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

• Published in: The American journal of surgical pathology Vol. 46; no. 3; p. 344
• Main Authors: Osako, Tomo, Kurisaki-Arakawa, Aiko, Dobashi, Akito, Togashi, Yuki, Baba, Satoko, Shiozawa, Satoshi, Ishigame, Hiroki, Ishige, Hiroyuki, Ohno, Shinji, Ishikawa, Yuichi, Takeuchi, Kengo
• Format: Journal Article
• Language: English
• Published: United States 01.03.2022
• Subjects: Adult; Anaplastic Lymphoma Kinase - genetics; Anaplastic Lymphoma Kinase - metabolism; Biomarkers - metabolism; Breast Diseases - diagnosis; Breast Diseases - genetics; Breast Diseases - metabolism; Breast Diseases - pathology; Female; Gene Rearrangement; Genetic Markers; Histiocytosis - diagnosis; Histiocytosis - genetics; Histiocytosis - metabolism; Histiocytosis - pathology; Humans; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism
• ISSN: 1532-0979
• DOI: 10.1097/PAS.0000000000001794

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. Therefore, ALK-positive histiocytosis can be accurately diagnosed through a combination of morphologic, immunohistochemical, and molecular analyses. In this entity, breast cases may have distinct clinicopathologic features: Asian women aged 30s to 40s, asymptomatic masses, and predominant spindled morphology. For pathogenesis, ALK rearrangements could be the driver alteration, and a subset of ALK-positive histiocytosis may harbor a lymphoid lineage. These findings can be utilized to improve the diagnosis of ALK-positive histiocytosis and better understand its pathogenesis.