Intraductal carcinomas of the salivary glands: systematic review and classification of 93 published cases

Intraductal carcinomas (IDCs) are rare, not well-characterized salivary gland tumors. A systematic literature review of pure IDCs (without stromal invasion) of low-grade (LG-IDCs) or high-grade (HG-IDCs) was performed: IDCs were classified using the apocrine (AR+/S100−) vs intercalated (S100+/AR−) classification. Eighty-two LG-IDCs and 11 HG-IDCs were identified (84% parotid; 11% oral; 3% submandibular; 1% lacrimal; and 1% unknown). Out of 11 HG-IDCs, 2 HG-IDCs (18%) recurred as HG-IDC or invasive carcinoma. IDCs were classified as follows: intercalated (30%); mixed apocrine and intercalated (27%); apocrine (11%); oncocytic (6%); intercalated with focal oncocytic features (1%); and unclassifiable (25%). Double AR/S100 expressors (4%) or discrepancies between morphology and immunophenotype (9%) were found. Apocrine features and necrosis were more frequent in HG-IDCs (55%; 45%). Pleomorphism favored HG-IDCs (especially when combined with >10 mitoses/10 HPFs and/or Ki67 index >10%), being associated with apocrine areas at least in 3 HG-IDCs (27%). IDCs were typically mammaglobin+/ER-/PR-/DOG1-. No immunomarker clearly distinguished HG-IDCs from LG-IDCs. About 57% IDCs (16 LG-IDCs, 1 HG-IDC) showed RET rearrangements, including NCOA4-RET (eight intercalated and two unclassifiable IDCs) and TRIM27-RET fusions (two mixed IDCs). No ETV6, ALK-1, ROS, NTRK3, MAML2, MAML3, or PLAG1 rearrangements were identified. Complete excision and total sampling should exclude invasive areas.