Gastric medullary carcinoma, a distinct entity associated with microsatellite instability-H, prominent intraepithelial lymphocytes and improved prognosis

AIMS: To determine the clinicopathological and molecular features of gastric medullary cancer. METHODS AND RESULTS: Clinicopathological review and microsatellite instability (MSI) analysis were carried out on 17 gastric medullary and 64 non-medullary cancers. In addition to characteristic histopathology, gastric medullary cancers had certain prominent features: (i) the average survival time was longer in medullary and low-grade non-medullary cancers than in high-grade (P = 0.004); (ii) serosal involvement was less common in medullary cancers (29.4%, 5/17) than in non-medullary cancers (9.4%, 6/64) (P < 0.05) while pushing borders were more common in medullary cancers (70.6%, 12/17 versus 17.2%, 11/64, P = 0); (iii) the presence of intraepithelial lymphocytes (IELs) in medullary and non-medullary cancers was 2380/10 high-power field (HPF) and 147/10 HPF (P = 0), respectively. Both peritumoural infiltrating lymphocytes (pTIL) and a Crohn's-like reaction were more common in medullary cancers than in non-medullary (pTIL 35.3%, 6/17 versus 3.1%, 2/64; a Crohn's-like reaction 70.6%, 12/17 versus 32.8%, 21/64; P < 0.05); (iv) medullary and high-grade non-medullary cancers were more associated with reduced ECD expression in comparison with low-grade cancers (P < 0.05); (v) higher MSI-H (Bat26+) rate was observed in medullary cancers (41.2%, 7/17) than in non-medullary (1.6%, 1/64) (P = 0). CONCLUSIONS: Gastric medullary cancer has distinct clinicopathological features and genetic alterations. Two subtypes of gastric medullary cancers, Bat26+ and Bat26-, might have prognostic implications, thus analysis of Bat26 may be of clinical value.