The patient had improvement after radiosurgery and was discharged on the following day. However, 5 years later, the patient came to West China Hospital with weakness on June 2015. Hormone measurements revealed hypofunction of both hypophysial-thyroid axis and hypophysial-gonadal axis (Table 1B). Other laboratory profiles were shown in Table 1A. Enhanced head computed tomography (CT) showed lesions (1.6 × 1.3 cm) in the sella region, and showed homogeneous enhancement, but no bony lesions (Fig. 2A). Extra-lesions were neither found on Chest CT nor abdominal ultrasonography. Recurrence of sella region tumor was suspected based on the above findings, and tumorectomy was performed and levothyrocine was given. Histologic examination of the surgical specimen showed eosinophils and lymphocytes infiltration (Fig. 3A). And the lymphohistiocytic infiltration was positive to Langerin (Fig. 3B), S-100 protein (Fig. 3C) and to CD1a (Fig. 3D), CD68 (Fig. 3E), and Ki-67 (Fig. 3F) antigen markers. Thus, central nervous system (CNS) LCH (hypothalamic-hypophysial axis restricted) was diagnosed. Post-operation CT (Fig. 2B) and MRI (Fig. 2C) showed no evident abnormalities. She was on regular follow up in our outpatient service since discharged. One year later, the patient came to West China Hospital of Sichuan University again because of fatigue, and further hypofunction of hypophysial-adrenal axis was noted (Table 1B). And MRI of sella region on June 2016 showed enhanced nodular shadow (about 0.8 cm) on the left hypothalamus (Fig.4A). Though recurrence was considered, observation only was suggested due to the small size of the lesion. Levothyrocine together with prednisone was given. And in the latest MRI on May 2017, the nodular shadow became larger (about 1.4 cm) (Fig. 4B). Thus, chemotherapy (prednisone and anti-inflammatory drugs such as rofecoxib) was given. Active vitamin D and bisphosphonate therapy including zoledronate was used to treat her osteoporosis. At 12-month follow-up, no local reoccurrence was noticed.
Langerhans’ cell histiocytosis, a group of diseases characterized by clonal proliferation of immature dendritic cells, mainly affects children. The accurate pathogensis of LCH is unknown, but there is a controversy over whether LCH is a clonal proliferative disease or an inflammatory disease.[12,13] The incidence of LCH is 5 per million individuals according to Surveillance, Epidemiology, and End Results (SEER) Program database (https://seer.cancer.gov/). And the incidence of adult-onset LCH is estimated to be 1 to 2 per million populations per year. Any organ or system of human body, including bone, skin, and pituitary can be involved.[15–19] And manifestations of LCH are totally diverse according to the sites and extents of the lesions. All lead to its high rate of misdiagnosis and missed diagnosis.
According to previous studies, the top 3 affected organs of LCH are bone (80% of patients), skin (33%), and pituitary (25%). Other less involved organs are liver (15%), lung (15%), lymph node (5–20%), central nervous system (CNS) LCH excluding pituitary (2–4%).[15,20,21] Single systemic disease (SS-LCH) and multisystemic disease (MS-LCH) are two kinds of LCH based on the extent of involvement at diagnosis. Though isolated CNS LCH is reported, CNS LCH is mainly diagnosed as multisystemic disease, and the majority of CNS LCH patients are men.[21,22] In this article, we present a rare case about a solitary hypothalamic-hypophysial axis involved female adult who develop central diabetes insipidus (CDI) and anterior pituitary hormone deficiency (APD).
Though difficult to be diagnosed, some manifestations can be meaningful when CNS is involved. The most common manifestations of CNS LCH are diabetes insipidus and neurodegeneration. And in 15% to 30% of these patients tend to develop CDI.[15,20,23] In addition, these patients incline to develop APD.[24,25] In a word, LCH should be highly suspected in patients who develop intracranial mass and CDI with or without APD.
The typical structure of the LCH affected tissues shows a mixture of immature dendritic cells and recruited inflammatory cells, including lymphocytes, eosinophils, and macrophages. Langerhans’ cells of the lesional region have abundant pink plasma, a coffee-bean like nucleus, and immunohistochemical positive staining for CD1a, S100, and (or) CD207 (Langerin).[15,26–29] LCH diagnosis should always be founded on such positive immunohistochemical findings in addition to clinical and radiological characterisics. Therefore, multi-disciplinary team (MDT) treatment mode is necessary in such rare cases. In this case, endocrinologist recognized the possible CNS LCH on the basis of clinical and radiological characteristics and transferred the patient to neurosurgeon, then, neurosurgeon completed the surgery and obtained the lesional specimen, and the pathologist assisted to establish the final diagnosis of CNS LCH.
Till now, there is no defined standard therapeutic approach to adult. Depending on the extent of the clinical symptoms and signs, the lesional sizes and locations, and the variety of the clinical courses (self-limited or rapidly progressed), treatment approaches vary from observation only to systemic chemotherapy.[15,20] According to current standard treatment in children, complete surgical excision achieves good efficacy only in treating isolated diabetes insipidus patients. But post-surgical recurrence is showed in some studies. Systemic treatment (vinblastine and steroid or 2-CdA monotherapy) is indicated when patients develop visual field alterations or an increase of lesional volume or brain (except pituitary stalk) or meningeal lesion is documented on the sequential MRI.[15,31,32] The presented case showed these criterions were suitable for adults as well. Gamma knife radiosurgery was showed to be effective by one case in a 48 months’ follow-up. However, it should not be considered as first-line treatment approaches. What is more, hormonal replacements are recommended when APD occurs. With the cooperation of endocrinologist, neurosurgeons and pathologists, the patient had good clinical efficacy received treatment with multi-disciplinary team (MDT).
For LCH, though difficult to be diagnosed and none defined standard therapeutic approach to adults, some manifestations can be meaningful when central nervous system (CNS) is involved. Surgery should be considered if there are neurological symptoms or histological diagnosis. The present study showed that multi-disciplinary team (MDT) treatment is helpful for better clinical efficacy.
The authors gratefully acknowledge the support of the nursing and technical staff of the Division of Endocrinology and Metabolism in West China Hospital for patient referrals and their excellent care of the patient with LCH. We would like to thank our patient and her daughter for all their help and enthusiasm. We would like to acknowledge Subrata Chakrabarti (Professor and Chair of Pathology and Laboratory Medicine, Western University, London, ON, Canada.) for help with the manuscript.
Conceptualization: Huiwen Tan.
Data curation: Huiwen Tan, Kai Yu, Zhengmei An.
Formal analysis: Huiwen Tan, Yu Kai
Investigation: Huiwen Tan, Zhengmei An, Jianwei Li.
Resources: Huiwen Tan, Jianwei Li, Zhengmei An
Supervision: An Zhengmei, Yu Yerong.
Validation: Huiwen Tan, Jianwei Li, Yerong Yu
Writing – original draft: Huiwen Tan, Yu Kai.
Writing – review & editing: Yerong Yu, Zhengmei An, Jianwei Li.
Huiwen Tan orcid: 0000-0002-0451-8283.
. Favara BE. Histiocytosis syndromes classification, diagnostic features and current concepts. Leuk lymphoma 1990;2:141–50.
. Favara BE. Langerhans’ cell histiocytosis pathobiology and pathogenesis. Semin Oncol 1991;18:3–7.
. Mehta B, Venkatramani R. Images in clinical medicine. Langerhans’-cell histiocytosis. N Engl J Med 2014;371:1050.
. Kumar M, Updesh Singh Sachdeva M, Naseem S, et al. Bone marrow infiltration in Langerhan's cell histiocytosis - An unusual but important determinant for staging and treatment. Int J Hematol Oncol Stem Cell Res 2015;9:193–7.
. Bannach AB, Garcia MTFC, Soares DFG, et al. Langerhans’ cell histiocytosis with neurological injuries diagnosed from a single cutaneous lesion. An Bras Dermatol 2017;92:540–2.
. Ianoşi ES, Mureşan M, Gurzu S, et al. Pulmonary Langerhans cell histiocytosis in a 26-year-old female: still a diagnostic challenge. Rom J Morphol Embryol 2017;58:1047–50.
. Stéphan JL. Langerhans and non-Langerhans histiocytosis. Arch Pediatr 2002;9:934–41.
. de Graaf JH, Mannes GP, Tamminga RY, et al. The role of cytokines in the pathogenesis of pulmonary Langerhans’ cell histiocytosis. Adv Exp Med Biol 1995;378:535–7.
. PDQ Pediatric Treatment Editorial Board (2018). Langerhans Cell Histiocytosis Treatment (PDQ®
): Patient Version. PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–2018 July 6.
. Montella L, Insabato L, Palmieri G. Imatinib mesylate for cerebral Langerhans’-cell histiocytosis. N Engl J Med 2004;351:1034–5.
. Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 2015;373:726–36.
. Willman CL, Busque L, Griffith BB, et al. Langerhans’ cell histiocytosis (histiocytosis X) - a clonal proliferative disease. N Engl J Med 1994;331:154–60.
. de Graaf JH, Tamminga RY, Dam-Meiring A, et al. The presence of cytokines in Langerhans’ cell histiocytosis. J Pathol 1996;180:400–6.
. Baumgartner I, von Hochstetter A, Baumert B, et al. Langerhans’ cell histiocytosis in adults. Med Pediatr Oncol 1997;28:9–14.
. Haupt R, Minkov M, Astigarraga I, et al. Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer 2013;60:175–84.
. Ni M, Yang X. Langerhans’ cell histiocytosis of the temporal bone: a case report. Exp Ther Med 2017;13:1051–3.
. Li X, Deng QI, Li YM. A case of Langerhans’ cell histiocytosis following Hodgkin's disease. Mol Clin Oncol 2016;5:27–30.
. Zhou Y, Li Y, Fan L, et al. A solitary pulmonary ground-glass nodule in adult systemic langerhans’ cell histiocytosis. Int J Clin Exp Pathol 2015;8:13561–4.
. Yi X, Han T, Zai H, et al. Liver involvement of Langerhans’ cell histiocytosis in children. Int J Clin Exp Med 2015;8:7098–106.
. Makras P, Alexandraki KI, Chrousos GP, et al. Endocrine manifestations in Langerhans cell histiocytosis. Trends Endocrinol Metab 2007;18:252–7.
. Haroche J, Cohen-Aubart F, Rollins BJ, et al. Histiocytoses: emerging neoplasia behind inflammation. Lancet Oncol 2017;18:e113–25.
. Le BH, Truex RC. 29-year-old male with seizure and syncope. Intracerebral Langerhans cell histiocytosis. Brain Pathol 2013;23:363–4.
. Dunger DB, Broadbent V, Yeoman E, et al. The frequency and natural history of diabetes insipidus in children with Langerhans-cell histiocytosis. N Engl J Med 1989;321:1157–62.
. Maghnie M, Cosi G, Genovese E, et al. Central diabetes insipidus
in children and young adults. N Engl J Med 2000;343:998–1007.
. Vaiani E, Malossetti C, Vega LM, et al. Predictor variables of developing anterior pituitary deficiencies in a group of paediatric patients with central diabetes insipidus
and langerhans cell histiocytosis. Horm Res Paediatr 2017;87:51–7.
. Chikwava K, Jaffe R. Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders. Pediatr Dev Pathol 2004;7:607–14.
. Lau SK, Chu PG, Weiss LM. Immunohistochemical expression of Langerin in Langerhans cell histiocytosis and non-Langerhans cell histiocytic disorders. Am J Surg Pathol 2008;32:615–9.
. Sabattini E, Bacci F, Sagramoso C, et al. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica 2010;102:83–7.
. Valladeau J, Ravel O, Dezutter-Dambuyant C, et al. Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 2000;12:71–81.
. Cagli S, Oktar N, Demirtas E. Langerhans’ cell histiocytosis of the temporal lobe and pons. Br J Neurosurg 2004;18:174–80.
. Ng Wing Tin S, Martin-Duverneuil N, Idbaih A, et al. Efficacy of vinblastine in central nervous system Langerhans cell histiocytosis: a nation wide retrospective study. Orphanet J Rare Dis 2011;6:83.
. Dhall G, Finlay JL, Dunkel IJ, et al. Analysis of outcome for patients with mass lesions of the central nervous system due to Langerhans cell histiocytosis treated with 2-chlorodeoxyadenosine. Pediatr Blood Cancer 2008;50:72–9.
Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
anterior pituitary hormone deficiency (APD); central diabetes insipidus; hypothalamic-hypophysial axial mass; langerhans’ cell histiocytosis (LCH); multi-diciplinary treatment (MDT)