Diagnostic challenges of rarely well-differentiated adenocarcinoma of the stomach

Abstract

Background: Fundic gland tumors are a rare subtype of gastric tumors with fundic gland differentiation. This group of tumors has a low incidence rate and shows indistinctive cellular atypia, obvious structural atypia, special tissue morphology, and clinical prognosis, thus leading to diagnostic challenges.

Aim: We aimed to investigate the clinical and endoscopic characteristics and pathological features of gastric adenocarcinoma of the fundic gland (GA-FG) to provide a better understanding of this disease.

Methods: We collected data from patients diagnosed as having GA-FG at Guangdong Provincial People's Hospital between January 2019 and April 2024. The analysis focused on their clinical data, endoscopic characteristics, pathological morphological characteristics, immunohistochemistry results, treatment, and prognosis.

Results: Among the four patients were two men and two women (age range, 52-65 years). The tumors were mainly located in the gastric fundus and gastric body, and the lesions commonly had a superficial bulge. Three patients had an initial diagnosis of oxyntic gland adenoma, which was diagnosed as GA-FG after complete resection. These tumors were negative for MUC5AC, but showed diffuse strong positivity for MUC6 and pepsinogen I, and synaptophysin expression.

Conclusion: GA-FG is a rare gastric tumor with unique morphological features. As it is difficult to diagnose with a biopsy, immunohistochemistry plays an important role in the differential diagnosis. Oxyntic gland adenoma can be regarded as the intramucosal stage of GA-FG. Although all patients were negative for MUC5AC expression, MUC6 and pepsinogen I can help the diagnosis of GA-FG.

Keywords: MUC6; diagnosis; gastric adenocarcinoma of the fundic gland; stomach neoplasms; welldifferentiated.

FIGURE 1

Each patient’s representative endoscopic images of GA-FG (arrows), which appears as a small swelling lesion in fundus of stomach in endoscopic images. Magnified narrow band imaging (B,D,F,H) revealed a mound-like protrusion, with a red, rough surface and faintly visible branching vessels. (A,B): Case 1 with an elevated tumor of 6 mm in diameter in the non-atrophic mucosa of the gastric fundus [(A), white-light image; (B), NBI-ME]. (C,D): Case 2 with an elevated tumor of 7 mm in diameter in the non-atrophic mucosa of the gastric fundus [(C), white-light image; (D), NBI-ME]. (E,F): Case 3 with an elevated tumor of 5 mm in diameter in the non-atrophic mucosa of the gastric fundus [(E), white-light image; (F), NBI-ME]. Finally, (G,H): Case 4 with an elevated tumor of 6 mm in diameter in the non-atrophic mucosa of the gastric body [(G), white-light image; (H), NBI-ME].

FIGURE 2

GA-FG pathology, (A–C) exhibited HE staining, while (D–J) displayed IHC staining. (A) Low magnification images of gastric adenocarcinoma of the fundic gland-type (GA-FG) (HE, ×40) showing the tumor (red arrow), which blends imperceptibly with normal oxyntic glands (left and right portions of the image). Note the submucosal invasion lacks any desmoplasia or myxoid change. (B) The complex glandular architecture seen at a higher magnification revealing an anastomosing and so-called “endless glands” pattern (HE, ×100). Note occasional cystic glands in the lesion that may mimic a fundic gland polyp (red arrow). (C) Higher power of GA-FG showing the tumor cell atypia is not obvious. (HE, ×100). (D) MUC6 (×100) and (E) pepsinogen I showed diffuse positive staining (×100). (F) Syn was positive (weak) (×40); (G) CgA was negative. (×40); (H) MUC5AC was negative (×100), and (I) showed that Ki-67 does not exhibit focal concentration (×40). (J) Desmin immunostaining (×100) revealed the breach of the muscularis mucosae by neoplastic glands invading into the superficial submucosa.