A Rare Case of Papillary Thyroid Carcinoma Metastasizing to the Spine.

Introduction

Thyroid cancer is the most common endocrine malignancy [ 1 ]. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (70-80% of cases) and is characterized by follicular cell differentiation and distinct nuclear features. PTC generally has the best prognosis among thyroid malignancies [ 2 ].

While PTC frequently metastasizes to regional lymph nodes, reported in 30-80% of patients, distant metastases are relatively uncommon, occurring in only 1-4% of cases. When distant spread does occur, it most commonly involves the lungs. Metastasis to the spine is extremely rare and has been sparsely documented in the literature [ 3 ].

Bone metastasis in differentiated thyroid cancers (DTC), including PTC and follicular thyroid cancer (FTC), occurs in 2-13% of cases, with a higher prevalence in FTC (7-28%) compared to PTC (1-7%) [ 4 , 5 ]. PTC accounts for most DTC cases but has a lower incidence of spinal metastasis, estimated at 1-7% [ 6 ]. This report presents a rare case of a metastatic spinal column lesion originating from PTC.

Case presentation

A 61-year-old female with a history of hypertension and diabetes presented to the emergency room complaining of progressively worsening lower back pain over the past four months. She denied fever, weight loss, night sweats, neurological symptoms, or urinary incontinence.

The patient further reported that she had noticed an enlarged neck for several months before experiencing back pain. A thyroid ultrasound performed a month prior revealed a 2.60×1.7×0.11 cm Thyroid Imaging Reporting and Data System, Category 4 (TIRADS-4) mass in the right thyroid lobe and a 0.7 cm TIRADS-2 lesion in the left thyroid lobe. No lymph node enlargement was noted. In light of these findings, she underwent fine needle aspiration (FNA), with results pending at the time of her hospital admission.

Additionally, A CT scan of the spine performed a month prior revealed a lytic lesion on T10, compressing the thecal sac and causing foraminal and spinal stenosis (Figure 1 ). This finding raised suspicion for multiple myeloma (MM), prompting a hematologist to recommend a workup for MM.

Physical examination in the emergency department revealed that the patient appeared well, with a blood pressure of 134/101 mmHg, pulse rate of 86 beats per minute, respiratory rate of 16 breaths per minute, body temperature of 37.0°C, and oxygen saturation of 97% on room air. Further evaluation showed good power in her lower limbs and normal sensations, with no tenderness upon spinal palpation. Laboratory tests did not reveal significant abnormalities including a thyroid panel, and the workup for multiple myeloma (MM) was within normal limits (Table 1 ). A chest x-ray showed no lung masses or bone lesions.

The thyroid biopsy results were received, confirming the diagnosis of papillary thyroid carcinoma (PTC). Spine magnetic resonance imaging (MRI) revealed an expansile lytic lesion in the T10 vertebra with a mass effect but without myelopathic signal changes in the spinal cord (Figure 2 ). Biopsy of the vertebral mass at T10 confirmed metastasis from PTC (histopathology of the spine lesion shown in Figure 3 ). The patient was subsequently referred to an oncologist who planned to perform a thyroidectomy. External beam radiation therapy (EBRT) was also initiated for the spinal metastasis.

Discussion

This report presents a rare instance of solitary spinal metastasis from PTC, a diagnosis often associated with advanced disease and multiple metastatic sites. Thyroid cancer (TC) is the most common type of endocrine malignancy, with over 90% of cases originating from differentiated thyroid cancer (DTC), which develops from follicular thyroid cells. DTC includes papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and Hürthle cell thyroid cancer, while medullary thyroid cancer originates from calcitonin-producing parafollicular C cells [ 7 ]. PTC and FTC are the most common differentiated thyroid cancers with a good prognosis, comprising 80-85% and 10-15% of all TC cases, respectively. In contrast, anaplastic thyroid cancer (ATC) is a rare, undifferentiated form (about 1% of cases) known for its aggressive behavior and poor prognosis, accounting for 15-40% of TC-related deaths [ 8 , 9 ].

Cervical lymph node metastasis in PTC occurs in 40-90% of cases and is a major risk factor for recurrence [ 10 , 11 ]. The classical variant (CVPTC) often invades the lymphatic system, while the follicular variant (FVPTC) behaves more like FTC, spreading via blood vessels to distant organs such as the lungs and bones. FVPTC is more likely to have RAS mutations and PAX8/PPARγ rearrangements [ 12 ].

The differential diagnosis for persistent back pain with lytic vertebral lesions includes primary bone tumors (osteosarcoma, chordoma), hematologic malignancies (multiple myeloma, lymphoma), infections (vertebral osteomyelitis, spinal tuberculosis), and metastatic cancers (lung, breast, prostate) [ 13 ]. Diagnostic evaluation should include a thorough physical examination, tumor markers, and imaging (MRI or PET-CT) to identify potential primary sites. Biopsy remains the gold standard for confirming malignancy [ 14 ]. In the present case, primary bone tumors, hematologic malignancies, and infections were excluded based on clinical evaluation (absence of fever, normal physical examination), laboratory results (no elevated inflammatory markers), and a negative multiple myeloma workup. A biopsy was performed to confirm the diagnosis of spinal metastasis from PTC.

Bone is the third most common site of DTC metastasis after lungs and liver [ 15 ]. Bone metastasis occurs in 7-28% of FTC cases and 12% of Hürthle cell thyroid cancer (HCTC) cases. PTC has a lower metastasis rate (1-7%) due to its preference for lymphatic spread [ 4 ].

More than 80% of bone metastases from DTC are located in the axial skeleton, which is rich in red marrow (vertebrae, ribs, and hips) [ 16 ]. Bone metastasis in spinal regions typically affects the thoracic (60-80%), lumbar (15-30%), and cervical bones (<10%) [ 17 ]. The vertebral body (85%) is the most common site. Lesions are mostly osteolytic, leading to bone destruction and spinal cord compression [ 17 ].

A bone biopsy is recommended for suspected skeletal metastasis, even in patients with known thyroid cancer, due to the possibility of another tumor type [ 6 ]. CT scans are effective for assessing bone involvement, while MRI is the gold standard for spinal metastasis imaging [ 17 ]. Spinal metastasis in PTC often indicates advanced disease and a poorer prognosis, contrasting with its typically favorable outcomes [ 3 ].

Treatment options for symptomatic or growing metastases depend on iodine uptake. If the metastases are iodine-avid, radioiodine therapy may be an option [ 18 ]. For those that do not show iodine uptake, alternative approaches include surgical resection (if possible), mutation-directed systemic therapy for unresectable disease, external beam radiation therapy (EBRT), and best supportive care [ 19 ]. Spinal metastases can lead to skeletal-related events like pathological fractures, spinal cord compression, and chronic pain. Early detection and aggressive treatment are critical [ 4 ].

This case highlights the rarity of spinal metastasis from PTC, especially as a solitary lesion. The diagnosis was confirmed with imaging and biopsy, and no neurological deficits were observed. This case emphasizes that while bone metastasis from PTC is rare, spinal metastasis should be considered in patients experiencing back pain and limb weakness. Additionally, it highlights the importance of using multiple imaging modalities to detect and assess bone metastatic lesions.

Conclusions

Distant metastasis from papillary thyroid cancer (PTC) is observed in 1-4% of patients and infrequently affects the spine. Understanding the features and manifestations of papillary thyroid carcinoma (PTC) - particularly its potential for spinal metastasis and the role of imaging techniques - is essential for effective management and accurate prognostic assessment. This case emphasizes the need for a thorough diagnostic evaluation of persistent back pain in patients with a history of thyroid abnormalities, highlighting the potential for metastatic PTC.

Disclosures

Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study.

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:

Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.

Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.

Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Author Contributions

Concept and design: Rami Jabareen, Ali Shalabi, Nizar Hijazi

Acquisition, analysis, or interpretation of data: Rami Jabareen, Zhalka Abdellatif, Ali Shalabi, Nizar Hijazi

Drafting of the manuscript: Rami Jabareen, Zhalka Abdellatif, Ali Shalabi, Nizar Hijazi

Critical review of the manuscript for important intellectual content: Rami Jabareen, Ali Shalabi, Nizar Hijazi

Supervision: Zhalka Abdellatif, Ali Shalabi, Nizar Hijazi

References

1 Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors J Cancer Epidemiol Pellegriti G Frasca F Regalbuto C Squatrito S Vigneri R 2013 2013 10.1155/2013/965212 PMC3664492 23737785

2 Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature ISRN Oncol Gonzalez-Gonzalez R Bologna-Molina R Carreon-Burciaga RG Gómezpalacio-Gastelum M Molina-Frechero N Salazar-Rodríguez S 2011 2011 10.5402/2011/915925 PMC3302055 22432054

3 Site-specific metastasis and survival in papillary thyroid cancer: the importance of brain and multi-organ disease Cancers (Basel) Toraih EA Hussein MH Zerfaoui M 13 2021 10.3390/cancers13071625 PMC8037301 33915699

4 Bone metastases from differentiated thyroid carcinoma: current knowledge and open issues J Endocrinol Invest Nervo A Ragni A Retta F 403 419 44 2021 32743746 10.1007/s40618-020-01374-7 PMC7878269

5 Bone metastases in thyroid cancer J Bone Oncol Iñiguez-Ariza NM Bible KC Clarke BL 21 2020 10.1016/j.jbo.2020.100282 PMC7058902 32154098

6 Approach to the thyroid cancer patient with bone metastases J Clin Endocrinol Metab Wexler JA 2296 2307 96 2011 21816796 10.1210/jc.2010-1996

7 Target therapy in thyroid cancer: current challenge in clinical use of tyrosine kinase inhibitors and management of side effects Front Endocrinol Puliafito I Esposito F Prestifilippo A 13 2022 10.3389/fendo.2022.860671 PMC9304687 35872981

8 Cancer stem cells in thyroid tumors: from the origin to metastasis Front Endocrinol Veschi V Verona F Lo Iacono M 11 2020 10.3389/fendo.2020.00566 PMC7477072 32982967

9 Primary cell cultures for the personalized therapy in aggressive thyroid cancer of follicular origin Semin Cancer Biol Fallahi P Ferrari SM Elia G 203 216 79 2022 32569821 10.1016/j.semcancer.2020.06.013

10 Risk factor analysis for predicting cervical lymph node metastasis in papillary thyroid carcinoma: a study of 966 patients BMC Cancer Liu C Xiao C Chen J Li X Feng Z Gao Q Liu Z 19 2019 10.1186/s12885-019-5835-6 PMC6593593 31238891

11 Lymph node metastases papillary thyroid carcinoma and their importance in recurrence of disease Med Arch Maksimovic S Jakovljevic B Gojkovic Z 108 111 72 2018 29736098 10.5455/medarh.2018.72.108-111 PMC5911164

12 Lymph node metastases in papillary and medullary thyroid carcinoma are independent of intratumoral lymphatic vessel density Eur Thyroid J Pereira F Pereira SS Mesquita M 57 64 6 2017 28589086 10.1159/000457794 PMC5422756

13 Fundamentals of Diagnostic Radiology. Third Edition Fundamentals of Diagnostic Radiology Philadelphia, PA Lippincott, Williams and Wilkins 2007 https://books.google.co.il/books?hl=en&lr=&id=Sossht2t5XwC&oi=fnd&pg=PP15&dq=Fundamentals+of+Diagnostic+Radiology&ots=koDFtt-4M7&sig=ryJJv6KJmLNBLmwCAV2zfg2peOc&redir_esc=y#v=onepage&q=Fundamentals%20of%20Diagnostic%20Radiology&f=false

14 Validity of negative bone biopsy in suspicious bone lesions Acta Radiol Open Lange MB Petersen LJ Nielsen MB Zacho HD 10 2021 10.1177/20584601211030662 PMC8323434 34377541

15 Skeletal metastases - the role of the orthopaedic and spinal surgeon Surg Oncol Eastley N Newey M Ashford RU 216 222 21 2012 https://www.sciencedirect.com/science/article/abs/pii/S0960740412000242?via%3Dihub 22554913 10.1016/j.suronc.2012.04.001

16 Bone metastases from differentiated thyroid carcinoma Endocr Relat Cancer Muresan MM Olivier P Leclère J 37 49 15 2008 18310274 10.1677/ERC-07-0229

17 Spinal metastasis in thyroid cancer Head Neck Oncol Ramadan S Ugas MA Berwick RJ Notay M Cho H Jerjes W Giannoudis PV 4 2012 10.1186/1758-3284-4-39 PMC3466148 22730910

18 Controversies, consensus, and collaboration in the use of 131I therapy in differentiated thyroid cancer: a joint statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association Thyroid Tuttle RM Ahuja S Avram AM 461 470 29 2019 30900516 10.1089/thy.2018.0597

19 Survival and therapeutic modalities in patients with bone metastases of differentiated thyroid carcinomas J Clin Endocrinol Metab Bernier MO Leenhardt L Hoang C 1568 1573 86 2001 11297585 10.1210/jcem.86.4.7390