The incidental finding of thyroid tissue in cervical lymph nodes during neck dissections performed in nonthyroidal cancer is rare. The prevalence reported in several previous studies ranged from 0.3%-1.6%[11–13]. We observed a prevalence of 1.2% (31/2650) in a large cohort of head and neck non-thyroid carcinoma. All the inclusions were found incidentally in the pathological examination of the neck dissection specimen, and no clinical history and suspicion of PTC was reported in clinical records. Among all the 57 involved lymph lodes, central neck level (level Ⅵ) was most frequently involved, accounting for 35.1%. It is not surprising, as Level Ⅵ is also the most common site and the first echelon for metastasis of papillary PTC. Of the 31 patients in our cohort, 27 were male and the median age were 62, indicating an older male predominance, which is very different from primary PTC that presents young female predominance. As for the initial non-thyroid tumors, 93.5% (29/31) were squamous cell carcinomas. These findings could be interpreted by the high incidence of squamous cell carcinomas in head and neck of male.
Although the incidental discovery of thyroid tissue in cervical lymph nodes is generally regarded as a metastatic lesion derived from thyroid gland, sometimes it remains controversial on the diagnosis between metastatic PTC and benign thyroid inclusions. Especially for the morphologically benign appearing thyroid follicles in lymph nodes, it is not easy to determine metastases or benign heterotopia. As salivary glands, naevus cells and Müllerian epithelia aberrantly occurred in lymph nodes have been well-established, the possibility of benign thyroid heterotopia has also been proposed[14–16]. In addition, diagnostic criteria have been suggested for benign heterotopia in lymph nodes: 1) adjacent to or in the lymph node capsule, 2) no more than two nodes involvement, 3) morphology of thyroid follicles and absence of nuclear features of thyroid papillary carcinoma, 4) absence of psammoma bodies and desmoplastic stroma, 5) inconsistent immunohistochemical and molecular profiling for thyroid cancer[14, 15]. The diagnosis of benign heterotopia might be considered only when all the conditions mentioned above are fulfilled. However, some pathologists contest the opinion of benign heterotopia in lymph nodes as no confirmed embryological or anatomic evidence for such inclusions. Moreover, it is not uncommon that metastatic well-differentiated follicular variant of PTC present normal like appearance in cervical lymph nodes. In the context of molecular evidence, the BRAF V600E point mutation has been reported in morphologically benign appearing thyroid inclusions of cervical lymph nodes[17]. This finding would question the notion of benign nodal thyroid heterotopia. Taken together, occult metastatic carcinoma in cervical lymph nodes must always be taken into consideration even if histopathologic studies do not reveal features of PTC. In our present study, 22 cases were available for morphological evaluation, 10 showed normal looking thyroid follicular morphology, and 12 presented at least one of the following feathers: papillary structure, nuclear features of PTC and psammoma bodies. Among the 10 cases with normal looking thyroid follicular morphology, 2 underwent thyroidectomy and PTC were found after a thorough sampling. It has been generally believed that a primary PTC is undoubtedly necessary for the development of an occult metastatic thyroid carcinoma. Identification of primary PTC in the 2 postoperative thyroid specimens in our study indicates the possibility of an occult metastasis rather than an ectopia of benign appearing thyroid follicles in cervical lymph nodes. It must be mentioned that the two primary PTC was considerably small (less than 1 millimeter in size), as most PTCs are not highly aggressive, it seems to be unusual for small tumors to metastasize. However, our observation emphasizes that no matter how small the tumor is, even less than 1 millimeter, it might have a significant potential to metastasis.
Subsequently, we performed BRAF V600E immunohistochemical staining in 17 cases with sufficient tumor cells, and 6 showed positive staining. Further BRAF V600E point mutation was detected in 5 of the 6 BRAF V600E positive cases. Regarding no BRAF V600E point mutation in 1 IHC positive case, we reexamined the HE slides and found less than 10% tumor cell content in the nodes. Probably, the negative molecular finding might be caused by the too small population of tumor cells. In our findings, the prevalence of BRAF V600E point mutation is slightly lower than that of primary thyroid origin PTC[4]. It is worth mentioning that one case showing bland-looking thyroid tissue was also positive for BRAF staining. This finding further supports the opinion of malignant PTC metastasis other than benign heterotopia.
When occult metastatic PTCs were identified in the cervical lymph nodes in the context of more aggressive squamous cell carcinomas, it is difficult to determine a single standard treatment as it should be based on overall survival of individual patients. Given the nature history of PTC, it is often less aggressive than the initial non-thyroid origin carcinomas of head and neck. Therefore, the prognosis of such patients usually depends on the more aggressive carcinomas but not PTC. Even so, evaluation of a thyroid tumor is also essential. When occult metastatic PTC was identified, imaging examination of thyroid should be carried out in routine clinical practice. Clinical management regarding surgery or surveillance hinges on both clinical and radiological features. In the cohort of 31 cases, imaging examination were performed in 25 patients, among them, 5 showed suspicious malignant thyroid nodules and 20 were normal or benign nodules. 12 underwent total thyroidectomy or lobectomy, and pathological results revealed PTC in 6 patients after a thorough sampling. However, among the 6 patients displaying PTC, 4 were less than 1mm in size. Moreover, PTCs were not identified in 50% (6/12) patients with surgery, suggesting that primary PTC of thyroid was not always identified in partial or total thyroid dissection specimen. Despite the negative thyroid finding of imaging or histopathology, the metastatic nature of the lymph node localization cannot be entirely excluded. The incidental discovery of PTCs in cervical lymph nodes, of course, are not always a metastasis but may occasionally be a primary lesion arising from heterotopic thyroid. On the other hand, although primary PTCs were found in 3 cases with benign imaging results, the lesions were considerably small. Therefore, if imaging shows normal or benign appearance, active surveillance could be recommended. However, when imaging reveals suspicious malignant thyroid nodules, the decision for thyroidectomy or conservative approach would be affected by multiple factors, including age, tumor size, pathological histological subtypes and clinical stage of initial non-thyroid carcinomas, as well as patient’s wishes. our results reveals that the majority of patients does not necessarily perform aggressive surgical dissection considering the minimal influence on patient outcome. These observations are also in consistent with several previous studies[18, 19].