Vulvar and Perineal Langerhans Cell Histiocytosis with BRAF V600E Mutation, Present in a Background of Condyloma Acuminatum

Abstract

Langerhans cell histiocytosis (LCH), previously known as Histiocytosis X, is a rare disorder characterized by clonal proliferation of bone marrow-derived, antigen-presenting Langerhans cells. Involvement of the lower female genital tract is quite unusual. Here we report a case of vulvar and perineal LCH with BRAF V600E mutation, present in a background of condyloma acuminatum. A 59-year-old woman with history of high grade squamous intraepithelial lesion (HSIL) presented with vulvar lesions. She underwent surgery involving cervix, vulva and perineal skin nodules. Grossly, the vulvar and perineal skin showed hair-bearing skin with partially crusted, vaguely nodular skin lesions. Microscopically, it showed a diffuse cellular infiltrate within the dermis with abundant pale cytoplasm, nuclear grooves and folds, fine nuclear chromatin and indistinct nucleoli. The differential diagnoses including LCH, Rosai-Dorfman disease and Erdheim-Chester disease. Condyloma acuminatum is present in the background. By Immunohistochemical studies (IHCs), the cells were positive for S100, CD1a and CD4 and were negative for pancytokeratin, CK7, CAM5.2, HMB45 and MART-1. SOX-10 showed cytoplasmic and high background staining. Toludine blue was negative. In summary, morphologic and IHCs profile was consistent with LCH. Further clinical history showed that this patient had been diagnosed with stage IV systemic LCH with multiple bone lesions. She showed BRAF V600E mutation and had been treated with oral Vemurafenib. In conclusion, LCH involving vulva and perineal skin, either isolated or as part of systemic disorder, is very rare. A careful histopathologic examination and immunohistochemical studies are necessary to confirm such a diagnosis.

[N A J Med Sci. 2026;19(1):008-011.   DOI: 10.7156/najms.2026.1901008]