An upper cervical cord compression secondary to occult follicular thyroid carcinoma metastases successfully treated with multiple radioiodine therapies: A clinical case report.

RATIONALE: The spine is the most common site of bone metastases due to thyroid cancer; however, spinal cord compression as a complication of metastatic thyroid cancer is very rare. PATIENT CONCERNS: A 48-year-old female patient was presented to the Neurosurgical Department, complaining of progressive back neck pain with bilateral upper extremities numbness and weakness for 4 months. DIAGNOSIS: Imaging studies revealed osteolytic destruction in bodies and accessories of the second and third cervical vertebrae with a huge soft-tissue mass compressing spinal cord and causing swelling. After the neurosurgical decompression surgery, the pathological examination established a metastatic follicular carcinoma originating from the thyroid gland.
INTERVENTIONS: Her cervical spinal metastases were hardly removed by surgery and the risks of external beam radiation therapy (EBRT) were very high. So she underwent a total thyroidectomy and received multiple radioiodine (RAI) and concomitant glucocorticoid therapies postoperatively. Radioiodine whole-body scan (WBS) showed multiple abnormal radioiodine uptakes. Then single-photon emission tomography/computed tomography (SPECT/CT) located these spinal metastases involving cervical, lumbar, and sacral vertebrae. OUTCOMES: After 5 times RAI therapy, her thyroglobulin obviously decreased, with the cervical lesion shrinkage and no spinal cord edema. LESSONS: RAI therapy and concomitant glucocorticoid therapy could be used for spinal metastases of FTC, even with spinal cord compression.

Introduction

Bone metastases originating from differentiated thyroid carcinoma (DTC) are not uncommon, and occur in approximately 2% to 13% of all DTC patients.[ Spinal metastases are found in approximately half of the patients with bone metastases.[ They is a frequent complication especially in FTC and it is associated with osteodynia, vertebral fractures, and spinal cord compression.[ Spinal cord compression, as a bone metastases complication of thyroid carcinoma, is uncommon and occurs mainly during the late stage of the disease.[ Current American Thyroid Association (ATA) guidelines state that surgical resection and stereotactic external beam radiation therapy (EBRT) are the mainstays of therapy for central nervous system (CNS) metastases and radioiodine (RAI) therapy and concomitant glucocorticoid therapy can be considered if CNS metastases concentrate RAI.[ As relatively few cases being described in the literature, RAI protocol of such patients with spinal metastases and spinal cord compression of DTC origin was insufficient.[ The aim of the present case report was to share our experience: how to treat patients with cervical spinal DTC metastases with RAI to improve understanding of this rare entity.

Case report

A 48-year-old female patient was presented to the Neurosurgical Department, complaining of progressive back neck pain with bilateral upper extremities numbness and weakness for 4 months. Transversal computed tomography (CT) and three-dimensional reconstruction showed osteolytic destruction in bodies and accessories of the second and third cervical vertebrae (Fig. 1A and B). In the same region, magnetic resonance imaging (MRI) demonstrated a huge mass, with a high signal intensity on the contrast-enhanced T1W image, compressing spinal cord (Fig. 1C, red arrow) and causing swelling (Fig. 1D, red arrow).

Figure 1

A and B, Transversal CT and three-dimensional reconstruction showed osteolytic destruction in bodies and accessories of the second and third cervical vertebrae. (C and D, red arrow) In the same region, MRI demonstrated a huge mass, with a high signal intensity on the contrast-enhanced T1W image, compressing spinal cord and causing it swelling. CT = computed tomography, MRI = magnetic resonance imaging.

After the neurosurgical decompression surgery, the pathological examination revealed a metastatic follicular carcinoma originating from the thyroid gland (Fig. 2A), which was determined by detecting the thyroglobulin (Tg), paired box gene 8 (Pax-8), and thyroid transcription factor 1 (TTF-1) expression on tumor cells (Fig. 2B, C, and D, respectively).

Figure 2

The pathological examination revealed a metastatic follicular carcinoma (A, H&E) originating from thyroid gland, which was determined by detecting Tg (B), Pax-8 (C), and TTF-1 (D) expression in tumor cells.

Her symptom of back pain and numbness gradually recovered, but the spine cord compression and edema still existed on postoperative MRI (Fig. 3A and B). Then the patient underwent a total thyroidectomy and central lymph node dissection, but the pathological examination only found multiple follicular adenomas without evidence of carcinoma and regional lymph node metastases. Staging for the patient was done (TxN0M1) in accordance with the 8th edition of the AJCC/UICC staging system. Given the difficulties in complete resection of cervical metastases and high risks of EBRT, RAI therapy was performed on October 10, 2013. Meanwhile, methylprednisolone and mannitol were prescribed to prevent radioactive inflammation of spinal cord (Table 1). There were no obvious spine cord compression symptoms or side effects of glucocorticoid during the period of treatment.

Figure 3

A and B, The spine cord compression and edema still existed on postoperative MRI. MRI = magnetic resonance imaging.

Table 1

Prescription of methylprednisolone and mannitol.

131I-WBS revealed multiple abnormal uptake lesions (Fig. 4A) and SPECT/CT located these osteolytic bone metastases involving C2 and C3 (Fig. 4B, red arrow), C5 spinous process (Fig. 4B, blue arrow), L1 (Fig. 4C, purple arrow), S1 (Fig. 4C, white arrow). There was little residual thyroid tissue on the right thyroid bed (Fig. 4B, yellow arrow). Even levothyroxine had been withdrawn for 5 weeks (because of nonavailability of rhTSH in Mainland China), her TSH was still low (3.97 mU/L, normal range, 0.27–4.2 mU/L) with normal FT3 (Table 2), which might be almost due to these functional bone metastases.

Figure 4

131I whole-body scan revealed multiple abnormal uptake lesions (A) and SPECT/CT located these osteolytic bone metastases involving C2 and C3 (B, red arrow), C5 spinous process (B, blue arrow), L1 (C, purple arrow), S1 (C, white arrow). There was little residual thyroid tissue on the right thyroid bed (B, yellow arrow). SPECT/CT = single-photon emission tomography/computed tomography.

Table 2

Thyroid function studies before and after RAI.

Given the favorable therapeutic reaction and little radioactive inflammation, the patient was preformed with other 4 RAI therapies (Table 3). And these four 131I-WBSs were similar to the first 131I-WBS previously (Fig. 5). Her last outpatient follow-up was on March 26, 2017. On physical examination, she was afebrile and normotensive without back neck pain or extremities numbness. Her workup included a TSH level of 0.059 mU/L (normal range, 0.27–4.2 mU/L), a FT3 level of 5.06 pmol/L (normal range, 3.6–7.5 pmol/L), an FT4 level of 18.46 pmol/L (normal range, 12–22 pmol/L), a sharply decreased Tg level of 45.75 ug/L compared with pre-RAI therapy of 451.2 ug/L (normal range, 1.4–78 ug/L), a TgAb level of <10 IU/mL (normal range, <115 IU/mL), normal blood routine, and normal albumin and liver enzyme levels. And imaging studies included the cervical vertebra of MRI which demonstrated significant shrinkage of cervical vertebrae lesions with no spinal cord edema (Fig. 6A and B) and chest CT with negative result.

Table 3

RAI therapy: time, time interval, and dose.

Figure 5

(A, B, C, and D, respectively) Other 4 131I-WBSs also revealed the same multiple abnormal uptake lesions as the first 131I-WBS depiction. WBS = whole-body scan.

Figure 6

A and B, The cervical vertebrae lesion was shrinkage and there was no spinal cord edema.

This case report was approved by the Ethics Committee of West China Hospital of Sichuan University, Chengdu, China, and the written informed consent was obtained.

Discussion

Distant bone metastases, as a common complication of FTC, occur mainly during the late stages of the disease.[ Spinal metastases typically affect the thoracic (60%–80%), lumbar (15%–30%), and cervical spine (< 10%).[ Upper cervical metastasis with spinal cord compression from follicular thyroid carcinoma is a rare event. The chief presenting symptom of spinal metastases is pain (83%–95%), and some patients may show incomplete paralysis or paraplegia. [

We surveyed the literature indicating that only a few sporadic cases of DTC patients with spinal cord compression are due to vertebral metastasis. Most of them underwent surgical approach, RAI and TSH suppression therapy, and other palliative treatments including laminectomy, excision, embolization, and EBRT.[ Among these sporadic cases, Selvakumar et al[ reported that a female with symptomatic cervical cord compression due to spinal metastases of papillary carcinoma but achieving neurologically stable after multidisciplinary treatments including surgery, EBRT, and a RAI therapy. Management of patients with spinal cord compression due to upper cervical metastases from FTC must involve a multidisciplinary approach including surgery (total thyroidectomy and resection of metastatic lesions), EBRT, RAI therapy, and TSH suppression therapy.[ A total thyroidectomy is to remove the primary tumor and to facilitate radioiodine therapy. Resection of metastatic lesions is associated with improved survival and quality of life.[ EBRT is a palliative treatment indicated only when pain, risk of fracture, and neurological complications of spinal cord compression are present.[ Radioiodine therapy is considered the first-line treatment for sodium-iodide symporter (NIS) positive metastatic lesions. TSH suppression therapy intends to reduce the impetus for further tumor growth.[ Glucocorticoids can relieve and prevent spinal cord compression during RAI therapy. Methylprednisolone is a synthetic corticosteroid with higher anti-inflammatory activity than prednisolone (1.25 times) and a low mineralocorticoid effect. It has been used to treat acute spinal cord injury and ease surgically related pain and inflammation.[ So we chose methylprednisolone instead of prednisolone for this patient. There are some studies that reported that glucocorticoids would reduce thyroidal uptake of RAI and lower its effective half-life in a dose-dependent manner, perhaps by increasing glomerular filtration rate and thus renal iodine clearance.[ So we performed 131I-WBS in 2, 5, 7 days after the treatment of 150 mCi 131I, respectively. And these 131I-WBS images showed no obviously decreasing radioactivities in the metastatic lesions, which indicated that high-dose glucocorticoid may not affect the uptake of iodine and its retention in these lesions.

The patient's thyroid status was nearly euthyroid after withdrawal of levothyroxine for 3 weeks or more. There are 3 reported potential mechanisms that might be involved in this situation. First, metastatic thyroid cancers may function autonomously to produce thyroid hormones.[ Second, the TSH receptor in the metastatic tumor may induce the formation of thyrotrophin receptor antibody (TRAb), favoring the production of thyroid hormone by the metastatic tissue. Finally, some metastases from FTC express 5’-iodothyronine deiodinase activity. If patients with these tumors receive levothyroxine, there could be an increase in the conversion of thyroxine to T3 in the metastatic tumor tissue.[ As for our patient, the reason may be that metastases that function autonomously produce thyroid hormones, because of multiple radioactive metastases and remarkable decrease of serum thyrogobulin after RAI.

As previously reported by Selvakumar et al,[ the current cervical spinal metastatic patient from an occult FTC also underwent surgery both for primary disease and metastatic lesions and RAI therapy. But our patient underwent multiple RAI concomitant glucocorticoid therapies compared with the patient reported by Selvakumar et al who just received only 1 time of RAI therapy without glucocorticoid therapy.

Compared with other similar cases published including reported by Selvakumar et al, [ there were some differences in our manuscript. The patient's cervical spinal metastases could not be completely resected, still existing spinal cord compression and edema, which may be worsened after RAI. With the regimen of methylprednisolone and mannitol, she underwent 5 RAI therapies without obvious side effects and achieved partial remission. Additionally, her metastases were functional lesions, as we discussed above.

To the best of our knowledge, this was the first reported case that attempted to use multiple RAI therapies concomitant glucocorticoid therapies to successfully treat a patient with spinal cord compression due to upper cervical metastases from occult FTC. During these 5 therapeutic processes, the patient did not have any significant adverse sequelae and her serum thyroglobulin obviously decreased with cervical lesions shrinkage. We recommended her to do resection of her cervical lesions again. However, she refused. So the patient will receive more RAI therapy when certain standards are met.

In conclusion, FTC with spinal cord compression should be early diagnosed and multidisciplinary approaches should be applied, including surgery, EBRT, RAI, and concomitant glucocorticoid therapy, to improve patients’ survival rate and quality of life.