This is the first report of a life-threatening intestinal hemorrhage caused by HGM in the intestine of an adult dog. Additionally, to the authors’ knowledge, this is the first case report describing the resolution of chronic diarrhea, after resection of intestinal HGM.
The dog presented in our case report had signs of acute vomiting, anorexia, abdominal pain and severe anemia. Gastrointestinal signs are one of the most common reasons for clinical presentation . Differential diagnoses for the acute onset of these clinical signs include gastroenteritis , gastrointestinal ileus , foreign bodies [25, 26], gastrointestinal tumors , gastrointestinal ulceration , gastrointestinal perforation or abscesses , pancreatitis , cholecystitis , cholelithiasis  and tumors of the pancreas or the biliary system . Anemia can be presented in correlation to gastrointestinal signs or as a comorbidity. When presented as a correlation to gastrointestinal signs, it is mostly related to gastrointestinal bleeding [29, 30]. Differential diagnoses for gastrointestinal bleeding include gastroenteritis , gastrointestinal ulcerations  and gastrointestinal neoplasms .
Tobleman and Sinnott  described a case of a 7-month-old dog with a congenital malformation of HGM with secondary bacterial infection located in the mid-jejunum, and although this dog presented a severe clinical condition, gastrointestinal signs were not present. A very severe case of gastrointestinal bleeding, leading to death, of a 7-year-old boy was described by Lambert et al. . The child had several hospital admissions for unexplained massive, life-threatening gastrointestinal hemorrhage. The source of bleeding was never identified, despite multiple times work up, and negative Meckel’s scan. On the last presentation, clinical examination revealed abdominal pain, non-bloody-diarrhea and vomiting. On work-up, intestinal perforation was diagnosed and after laparotomy with primary closure of perforation and resection of an adjacent segment of abnormal-appearing bowel, the patient died within 24 h from overwhelming sepsis. The pathologic report of the resected small bowel segment removed prior to death showed gastric mucosa of fundic type but merged with foci of small intestinal mucosa. Like in the previously described case, our patient was presented with painful abdomen and vomiting. In both cases gastrointestinal problems occurred before, but further work-up did not find the cause. Also, the life-threatening gastrointestinal bleeding was caused by HGM located in the intestine, and for both cases there were three different localizations showing pathological findings. However, although in the case described by Lambert et al. the three large areas found during the autopsy were consistent with gastric fundic mucosa, there was no evidence of ulceration or acute inflammation . Contrary to the previously described patient, in our case, there was no perforation of the intestine and no signs of septic peritonitis or likelihood of it progressing to sepsis. Nevertheless, the dog in our report had a life-threatening clinical presentation demanding an aggressive therapy, since the clinical deterioration and anemia were rapidly progressing.
Several publications described intestinal neoplasms in dogs [35,36,37] and their outcome. Owners and veterinarians should be aware of the possible differential diagnosis of changes like HGM when discussing treatment options. Given the fact that the dog in our case report was treated for food intolerance before surgery, and that up to two years after the surgical resection of HGM the dog did not present diarrhea or other gastrointestinal signs, it is likely that HGM could have been the etiology of these signs. Food intolerance has been described in dogs and cats before, but the mechanism remains undetermined, and the lack of specific testing and the variability of clinical signs have shown that our understanding is limited . Our report shows that ultrasonographic tumor-like intestinal changes, although accompanied with severe clinical signs, can have a good prognosis.
One of the main difficulties in diagnosing HGM is the lack of a specific test. Different methods have been described but they have variable sensitivity and specificity. In our case, ultrasonography was sensitive in diagnosing the intestinal mass but lacked in specificity for the final diagnose. Blood examinations showed unspecific findings: increased white blood cells count showed an unspecific inflammatory process; decreased erythrocytes, hematocrit and hemoglobin and elevated reticulocytes showed an unspecific regenerative anemia, increased lipase enzymes without increase in liver enzymes could have been related to the gall bladder sludge, increased platelet cells and decreased prothrombin time could have been related to the intestinal bleeding. Therefore, blood examination did not show any specific findings that could have been related to HGM.
In human medicine, endoscopy seems to be one of the most sensitive methods for esophageal and rectal HGM [2, 23] and, for intestinal HGM, capsule endoscopy has been successfully used to localize the lesion prior to surgery [3, 13]. In veterinary medicine, since HGM is a rare incidental finding, necropsy is the most commonly described diagnostic method [16, 18]. However, with constant improvement in treatment options and increasing compliance of owners, some symptomatic cases with heterotopia have been found in the living animal [33, 39]. In these cases, the final diagnosis was made by histopathological examination of resected specimens. Nevertheless, capsule endoscopy has been also used in dogs, and the site of gastrointestinal bleeding could be localized in 24 out of 39 recordings . Unfortunately, the final diagnosis brought by biopsy, is currently not technically available with capsule endoscopy.
Described HGM in dogs often consists of several epithelial cell types, corresponding to normal gastric mucosa [16, 17, 33]. These could also extend into the submucosa , which has been also reported in humans . They also have been associated with diverticular lesions of the intestine [33, 41]. Terada  hypothesized that HGM made up of several cell types is more likely of congenital origin representing a malformation, in contrast to areas of purely foveolar gastric cells inside the intestinal mucosa, which could rather be the result of metaplasia. Thus, it is likely that in the case presented here, the lesions were of congenital origin. Although the expansion of the HGM into the submucosa and muscularis resulted in extensive cystic expansion of the intestinal wall, the histological picture of the heterotopic cells does not support a neoplastic process as described by Panigrahi et al. . The cells did show disorderly arrangement and some activation but no frank atypia, invasive growth or increased mitotic rate. Also, a simultaneous malignant transformation of different cell types at three unconnected areas of HGM seems unlikely.
In conclusion, the authors support histopathological examination of all resected specimens of intestine, regardless of the macroscopic appearance, for a proper assessment of the prognosis and further treatment options. Based on this case report, we would recommend including heterotopic gastric mucosa as one of the differential diagnoses for gastrointestinal symptoms, regardless of their severity. Because no recurrent diarrhea episodes occurred after surgical resection of the ectopic tissue, it is likely that the heterotopic gastric mucosa was the cause of the food intolerance signs in this dog.