma.3–6 Gastric cancer in dogs is reportedly rare and accounts lor < 1% of all malignant neoplasms in this species.4,7 Most cases of canine gastric neoplasia involve malignant tumors of epithelial origin, especially carcinomas.1,4,5,7,8 Gastric carcinomas typically affect middle-aged to older dogs and, similar to what has been reported in the human medical literature, they develop slightly more frequently in males.7–9 Although some studies5 have identified breed predispositions for the development of gastric carcinomas in dogs, with Cairn Terriers, West Highland White Terriers, Staffordshire Bull Terriers, Collies, and Belgian Shepherds being overrepresented, other studies5,7 have failed to detect such patterns. A possible link between the development of gastric tumors and Helicobacter infection in humans has been postulated, but no such connection has been definitively established for gastric tumors in dogs.5
Similar to the case described in the present report, dogs with gastric neoplasia often have nonspecific clinical signs related to the presence of a gastric lesion, such as chronic vomiting, anorexia, lethargy, and wasting.5,6 In the dog of this report, hypochloremic metabolic alkalosis was likely a result of vomiting or obstruction of gastric outflow. The low BUN concentration was likely associated with decreased protein intake related to anorexia because no major liver changes were observed. Subcutaneous administration of fluids also may have decreased the renal medullary concentration gradient, thereby contributing to further loss of circulating BUN. The high serum alkaline phosphatase activity was considered to be either secondary to steroid-induced alkaline phosphatase isoenzyme (a result of steroid administration during the period of supportive care) or secondary to the hepatic nodular hyperplasia. The high canine pancreatic lipase immunoreactivity was considered to be associated with the presence of gastric neoplasia.10
In dogs, the most common gross appearance of gastric carcinomas is an ulcerated plaque on the gastric mucosa.5 A less common feature is diffuse neoplastic infiltration throughout the gastric wall (such as that observed in the dog of the present report). Some gastric carcinomas in dogs produce a raised mucosal polyp.5 Histologically, gastric carcinomas are classified as tubular, papillary, or tubulopapillary adenocarcinomas; mucinous carcinomas; signet-ring cell carcinomas; squamous cell carcinomas; and undifferentiated carcinomas.6 Because more than 1 histologic pattern may coexist in the same animal, the final diagnosis is usually based on the predominant pattern of neoplastic cells.6 Although mucin-producing cells were observed in the dog of the present report, the predominant neoplastic cell population infiltrating the gastric wall did not have any evidence of glandular or squamous differentiation, similar to what has been described for undifferentiated gastric carcinomas.6 Dogs with gastric carcinoma often have severe advanced disease at the time of diagnosis, including distant metastasis or carcinomatosis of the serosal surfaces of other organs.5
Although the diagnosis of gastric carcinomas usually presents little challenge, diagnosis of poorly differentiated or undifferentiated carcinomas may depend on immunohistochemical confirmation.5 In the dog of the present report, neoplastic cells were consistently immunopositive for pancytokeratin; this finding was sufficient to confirm the diagnosis of gastric carcinoma. In humans, cytokeratin 20 is an epithelial cell marker specific for the gastrointestinal tract, urothelium, and Merkel cells but has also been found in carcinomas from breasts, lungs, and endometrium.11 This antigen has been reported to be widely expressed in canine and feline intestinal carcinomas, but only in about 50% of canine gastric carcinomas.3 In accordance with these findings, only scattered neoplastic cells had positive immunoreactivity for cytokeratin in the dog of the present report, indicating that immunostaining for pancytokeratin is more sensitive for diagnostic confirmation of canine gastric carcinomas.
Complete excision is usually the treatment of choice for gastric carcinomas, but surgery is not effective in animals with diffuse gastric involvement or metastatic disease.8 The differential diagnoses for diffuse gastric wall thickening in dogs should include diffuse, invasive, undifferentiated gastric carcinoma, even though it is not the most common type of canine gastric carcinoma.
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