Diagnostic challenge of primary colonic poorly cohesive adenocarcinoma exhibiting gastric‑type immunohistochemistry profile and focal signet‑ring differentiation

Colorectal adenocarcinoma infrequently exhibits a diffuse, poorly cohesive architecture and a gastric-type immunophenotype, closely resembling diffuse-type gastric carcinoma and posing a formidable diagnostic challenge. This report describes a 65-year-old woman who presented with non-specific abdominal discomfort and was found by colonoscopy to have a 6.5 cm ulceroinfiltrative lesion in the hepatic flexure. Histologically, the tumor comprised discohesive cells with focal signet-ring morphology, accompanied by extensive lymphovascular and perineural invasion, necrosis, and a marked peritumoral lymphoid response. Immunohistochemical analysis demonstrated a gastric-type profile (CK7+, CK20-, SATB2-, CDX2 weak/focal, MUC5AC+, MUC2-), whereas panels excluding breast, urothelial, Müllerian, neuroendocrine, and hematolymphoid differentiation were uniformly negative. Comprehensive imaging and endoscopic evaluation excluded an extra-colonic primary malignancy/carcinoma. Mismatch repair testing revealed loss of MLH1/PMS2 expression with preserved MSH2/MSH6. This case underscores that, in such uncommon colorectal variants, reliance on immunophenotype alone may mislead, and that definitive diagnosis necessitates integrated clinicopathologic correlation, exhaustive sampling, and exclusion of alternative primaries/primary malignancies/carcinomas to confirm a primary colonic poorly cohesive adenocarcinoma with focal signet-ring differentiation.