Case Report: A case of synchronous multiple early gastric cancer with a microsatellite instability-high phenotype

Abstract

Synchronous multiple early gastric cancer (SMEGC) is a relatively uncommon variant of early gastric cancer (EGC). In this report, we present a case of SMEGC accompanied by a microsatellite instability-high (MSI-H) phenotype. The patient was a 69-year-old man who presented to our hospital with abdominal pain. The endoscopic examination revealed two lesions. Both lesions were pathologically confirmed as EGC, then the patient subsequently underwent endoscopic submucosal dissection (ESD). Nine months post-procedure, the patient returned with recurrent abdominal pain, leading to the diagnosis of a new EGC. Immunohistochemical analysis demonstrated that all lesions exhibited an MSI-H phenotype and BRAF mutant expression, suggesting that these lesions are not associated with Lynch syndrome-related EGC. The case was ultimately diagnosed as SMEGC with an MSI-H phenotype. The current evidence and clinical experience suggest that patients with advanced MSI-H are likely to benefit from immunotherapy and should be considered for early systemic treatment with immunotherapy as a central component. At present, research studies on the molecular characteristics of SMEGC are limited, underscoring the importance of conducting comprehensive molecular diagnostics of each EGC patient, which could help clinicians thoroughly understand the lesion's characteristics.

Keywords: BRAF mutation; MSI-H; SMEGC; case report; immunotherapy.

Figure 1

Endoscopic images of the major lesion (A-C) and the minor lesion (D-F). (A) The white light endoscopic examination revealed a rough, red, slightly elevated, depressed lesion in the lesser curvature of the gastric antrum (Black arrow). (B) M-NBI showed an irregular microvascular pattern and a well-defined boundary (Black arrows). (C) The NBI showed the small and dense vessels with an epithelial circle (VEC) pattern. (D) The white light endoscopic examination revealed a rough, red, protruding lesion in the greater curvature of the gastric antrum (Black arrow). (E) M-NBI showed an irregular microvascular pattern and a well-defined boundary (Black arrows). (F) The size, morphology, and directionality of the glandular duct structure were inconsistent.

Figure 2

HE and immunohistochemistry staining images of the major lesion. (A) The red frame and the yellow frame indicate the papillary structure and tubular structure, respectively (the scale bar represents 1,000μm). (B) The high-power field images of the yellow frame in (A) the tumor cells displayed significant architectural atypia and low-grade cellular atypia in the surface papillary structure area (the scale bar represents 400μm). (C) The glandular duct fusion of the deep tubular tumors with a crawling growth pattern (the scale bar represents 400μm). (D) The focal poorly differentiated mucinous adenocarcinoma (the scale bars represent 400μm). (E) The lesion had a diffuse, strongly positive expression for MUC5AC. The lesion had a partially positive expression for MUC6 (F) and MUC2 (G). (H) The index of Ki-67 was high (70%). (I) The lesion had a wild-type expression of P53. The mismatch repair (MMR) proteins MLH1 (J) and PMS2 (K) were negatively expressed, while MSH2 (L) and MSH6 (M) were positively expressed. (N) The lesion displayed BRAF mutant expression (the scale bars represent 500μm).

Figure 3

HE and immunohistochemistry staining images of the minor lesion. (A) The lesion had an obvious architectural atypia and low-grade cellular atypia. The blue arrows show the boundaries of the tumor (the scale bar represents 2,000μm). (B) The superficial structures of the lesion had a complex composition: branching, elongated villiform and papillary structures (the red frame) were found in the lesion, and slit-like serrations and ectopic glandular ducts were also revealed (the yellow frame; the scale bar represents 500μm). (C) The glandular ducts were fused, showing a crawling growth pattern (the scale bar represents 500μm). (D) The lesion had a diffuse strongly positive expression of MUC5AC but a partially positive expression of MUC6 (E) and MUC2 (F). (G) The index of Ki-67 was high (50%). (H) The lesion had a wild-type expression of P53. The MMR proteins MLH1 (I) and PMS2 (J) were negatively expressed, while MSH2 (K) and MSH6 (L) were positively expressed. (M) The lesion had BRAF mutant expression (the scale bars represent 1,000μm).

Figure 4

The endoscopic, HE, and immunohistochemistry staining images of the third lesion. (A) The white light endoscopic examination revealed a patchy, rough, well-defined, slightly elevated lesion on the posterior wall of the gastric antrum (black arrow). (B) The M-NBI showed a slightly elevated lesion with a well-defined boundary (black arrows). (C) The blue arrows show the boundaries of the tumor. The red frame and yellow frame indicate the superficial papillary structures and the deeper glandular tubular structures, respectively (the scale bar represents 500μm). (D) The tumor cells exhibited a slightly increased nucleo-cytoplasmic ratio, undisturbed nuclear polarity, eosinophilic cytoplasm, and the lack of mucus with remarkable architectural atypia and low cellular atypia (the scale bar represents 100μm). (E) The lesion had a diffuse, strongly positive expression of MUC5AC, with a partially positive expression of MUC6 (F) and MUC2 (G). (H) The index of Ki-67 was high (70%). (I) The lesion had a wild-type expression of P53. The MMR proteins MLH1 (J) and PMS2 (K) were negatively expressed, while MSH2 (L) and MSH6 (M) were positively expressed. (N) The lesion had BRAF mutant expression (the scale bars represent 500μm).