Adult-Onset Multisystem Langerhans Cell Histiocytosis: Atypical Skeletal and Endocrine Manifestations.

Langerhans cell histiocytosis (LCH) is a rare clonal histiocytic neoplasm that is uncommon in adults and may be diagnostically challenging because of its heterogeneous clinical presentation. We report a case of a 55-year-old male who presented with persistent right ankle pain and multifocal lytic lesions involving the distal tibia, fibula, talus, calcaneus, and cuboid. His medical history was notable for a pituitary lesion with central diabetes insipidus diagnosed two years earlier. Open biopsy of the tibia demonstrated a mixed infiltrate containing characteristic Langerhans cells with grooved nuclei and numerous eosinophils. Immunohistochemistry showed strong positivity for CD1a, S100, and langerin (CD207), confirming LCH. Staging studies revealed pituitary involvement and mild radiologic splenomegaly, without evidence of hematopoietic or hepatic risk-organ dysfunction. Retrospective molecular testing on stored tissue was negative for BRAF V600E. The patient was treated with vinblastine and prednisolone, along with desmopressin and somatotropin replacement. Zoledronic acid was added for osseous disease. Over 70 months of follow-up, the patient achieved durable clinical and radiologic disease control, with pain improving from 7/10 to 1/10 and no evidence of relapse at last contact. Treatment-related toxicity was limited to mild peripheral neuropathy. This case highlights an unusual presentation of adult LCH with distal lower-extremity and tarsal bone involvement, as well as hypothalamic-pituitary disease preceding osseous diagnosis by two years. It underscores the importance of considering LCH in adults with unexplained multifocal lytic bone lesions and endocrine dysfunction, and it demonstrates that durable disease control can be achieved with systemic therapy.