title: Clinicopathological features and BRAFV600Emutations in patients with isolated hypothalamic-pituitary Langerhans cell histiocytosis.
abstract: BACKGROUND
  Isolated hypothalamic-pituitary Langerhans cell histiocytosis (HPLCH) is very rare. We investigated the clinicopathological characteristics, endocrine function changes, BRAFV600Emutations 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 BRAFV600Ewere 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 BRAFV600Emutation 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 BRAFV600Emutation 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.
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huo
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Endocrine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Ping
authors.affiliation: Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, BeiJing, 100730, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Cerebral Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, BeiJing, 100730, China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China.
authors.forename: Dachun
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China. zhongdingrong@sina.com.
authors.forename: Dingrong
authors.initials: D
authors.lastname: Zhong
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D020790:Diabetes Insipidus, Neurogenic / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006646:Histiocytosis, Langerhans-Cell / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007027:Hypothalamic Diseases / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010900:Pituitary Diseases / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D010903:Pituitary Gland, Anterior / Q000378:metabolism / Q000503:physiopathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Anterior pituitary function; BRAF mutation; Central diabetes insipidus; Hypothalamic-pituitary; Langerhans cell histiocytosis