Distinct Clinicopathologic Features and Possible Pathogenesis of Localized ALK-positive Histiocytosis of the Breast

Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare emerging entity characterized by systemic or localized proliferation of histiocytes harboring ALK rearrangements. Breasts are reportedly affected by ALK-positive histiocytosis. Here, we evaluated 2 localized cases of breast ALK-positive histiocytosis through a comprehensive clinicopathologic, molecular, and genomic analysis to further delineate this entity and better understand its pathogenesis. The cases involved 2 undiagnosed ALK-positive spindle-cell breast lesions. Both cases were Asian women aged 30s to 40s who underwent excisions for asymptomatic breast masses. Macroscopically, both lesions were well-circumscribed, solid masses. Microscopically, both lesions were predominantly composed of fascicles with uniform, bland spindle cells, admixed with epithelioid histiocyte–like cells and lymphoid aggregates. Immunohistochemically, the spindle and epithelioid cells coexpressed ALK and histiocytic markers (eg, CD68, CD163). Genetically, both lesions harbored KIF5B-ALK, confirmed by fluorescence in situ hybridization and polymerase chain reaction–direct sequencing analyses. Combining these results, both cases were successfully diagnosed as ALK-positive histiocytosis. Furthermore, no common or previously annotated somatic alterations were identified by whole-exome sequencing. One case harbored clonal immunoglobulin gene rearrangements according to the polymerase chain reaction–based BIOMED-2 protocol. Theref...
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research