Immunocytochemical investigation of Langerin (CD207) is a valuable adjunct in the cytological diagnosis of Langerhans cell histiocytosis of the thyroid

Abstract

Langerhans cell histiocytosis (LCH) is an uncommon disease encompassing three clinically different entities: eosinophilic granuloma, Hand-Schüller-Christian disease, and Abt-Letterer-Siewe disease. Despite usually being a multisystemic disease affecting numerous different organs, involvement of the thyroid gland is extremely rare, and only a few cases in adults have been described in the literature. Herein, we present the case of a 28-year-old male patient presenting with LCH involving the skin, the skeletal system, and the thyroid gland. Fine needle aspiration (FNA) of the thyroid was performed and showed the typical Langerhans cells (LC) with foamy cytoplasm and slender nuclei with longitudinal grooves against a background of inflammatory cells with only a few eosinophilic granulocytes. Immunocytochemically, the LC showed positive staining with antibodies against CD1a and Langerin, a recently detected glycoprotein exclusively expressed in LC. Langerin is the major protein that makes up the so-called Birbeck granules, the electronmicroscopical hallmark of LC. Since LCH involvement of the thyroid is occasionally mistaken for papillary thyroid carcinoma cells, we propose that application of Langerin in combination with CD1a is a helpful diagnostic adjunct for the correct assessment of LCH affecting the thyroid gland.

Introduction

Langerhans cell histiocytosis (LCH, formerly referred to as histiocytosis X) is an uncommon disease of hitherto unknown pathogenesis [5]. The entity shows numerous different clinical manifestations and has been subcategorized into three distinct forms: (1) eosinophilic granuloma, a benign disease involving the skeletal system and lungs [14]; (2) Hand-Schüller-Christian disease, usually affecting children younger than 10 years presenting with diabetes insipidus, exophtalmos, hepatosplenomegaly, and bony lesions [1], [11]; and (3) Abt-Letterer-Siewe disease, the rarest and most aggressive form of Langerhans histiocytic proliferations affecting children under 2 years with visceromegaly, lymphadenopathy, bile duct damage, and neuropsychological deficits [7]. Attempts to outline genetic, infectious, or environmental etiological factors that cause LCH have failed [1]. Recently, monoclonality was demonstrated and supports a neoplastic origin of LCH [17]. Despite being a multisystemic disease, involvement of the thyroid gland is rare and may be either isolated or presented as part of a multifocal process. Involvement of the thyroid gland can be focal or diffuse and results in organ enlargement, occasionally accompanied by nodular goiter, lymphocytic thyreoiditis, or papillary carcinoma [4].

The principal cell present in all LCH forms is a non-pigmentary dentritic cell of the monocytic lineage residing in the epidermis [5]. Langerhans cells (LC) resemble other monocytic elements, but show a vesicular nucleus with a groove parallel to the long axis and vacuolated cytoplasm (“coffee-bean-appearance”) [8]. By electron microscopy, characteristic linear rod-shaped cytoplasmic inclusions are demonstrated (Birbeck granules) [13]. Moreover, numerous eosinophilic granulocytes are often found in LCH lesions. LC can be demonstrated with antibodies directed against CD40, CD52, CD154, CD1a, and S-100 protein [10]. Langerin is a recently identified 40 kDa glycoprotein, which is selectively expressed on both the surface and the cytoplasm of immature dentritic cells/Langerhans cells [16]. Antibodies directed against this protein are commercially available and can be used for immunocytochemical characterization of LC. We report a case of a 28-year-old male patient, who presented with LCH with thyroid involvement, which was diagnosed in a fine needle aspiration (FNA) biopsy based on both cytomorphology and immunocytochemistry.