Histologic spectrum of BRCA-associated pancreatic ductal adenocarcinoma: A descriptive morphologic study

Pancreatic ductal adenocarcinoma arising in carriers of germline BRCA1 or BRCA2 mutations represents a molecularly defined subgroup characterized by defective homologous recombination DNA repair, yet its histologic phenotype remains incompletely characterized.

To characterize the histologic spectrum of resected pancreatic ductal adenocarcinomas associated with germline BRCA mutations and to describe recurring morphologic features that may reflect underlying DNA-repair deficiency.

A retrospective cohort study of surgically resected pancreatic ductal adenocarcinomas from patients with confirmed germline BRCA1 or BRCA2 mutations treated at a tertiary referral center. All hematoxylin-eosin-stained slides were jointly reviewed, and architectural, cytologic, stromal, and peritumoral features were assessed semiquantitatively.

Thirty-two tumors with residual carcinoma were evaluable. Tumors demonstrated marked morphologic heterogeneity, including vacuolated morphology (21/32, 65.6%), clear-cell areas (12/32, 37.5%), large-duct pattern (8/32, 25.0%), and micropapillary growth (9/32, 28.1%). A high gland-to-stroma ratio was present in 21 of 32 cases (65.6%), accompanied by stromal hyalinization (23/32, 71.9%) and myxoid change (28/32, 87.5%). Marked nuclear pleomorphism (29/32, 90.6%) and loss of polarity (30/32, 93.8%) were common. Peritumoral lymphoid follicles were identified in 20 of 32 tumors (62.5%).

BRCA-associated pancreatic ductal adenocarcinomas demonstrate recurrent morphologic patterns, including increased glandularity, stromal hyalinization, myxoid stromal change and architectural heterogeneity. These observations provide a framework for future comparative studies investigating morphologic correlates of homologous recombination deficiency in pancreatic cancer. Recognition of these patterns may support consideration of germline or somatic DNA-repair gene testing in appropriate clinical settings.