From local control to systemic management: radiotherapy and sequential methotrexate therapy in an adult BRAF-negative hypothalamic-pituitary Langerhans cell histiocytosis – a case report with 15-month follow-up

Abstract

Langerhans cell histiocytosis (LCH) is a rare clonal neoplastic disorder characterized by the proliferation of CD1a+/Langerin+ dendritic cells. Hypothalamic-pituitary region (HPR) involvement in adults—particularly when followed by multisystem progression after local therapy—remains poorly characterized. We report a 35-year-old female with HPR-LCH who achieved durable local metabolic remission after radiotherapy but later developed systemic progression, which was successfully managed with systemic chemotherapy. A 35-year-old woman presented with progressive memory decline, polydipsia, polyuria, 15-kg weight gain over six months, and one year of amenorrhea. Endocrine evaluation revealed central diabetes insipidus (CDI) and hyperprolactinemia (prolactin 94.19 ng/mL). Pituitary MRI demonstrated a 2.0 × 1.4 cm enhancing hypothalamic mass with pituitary stalk thickening. A pterional craniotomy was performed for histopathological sampling, and immunohistochemistry confirmed LCH (CD1a+/Langerin+/S100+); BRAF V600E mutation was negative by quantitative PCR. The patient received involved-field intensity-modulated radiotherapy (IMRT, 22 Gy/11 fractions) targeting the HPR lesion. At 15-month follow-up, 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET-CT) demonstrated complete metabolic remission of the hypothalamic lesion, with resolution of memory and mood symptoms. However, new progressive skull bone destruction, skin ulcers, and pulmonary nodules emerged. She was subsequently treated with a full initial course of high-dose methotrexate (MTX 9 g IV weekly for 3 weeks, 12 g weekly for 2 weeks, and 16 g weekly for 2 weeks) at a Peking Union Medical College Hospital-affiliated institution, achieving significant improvement in skin ulcers, bone pain, and galactorrhea. A second consolidation course is scheduled. This case illustrates that involved-field IMRT can achieve durable local control of HPR-LCH even in BRAF V600E-negative cases. However, local control does not equate to systemic cure; close surveillance for extracranial progression is essential, and timely systemic chemotherapy (e.g., high-dose MTX) is critical for managing multisystem disease. Lifelong endocrine surveillance remains mandatory.