Objective: Langerhans cell histiocytosis (LCH) is an uncommon neoplasm of dendritic cells and predominantly occurs in children and young adults. The study aims to evaluate cytopathologic features and current diagnostic concepts in a large series of LCH on fine needle aspiration (FNA). Study Design: We retrospectively searched the pathology archives of The Johns Hopkins Hospital (JHH) and Emory University Hospital (EUH) to identify all FNA cases diagnosed as LCH in a period of 21 years. Cytologic material and immunohistochemical stains were reviewed. Results: A total of 37 LCH patients (26 from JHH and 11 from EUH) with FNA diagnoses were identified. The sites of LCH included bone in 28, soft tissue of head and neck in 6, and lymph nodes in 3. Thirty-one patients (84%) were diagnosed as LCH, 4 (11%) had a descriptive diagnosis suggesting scant cellularity with epithelioid/histiocyte-like cells and mixed inflammation, and 2 (5%) were non-diagnostic due to insufficient cellularity. Immunohistochemical stains were performed on cell block sections in 26 cases, showing 24 of 24 (100%) positive for CD1a, 22 of 23 (96%) positive for S100-protein, and 3 of 3 (100%) positive for CD68. Conclusions: LCH can be accurately diagnosed in FNA based on the characteristic cytomorphology and selected immunohistochemistry. Diagnosis may be difficult in cases with scant or insufficient cellular material.

Allen CE, Li L, Peters TL, Leung HC, Yu A, Man TK, Gurusiddappa S, Phillips MT, Hicks MJ, Gaikwad A, Merad M, McClain KL: Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol 2010;184:4557-4567.
Jaffe R, Weiss LM, Facchetti F: Tumours derived from Langerhans cells; in Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. Geneva, World Health Organization, 2008, pp 358-360.
Titgemeyer C, Grois N, Minkov M, Flucher-Wolfram B, Gatterer-Menz I, Gadner H: Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study. Med Pediatr Oncol 2001;37:108-114.
Morimoto A, Ishida Y, Suzuki N, Ohga S, Shioda Y, Okimoto Y, Kudo K, Ishii E; HLH/LCH Committee of the Japanese Society of Pediatric Hematology: Nationwide survey of single-system single site Langerhans cell histiocytosis in Japan. Pediatr Blood Cancer 2010;54:98-102.
Minkov M, Grois N, Heitger A, Pötschger U, Westermeier T, Gadner H; DAL-HX Study Group: Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator. Med Pediatr Oncol 2002;39:581-585.
Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society: Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood 2013;121:5006-5014.
Pileri SA, Grogan TM, Harris NL, Banks P, Campo E, Chan JK, Favera RD, Delsol G, De Wolf-Peeters C, Falini B, Gascoyne RD, Gaulard P, Gatter KC, Isaacson PG, Jaffe ES, Kluin P, Knowles DM, Mason DY, Mori S, Müller-Hermelink HK, Piris MA, Ralfkiaer E, Stein H, Su IJ, Warnke RA, Weiss LM: Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 2002;41:1-29.
Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, Kuo FC, Ligon AH, Stevenson KE, Kehoe SM, Garraway LA, Hahn WC, Meyerson M, Fleming MD, Rollins BJ: Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 2010;116:1919-1923.
Héritier S, Emile JF, Barkaoui MA, Thomas C, Fraitag S, Boudjemaa S, Renaud F, Moreau A, Peuchmaur M, Chassagne-Clément C, Dijoud F, Rigau V, Moshous D, Lambilliotte A, Mazingue F, Kebaili K, Miron J, Jeziorski E, Plat G, Aladjidi N, Ferster A, Pacquement H, Galambrun C, Brugières L, Leverger G, Mansuy L, Paillard C, Deville A, Armari-Alla C, Lutun A, Gillibert-Yvert M, Stephan JL, Cohen-Aubart F, Haroche J, Pellier I, Millot F, Lescoeur B, Gandemer V, Bodemer C, Lacave R, Hélias-Rodzewicz Z, Taly V, Geissmann F, Donadieu J: BRAF mutation correlates with high-risk Langerhans cell histiocytosis and increased resistance to first-line therapy. J Clin Oncol 2016;34:3023-3030.
Elsheikh T, Silverman JF, Wakely PE Jr, Holbrook CT, Joshi VV: Fine-needle aspiration cytology of Langerhans' cell histiocytosis (eosinophilic granuloma) of bone in children. Diagn Cytopathol 1991;7:261-266.
Van Heerde P, Maarten Egeler R: The cytology of Langerhans cell histiocytosis (histiocytosis X). Cytopathology 1991;2:149-158.
Akhtar M, Ali MA, Bakry M, Sackey K, Sabbah R: Fine-needle aspiration biopsy of Langerhans histiocytosis (histiocytosis-X). Diagn Cytopathol 1993;9:527-533.
Kakkar S, Kapila K, Verma K: Langerhans cell histiocytosis in lymph nodes. Cytomorphologic diagnosis and pitfalls. Acta Cytol 2001;45:327-332.
Kumar PV, Mousavi A, Karimi M, Bedayat GR: Fine needle aspiration of Langerhans cell histiocytosis of the lymph nodes. A report of six cases. Acta Cytol 2002;46:753-756.
Layfield LJ, Bhuta S: Fine-needle aspiration cytology of histiocytosis X: a case report. Diagn Cytopathol 1988;4:140-143.
Kirchgraber PR, Weaver MG, Arafah BM, Abdul-Karim FW: Fine needle aspiration cytology of Langerhans cell histiocytosis involving the thyroid. A case report. Acta Cytol 1994;38:101-106.
Harbour JW, Char DH, Ljung BM, Luna-Fineman S: Langerhans cell histiocytosis diagnosed by fine needle biopsy. Arch Ophthalmol 1997;115:1212-1213.
Lee JS, Lee MC, Park CS, Juhng SW: Fine needle aspiration cytology of Langerhans cell histiocytosis confined to lymph nodes. A case report. Acta Cytol 1997;41:1793-1796.
Sahoo M, Karak AK, Bhatnagar D, Bal CS: Fine-needle aspiration cytology in a case of isolated involvement of thyroid with Langerhans cell histiocytosis. Diagn Cytopathol 1998;19:33-37.
SenGupta SK, Vince JD, Chakravorty P, Sinha SK: Langerhan cell granulomatosis with unusual FNAC findings. Diagn Cytopathol 1998;18:349-351.
Dey P, Luthra UK, Sheikh ZA: Fine needle aspiration cytology of Langerhans cell histiocytosis of the thyroid. A case report. Acta Cytol 1999;43:429-431.
el-Halabi DA, el-Sayed M, Eskaf W, Anim JT, Dey P: Langerhans cell histiocytosis of the thyroid gland. A case report. Acta Cytol 2000;44:805-808.
Zhu H, Hu DX: Langerhans cell histiocytosis of the thyroid diagnosed by fine needle aspiration cytology. A case report. Acta Cytol 2004;48:278-280.
Bhadani PP, Sah SP, Agarwal A, Tewari A: Fine needle aspiration diagnosis of congenital langerhans cell histiocytosis of the lymph nodes with isolated skin involvement. Acta Cytol 2005;49:114-116.
Kini U, Bhat PI, Jayaseelan E: FNA diagnosis of primary adult onset lymphocutaneous Langerhans' cell histiocytosis masquerading as deep fungal mycosis. Diagn Cytopathol 2005;32:292-295.
Ramadas PT, Kattoor J, Mathews A, Abraham EK: Fine needle aspiration cytology of Langerhans cell thyroid histiocytosis and its draining lymph nodes. Acta Cytol 2008;52:396-398.
Scuderi RT, Makani SS, Channick CL, Renner JW, Alexander TH, Brumund KT, Read WL, Weidner N: Pulmonary Langerhans cell histiocytosis diagnosed in a cervical lymph node: a case report. Acta Cytol 2010;54:618-622.
Kumar N, Sayed S, Vinayak S: Diagnosis of Langerhans cell histiocytosis on fine needle aspiration cytology: a case report and review of the cytology literature. Patholog Res Int 2011;2011:439518.
Pusztaszeri MP, Sauder KJ, Cibas ES, Faquin WC: Fine-needle aspiration of primary Langerhans cell histiocytosis of the thyroid gland, a potential mimic of papillary thyroid carcinoma. Acta Cytol 2013;57:406-412.
Oza N, Sanghvi K, Menon S, Pant V, Patil M, Kane S: Cytological diagnostic approach in 3 cases of Langerhans cell histiocytosis presenting primarily as a thyroid mass. Acta Cytol 2015;59:418-424.
Roy M, Jain D, Bakhshi S, Mathur S, Iyer VK: Primary Langerhans cell histiocytosis of the thyroid gland: role of langerin in FNA cytological diagnosis. Cytopathology 2015;26:128-130.
Sangtian J, Riangwiwat T, Triamchaisri S, Kanoksil W, Sriphrapradang C: Fine-needle aspiration biopsy of langerhans cell histiocytosis of thyroid gland. J Clin Endocrinol Metab 2015;100:15-16.
Saqi A, Kuker AP, Ebner SA, Ausiello J, Jobanputra V, Bhagat G, Giorgadze TA: Langerhans cell histiocytosis: diagnosis on thyroid aspirate and review of the literature. Head Neck Pathol 2015;9:496-502.
Kuhn E, Ragazzi M, Zini M, Giordano D, Nicoli D, Piana S: Critical pitfalls in the use of BRAF mutation as a diagnostic tool in thyroid nodules: a case report. Endocr Pathol 2016;27:220-223.
Lichtenstein L: Histiocytosis X; integration of eosinophilic granuloma of bone, Letterer-Siwe disease, and Schüller-Christian disease as related manifestations of a single nosologic entity. AMA Arch Pathol 1953;56:84-102.
Nezelof C, Basset F, Rousseau MF: Histiocytosis X histogenetic arguments for a Langerhans cell origin. Biomedicine 1973;18:365-371.
Yu RC, Chu C, Buluwela L, Chu AC: Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet 1994;343:767-768.
Willman CL, Busque L, Griffith BB, Favara BE, McClain KL, Duncan MH, Gilliland DG: Langerhans'-cell histiocytosis (histiocytosis X) - a clonal proliferative disease. N Engl J Med 1994;331:154-160.
Berres ML, Allen CE, Merad M: Pathological consequence of misguided dendritic cell differentiation in histiocytic diseases. Adv Immunol 2013;120:127-161.
Rastogi V, Sharma R, Misra SR, Yadav L, Sharma V: Emperipolesis - a review. J Clin Diagn Res 2014;8:ZM01-ZM02.
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