Introduction

Ectopic thyroid tissue (ETT) refers to thyroid follicular tissue that is located outside of the thyroid bed, which is a rare phenomena, primarily caused by embryologic disorders and dysgenesis and has an incidence of 1 case per 1,00,000 individuals. The base of the tongue(~90%) is the most common ectopic site and is followed by sublingual and intratracheal region in the midline neck(1). Ectopic thyroid tissue is occasionally encountered within the lateral neck node resected from patients with thyroid carcinomas which accounts for only 1% - 3% of thyroid ectopies(2). Distinguishing benign thyroid tissue and a nodal metastasis can be challenging and has direct impact on staging and treatment(3).

Case Report

A 64 year old male presented with anterior neck swelling for the past 20 years. On examination a swelling of size 5 x 5 cm was present in the anterior aspect of neck, firm in consistency and lower lobes were not palpable. Fine needle aspiration cytology of thyroid showed thyroid follicular cells with overcrowding and many nuclei showing nuclear grooving, suggestive of Bethesda category III- Atypia of undetermined significance.

Patient underwent total thyroidectomy with bilateral neck node dissection. Gross examination showed an ill defined infiltrating lesion of size 6 x 3.5 x 1.5 cm; 3.9 x 1.9 x 1.4 cm and 0.4 x 0.4 cm involving right lobe, left lobe and isthmus respectively with macroscopic extension into the adjacent strap muscles. Histopathology revealed an infiltrating tumor arranged in broad papillae with tumor cells exhibiting moderate nuclear pleomorphism and mitosis of <3 per mm², with foci of nuclear crowding, overlapping and infiltration into strap muscles. Microscopic examination of bilateral neck nodes showed an incidental finding with foci of thyroid inclusion consisting of normal appearing thyroid follicles in the subcapsular region of the lymph node. They exhibited no papillarity or nuclear atypism and no psammoma bodies, with rest of the lymph nodes showing reactive lymphoid hyperplasia. On retrospective examination of lymph nodes, the cut surface of both the lymph nodes were unremarkable. Considering all these factors, a comprehensive diagnosis of conventional papillary carcinoma thyroid, involving both lobes of thyroid and isthmus with extrathyroidal extension into strap muscles and benign thyroid inclusions of bilateral neck nodes was made.

Figure 1: Right and left lobe of thyroid with isthmus (a); cut surface showing ill-defined grey-white infiltrating lesion (b); tumor cells arranged in papillae (c,d); tumor infiltrating into the strap muscles (e)

Figure 2: Bilateral neck nodes- showing well-formed thyroid inclusions containing clusters of normal appearing thyroid follicles lined by flattened to cuboidal epithelium filled with colloid. No papillary/nuclear features seen.

Discussion

Benign thyroid inclusions occur in various anatomical site and clinical conditions and includes both benign and malignant differential diagnosis. During embryonic development, migration of thyroid tissue can result in ectopic depositions in different parts of the body. ETTs have been reported in heart, lung, mediastinum, ovaries, adrenals, duodenum, pancreas, intestine and various locations in the neck and throat(4). There have only been 17 reports of benign thyroid tissue in neck lymph nodes in the previous 20 years, making it an uncommon condition(5,6). It has been proposed that abnormalities that result in ejection of thyroid tissue from the gland, and migration via the lymphatic system during embryogenesis may result in ETT in lymph nodes(5).

Thyroid inclusions in neck lymph nodes need to be differentiated from several other conditions. These include (a) Displaced masses of thyroid tissue, in the neck outside of lymph nodes, for which a connection to the thyroid gland is often demonstrated; (b) Lateral aberrant thyroid tumors, which are thought to be metastatic papillary carcinomas; (c) struma lymphomatosa, characterized by hyperplastic lymphoid tissue with germinal centers surrounding the group of thyroid follicles within the thyroid gland and (d) thyroid tissue can be implanted in the soft tissue of the neck following a thyroidectomy, even at a considerable distance from the site of the incision(7).

Distinguishing nodal metastasis of primary thyroid cancer from ETT in neck lymph nodes can be challenging. This is due to the fact that all thyroid tissue found in lymph nodes are often considered as malignant(3,8). Histologic criteria has been proposed to distinguish benign thyroid inclusions from malignant in lymph nodes(5,6). This comprises the extent and morphology of thyroid follicles, absence of psammoma bodies, absence of desmoplastic stroma, immunohistochemistry and molecular profiling(3). It is possible to differentiate benign thyroid tissue and thyroid carcinoma in lymph node; if the thyroid tissue satisfies the criteria in Table 1.(5,9)

According to autopsy or neck dissection, the probability of benign thyroid inclusions or psammoma bodies in patients who have had cervical lymphadenectomy is about 0.8% and 0.6 to 0.5% in head and neck lymph nodes respectively(6,10). Thus the discrimination requires caution because benign intranodal thyroid tissue may falsely show up as metastasis of occult thyroid carcinoma in neck lymph nodes. In the present case, bilateral neck node dissection done for suspicion of thyroid carcinoma showed clusters of thyroid follicles lined by flattened to cuboidal epithelium containing abundant colloid located within subcapsular region of the lymph node, histopathologicaly confirmed as benign thyroid inclusions considering the macroscopic, cytologic and nuclear features. Since the histopathological examination was imperative of benign appearing thyroid glandular tissue with colloid and flattened epithelial lining, confirmation using immunohistochemistry was not done.

To conclude, thyroid inclusions within lateral neck nodes is a rare benign entity and does not always indicate nodal metastasis of thyroid malignancy. Distinguishing benign thyroid tissue from malignant and other non-neoplastic conditions is essential as it has direct impact on staging, treatment and further management.

References

1. Zhang Y, Zheng X, Wang X et al. Ectopic thyroid tissue in the lateral lymph nodes: A rare case and literature review, 05 September 2023, PrePrint (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3292286/v1]
   
2. Prado H, Prado A, Castillo B. Lateral ectopic thyroid: a case diagnosed preoperatively. Ear Nose Throat J. 2012 Apr;91(4):E14-8. doi: 10.1177/014556131209100417.
3. Gijsen AF, De Bruijn KMJ, Mastboom W. Thyroid tissue in cervical lymph nodes, not always malignant. Clin Case Rep. 2022 Sep 6;10(9):e6261. doi: 10.1002/ccr3.6261.
4. Noussios G, Anagnostis P, Goulis DG, Lappas D, Natsis K. Ectopic thyroid tissue: anatomical, clinical, and surgical implications of a rare entity. Eur J Endocrinol. 2011 Sep;165(3):375-82. doi: 10.1530/EJE-11-0461.
5. Triantafyllou A, Williams MD, Angelos P et al. Incidental findings of thyroid tissue in cervical lymph nodes: old controversy not yet resolved? Eur Arch Otorhinolaryngol. 2016 Oct;273(10):2867-75. doi: 10.1007/s00405-015-3786-3.
6. Ansari-Lari MA, Westra WH. The prevalence and significance of clinically unsuspected neoplasms in cervical lymph nodes. Head Neck. 2003 Oct;25(10):841-7. doi: 10.1002/hed.10304.
7. Roth LM. Inclusions of Non-Neoplastic Thyroid Tissue Within Cervical Lymph Nodes. Cancer. 1965 Jan;18:105-11.
8. Butler JJ, Tulinius H, Ibanez ML, Ballantyne AJ, Clark RL. Significance of thyroid tissue in lymph nodes associated with carcinoma of the head, neck or lung. Cancer. 1967 Jan;20(1):103-12.
9. Meyer JS, Steinberg LS. Microscopically benign thyroid follicles in cervical lymph nodes. Serial section study of lymph node inclusions and entire thyroid gland in 5 cases. Cancer. 1969 Aug;24(2):302-11.
10. Lee YJ, Kim DW, Park HK, Ha TK, Kim DH, Jung SJ, Bae SK. Benign intranodal thyroid tissue mimicking nodal metastasis in a patient with papillary thyroid carcinoma: A case report. Head Neck. 2015 Sep;37(9):E106-8. doi: 10.1002/hed.23886.