Clinicopathological features and BRAF(V600E) mutations in patients with isolated hypothalamic-pituitary Langerhans cell histiocytosis

BACKGROUND: Isolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the clinicopathological characteristics, endocrine function changes, BRAF(V600E) mutations and treatments of isolated HPLCH. METHODS: We identified seven patients with isolated HPLCH by reviewing the clinical and pathological files in our hospital from 2007 to 2015. The clinical characteristics of the seven patients were retrospectively reviewed, especially the endocrine function changes. Immunostaining and mutation profiling of BRAF(V600E) were performed. RESULTS: The seven HPLCH patients included three men and four women, aged 9–47 years. All patients presented with symptoms of central diabetes insipidus (CDI), and four displayed anterior pituitary hypofunction as well. Magnetic resonance imaging showed hypothalamic-pituitary axis involvement in all patients. There was no evidence for the involvement of other organs in all seven patients. Langerhans cell histiocytosis was confirmed by neuroendoscopic procedures, and immunohistochemical staining showed that all cases (7/7) were positive for CD68, CD1a, Langerin, and S-100. The BRAF(V600E) mutation was detected in three of the six cases (3/6). Six patients had follow-up information; all received desmopressin acetate and high-dose corticosteroid therapy, and two patients received radiotherapy. CONCLUSIONS: Our study indicated that all patients with isolated HPLCH had CDI as the earliest symptom, and more than half of the patients had anterior pituitary deficiencies. The BRAF(V600E) mutation is a common genetic change in HPLCH patients. Treatment of HPLCH patients is difficult, and the progressive loss of endocrine function is irreversible in most cases.