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Rare Presentation of Mandibular Metastases from Differentiated Thyroid Carcinoma: A Case Series – Experience from a Single Tertiary Care Hospital
Address for correspondence: Dr. Ashwani Sood, Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 015, India. E-mail: sood99@yahoo.com
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Received: ,
Accepted: ,
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Metastasis from differentiated thyroid cancer frequently occurs in regional lymph nodes, followed by the lungs and bones. However, mandibular metastases related to thyroid carcinoma are exceedingly rare and may represent the sole manifestation of an undiagnosed underlying malignancy. This study aims to analyze the presentation, management, and survival outcomes in a case series of differentiated thyroid carcinoma patients having mandibular metastasis.
Keywords
Follicular thyroid cancer
mandible
mandibulectomy
metastasis
papillary thyroid cancer
radioactive iodine treatment
Introduction
Metastasis from differentiated thyroid cancer (DTC) commonly involves regional lymph nodes, followed by the lungs and bones. However, mandibular metastases from thyroid carcinoma are exceedingly rare and may present either as the sole manifestation of an undiagnosed malignancy or as the part of disseminated disease, especially skeletal metastases. This study analyzes the clinical presentation, diagnosis, management, and survival outcomes in a case series of patients with thyroid carcinoma having mandibular metastases.
Case Reports
Case 1
A 54-year-old woman presented with pain and swelling in the right jaw for 6 months. Computed tomography (CT) imaging revealed an expansile lytic lesion measuring 2.0 cm × 1.2 cm × 2.3 cm in the right mandible. Based on clinical and radiological findings, a provisional diagnosis of ameloblastoma was made. Histopathological examination (HPE) after segmental mandibulectomy confirmed papillary thyroid carcinoma (PTC) metastasis. Immunohistochemistry was positive for thyroglobulin (Tg), thyroid transcription factor 1, and paired box gene 8, and negative for S100 protein and calretinin. Ultrasonography (USG) of the neck revealed microcalcifications and increased vascularity in the left thyroid lobe along with hypoechoic lesions in both lobes. The patient underwent total thyroidectomy (TT) and central neck dissection and histopathology confirmed micropapillary carcinoma. Postoperative serum Tg level was 22 ng/ml. A radioactive iodine (RAI) dose of 50 mCi was administered following a whole-body iodine scan (WBIS), which showed iodine avidity only in the remnant thyroid tissue. At a 6-month follow-up, she showed an excellent response to RAI, with Tg levels reduced to 0.57 ng/ml.
Case 2
A 55-year-old male, with a history of TT 15 years ago, presented with bilateral hip and back pain along with a fracture of the right femoral neck. 18F-Fluorodeoxyglucose positron emission tomography CT (18F-FDG PET/CT) showed a tracer-avid osteo-expansile mass in the left iliac bone, multiple skeletal lesions in the thoracolumbar vertebrae, bilateral femoral necks, bilateral lung nodules, and a lytic expansile lesion in the left hemi-mandible.
HPE from the mandibular lesion and iliac bone confirmed follicular thyroid cancer (FTC) metastasis. Palliative external-beam radiation (20 Gy) was delivered to the thoracolumbar vertebrae and left iliac bone. At presentation after 15 years, Tg was more than 500 ng/ml. WBIS revealed multiple iodine-avid lung nodules and skeletal lesions. He received two doses of 200 mCi RAI at 6-month intervals. Posttherapy scan after the second dose showed reduced iodine avidity in a few of the lesions. He was referred to orthopedics for further management of the femoral neck fracture.
Case 3
A 68-year-old male presented with a 5-month history of a rapidly progressive left jaw swelling. Initial imaging revealed a locally aggressive expansile lytic lesion in the left hemimandible, provisionally diagnosed with ameloblastoma. However, HPE following a left hemi-mandibulectomy and fibular graft reconstruction confirmed metastatic FTC. The neck USG showed an enlarged thyroid gland with multiple iso-to hypoechoic nodules, including a TIRADS IV lesion in the right lobe. The patient subsequently underwent TT. A postoperative WBIS demonstrated iodine-avid thyroid tissue remnant, bilateral lung nodules, and postoperative bed of left hemi-mandibular lesion, with an elevated serum Tg level of 500 ng/ml. He received three 200 mCi RAI doses at 6-month intervals. The patient was then lost to follow-up for 2 years due to the COVID-19 pandemic. At subsequent follow-up, WBIS demonstrated faint radioiodine uptake in bilateral pulmonary nodules, with a serum Tg level of 36 ng/mL. The patient was administered an additional dose of 150 mCi of RAI. Six months posttherapy, stimulated Tg levels declined to 19 ng/mL, with no evidence of iodine-avid lesions on repeat WBIS. The patient remained under surveillance with serial measurements of unstimulated serum Tg and anti-Tg antibody levels.
Case 4
A 55-year-old male underwent TT, with histopathology proven FTC, for right mandibular swelling and anterior neck swelling and an expansile lytic lesion with soft tissue component in the right hemi-mandible on contrast-enhanced computed tomography of 5 months’ duration. Diagnostic WBIS showed iodine avidity in the remnant thyroid and right hemimandible, with a Tg level of 341 ng/ml, [Figure 1a-c].
He received the first dose of 200 mCi of RAI. At a 6-month follow-up, WBIS showed persistent iodine avidity in the right mandibular region only with raised Tg value of 2999 ng/ml (absolute value). A second 200 mCi dose of RAI was administered, followed by surgical curettage of the mandibular lesion with HPE confirmed FTC metastasis. Postcurettage WBIS revealed persistent uptake in the same lesion, with stimulated Tg level of 191 ng/ml, prompting a third 200 mCi dose of RAI, [Figure 1d-f].
On further follow-up, WBIS showed faint uptake only in the mandibular lesion, with Tg dropping to 132 ng/ml, he received fourth dose of 200 mCi of RAI. He then underwent right segmental hemi-mandibulectomy and iliac crest graft reconstruction. HPE confirmed FTC metastases involving bony margins. Postsurgery, the diagnostic scan was negative, but Tg remained high (115 ng/ml) [Figure 1g-i].
FDG PET/CT was also performed later on to rule out iodine-resistant disease and it revealed faint FDG uptake in the soft tissue of the postoperative bed. He was placed on unstimulated follow-up, with Tg levels of 204 ng/ml and 162.1 ng/ml at two consecutive 6-month intervals and on follow-up presently with suppressive dose of thyroid hormones.
Case 5
A 68-year-old male with a history of TT and bilateral neck dissection a decade prior presented with neck pain and weight loss 6 months. No histopathological documentation or long-term follow-up data were available. 18F-FDG PET/CT revealed a mildly avid expansile lytic lesion in the right mandible. WBIS showed iodine-avid cervical nodes and a nonavid mandible lesion. Serum Tg was 3000 ng/ml. He received 150 mCi RAI but was lost to follow-up. Two years later, he presented with a progressively enlarging right jaw swelling. WBIS was negative and Tg was >300 ng/ml.
18F-FDG PET/CT demonstrated an FDG avid mandibular lesion and faintly avid lung nodules. Fine-needle aspiration cytology (FNAC) from the mandible was inconclusive. He received another 150 mCi RAI and posttherapy scans showed iodine avidity in both the mandibular lesion and lung nodules. Surgical resection with or without adjuvant radiotherapy was planned; however, the patient remained noncompliant with levothyroxine therapy and did not return for the proposed treatment. He subsequently succumbed to disease progression within a year.
Case 6
An 89-year-old woman with a history of TT 13 years prior, without available records of HPE or RAI therapy, presented with a 2-year history of left-sided neck swelling. FNAC revealed metastatic PTC in the left cervical lymph nodes, which were surgically excised.
A diagnostic WBIS showed iodine-avid left supraclavicular lymph nodes and faintly FDG-avid lung nodules, with a serum Tg level of 2529 ng/mL. She received 150 mCi of RAI. The whole-body post-therapy scan [Figure 2a, b] and fused single-photon emission CT/CT images of the head region [Figure 2c, d] demonstrated an iodine-avid sclerotic focus in the left mandibular ramus, an avid left supraclavicular lymph node, non- to faintly avid nodules in the left lung, and a 1.7 × 1.2 cm paraesophageal/prevertebral soft-tissue lesion with probable infiltration of the cervical esophagus.
Subsequent endoscopy and barium swallow showed a nonnegotiable narrowing with extrinsic compression. Four months later, with worsening dysphagia, a tyrosine kinase inhibitor was recommended but declined by the patient.
After 6 months, she received a second dose of 200 mCi RAI. The posttherapy scan revealed findings similar to the first, with reduced tracer avidity. Two months later, she presented with progressive dysphagia, weight loss, and neck fullness, and passed away within a month while receiving symptomatic care.
Discussion
Metastases most frequently occur in the bone and lung through angioinvasion in 10-15% of FTCs. Treatment of DTC includes surgical resection of the primary tumour, followed by radioiodine administration for the management of metastases.[12] Since radioiodine concentrations in skeletal metastases are not that high, treatment efficacy is expected to be only 55%.[1] Nevertheless, high doses of radioiodine are frequently used. Palliative treatment may be provided by the external beam radiation therapy.[12]
The true incidence of metastatic tumors to the jaw bones is unknown; however, metastatic mandibular lesions make up around 1% of all oral malignancies.[34] Metastatic cancer may invade both the jaws and soft tissues of the oral cavity, with a predilection for the mandible and gingiva.[34] Breast and thyroid are the most common primary tumour sites that tend to metastasize to the jaw bones rather than the soft tissues of the oral cavity.[5] The abundant blood circulation in the medullary cavity of the ramus and angle of the mandible has been proposed as the reason for the predisposition to metastasis in these areas.
Mandibular metastases originating from thyroid carcinoma are uncommon, with most cases attributed to follicular thyroid carcinoma, which predominantly disseminates via the hematogenous route.[678] The metastatic tumor in the mandible can cause paraesthesia, pain, swelling, loosening of teeth, cervical lymphadenopathies, and, in rare cases, pathologic fractures.[9] These presenting symptoms or signs may be of important clinical significance, as their presentation may be the only manifestation of an unknown disseminated malignancy in some cases.[910]
Isolated mandible metastasis may be treated with surgical resection, RAI, external beam radiation, or combinations of these three treatment modalities. The free fibula flap can be used for mandibular reconstruction after surgical resection.[610] Three of six patients (50%) underwent hemi-mandibulectomy and reconstruction, whereas two of these patients were also given RAI. The remaining patients underwent RAI administration only [Table 1].
| Age/Sex | Presentation | Site | HPE | Other metastatic sites | Time of presentation of mandible metastasis | Treatment | Follow up since initial presentation | Stimulated Tg (ng/ml) | |
|---|---|---|---|---|---|---|---|---|---|
| Initial | Last Follow-up | ||||||||
| 54/female | Jaw pain and swelling | Body (R) | Micro-papillary | None | First manifestation | Segmental mandibulectomy | 1.5 years (alive) | 22 | 0.57 |
| 55/male | Hip and back pain | Ramus (L) | FTC | Femur, lung | After 15 years | RAI | 14 years (alive) | >500 | 443 |
| 68/male | Jaw swelling | Ramus (L) | FTC | Lung | First manifestation | Left hemi- mandibulectomy with fibular grafting, RAI | 8 years (alive) | 500 | 18.9 |
| 55/male | Jaw swelling | Body (R) | FTC | None | First manifestation | Curettage, right mandibulectomy, RAI | 5 years (alive) | 341 | 115 |
| 68/male | Jaw swelling | Ramus (R) | FTC | Lung, lymph nodes | After 10 years | RAI | 16 years (died) | 3000 | 300 |
| 89/female | Thyroid swelling | Ramus (L) | PTC | Lung, lymph nodes, paraesophageal mass | After 13 years | Segmental mandibulectomy | 1.5 years (alive) | 2529 | 178 |
RAI: Radioactive-iodine, Tg: Thyroglobulin, FTC: Follicular thyroid carcinoma, HPE: Histopathological examination, PTC: Papillary thyroid carcinoma, L: Left, R: Right
In general, metastasis to the jaw bones is associated with metastases to several other sites and carries a poor prognosis. In this case series, two of our patients who presented with mandibular metastasis a decade after TT died within a year of presentation, with one of them also having extensive metastasis at other sites. The remaining four patients are alive, with a decreasing Tg trend on the follow-up.
Conclusion
Mandibular metastases can present with a range of symptoms and may mimic other conditions, particularly when they represent the initial manifestation of the disease. These cases highlight the significance of taking metastasis into account when making a differential diagnosis of mandible swelling, even though the patient had no prior history of a malignant disease. Surgical resection and reconstruction, with or without adjuvant RAI, appear to offer the most favorable survival outcomes.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest
There are no conflicts of interest.
Nil.
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