Adult-Onset Langerhans Cell Histiocytosis With Calvarial and Hypothalamic Involvement: Two Cases

Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder of bone marrow-derived dendritic cells that is uncommon in adults. Its clinical presentation varies depending on the organ involved. Central nervous system (CNS) involvement poses a critical therapeutic challenge because of permanent neurological dysfunction. Here, we report two contrasting cases of adult-onset LCH with distinct clinical outcomes. Case 1 involved a 36-year-old woman presenting with a persistent headache. Neuroimaging revealed a solitary osteolytic lesion in the left parietal bone with dural thickening. Surgical resection was performed, and histopathological examination revealed characteristic Langerhans cells with positive S-100 immunostaining, confirming the diagnosis of LCH limited to the calvarium. The patient was treated with bisphosphonates and remained stable without systemic involvement. Case 2 involved a 26-year-old man presenting with cognitive impairment, somnolence, polyuria, and endocrine dysfunction. Magnetic resonance imaging revealed an enhancing hypothalamic lesion. Histopathological and immunohistochemical analyses confirmed LCH with CD1a and S-100 positivity. BRAF V600E mutation was not detected via pyrosequencing. Systemic chemotherapy with cladribine resulted in partial tumor regression; however, the cognitive dysfunction persisted. These contrasting cases highlight that disease distribution, particularly CNS involvement, influences therapeutic strategies and neurological outcomes in adult LCH. Our findings emphasize that early diagnosis and proactive systemic evaluation are essential as functional recovery remains limited once neurological damage occurs, even with successful cytoreductive therapy.