Extra-appendiceal low-grade mucinous neoplasm-like lesions: clinicopathologic and molecular characteristics

We identified three extra-appendiceal low-grade appendiceal mucinous neoplasms (LAMN)-like lesions occurring in the absence of appendiceal involvement, raising uncertainty regarding their classification, biologic nature, and clinical significance.

We identified three cases of LAMN-like lesions arising in duplication cysts, anatomically separate from the appendix. These cases were evaluated by detailed histologic and immunohistochemical analysis and compared with other gastrointestinal duplication cysts diagnosed at the same institution. Whole-exome sequencing was performed in all three LAMN-like cases.

All three lesions demonstrated defining histologic features of LAMN, including low-grade mucinous epithelium with apical mucin, abundant luminal mucin, undulating or papillary architecture, obliteration of the lamina propria, effacement of the muscularis mucosae and mural fibrosis. Features of a background duplication cyst were at least focally present, and appendiceal involvement was absent in all cases. The epithelium showed an intestinal immunophenotype with strong CK20 and CDX2 expression and absent or minimal CK7 staining. Molecular analysis revealed activating KRAS or GNAS mutations in all three cases, including one case with co-occurring mutations, mirroring the molecular profile of conventional appendiceal LAMN.

We describe extra-appendiceal LAMN-like lesions that recapitulate the morphologic, immunophenotypic, and molecular features of appendiceal LAMN despite the absence of appendiceal involvement. These findings support the interpretation of these lesions as true neoplastic proliferations arising within non-lumen-communicating cystic epithelial compartments, such as duplication cysts. Recognition of this rare phenomenon is critical to avoid misclassification and may have implications for staging, surveillance, and clinical management analogous to appendiceal LAMN.