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A female in her early 80s presented with chronic anal fissures which were unresponsive to conservative therapies. Examination was concerning for possible perianal Crohn’s disease, but subsequent colonoscopy and biopsies revealed Langerhans cell histiocytosis (LCH) involving the colon and anus, diagnosed per 2022 WHO Classification of Haematolymphoid Tumours criteria and confirmed by BRAF V600E mutation. Systemic staging identified two unrelated malignancies of the breast and kidney. The patient was treated with cladribine as systemic chemotherapy, resulting in complete remission of LCH symptoms and lesions.This case illustrates key diagnostic and therapeutic considerations for clinicians: LCH can mimic inflammatory bowel disease and should be included in the differential for atypical or refractory perianal disease, especially in older adults. Histological confirmation and molecular profiling are essential for accurate diagnosis and treatment planning. Additionally, cladribine is a well-tolerated and effective option for adult LCH with gastrointestinal tract involvement. Early recognition and systemic staging are critical to guide therapy and identify potential coexisting malignancies.