Thyroid carcinoma is one of the most common endocrine cancers worldwide. The prevalence of differentiated thyroid cancer (DTC) accounts for 90% of all thyroid cancer types with a favorable prognosis [1]. However, brain metastases from DTC are rare but sometimes become the cause of mortality [2, 3]. The management of patients with brain metastases from DTC is challenging. The number of retrospective studies with more than 20 patients was limited [4,5,6]. Characterization of clinicopathological features and the possible impact of radio-iodine, tyrosine kinase inhibitors, surgery, stereotactic radiosurgery, external beam radiotherapy, and whole-brain radiation therapy in patients with brain metastases from DTC have been reported in previous studies [7, 8]. However, there is no standard guideline for managing brain metastases from DTC. We have identified five patients with brain metastases among 5000 patients with DTC attending our center between 2016–2022. This case series aims to review our experience in a single center of managing brain metastases from DTC.
Case 1
A 66 year-old-woman was diagnosed with papillary thyroid carcinoma (PTC), regional cervical and right supraclavicular metastases (pT1N1M1). Diagnostic 131I- whole body scan showed multiple focal increased 131I-uptake in the head, neck, chest, abdomen, and pelvis, consistent with multi-organ metastases (Fig. 1). At the same time, the patient developed headaches and weakness on the right side, which suggested focal brain lesions. The head and neck 131I-SPECT/CT showed uptakes in the focal lesions seen in the 131I—whole body scan (Fig. 2). A hypodense lesion measuring 10 mm in diameter in the right frontal lobe and another hypodense lesion measuring 23 × 17 mm in the pons and right cerebral peduncle suggesting brain metastases were identified. She was treated empirically with high dose 131I (150 mCi) combined with Dexamethasone (16 mg/day). After the 131I treatment, her MRI brain (T1-weighted with contrast enhancement) showed a lesion in the right frontal cortex of 8 mm with focal enhancement and another in the right cerebral peduncle measuring 14 × 17 mm with central necrosis, peritumoral edema and heterogenous enhancement (Fig. 3). The patient underwent stereotactic surgery (SRS) with 24 Gy/1fraction (fx) for the right frontal and 22.5 Gy/3fx for pedicular lesions. After three months, the brain MRI scan showed a partial response tumors with improvement in symptoms. Radioiodine therapy was continued to treat multiple metastatic lesions and follow-up.
Case 2
A 40-year-old woman presented with dyspnea and a palpable cervical mass. Neck ultrasound showed multiple calcified large thyroid nodules and bilateral neck lymphadenopathy. Chest X-ray also showed multiple opacity ground glass opacities on both lungs. The patient underwent total thyroidectomy and lymph node dissection. Postoperative histopathology confirmed PTC (pT4N1b). Diagnostic 131I—whole body scan showed multifocal uptake on the thyroid bed, chest, abdomen and bone, in keeping with multiple metastases (Fig. 4a). An empirical treatment with high dose 131I (150 mCi) was given, and a post-therapy 131I—whole body scan showed an additional focal uptake on the head (Fig. 4b). Brain MRI revealed a solitary lesion in the left frontal lobe measuring 33 × 31 mm, remarkedly enhanced with peritumoral edema and mass effect causing cingulate herniation, consistent with a brain metastasis. Palliative radiotherapy was given for recurrent lesions on the left thyroid bed and cervical lymph node metastasis. SRS with a dose of 1800 cGy/1fx was used to treat the metastatic brain lesion. The partial response was seen on an MRI performed 3 months after the treatment (Fig. 5). The high empirical dose of radioiodine therapy was continued to treat thyroid beds and lung metastases. The progression-free survival of this patient has been 58 months and the patient is still under follow–up.
Case 3
A 33-year-old woman developed PTC with regional lymph node confirmed by ultrasound guided fine-needle aspiration (FNA) and lung metastases on chest CT (cT4aN1bM1). After total thyroidectomy and lymph node dissection, she subsequently underwent radioiodine therapy three times with a total activity of 450 mCi 131I since 2018. After the third treatment, post-therapy 131I- whole body scan showed no uptake. However, the serum thyroglobulin level was 500 ng/ml. The patient underwent 18F-FDG PET/CT for screening for nonradioiodine avid metastases. That showed multiple focal lesions with increased FDG uptake on the thyroid bed, bilateral lymph nodes, and a hypodense mass without FDG avidity, measuring 50 × 46 mm in total diameter on the left temporal lobe (Fig. 6). A brain MRI showed a 38 × 33 mm lesion with cystic and solid component in the left frontal lobe, showing a strong contrast enhancement on T2-weight and hypo signal on T1-weight, consistent with a solitary metastatic focus (Fig. 7a). The large intracranial mass, the thyroid bed lesion, and the bilateral lymph nodes were treated with surgery. The postoperative pathological and immunohistochemical report confirmed that brain metastasis from PTC (Fig. 8). There was no residual brain lesion on MRI after surgery; hence the patient did not undergo adjuvant radiosurgery (Fig. 7b). TSH-suppressive levothyroxine therapy was maintained. The patient has been followed-up for 28 months after the detection of the brain metastases.
Case 4
A 63-year-old female underwent total thyroidectomy and lymph node dissection, and subsequently followed by remnant ablation and adjuvant 131I- therapy with the diagnosis of PTC (cT3N1M0). Post-therapy 131I- whole body scan no uptake. Twelve months after the radioiodine treatment, the patient presented to the emergency department with seizures. The head MRI showed a 23 × 25 mm lesion (enhancing on T2-weighted image and co-signal with cortex on T1-weighted image) in the right frontal lobe without peri-tumor edema, consistent with brain metastasis. She underwent a resection of her cranial tumor. Histopathology confirmed brain metastasis from PTC. The patient is under followed-up, and there has been no evidence of progression.
Case 5
A 42-year-old man was diagnosed with PTC and underwent total thyroidectomy, dissection of metastatic neck lymph nodes, and adjuvant radioiodine therapy in 2015. After the third radioiodine treatment, 131I- whole body scan was negative with the thyroglobulin level at 300 ng/ml. The patient undertwent 18F- FDG PET/CT which showed a sub-centimeter recurrent lesion in the thyroid bed and cervical metastatic lymph nodes at level VI with high FDG avidity. The patient was under follow-up with TSH-suppressive levothyroxine therapy. In March 2021, he presented to the emergency department with persistent severe headache. A non-contrast cranial CT showed hyper-dense lesion at the right caudal nucleus, measuring 13 × 19 mm. In addition, there was a 37 × 38 cm lesion in the right ventricular occipital edge, associated with surrounding cerebral edema consistent with hemorrhage within a metastasis. Brain MRI showed 39 × 43 mm, and 30 × 34 mm solid lesions enhancing brightly on T1-weighted MRI in the right frontal and the right temporal lobe adjacent to the lateral ventricle, respectively. Contrast enhancement strongly infiltrated the centers of the lesions (Fig. 9). Dexamethasone, 4 mg twice a day, was initiated, along with pain control. The patient refused surgery and tyrosine kinase therapy, and he was followed-up. After two months, 18F-FDG PET/CT revealed new lesions in the brain, cervical lymph nodes, right scapula and right rectus abdominal muscle with high FDG uptake.