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01.12.2017 | Case report | Ausgabe 1/2017 Open Access

BMC Cancer 1/2017

Follicular thyroid carcinoma metastasis to the facial skeleton: a systematic review

Zeitschrift:
BMC Cancer > Ausgabe 1/2017
Autoren:
Varun V. Varadarajan, Elizabeth K. Pace, Vatsal Patel, Raja Sawhney, Robert J. Amdur, Peter T. Dziegielewski
Wichtige Hinweise
Manuscript Presentation: This study was presented as a poster presentation at the 9th International Conference on Head and Neck Cancer on July 17, 2016 in Seattle, Washington, USA.
Abbreviations
CT
Computerized tomography
FTC
Follicular thyroid carcinoma
NR
Not reported
PTC
Papillary thyroid carcinoma
RAI
Radioactive iodine therapy
XRT
External beam radiation therapy

Background

Follicular thyroid carcinoma (FTC) is the second most common thyroid carcinoma. It accounts for ~10% of thyroid malignancies, with a higher occurrence in women aged 40–60 years [ 1]. Follicular thyroid carcinoma is known to disseminate hematogenously and metastasize in advanced cases. Distant metastases are seen in ~10–15% cases, with bone and lungs as preferred metastatic targets [ 2]. FTC metastases to the facial skeleton are exceedingly rare and present a treatment challenge.
FTC facial bone metastasis can present in the gnathic bones, the paranasal sinuses, or the orbit. Metastasis to the facial skeleton may be the first clinical sign of an underlying malignancy and clinical presentation varies depending on site of presentation as well as the primary site [ 37]. Oral cavity and maxillofacial region metastasis is uncommon and represent 1–2% of all oral and maxillofacial malignancies [ 35]. Prognoses of such lesions are assumed to be poor; however, there is a paucity of evidence to guide management of these scenarios.
In this report, a case of FTC metastasizing to the mandible is presented and a systematic review of the literature is performed. The purpose is to describe the clinical presentation, treatment, and survival outcomes of thyroid metastasis to the facial skeleton.

Case presentation

A 73-year-old female patient was evaluated at the Head and Neck Surgery Clinic at the University of Florida. Her presenting complaint was numbness and swelling of her left mandible and an intraoral lesion associated with recurrent bleeding episodes. Symptoms were present for several weeks and had initially been presumed to represent an episode of sialadenitis by an outside provider. Her past medical history was significant for a thyroid nodule and no chronic medical conditions. She had no history of tobacco or alcohol abuse. Physical exam demonstrated a left mandibular lesion approximately 5 cm in size, with fullness of the gingival mucosa overlying the mass. A mucosal punch biopsy was performed and the histology demonstrated a pyogenic granuloma.
Computerized tomography (CT) showed an aggressive mass destroying the mandibular body (Fig. 1) as well as enlarged pulmonary nodules and a lytic bone lesion at T10. Imaging also demonstrated a multinodular thyroid gland with minimal irregularity along the anterior right border. A 4.6 cm nodule was noted in the right thyroid lobe. Fine needle aspiration of the right thyroid mass was interpreted as a follicular lesion of undetermined significance (FLUS). Because the pathology findings were inconsistent with the CT scan, an open biopsy in the OR was performed. A mucosal incision was made over the mass and a biopsy was taken. The lesion was found to be extremely friable and bled significantly requiring ligation of the facial artery. Final pathology demonstrated FTC.
Multidisciplinary tumor board review recommended surgery followed by radioactive iodine and external beam radiotherapy. The patient underwent total thyroidectomy, neck dissection, segmental mandibulectomy, and bone-impacted fibular free flap reconstruction [ 6]. Intraoperative findings included a 10 cm thyroid mass of the right thyroid lobe that extended beneath the sternum to the innominate vein. A segment of mandible was taken from left angle to right parasymphysis, resulting in a defect from right lateral incisor to angle of mandible (Fig. 2). Reconstruction was undertaken via a right bone-impacted fibular free flap with skin paddle in addition to a 2.0 mm mandibular reconstruction bar. Final pathology showed mandibular metastasis of FTC with extension into the tongue and soft tissues of the neck (Fig. 3). Margins were negative. The 4.6 cm thyroid follicular carcinoma appeared to arise from a calcified pre-existing degenerative follicular adenoma. There was evidence of capsular invasion and extensive lymphovascular invasion. The patient underwent post-operative stereotactic body radiation to the T-10 metastatic lesion and 200 mCi of radioactive Iodine-131. She has been disease free for 18 months.
A systematic review of the English literature was performed using PubMed, Medline, Embase, and Scopus databases. Search terms describing FTC presenting as a metastatic lesion in the facial skeleton were compiled and implemented. These terms included: “thyroid,” “cancer,” “thyroid carcinoma,” “thyroid cancer”, “metastasis,” and “malignancy” with “oral cavity,” “maxilla,” “mandible,” “sinus,” “paranasal,” and “orbit.” Papers were gleaned for diagnoses of well-differentiated thyroid cancer, FTC, and metastases to the facial skeleton. Reports of metastasis that only involved the soft tissues were excluded. The reports were organized by subsite: mandible, maxilla, jawbone not otherwise specified, nasal cavity or paranasal sinus, and orbit. Data points obtained from literature review included age, gender, primary oncologic diagnosis, site of metastasis, clinical presentation, treatment modality, survival outcome, and time to follow-up were obtained. Statistical analysis was performed with SPSS 23.0 software package (SPSS Inc., Chicago, IL). Survival was estimated by a Kaplan-Meier analysis to the account for censored data. Survival by treatment was analyzed and compared using the log rank test.
Literature review identified 64 studies reporting 97 cases of thyroid cancer metastasis to the facial skeleton in the English literature. All metastases were present at the time of presentation. 59 case reports specified well-differentiated thyroid cancer as the diagnosis. Table 1 demonstrates details of these cases. 38 case reports did not specify the diagnosis and were not included [ 718]. The gender distribution was 9 males, 48 females, and 2 cases in which gender was not specified. While the majority of metastases were to the mandible, other craniofacial sites were also found to be involved.
Table 1
List of reported cases of thyroid cancer metastasis to the facial skeleton
Author of report
Age, Gender
Primary tumor
Site of presentation
Clinical presentation
Treatment of metastases
Survival
Time to follow-up
Agarwal et al. [ 26]
45, F
FTC
Mandible
Facial swelling
Resection
Yes
2 weeks
Algahtani et al. [ 40]
66, F
FTC
Mandible
Pathologic fracture
Resection
NR
NR
Anil et al. [ 72]
61, F
FTC
Mandible
Mandibular swelling
NR
NR
NR
Bhadage et al. [ 28]
40, F
FTC
Mandible
Facial swelling
NR, referred out
NR
NR
Bingol et al. [ 27]
33, F
PTC
Mandible
Painless mass of mandibular angle
Surgery, RAI
No
5 years
Colella et al. [ 75]
50, F
PTC
Mandible
Pain and swelling in RMT
NR
NR
NR
Draper et al. [ 44]
NR, F
FTC
Mandible
Ulcerated oral lesion
XRT, RAI
NR
NR
Erdag et al. [ 23]
53, F
PTC
Mandible
Right sided facial swelling
Surgery, RAI
Yes
2.5 years
Essakalli et al. [ 41]
50, F
PTC
Mandible
Painful swelling of jaw
Resection, RAI
Yes
2 months
Germain et al. [ 42]
50, F
PTC
Mandible
Jugular, carotid lymphadenopathy
Resection
Yes
17 months
Ismail et al. [ 30]
70, F
FTC
Mandible
Pain, “loose teeth”
NR
NR
NR
Kahn and McCord [ 31]
82, F
FTC
Mandible
Painful oral swelling
XRT, surgical salvage
No
18
Kumar RVK et al. [ 32]
58, F
FTC
Mandible
Painless facial swelling
Resection, mandible reconconstructive bar, second stage thyroidectomy
Yes
2 years
Lavanya et al. [ 29]
76, M
FTC
Mandible
Painless mandibular swelling
NR, referred out
NR
NR
Liu et al. [ 33]
66, M
PTC
Mandible
Cheek mass
Resection, RAI
Yes
3 years
Markitziu et al. [ 46]
69, F
PTC
Mandible
Facial swelling
XRT
Yes
18 months
McDaniel et al. [ 76]
77, F
FTC
Mandible
Pain, swelling
Resection, parotidectomy, RAI
Yes
4 years
Meyer and Shklar [ 3]
51, F
FTC
Mandible
NR
NR
NR
NR
Muttagi et al.: 2 cases [ 34]
NR
PTC
Mandible
NR
Surgery
NR
NR
NR
FTC
Mandible
NR
Surgery
NR
NR
Nishikawa et al. [ 39]
83, F
PDFTC
Mandible
Painful swelling of jaw and face
None
No
19 months
Osguthorpe and Bratton [ 35]
53, M
FTC
Mandible
Slowly enlarging parotid mass
Resection, RAI
Yes
3 years
Ostrosky et al. [ 25]
72, M
FTC
Mandible
Painful vascular lesion
Resection, iliac crest graft
NR
NR
Pasupula et al. [ 36]
40, F
FTC
Mandible
Painful left parotid swelling
Resection
NR
NR
Tamiolakis et al. [ 4]
69, F
PTC
Mandible
Facial swelling, mucosal ulcerations
Inoperable
NR
NR
Tovi et al. [ 47]
33, M
FTC
Mandible
Mimicking AVM
RAI
No
17 days
Vazifeh et al. [ 37]
58, F
FTC
Mandible
Facial swelling
Resection
NR
NR
Vishveshwaraiah et al. [ 38]
56, F
FTC
Mandible
Painless facial swelling, face and lip paresthesia
NR, referred out
NR
NR
Vural and Hanna [ 24]
64, F
FTC
Mandible
Tender, pre-auricular mass
Resection, post op iodine ablation
Yes
6 weeks
Zandi et al. [ 11]
64, F
FTC
Mandible
NR
NR
NR
NR
75, F
FTC
Mandible
NR
NR
NR
NR
63, F
PTC
Mandible
NR
NR
NR
NR
44, F
PTC
Mandible
NR
NR
NR
NR
35, F
PTC
Mandible
NR
NR
NR
NR
51, F
PTC
Mandible
NR
NR
NR
NR
Antunes et al. [ 22]
13, F
PTC
Maxilla
NR
NR
NR
NR
Fatahzadeh et al. [ 48]
43, F
PTC
Maxilla
Hemorrhagic mass with ulceration and bleeding
XRT
NR
NR
Hefer et al. [ 52]
58, M
FTC
Maxilla
Left hard palate pain
Resection
Yes
2 years
Kumar CS et al. [ 51]
31, F
FTC
Maxilla
Painful swelling, mobile teeth
RAI
Yes
7 years
Nikitakis et al. [ 49]
63, M
PTC
Maxilla
Painful swelling of right posterior maxilla
XRT, palliative chemotherapy
Yes
2 years
Slim et al. [ 50]
67, F
PTC
Maxilla, zygoma
Painless malar swelling
Resection, postoperative iodine ablation
Yes
NR
Cinberg et al. [ 64]
80, F
FTC
Maxillary sinus
Epistaxis
RAI
NR
NR
Altinay et al. [ 69]
68, F
FTC
Nasal Cavity, orbit, skull base
Left eye puffiness, proptosis, vision Loss, facial numbness
XRT
Yes
1 month
Malhotra et al. [ 60]
55, F
FTC
Orbit (Anterolateral orbit)
Proptosis, vision Loss
Resection, RAI
NR
NR
Rocha Filho et al. [ 57]
66, F
PTC
Orbit (Frontal bone)
Frontal bone mass
Palliative chemo
Yes
NR
Bernstein-Lipschitz et al. [ 55]
56, F
FTC
Orbit (Lacrimal fossa, orbital roof)
Diplopia, ptosis, orbital Pain
Resection
NR
NR
Shyla et al. [ 54]
70, F
PTC
Orbit (Posterior orbit extending to ethmoid bone)
Vision loss
Resection, XRT
Yes
NR
Boughattas et al. [ 56]
25, F
PTC
Orbit (Supraorbital)
Asymptomatic
NR
NR
NR
Daumerie et al. [ 58]
59, F
PTC
Orbit (Supratemporal quadrant)
Left upper eyelid swelling, exophthalmos
RAI
Yes
2 months
Pagsisihan et al. [ 59]
49, F
PTC
Orbit (Supraorbital)
Supraorbital mass
RAI
Yes
6 months
Argibay-Vasquez [ 77]
53, F
PTC
Sphenoid
Headache, paresthesia in the right eye region, left monocular diplopia
RAI, subtototal resection, XRT, RAI
Yes
3 years
Yamasoba et al. [ 67]
34, F
FTC
Ethmoid, sphenoid, maxillary, intracranial
Cheek hypoesthesia, hearing Loss
Embolization, resection
Yes
NR
Renner et al. [ 65]
61, F
FTC
Sphenoid sinus
Epistaxis, anosmia, visual loss
RAI, XRT
Yes
5 months
Barrs et al. [ 63]
54, F
FTC
Sphenoid sinus, orbit
Visual loss
RAI, XRT
No
5 years
Altman et al. [ 68]
81, M
FTC
Sphenoid, ethmoid, skull base
Headache
XRT
No
1 year
Freeman et al. [ 78]
50, M
PTC
Sphenoid, ethmoid
Facial pain, proptosis of the left globe, left horner’s syndrome
XRT, RAI
Yes
1 year
Madronio et al. [ 79]
53, F
PTC
Sphenoid, ethmoid
Headache, galactorrhea, vision loss
Surgical debulking
Yes
13 months
Cumberworth et al. [ 66]
74, F
FTC
Sphenoid, frontal, ethmoid, and maxillary sinuses
Nasal obstruction
None
No
1 week after diagnosis
FTC Follicular Thyroid Carcinoma, NR not reported, PTC Papillary Thyroid Carcinoma, RAI Radioactive Iodine Therapy, XRT External Beam Radiation Therapy
Treatment varied between studies and included: Surgery with or without preoperative embolization and radioactive iodine therapy, external beam radiation (primary or adjuvant treatment), and palliative chemotherapy. 22 patients were treated with surgery as initial treatment with or without postoperative radioactive iodine or external beam radiation. 11 patients were treated with external beam radiation as primary treatment. 14 reports did not specify treatment. 4 patients were treated with palliative care; 2 of these patients received palliative chemotherapy. Cases were grouped into: a surgical arm (those treated with surgery and RAI) and a non-surgical arm. 32 studies reported survival outcome and 27 studies reported time-to-follow up. 24 patients survived treatment and 8 patients expired.
Overall survival for all patients at 2 years was 96% and at 5 years was 59%. Disease specific survival at 2 years was 96% and at 5 years was 72%. Patients treated with surgery and RAI versus those treated by non-surgical means were compared. There was no statistical difference in overall survival ( p = 0.27) with the surgical group having 2 and 5 year overall survival of 100% and 71%, respectively and those in the non-surgical arm having rates of 92% and 46%.
Disease specific survival for all patients at 2 years was 96% and at 5 years was 72% (Fig. 4). There was a statistically significant difference in disease specific survival (DSS) between patients treated with surgery and RAI versus those treated by non-surgical means ( p = 0.03). DSS for surgically treated patients at 2 and 5 years was 100% and for non-surgically treated patients was 92% and 46%, respectively.

Discussion and conclusions

FTC is the second most common thyroid cancer, following papillary thyroid carcinoma (PTC). 10–15% of FTCs will disseminate hematogenously via angioinvasion. The most common sites of metastases include bone and lungs and less commonly brain, liver, bladder, and skin. Bone metastases can occur in the vertebral bodies followed by the pelvis, femur, skull, and ribs [ 2, 19]. Treatment often involves high dose radioiodine; however, bony metastases are less likely to concentrate radioiodine, and thus, the efficacy is estimated at 55%. External beam radiation therapy may be used for palliation [ 2].
Metastasis comprises 1% of all oral-maxillofacial malignancies. Primary sites of tumors metastatic to the facial skeleton are most commonly from the breast and lungs [ 20]. Thyroid malignancy represents 2% of facial skeleton metastasis [ 20] and 4.2–6.1% of all jaw metastases [ 7, 15, 21] 41% of facial skeleton metastasis from thyroid cancer occurs in the mandible; 59% of these metastases are well-differentiated thyroid cancer. There have been 41 reported cases in the literature of thyroid malignancy with metastasis to the mandible of which 21 reported cases were FTC [ 4, 912, 2247]. There have been 6 reported cases of metastasis to the maxilla; 2 were FTC [ 22, 4852].
The majority of metastatic tumors to the mandible present with facial swelling and an osteolytic lesion. A rapid progression of intraoral or extraoral swelling associated with chin paresthesia and pain is not uncommon [ 21, 29, 36, 53]. As the tumor invades oral mucosa, a granulation-like mass may form and result in significant bleeding, infection, fractures, and disturbances in swallowing and mastication [ 32, 40].
Isolated facial skeleton metastasis may be treated with surgical resection, radioactive iodine, external beam radiation or combinations of the three. The patient presented here was treated with a composite resection and radioactive iodine. Her defect was reconstructed with a bone-impacted osteocutaneous fibula free flap. Follow-up CT scanning demonstrated that the neo-mandible retained a dense bone stock from the bone impaction. Free flap reconstruction for metastatic thyroid cancer to the mandible has only been reported once in the literature [ 42]. The current case is the first report of a bone-impacted fibular free flap used in this scenario.
Metastatic thyroid carcinomas are also reported in the orbit and paranasal sinuses. 9 cases have been described in the bony orbit; 4 of these were FTC [ 16, 5461]. Surgical debulking of the metastatic foci may restore vision in cases of sudden onset vision loss; radioiodine treatment has also been documented as treatment for tumors that uptake iodine. External beam radiation can also be an option. There are 17 reported cases of thyroid malignancy presenting as a paranasal sinus mass (14.1%); 7 of these cases were FTC [ 8, 13, 14, 17, 18, 6269]. Two cases presented simultaneously in the paranasal sinus and the bony orbit [ 63, 69]. Clinical manifestations include epistaxis, nasal obstruction, visual disturbances, and facial or intraoral swelling [ 70, 71]. The maxillary sinus is the most commonly involved sinus followed by the sphenoid sinus, ethmoid, and frontal sinus [ 70, 72]. The vertebral venous plexus, which allows retrograde spread of tumor emboli, could explain the etiology of paranasal sinus and orbital metastasis [ 71, 73]. Craniofacial resection or debulking with or without preoperative vascular embolization can be considered, however, the proximity of the metastatic tumor to the skull base may preclude surgical extirpation [ 59, 67, 69]. Radioiodine therapy, external beam radiation, chemotherapy, or palliative therapy can be considered in these patients [ 57, 59, 68, 74].
Survival analysis suggests that surgical resection of involved craniofacial structures with or without adjuvant treatment is the optimal treatment for FTC metastatic to the facial bones. Given the rarity of the condition, the sample size is limited; however, survival analysis demonstrated convincing statistically significant advantages with surgical resection. Treatment plans should be formulated with a multidisciplinary team involving surgical oncology, radiology, pathology, endocrinology, medical oncology, radiation oncology, and possibly palliative care.
In conclusion, facial skeleton metastasis of FTC is a rare clinical challenge. If feasible, surgical-based treatment options offer the best survival outcomes. When mandibular defects are present, reconstruction with a bone impacted fibular free flap may provide a reconstruction with a robust bone stock.

Acknowledgements

The authors have no acknowledgements.

Funding

The authors of this study declare no sources of funding for this study.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Authors’ contribution

VV participated in the design of the study, data collection, participated in statistical analysis, and drafted the manuscript. EP participated in data collection, statistical analysis, and in drafting the manuscript. VP participated in data collection, histopathology interpretation, and drafting the manuscript. RS participated in the design of the study and in conceiving the study. RA participated in critically revising the manuscript for important intellectual content. PD conceived and designed the study, performed statistical analysis, and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Authors’ information

VV is an Otolaryngology –Head and Neck Surgery resident physician at the University of Florida in Gainesville, Florida. EP is a senior medical student at the University of Florida College of Medicine in Gainesville, Florida. VP is a Pathology resident physician at the University of Florida in Gainesville, Florida. RS is an Assistant Professor in the University of Florida Department of Otolaryngology – Division of Facial Plastic Surgery in Gainesville, Florida. RA is a Professor in the University of Florida Department of Radiation Oncology. PD is an Assistant Professor at the University of Florida Department of Otolaryngology and Chief of the Division of Head and Neck Oncologic Surgery in Gainesville, Florida.

Competing interests

The authors of this study manuscript declare that they have no competing interests.

Consent for publication

Written informed consent was obtained from the patient for publication of this Case report and any accompanying images.

Ethics approval and consent to participate

Ethics approval was not necessary for this study and manuscript due to the type of study design (Case Report, Literature Review). All patient data and photographs are de-identified.

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