Several theories have been advanced to explain the pathogenesis and occurrence of pancreatic heterotopia. The most tenable and plausible implicates migration and/or rests of branching pancreatic tissue buds from the developing pancreas during embryogenesis. This theory is most likely when one considers gastrointestinal pancreatic heterotopia; however, pancreatic tissue occurring in more exotic, anatomically remote sites, such as the thyroid gland or fallopian tube, may have a different pathogenesis. The possibility of origin from teratomas has been advanced in these instances.
Heterotopic pancreas in the stomach is usually located within 5 cm of the pylorus, may occur on either anterior or posterior gastric walls, and is more common along the greater curve.1,11
Most cases are located within the submucosa, but intramuscular and subserosal localisation has also been encountered.1
The submucosal lesions may be sessile, polypoid, or nipple-like, where the duct associated with the heterotopic pancreas may communicate with the gastric lumen.1
Gaspar-Fuentes and colleagues modified von Heinrich’s classification of pancreatic heterotopia.12,13
Type I was total pancreatic heterotopia with all pancreatic cell types present, type II is composed of pancreatic ducts only (the so called canalicular variety), type III comprises acinar tissue only (exocrine pancreas), and type IV is made up of islet cells only (endocrine pancreas). The histological classification of the heterotopic pancreas in our case is type I because all elements were present, although the ductal component dominated.
As mentioned earlier, gastric heterotopic pancreas is most frequently asymptomatic, but when symptoms do arise they do so because of gastric mucosal erosion, so that abdominal pain, melaena, anaemia, and nausea are the usual symptoms. Unusually, obstruction of the pyloric outflow tract and mucous retention have been described.
“The independent existence of two distinct pathologies—pancreatic heterotopia and neuroendocrine carcinoma—cannot entirely be excluded”
The risk of malignancy arising in heterotopic pancreas is exceedingly rare, but several documented cases have appeared in the literature.8,14–18
Guillou and colleagues suggested that three criteria had to be fulfilled before a diagnosis of adenocarcinoma arising within the setting of heterotopic pancreas could be made.7
First, they stated that the tumour must be within or near the heterotopic pancreas; secondly, a transition between the pancreatic tissue and the tumour should be established (they alluded to dysplastic ducts); and thirdly, the non-neoplastic pancreatic tissue should show well developed ducts and acini. However, the third criterion does not necessarily apply, given the suggested histological classification of Gaspar-Fuentes et al
In the case described here, all three criteria are met, although endocrine cell dysplasia is not strictly applicable in this particular context. It is felt that our case illustrates a neuroendocrine carcinoma (grade I) arising within the context of heterotopic pancreas in the stomach, an occurrence not described previously. A less likely scenario is a metastatic neuroendocrine carcinoma to the stomach or a primary gastric neuroendocrine carcinoma with unrelated pancreatic heterotopia of the stomach, although the precise anatomical colocalisation of the two lesions argues against either of these possibilities. Furthermore, the neuroendocrine carcinoma appeared to merge or show transition with the heterotopic pancreatic tissue. Primary neuroendocrine carcinomas of the stomach are associated with G cell hyperplasia and chronic atrophic gastritis in most cases. These last two features were not present in our case. Metastatic neuroendocrine carcinoma is not likely in view of the absence of a lesion in other abdominal sites, the pelvis, and the lungs. However, the independent existence of two distinct pathologies—pancreatic heterotopia and neuroendocrine carcinoma—cannot entirely be excluded.
Of interest is the focus of high grade (grade III) neuroendocrine carcinoma within an otherwise low grade tumour. Although not completely unexpected (given the morphological spectrum of grade I through to grade III that is described in neuroendocrine carcinoma), it is felt that the overall behaviour of the tumour may be influenced by the high grade focus.