http://jsms.sch.ac.kr 131

Cytological Features of a Lymphoepithelial Cyst Collected from Fine Needle Aspiration of the Thyroid Gland That Mimicked Papillary Thyroid Carcinoma: A Case ReportIn Ho Choi1, Sun-Wook Kim2, Jee Soo Kim3, Young-Lyun Oh4

1Department of Pathology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul; Departments of 2Medicine, 3Surgery, and 4Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Since its first description in 1989, lymphoepithelial cyst of the thyroid gland (LEC-T) has been generally considered a branchial cleft derivative similar to its presentation in other sites, including thymus, parathyroid, and pancreas. However, its characterization has mainly focused on histologic and sonographic findings, and cytological findings are generally described simply or left out entirely. Fine needle aspiration cytology (FNAC) of our case showed large tissue fragments of epithelial cells on a background of lympho-cytes. Some areas showed sheets or small nests of squamoid cells, which were closely admixed with clusters of lymphoid cells. Squamous cells contained relatively moderate to large amounts of eosinophilic cytoplasm and vesicular nuclei with occasional nu-clear grooves that lacked intranuclear inclusions. Some cells demonstrated keratinization and nuclear atypia. Herein, we describe FNAC findings of LEC-T and review other possible diagnoses.

Keywords: Thyroid gland; Branchioma; Cyst; Cell biology

INTRODUCTION

The lymphoepithelial cyst of the thyroid gland (LEC-T) has been generally considered as a branchial cleft derivative, and it has been unusual occurring site like other unusual sites such as the thymus, oral cavity, parotid gland, and pancreas [1]. Since the first report of a LEC-T in 1989, its histological resemblance to branchial cleft cysts and embryological branchial cleft derivatives in the thyroid, thy-mus, and parathyroid have led to general consensus of its branchial origin [2]. Although there have been several reports of histological and immunohistochemical findings of LEC-T [1], its cytological characteristics have been described in only a few reports [3-5]. Here-in, we describe the cytological findings on fine needle aspiration cy-tology (FNAC) of a 54-year-old woman with LEC-T mimicking papillary thyroid carcinoma (PTC).

CASE REPORT

1. Patient history

A 54-year-old woman with no previous medical problems visited hospital due to a palpable neck mass. Laboratory findings showed increased microsomal antibody (1,175.4 μ/mL; normal, 0-60 μ/mL) but normal findings in other thyroid function test, parathyroid hor-mone, and calcitonin. Sonographically, the mass was a 1.6-cm, ir-regular, calcified, hypoechoic nodule (Fig. 1A) in the inferior pole of the right thyroid with multiple hypoechoic lesions in bilateral cervi-cal lymph nodal enlargement. Due to suspicion for malignancy, so-no-guided FNAC and BRAF study (result: not detected) were per-formed. Computed tomography revealed a 1.4-cm, mildly enhanc-ing soft-tissue mass in the right thyroid lobe (Fig. 1B) with multiple suspicious metastatic nodes. Total thyroidectomy was performed due to concern for thyroid cancer.

Soonchunhyang Medical Science 20(2):131-135, December 2014 pISSN: 2233-4289 I eISSN: 2233-4297

CASE REPORT

Correspondence to: Young-Lyun OhDepartment of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, KoreaTel: +82-2-3410-2805, Fax: +82-2-3410-0025, E-mail: yl.oh@samsung.comReceived: Sep. 30, 2014 / Accepted after revision: Oct. 27, 2014

© 2014 Soonchunhyang Medical Research InstituteThis is an Open Access article distributed under the terms of the

Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

Choi IH, et al. • Cytology of Lymphoepithelial Cyst in Thyroid Gland

Soonchunhyang Medical Science 20(2):131-135132 http://jsms.sch.ac.kr

2. Cytological findings of lymphoepithelial cyst of the

thyroid gland

FNAC of LEC-T showed large tissue fragments of epithelial cells

on a background of lymphocytes (Fig. 2A). Most of these syncytial fragments demonstrated overwhelming cellularity with no notice-able architectural configuration. However, focal areas showing a

A B

Fig. 1. Radiologic findings of a lymphoepithelial cyst of the thyroid gland. (A) Ultrasonography reveals a 1.6-cm, irregular, hypoechoic nodule in the inferior pole of the right lobe and multiple hypoechoic lesions in the mid and superior poles. (B) Computed tomography reveals a 1.4-cm, mildly enhanced soft-tissue mass in the right lobe and heterogeneous attenuation in the parenchyma of both lobes.

A C

D E F

Fig. 2. Fine needle aspiration cytology of the lymphoepithelial cyst of the thyroid gland. (A) Syncytial tissue fragments are present in the lymphocytic background. (H&E, × 12.5). (B) Cellular fragments show papillary-like configuration with fibrovascular stroma (H&E, × 40). (C) Area suggesting squamous metaplasia is identified in the tissue fragments (H&E, × 100). (D) Squamous components (left side) and clusters of lymphoid cells (center and superior side) are closely blended (H&E, × 200). (E) Some areas of squamous cells show unorganized arrangement and mild cellular atypia (H&E, × 400). (F) Several small solid cell nests and detached cells are intermin-gled with lymphocytes (H&E, × 400).

B

Cytology of Lymphoepithelial Cyst in Thyroid Gland • Choi IH, et al.

Soonchunhyang Medical Science 20(2):131-135 http://jsms.sch.ac.kr 133

papillary-like configuration with fibrovascular stroma (Fig. 2B) and suggesting squamous metaplasia were also noted (Fig. 2C). Sheets of squamoid cells were closely admixed with clusters of lymphoid cells (Fig. 2D). These cells contained relatively moderate to large amounts of eosinophilic cytoplasm and vesicular nuclei, which varied in size from micro- to macronucleoli. Nuclear grooves were occasionally present, but intranuclear inclusions were not identified. Some cells demonstrated keratinization and nuclear atypia (Fig. 2E). Small sol-id nests and single squamoid cells were dispersed on the back-ground of lymphocytes (Fig. 2F). Scattered lymphocytes showed polymorphous features without atypia, but eosinophils were not easily recognized. FNAC was interpreted as suspicious for PTC on a

background of Hashimoto’s thyroiditis.

3. Histological findings of lymphoepithelial cyst of the

thyroid gland

Grossly, the resected specimen showed a multinodular, yellowish-gray, solid lesion (Fig. 3A, arrowhead) in the inferior pole of the right thyroid lobe. The surrounding parenchyma of both lobes showed multiple tiny, patchy lesions. Microscopically, the lesion consisted of labyrinth-like cystic spaces lined by squamous epithelial cells with florid lymphoid hyperplasia forming follicles and germinal cen-ters (Fig. 3B, C). Some squamoid cells had solid or pseudopapillary architectures (Fig. 3D, E), and several necrotic foci with cholesterol

A B C

D E F

G H I

Fig. 3. Macroscopic and microscopic findings of the lymphoepithelial cyst of the thyroid gland. (A) Grossly, the specimen has a multinodular, yellowish-gray, solid le-sion (arrowhead). (B-F) The lesion is a labyrinth-like cystic lesion lined by squamous epithelial cells with florid lymphoid hyperplasia and focal desquamating keratin. The epithelial components show solid and papillary architecture. Some damaged cellular lesions shows lymphocytic and eosinophilic infiltration (H&E stain; B, × 12.5; C,× 100; D&E,× 200; F, × 400). (G) The p63 is positive in the squamous components (× 200). (H) Ki-67 proliferation index is less than 2% (× 200). (I) Opposite lobe con-tains a 0.2-cm papillary microcarcinoma, follicular variant (H&E, × 200).

Choi IH, et al. • Cytology of Lymphoepithelial Cyst in Thyroid Gland

Soonchunhyang Medical Science 20(2):131-135134 http://jsms.sch.ac.kr

crystals and calcification were also noted. Some damaged areas of the squamous epithelium demonstrated cellular atypia and an in-filtration of lymphocytes and eosinophils (Fig. 3F). The squamous elements showed positivity for p63 (Fig. 3G). Indeed, Ki-67 prolif-eration index of theses squamous elements was less than 2%, sug-gesting a benign lesion (Fig. 3H). No atypical lymphoid tissue was identified. The surrounding parenchyma showed lymphocytic in-filtration with lymphoid aggregation. Incidentally, a minute PTC (0.2 cm), follicular variant was found in the opposite lobe but was not detected during preoperative radiologic examinations (Fig. 3I). No lymph node metastasis was noted.

DISCUSSION

LEC-T has been postulated to originate from solid cell nests of the thyroid gland, which are derivatives of the embryonic ultimo-branchial body [6], and are associated with chronic or Hashimoto’s thyroiditis. Previous reports about LEC-T focused on its histologi-cal and sonographic findings, and almost all cases demonstrated benign sonographic findings with rare calcification [4,5]. Other-wise, previous reports of cytological features of LEC-T on FNAC were sparsely documented and simple, despite the practical useful-ness of FNAC today [3-5].

The key feature of the present case is squamous metaplasia with a lymphocytic background. Large syncytial clusters or small solid nests of squamous epithelial cells and clusters of lymphoid cells were closely mixed (Fig. 2C-F). A variety of thyroid lesions can exhibit squamous differentiation, and it is problematic and challenging to differentiate metaplastic from neoplastic origin. Nodular, tumor-like squamous metaplasia can appear as an evolution of Hashimoto’s thyroiditis and nodular goiter [7,8]. However extensive squamous metaplasia is rarely present on thyroidal FNAC and requires a thor-ough approach to diagnosis and treatment [7].

Given squamous metaplasia with lymphocytic background on cytology, several other entities can be considered in the differential diagnosis, including mucoepidermoid carcinoma, squamous cell carcinoma, and Warthin-like variant of PTC. High-grade muco-epidermoid carcinoma can exhibit malignant cells similar to squa-mous or anaplastic carcinoma. In particular, sclerosing mucoepi-dermoid carcinoma with eosinophilia often occurs on the back-ground of Hashimoto’s thyroiditis, and its cytological findings are characterized by tissue fragments of squamous cells with varying degrees of differentiation. Mucoepidermoid carcinoma of the thy-

roid gland is known to show mucin-producing cells, intermediate cells, and squamous cells on FNAC, consistent with salivary gland origin. However, the present case showed no glandular differentia-tion or eosinophilia.

Most cases of squamous cell carcinoma of thyroid are present with primary papillary carcinoma or anaplastic carcinoma of thy-roid, remaining rare cases with pure squamous cell carcinoma (less than 1% of all thyroid cancer). Consequentially, the aspiration cy-tology of squamous cell carcinoma in thyroid, whether the pure form or the combined form with papillary or anaplastic carcinoma, can show large sheets of squamous epithelium. However, it usually shows marked nuclear atypia, frequent mitoses, and necrotic back-ground comparing to LEC-T; therefore, absence of these atypical findings may help identify the true diagnosis of LEC-T.

Among the other neoplasms, squamous metaplasia is occasion-ally seen in PTCs (range, 20% to 40%), including conventional and Warthin-like variant (W-PTC) [9]. If syncytial tissue fragments of epithelial cells with abundant cytoplasm with or without papillary architecture are closely admixed with lymphoid tissue, a specimen can be mistaken for W-PTC. Our case showed squamoid syncytial fragments closely intermingled with lymphoid tissue, matching histological findings showing the squamous epithelium and sub-epithelial lymphoid aggregates (Figs. 2D, 3C). W-PTC can show predominant cystic change, but it usually occurs in the lateral lobe and is composed of Hurthle cells [10], which is opposed to present case having no oncocytic cells on FNAC. Indeed, no case of the Warthin-like variant of PTC with extensive squamous metaplasia has been reported in literature of thyroid FNAC.

Although some authors have insisted that LEC-T should be con-sidered for solid thyroidal masses with respiratory epithelium on FNAC [5], cases without respiratory cells and extensive lymphocyte and squamous tissue fragments may still be malignant, especially when some cells show PTC-like nuclei. Additionally, microscopic findings with mild nuclear atypia squamous metaplasia on lym-phocytic background and the additional radiologic findings suspi-cious for lymph node metastasis like present case led to the misdi-agnosis of PTC, in spite of the first impression of lymphocytic thy-roiditis with extensive squamous metaplasia.

To conclude, it is important to know the cytological pitfalls of LEC-T, which may hinder correct diagnosis and prevent appropri-ate conservative management. Identifying the definite cytological atypia of squamous cells and nuclei of PTC may help cytopatholo-gists to make the diagnosis of LEC-T as opposed to malignancy.

Cytology of Lymphoepithelial Cyst in Thyroid Gland • Choi IH, et al.

Soonchunhyang Medical Science 20(2):131-135 http://jsms.sch.ac.kr 135

REFERENCES

1. Carter E, Ulusarac O. Lymphoepithelial cysts of the thyroid gland: a case report and review of the literature. Arch Pathol Lab Med 2003;127:e205-8.

2. Apel RL, Asa SL, Chalvardjian A, LiVolsi VA. Intrathyroidal lymphoepi-thelial cysts of probable branchial origin. Hum Pathol 1994;25:1238-42.

3. Mitteldorf CA, Misiara AC, de Carvalho IE. Multicystic autoimmune thy-roiditis-like disease associated with HIV infection: a case report. Acta Cytol 1999;43:862-6.

4. Ahuja AT, Chang AR, To E, Pang P, Ching AS, King AD, et al. Intrathyroi-dal lymphoepithelial (branchial) cyst: sonographic features of a rare lesion. AJNR Am J Neuroradiol 2000;21:1340-3.

5. Kwak JY, Kim EK, Jung HK, Park HL, Kim GI. Lymphoepithelial cyst of the thyroid mimicking malignancy on sonography. J Clin Ultrasound 2006; 34:298-300.

6. Beckner ME, Shultz JJ, Richardson T. Solid and cystic ultimobranchial body remnants in the thyroid. Arch Pathol Lab Med 1990;114:1049-52.

7. Leung AH, Kort KC, Khurana KK. Reparative change with extensive squa-mous metaplasia: a potential diagnostic pitfall on thyroid aspiration. South Med J 2010;103:268-71.

8. Musso-Lassalle S, Butori C, Bailleux S, Santini J, Franc B, Hofman P. A di-agnostic pitfall: nodular tumor-like squamous metaplasia with Hashimo-to’s thyroiditis mimicking a sclerosing mucoepidermoid carcinoma with eosinophilia. Pathol Res Pract 2006;202:379-83.

9. Ryska A, Ludvikova M, Rydlova M, Cap J, Zalud R. Massive squamous metaplasia of the thyroid gland: report of three cases. Pathol Res Pract 2006; 202:99-106.

10. Baloch ZW, LiVolsi VA. Warthin-like papillary carcinoma of the thyroid. Arch Pathol Lab Med 2000;124:1192-5.