Rare Late Mandibular Metastasis in Follicular Variant of Papillary Carcinoma Thyroid: ‘Resurgence of the Sleeping Tumour’

Cancer of the thyroid gland is the most common endocrine malignancy constituting for less than 1% of all reported human cancers1. The propensity of occurrence of thyroid carcinomas is two to four times more in females as compared to males with a median age at diagnosis being 45–50 years [1,2]. Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid cancer and accounts for more than 80 % of thyroid malignancies. Classical PTC (cPTC) is the most common (80%) sub-type of papillary thyroid carcinoma followed by follicular variant (FVPTC) which is found in 9–22.5% of patients [3].


Introduction
Cancer of the thyroid gland is the most common endocrine malignancy constituting for less than 1% of all reported human cancers1. The propensity of occurrence of thyroid carcinomas is two to four times more in females as compared to males with a median age at diagnosis being 45-50 years [1,2]. Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid cancer and accounts for more than 80 % of thyroid malignancies. Classical PTC (cPTC) is the most common (80%) sub-type of papillary thyroid carcinoma followed by follicular variant (FVPTC) which is found in 9-22.5% of patients [3]. FVPTC was fi rst described by Crile and Hazard in 1953 as alveolar variant of PTC. It was subsequently confi rmed by Lindsay, Chen and Rosai as an independent entity with typical nuclear features and follicular growth pattern. FVPTC further has histological variants namely, completely encapsulated form, well circumscribed form, and infi ltrative form, the last being the most aggressive [2,4]. The encapsulated variant is relatively more prevalent than the other sub-type and is non-aggressive in nature. In order to distinguish it from the invasive variant, histologically, it has been renamed as 'noninvasive follicular thyroid neoplasm with papillary-like nuclear features'.
Invasive follicular variant of PTC presents several diagnostic and management challenges [5]. Late metastasis to the mandible is extremely rare and could be the only sign of a silent underlying neoplasm. Such lesions may resemble odontogenic lesions and should be carefully differentiated from them. This case report is a description of rare late mandibular metastases in a previously diagnosed case of invasive follicular variant of papillary carcinoma thyroid. It reiterates the signifi cance of vigilant screening during follow-up visit so as not to miss timely diagnosis.

Case Report
A 58 year old lady reported with a persistent soft, nontender swelling of 1 month duration over the left side of her face. The swelling was sudden in onset and there was no associated paresthesia reported.

Examination
On extra oral examination, a solitary, oval diffuse swelling was observed over the left side of face measuring 5 x 6 cms over left ramus of the mandible (Figure 1a). It was palpable deep to the masseter extending from the pre-auricular region to the angle of the mandible inferiorly.
Intra-oral examination revealed hypertrophic tissue in the left retro-molar trigone area with no other associated abnormality ( Figure 1b). There was no tooth mobility or any evidence of ulcero-proliferative growth seen. The patient gave no history of recent extraction or spontaneous exfoliation of any tooth.

Past medical history
The patient had fi rst reported to our hospital 3 years ago   Metastatic carcinomas affecting either maxilla or mandible should always be considered in the differential diagnosis of a long-standing, painless facial swelling in old individuals. Such carcinomas are diffi cult to be distinguished from infl ammatory and reactive lesions of oral and maxillofacial region [6]. Extra care should be taken so as not to miss any such metastatic lesion affecting ramus since it is covered by the parotid gland [5].
In this presented case, mandibular ramus was affected and OPG showed extensive area of radiolucency with illdefi ned borders over the left ramus extending upto the condyle superiorly, anterior border of ramus anteriorly and angle of the mandible inferiorly. These fi ndings were confi rmed in a CECT scan and were thus, consistent with a differential diagnosis of an odontogenic carcinoma and/or, metastatic disease.
Invasive FVPTC presents several diagnostic and management challenges to the clinician. It has hybrid metastatic capacities with lymph node metastasis via the lymphatic system similar to conventional papillary thyroid carcinoma (c-PTC), as well distant metastasis via the bloodstream similar to follicular thyroid carcinoma (FTC) [5].
Only about 20% of patients with differentiated thyroid carcinomas show a metastatic evolution. In 50-80% of cases, there are multiple bone metastases. According to different studies, bone metastases are more common in patients with follicular carcinomas (15.2-33.7%) than in those with papillary carcinomas (0.6-6.9%). Sternum, ribs, and spine are the most frequent sites of osseous metastases in such differentiated thyroid carcinomas [9].
A literature review done by Nikitakis et al. [10], in 2012 revealed only 37 published cases collectively, of all forms of thyroid cancer metastizing to the oral cavity . Metastases to the maxilla and/or, mandible are extremely rare in histologically invasive FVPTC with literature reports of only a few cases. Pal et al. [41], Bhadage et al. [42], Bingol et al. [6], and others [7,43], have reported metastasis to the body and angle of mandible manifesting in invasive form of FVPTC. However ramus metastasis is extremely rare and has been described in the literature by Saha et al. [8], and Noolkar et al. [44]. A solitary case of maxillary metastases has been cited by Bhansali et al. [45].
In the presented case, the patient was diagnosed with invasive FVPTC with sacral metastases in the fi rst instance. In accordance with the Tata Memorial Hospital guidelines for evidence-based management vol. XI A 2012 [46], total thyroidectomy followed by 260 mCi of I13, radioactive ablation was carried out. Palliative EBRT of 20 Gy equally distributed in 5 fractions was given to locally manage sacral metastases.
Distant metastases to the ramus of mandible were detected after 2.5 years of completion of the primary treatment. Moreover, the patient was pain-free and had reported to the department with a complaint of seemingly 'harmless' swelling. On further investigations it was confi rmed as a metastatic lesion involving the ramus of the mandible for which 30 Gy of palliative EBRT equally distributed in 10 fractions was advised. However, in a patient affected by metastases to the mandibular body region, Bingol et al. [6], performed hemi-mandibulectomy followed by reconstruction with costo-chondral rib graft as a defi nitive procedure.

Conclusion
Metastasis from invasive FVPTC to mandible is a rare occurrence and should be kept in mind with the other differential diagnoses of tumors in the facial region. Despite the relatively indolent behavior of encapsulated follicular thyroid neoplasm, the 5-year survival rate in patients detected with bony metastases in invasive FVPTC is reported to be 79.4% with 10-year survival rate being 52.9% [47].
Hence, there is need for a long term, strict vigilant follow up of a patient diagnosed with invasive FVPTC as evident with our experience. Metastatic FVPTC is of greater signifi cance, since at times its appearance may be the only symptom of an undiscovered underlying malignancy and metastatic lesions may be the fi rst or only clinical manifestation.