Background: The clinical presentation of Langerhans cell histiocytosis (LCH) as a primary solitary nodule in the thyroid gland is rare. As a result, there are few reports of its cytologic features in thyroid aspirates where it can pose a diagnostic pitfall. Case and Conclusion: To foster familiarity with its cytomorphology, we report the fine-needle aspiration biopsy (FNAB) findings of 3 specimens from 2 patients with LCH presenting as a solitary thyroid nodule. All aspirates contained numerous dispersed cells with prominent nuclear grooves, and the background showed a mixed pattern of chronic inflammation including scattered eosinophils. The aspirate from patient 1 raised a differential diagnosis that included chronic lymphocytic thyroiditis and a thyroglossal duct cyst, while the aspirate from patient 2 was interpreted as ‘suspicious for papillary thyroid carcinoma'. The diagnosis of LCH was confirmed in both patients after lobectomy and immunohistochemical studies that revealed positive reactivity for CD1a and S-100. LCH of the thyroid gland is rare and can pose significant diagnostic challenges, but increased familiarity with its characteristic cytomorphology can help in avoiding diagnostic pitfalls.

1.
Merad M, Ginhoux F, Collin M: Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol 2008;8:935-947.
2.
Birbeck MS, Breathnach AS, Everall JD: An electron microscope study of basal melanocytes and high-level clear cells (Langerhans cells) in vitiligo. J Invest Dermatol 1961;37:51-64.
3.
Cella M, Sallusto F, Lanzavecchia A: Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol 1997;9:10-16.
4.
Hart DN: Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 1997;90:3245-3287.
5.
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.
6.
Valladeau J, Duvert-Frances V, Pin JJ, et al: The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface. Eur J Immunol 1999;29:2695-2704.
7.
Dezutter-Dambuyant C, Schmitt D, Staquet MJ, Gaucherand M, Cambazard F, Thivolet J: DMC1: a monoclonal antibody produced from histiocytosis X cells which reacts with the native CD1a molecule of human epidermal Langerhans cells. Hybridoma 1989;8:199-208.
8.
Coventry B, Heinzel S: CD1a in human cancers: a new role for an old molecule. Trends Immunol 2004;25:242-248.
9.
Weiss LM, Grogan TM, Muller-Hermelink HK, et al: Langerhans cell histiocytosis; in: Jaffe ESHN, Stein H, Vardiman JW (ed): World Health Organization Classification of Tumors. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon, IARC Press, 2001, pp 280-282.
10.
Avery ME, McAfee JG, Guild HG: The Course and Prognosis of Reticuloendotheliosis (Eosinophilic Granuloma, Schuller-Christian Disease and Letterer-Siwe Disease): a Study of Forty Cases. Am J Med 1957;22:636-652.
11.
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.
12.
Nicholson HS, Egeler RM, Nesbit ME: The epidemiology of Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998;12:379-384.
13.
Lichtenstein L: Histiocytosis X: integration of eosinophilic granuloma of bone, Letterer-Siwe disease, and Schüller-Christian disease as related manifestation of a single nosologic entity. AMA Arch Pathol 1953;56:84-102.
14.
Lieberman PH, Jones CR, Steinman RM, et al: Langerhans cell (eosinophilic) granulomatosis. A clinicopathologic study encompassing 50 years. Am J Surg Pathol 1996;20:519-552.
15.
Kabel PJ, Voorbij HA, van der Gaag RD, Wiersinga WM, de Haan M, Drexhage HA: Dendritic cells in autoimmune thyroid disease. Acta Endocrinol Suppl (Copenh) 1987;281:42-48.
16.
Kabel PJ, Voorbij HA, De Haan M, van der Gaag RD, Drexhage HA: Intrathyroidal dendritic cells. J Clin Endocrinol Metab 1988;66:199-207.
17.
Hilly O, Koren R, Raz R, et al: The role of s100-positive dendritic cells in the prognosis of papillary thyroid carcinoma. Am J Clin Pathol 2013;139:87-92.
18.
Xu W, Li X, Chen S, et al: Expression and distribution of S-100, CD83 and apoptosis-related proteins (Fas, FasL and Bcl-2) in tissues of thyroid carcinoma. Eur J Histochem 2008;52:153-162.
19.
Ugolini C, Basolo F, Proietti A, et al: Lymphocyte and immature dendritic cell infiltrates in differentiated, poorly differentiated, and undifferentiated thyroid carcinoma. Thyroid 2007;17:389-393.
20.
Schröder S, Schwarz W, Rehpenning W, Löning T, Böcker W: Dendritic/Langerhans cells and prognosis in patients with papillary thyroid carcinomas. Immunocytochemical study of 106 thyroid neoplasms correlated to follow-up data. Am J Clin Pathol 1988;89:295-300.
21.
Yamakawa M, Yamada K, Orui H, et al: Immunohistochemical analysis of dendritic/Langerhans cells in thyroid carcinomas. Anal Cell Pathol 1995;8:331-343.
22.
Yamakawa M, Kato H, Takagi S, Karube Y, Seki K, Imai Y: Dendritic cells in various human thyroid diseases. In Vivo 1993;7:249-256.
23.
Batistatou A, Zolota V, Scopa CD: S-100 protein+ dendritic cells and CD34+ dendritic interstitial cells in thyroid lesions. Endocr Pathol 2002;13:111-115.
24.
Pusztaszeri MP, Sadow PM, Faquin WC: Association of CD1a-Positive Dendritic Cells with Papillary Thyroid Carcinoma in Thyroid FNAs: A Cytological and Immunocytochemical Evaluation. Cancer Cytopathol 2012 DOI: 10.1002/cncy.21239 [Epub ahead of print].
25.
Elliott DD, Sellin R, Egger J, Medeiros LJ: Langerhans cell histiocytosis presenting as a thyroid gland mass. Ann Diagn Pathol 2005;9:267-274.
26.
Foulet-Roge A, Josselin N, Guyetant S, et al: Incidental Langerhans cell histiocytosis of thyroid: case report and review of the literature. Endocr Pathol 2002;13:227-233.
27.
Thompson LD, Wenig BM, Adair CF, Smith BC, Heffess CS: Langerhans cell histiocytosis of the thyroid: a series of seven cases and a review of the literature. Mod Pathol 1996;9:145-149.
28.
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.
29.
Dey P, Luthra UK, Sheikh AZ: Fine Needle Aspiration Cytology of Langerhans Cell Histiocytosis of the Thyroid: A Case Report. Acta Cytol 1999;43:429-431.
30.
Sahoo M, Darak AK, Bhatnagar D, Bal C: Fine-Needle Aspiration Cytology in a Case of Isolated Involvement of Thyroid With Langerhans Cell Histiocytosis. Diagn Cytopathol 1998;19:33-37.
31.
Pohar-Marinsek Z, Us-Krasovec M: Cytomorphology of Langerhans Cell Histiocytosis. Acta Cytol 1995;40:1257-1264.
32.
Akhtar M, Ali MA, Bakry M, Sackey K, Sabbah R: Fine-needle aspiration biopsy of Langerhans histiocytosis (Histiocytosis-X). Diagn Cytopathol 1993;9:427-533.
33.
Elsheikh T, Silverman JF, Wakely PE, Holbrook CT, Joshi VV: Fine-needle aspiration cytology of Langerhans' cell histiocytosis (eosinophilic granuloma) of bone in children. Diagn Cytopathol 1991;7:261-266.
34.
Kitahama S, Litaka M, Shimizu T, et al: Thyroid involvement by malignant histiocytosis of Langerhans' cell type. Clin Endocrinol (Oxf) 1996;45:357-363.
35.
Wang W, Liu J, Hsieh R, Yen C, Chen P: Langerhans' Cell Histiocytosis with Thyroid Involvement Masquerading as Thyroid Carcinoma. Jpn J Clin Oncol 1997;27:180-184.
36.
Goldstein N, Layfield LJ: Thyromegaly secondary to papillary carcinoma and histiocytosis X. Acta Cytol 1991;35:422-426.
37.
Braiteh F, Kurzrock R: Case 1. Langerhans Cell Histiocytosis of the Thyroid. J Clin Oncol 2006;24:522-523.
38.
Saiz E, Bakotic BW: Isolated Langerhans cell histiocytosis of the thyroid: a report of two cases with nuclear imaging-pathologic correlation. Ann Diagn Pathol 2000;4:23-28.
39.
Green I, Behar AJ, Shanon E, Gorsky M: Multifocal extraosseous eosinophilic granuloma of the head and neck. Arch Otolaryngol Head Neck Surg 1988;114:561-563.
40.
Patten DK, Wani Z, Tolley N: Solitary langerhans histiocytosis of the thyroid gland: a case report and literature review. Head Neck Pathol 2012;6:279-289.
41.
Maurea S, Lastoria S, Klain M, et al: Diagnostic evaluation of thyroid involvement by histiocytosis X. J Nucl Med 1994;35:263-265.
42.
Behrens RJ, Levi AW, Westra WH, Dutta D, Cooper DS: Langerhans Cell Histiocytosis of the Thyroid: A Report of Two Cases and Review of the Literature. Thyroid 2001;11:697-705.
43.
Renshaw AA: ‘Histiocytoid' cells in fine-needle aspirations of papillary carcinoma of the thyroid: frequency and significance of an under-recognized cytologic pattern. Cancer 2002;96:240-243.
44.
Harshan M, Crapanzano JP, Aslan DL, Vazquez MF, Saqi A: Papillary thyroid carcinoma with atypical histiocytoid cells on fine-needle aspiration. Diagn Cytopathol 2009;37:244-250.
45.
Sofiadis A, Dinets A, Orre LM, et al: Proteomic study of thyroid tumors reveals frequent up-regulation of the Ca2+-binding protein S100A6 in papillary thyroid carcinoma. Thyroid 2010;20:1067-1076.
46.
Vergez S, Rouquette I, Ancey M, Serrano E, Caron P: Langerhans cell histiocytosis of the thyroid is a rare entity, but an association with a papillary thyroid carcinoma is often described. Endocr Pathol 2010;21:274-276.
47.
Broadbent V, Gadner H: Current therapy for Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998;12:327-338.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.