1. August S. Tuan Yin Jie Chen Elizabeth Cottrill James Kearney Diana Noitin Jui-Han Huang Laurie A. Loevner Kim O. Learned Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

2. Disclosures  The authors report no disclosures

3. Purpose  Lymphoepithelial cysts of the thyroid gland is a rarely recognized entity that may present as an enlarging neck mass or may be found incidentally.

4. Clinical Summary  66-year-old caucasian man with hypothyroidism who was referred to Otorhinolaryngology for 5-6 months of enlarging thyroid goiter and progressive dysphagia.  The patient was on daily thyroid hormone replacement.  No history of irradiation.  No family history of thyroid cancer.  FNA was nondiagnostic; findings were suspicious for but not conclusive of malignancy in the very large left thyroid lobe.  Physical examination: Thyroid mass with left lobe more enlarged than the right. No tenderness to palpation. No palpable cervical lymph nodes.

5. Imaging  The thyroid gland is enlarged, cystic, and multi-septated.  Mild displacement of the patent airway and adjacent vascular structures.  No pathologic cervical lymph nodes.

6. Imaging  Thyroid ultrasound demonstrates mass-like areas of varying echogenicity, some which appear complex cystic, and some vascularity in the cyst walls and septations.

7. Management  Although malignant pathology was not definitive, the patient was symptomatic from the very large thyroid mass and elected to undergo total thyroidectomy.

8. Operative Summary  Total thyroidectomy was performed in the normal fashion through a midline incision.  The thyroid was composed almost entirely of numerous 1 to 3 cm, tense, thin-walled cystic structures.  While removing the right thyroid lobe, several cysts burst with gentle retraction on the gland and caused considerable “deflation” of the lobe. The fluid was clear with a glistening sheen and was light yellow-green in color.  The isthmus was transected and the right lobe was removed. The left thyroid lobe which was somewhat larger in size with a similar cystic appearance and also removed.

9. Enlarged and cystic left thyroid lobe

10. The left thyroid lobe measured approximately 12-13cm

11. Pathology Findings  Final Diagnosis Lymphoepithelial cyst. No thyroid tissue seen. Multiple cervical lymph nodes with reactive hyperplasia.  Details The specimen is received fresh. The specimen consists of a total thyroid measuring 13.3 x 7.4 x 3.1 cm overall and weighing 226 grams. The right lobe measures 9.9 x 2.2 x 1.6 cm. The left lobe measures 13.3 x 5.8 x 2.6 cm. The isthmus measures 4.1 x 1.1 x 1.2 cm. The surface of the thyroid is red in color and nodular. The right lobe is serially sectioned to reveal diffuse multi-loculated cyst with hemorrhage measuring 0.5-1.1 cm in greatest dimension and tan-white discoloration. The left lobe is serially sectioned to reveal diffuse multi-loculated cyst with smooth to irregular wall and focal hemorrhage measuring 0.5-4.0 cm in greatest dimension. The isthmus appears cystic.”

12. Histology  H&E stained sections showed diffuse, polymorphous, lymphoid tissue with prominent germinal centers surrounding multiple squamous-lined epithelial cysts.  Cyst lumen contained keratin and debris with cholesterol clefts.  No residual thyroid tissue.

13. Clinical Features  Lymphoepithelial cysts of the thyroid gland is a rarely recognized entity. Less than 25 reported cases. Only 6 cases involved both thyroid lobes.  Histologically similar to branchial cleft cysts found in the lateral neck. Cysts have an epithelial lining that is usually stratified squamous epithelium but may focally include respiratory-type epithelium. Morphological similar to branchial cleft cysts which are derived from the embryonic remnants of the branchial pouch, embryonic rests have been considered for the origin of lymphoepithelial cysts in most organs.  They have been reported to occur in unusual sites or organs Oral cavity Parotid gland Pancreas Parathyroid gland

14. Clinical Features  Demographics: Average age is 40 years A 2:1 female to male ratio.  Patients typically present with a thyroid nodule or goiter.  The literature shows a trend toward multiple, bilateral, and large-sized lymphoepithelial cysts in patients with Hashimoto’s or lymphocytic thyroiditis, however, bilateral and multiple cysts have been reported without these conditions as were present in our patient.  In all of the previous reported cases, only portions of the thyroid glands were replaced by lymphoepithelial cysts with some residual thyroid tissue seen at pathology. In contrast, our patient had no residual identifiable thyroid gland on both gross pathology and microscopic level despite additional sampling and has not been previously reported in the literature.

15. Pathology Features  On gross pathology: Lymphoepithial cysts of thyroid gland appear as multilocular cysts Various cyst sizes (from subcentimeter in some cases to occupying the entire gland as in our case). Cysts contain fluids of varying colors (including dark brown, red / hemorrhagic, clear, yellow, and green).  On histology: Lymphoepithelial cysts are lined by predominantly stratified squamous epithelium and focal respiratory epithelium Contain keratin and debris with cholesterol clefts. Abundant lymphoid aggregates with prominent germinal centers surround the cysts.

16. Imaging Characteristics  Ultrasound: Lymphoepithelial cysts most commonly appear as heterogeneous cystic lesions with or without more solid appearing internal components. Occasionally they may appear as a solid mass, leading to a more suspicious appearance, especially if calcifications are also seen. Color Doppler may show vascularity associated with the more solid appearing components.  CT: Lymphoepithelial cysts may appear as multi-septated cysts (or as a unilocular cyst if very small). Enlarge the involved thyroid lobe. Produce potential mass effect on surrounding structures.

17. Treatment and Prognosis  Although these cysts are histologically benign, they may raise clinical suspicion of a neoplastic process, and as with our case, FNA may be unable to provide definitive diagnosis.  Additionally, these cystic lesions may enlarge and cause compressive airway symptoms or dysphagia. Therefore, many of these lesions undergo elective total or hemi-thyroidectomy.  After surgical removal, there have been no reports of recurrence.

18. Summary  Lymphoepithelial cysts of the thyroid gland is a rarely recognized entity that may present as an enlarging neck mass or may be found incidentally.  Histopathogenesis is poorly understood, however, it is postulated that lymphoepithelial cysts arise from solid cell nests of embryonic remnants of the ultimobranchial bodies during gland embryogenesis.  While benign, they may enlarge and cause compressive airway symptoms or dysphagia.  FNA may be unreliable or indeterminate and surgical excision may be needed for definitive diagnosis.  There is no previously reported case where lymphoepithelial cysts have completely replaced the entire thyroid gland.

19. References  Nakazawa T, Kondo T, Oishi N, et al. Branchial Cleft-Like Cysts Involving 3 Different Organs: Thyroid Gland, Thymus, and Parotid Gland. Medicine (Baltimore). 2015;94:e1758.  Choi CJ, Choi SW, Cho JG, Woo JS. Bilateral lymphoepithelial cysts of the thyroid gland. Thyroid. 2010;20:111-113.  Kwak JY, Kim EK, Jung HK, Park HL, and Kim GI. Lymphoepithelial cyst of the thyroid mimicking malignancy on sonography. J Clin Ultrasound. 2006;34:298-300.  Carter E and Ulusarac O. Lymphoepithelial cysts of the thyroid gland. A case report and review of the literature. Arch Pathol Lab Med. 2003;127:e205-208.  Ryska A, Vokurka J, Michal M, and Ludvikova M. Intrathyroidal lymphoepithelial cyst. A report of two cases not associated with Hashimoto's thyroiditis. Pathol Res Pract. 1997;193:777-781.