INTRODUCTION
Gastric adenomas are relatively rare,1,2 estimated to represent 10% of all gastric polyps.3 These typically arise in the setting of chronic mucosal inflammation and are thought to represent a premalignant phase along the inflammation-dysplasia-neoplasia sequence during which intervention can prevent or minimize progression to carcinoma.4 Gastric foveolar-type adenomas (GFA), however, typically arise in areas of relatively unremarkable gastric mucosa and are generally less aggressive than other adenoma subtypes.5 These lesions are commonly associated with hereditary tumor syndromes such as familial adenomatous polyposis but can also occur sporadically.6 Equally as rare are gastric neuroendocrine tumors (GNETs) which arise from the enterochromaffin-like cells of the stomach and are typically classified into 3 subgroups according to the background gastric pathology.7,8 Type 3 GNETs are usually larger in size, well-differentiated, associated with angioinvasion and metastasis, and not associated with other gastric conditions.9 Type 3 GNETs have a poor prognosis and are often diagnosed incidentally.
We present a newly identified iron deficiency anemia that was found to have a GFA as a rare cause of gastrointestinal blood loss, with incidental finding of a type 3 GNET.
CASE REPORT
A 73-year-old man with likely secondary granulomatous hepatitis in the setting of psoriasis and metabolic syndrome presented for evaluation of a new iron deficiency anemia. Iron panel showed a low iron level of 35, ferritin of 291, borderline low total iron binding capacity of 264, and low percent saturation of 13, consistent with a mixed anemia. Colonoscopy was notable for one 3 mm polyp in the transverse colon. Esophagogastroduodenoscopy revealed a 15 mm sessile gastric polyp with a raspberry appearance in the cardia with stigmata of bleeding (Figure 1), making this the likely cause of his occult gastrointestinal blood loss. An additional 5 mm sessile polyp with mild central depression was found in the gastric body (Figure 2). The larger gastric polyp was removed with a cold snare, and the smaller polyp was removed with a cold biopsy forceps.
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Figure 1.: Gastric polyp with rasbperry gastric-like appearance located in the cardia. Stigmata of recent bleeding seen.
Figure 2.: Multiple sessile polyps without stigmata of recent bleeding seen in the gastric body.
Histology revealed that the larger polyp had polypoid low-grade dysplasia consistent with a GFA (Figure 3). The smaller polyp was found to be a well-differentiated neuroendocrine tumor with a Ki-67 proliferative index of 5.45%, consistent with grade 2. Histology revealed large aggregates of round cells with background oxyntic mucosa, classifying the GNET as type 3 (Figure 4). Immunohistochemical stains were notable for diffuse and strong positivity for Cam 5.2, synaptophysin, and chromogranin, supporting the diagnosis of GNET (Figure 5). The singular colonic polyp returned as a simple tubular adenoma.
Figure 3.: Histology of gastric foveolar-type adenoma showing surface papillary projections lined with foveolar-type epithelium. Surface epithelium with cytoplasmic neutralmucins.
Figure 4.: Histology of type 3 gastric neuroendocrine tumor showing large aggregates of round cells with background oxyntic mucosa. There were no signs of atroptic gastritis or hyperplasia.
Figure 5.: Chromogranin staining of type 3 gastric neuroendocrine tumor showing strong positivity.
The decision was made to pursue surveillance endoscopy because of the relatively low proliferative index. Although GNETs less than 1 cm can be followed up in 6-12 months, repeat endoscopy was obtained at 4 months because of the aggressive nature of type 3 GNETs. Esophagogastroduodenoscopy revealed three 2–4 mm sessile polyps with no bleeding and no stigmata of recent bleeding in the gastric body, which were removed with a cold snare.
Histology revealed well-differentiated neuroendocrine tumor with a Ki-67 proliferative index of <3%, consistent with grade 1. The patient was referred to a medical oncologist with planned computed tomography of abdomen beforehand, which showed no new suspicious pancreatic or hepatic lesions and stable mildly enlarged retroperitoneal and mesenteric lymph nodes. Oncology recommended surveillance upper endoscopies every 6 months, without acute indication for surgical intervention or initiation of chemotherapy. On follow-up, the patient's hemoglobin had improved, and ferritin had normalized.
DISCUSSION
Very few cases of GFAs have been reported in the literature.5,6,10,11 Classically, these lesions are associated with hereditary tumor syndromes such as familial adenomatous polyposis and gastric adenocarcinoma and proximal gastric polyposis.11 In addition, these lesions are typically described as small, flat, or depressed and arise in areas of unremarkable gastric mucosa, rarely resulting in clinically relevant symptoms.
One recent single-center study describes a type of sporadic GFA with a raspberry-like appearance, which the authors theorize to be a subtype of sporadic GFAs.6 In their study, the lesions were described as small, reddish polyps with granular surfaces, with a mean lesion size of 3.2 mm. All lesions were in the upper or middle stomach.6 A second study by Jian Guan et al5 describes the “first case” of a large (2.3 cm), protruding GFA in the junction of the gastric body/antrum leading to clinically relevant symptoms of gastrointestinal bleeding. The lesion they identified was described as a broad-based polyp with a papillary or gyrus-like appearance on the surface.5 From the images included in their study, the lesion appeared pedunculated. Our case describes the first instance of a sporadic moderate-sized sessile gastric foveolar adenoma with a strawberry-like appearance developing in the gastric cardia, causing the clinically relevant symptoms of gastrointestinal bleed.
Our case also showed an incidental finding of type 3 GNET. Type 3 GNETs account for 14%–25% of all GNETs and are typically singular, large (>2 cm), have a relatively high proliferative index (>2%), and are often poorly differentiated.9 Although there is no consensus regarding the management of GNETs, type 3 lesions that are large and poorly differentiated typically require urgent surgical resection and chemotherapy because of the high risk for angioinvasion and metastasis.11 Endoscopic resection with close follow-up is sufficient for smaller, well-differentiated lesions, although the follow-up intervals are not well-defined.12 There is also no current consensus regarding preferred imaging modalities to rule-out of malignant disease. Our case showed a small (5 mm), well-differentiated, type 3 GNET with a high proliferative index (5.45%) that was managed with endoscopic resection, computed tomography imaging to rule out metastatic disease, and follow-up in under 6 months.
In summary, we presented a moderately sized GFA which appeared at the gastric cardia and caused chronic oozing bleed as the main reason for iron-deficiency anemia. Although GFAs are usually benign, this case had low-grade dysplasia. In addition, this patient also needed prompt evaluation regarding the management of GNET. This case is different from those previously reported because of the unique appearance and clinical relevance of the identified GFA. Although these lesions are typically identified incidentally, it is important for the gastroenterologist to keep them in the differential for common complaints such as gastrointestinal bleeding and be aware of the next steps required in management. This case highlights the importance of early endoscopic evaluation of gastrointestinal bleeding and emphasizes the broad scope of clinical manifestations of GFAs.
DISCLOSURES
Author contributions: P. Travers made substantial contributions to the conception or design of the work and acquisition, analysis, and interpretation of the data; drafted the work and revised it critically for important intellectual content; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. M. Pang revised the work critically for important intellectual content and gave final approval of the version to be published and is the article guarantor.
Financial disclosure: None to report.
Previous presentation: The following work has been accepted for poster presentation at ACG 2022; October 23, 2022; Charlotte, North Carolina.
Informed consent was obtained for this case report.
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