Medullary Thyroid Carcinoma: An Update on Imaging

Abstract

Medullary thyroid carcinoma (MTC), arising from the parafollicular C cells of the thyroid, accounts for 1-2% of thyroid cancers. MTC is frequently aggressive and metastasizes to cervical and mediastinal lymph nodes, lungs, liver, and bones. Although a number of new imaging modalities for directing the management of oncologic patients evolved over the last two decades, the clinical application of these novel techniques is limited in MTC. In this article, we review the biology and molecular aspects of MTC as an important background for the use of current imaging modalities and approaches for this tumor. We discuss the modern and currently available imaging techniques-advanced magnetic resonance imaging (MRI)-based techniques such as whole-body MRI, dynamic contrast-enhanced (DCE) technique, diffusion-weighted imaging (DWI), positron emission tomography/computed tomography (PET/CT) with 18F-FDOPA and 18F-FDG, and integrated positron emission tomography/magnetic resonance (PET/MR) hybrid imaging-for primary as well as metastatic MTC tumor, including its metastatic spread to lymph nodes and the most common sites of distant metastases: lungs, liver, and bones.

Figure 1

Imaging of metastatic medullary thyroid carcinoma using different radiological techniques: (a) whole-body magnetic resonance imaging, diffusion-weighted sequence (DWI), (b) whole-body contrast-enhanced magnetic resonance imaging, T1 weighted images (3D rendering DCE); (c) positron emission tomography/magnetic resonance imaging (18F-FDG-PET/MR imaging fusion technique); (d) positron emission tomography/computed tomography with 18F-FDG (18F-FDG PET/CT). Please note the excellent visualization of the multiple liver metastases (yellow arrow), mediastinal metastases (red arrow), and a large left iliac bone metastasis (green arrows) on DWI and DCE, comparable with 18F-FDG PET/CT, although they interrogate completely different biophysical tissue properties. Note that the images are not quite coregistered (arms up during PET acquisition and with arms down during MR imaging).

Figure 2

Mechanisms of uptake and localization of different radiopharmaceuticals, which can be used for medullary thyroid carcinoma. Please see explanations in the text.

Figure 3

Imaging of the primary tumor in medullary thyroid carcinoma. (a)-(c) Ultrasound (US) features of primary medullary thyroid carcinoma of different patients (red arrows). US of the thyroid gland shows markedly hypoechoic nodules with marked calcifications. (d)-(f) US of the neck, computed tomography, and magnetic resonance tomography (T2 weighted images of the neck) of the same patient with bilateral medullary thyroid carcinomas (green arrows).

Figure 4

Imaging of the medullary thyroid carcinoma with metastasis to lymph node. Medullary thyroid carcinoma of the right thyroid lobe (red arrows) visualized on axial computed tomography (CT) (a) and transverse ultrasound (US) scan (b). A large metastatic lymph node (orange arrows) is demonstrated on axial CT of the neck (c) and sagittal US (d).

Figure 5

The proposed management approach for patients with medullary thyroid carcinoma. Please see explanations in the text.

Figure 6

Mapping of the metastatic lymph nodes in medullary thyroid carcinoma. Asymptomatic patient after thyroidectomy for medullary thyroid carcinoma and elevated calcitonin level (54 pg/ml) was evaluated for possible neck lymph node metastases. Ultrasound of the neck showed several suspicious lymph nodes (not shown). One of the lymph nodes (b) was found to be positive on only 18F-FDOPA-PET/CT (c), while 18F-FDG-PET/CT and 68Ga-DOTATATE-PET/CT were negative.

Figure 7

Mapping of the metastatic lymph nodes in medullary thyroid carcinoma. In 2015 patient underwent thyroidectomy for medullary carcinoma (a) and 2 years later presented with elevated calcitonin level (304 pg/ml). Ultrasound of the neck, CT of the neck, and MRI of the neck were all false negative (not shown); however, 18F-FDOPA-PET/CT (c), 18F-FDG-PET/CT, and 68Ga-DOTATATE-PET/CT were positive for a metastatic lymph node. Please note that patients with neck pathology should ideally be scanned with arms down (in this case the study was obtained with patient's arms up as it was a whole-body imaging for detection mediastinal metastases).

Figure 8

Computed tomography of the chest of different patients with metastatic medullary thyroid carcinoma. Disseminated pulmonary metastases (red arrows) (a). Solitary pulmonary metastases (yellow arrow) (b). Extensive metastatic mediastinal lymphadenopathy (green arrows) (c).

Figure 9

Imaging of hepatic metastases in medullary thyroid carcinoma of the same patient using contrast-enhanced computed tomography (CT) (a), magnetic resonance imaging (MRI), diffusion-weighted sequence (b); contrast-enhanced MRI, T1 weighted images (DCE)(c); MRI, T2 weighted image (d). MRI shows improved visualization of metastatic lesions compared to CT (red arrows) and can also detect very small metastases (green arrows), which may not be visible on CT.

Figure 10

Imaging of bone metastases in medullary thyroid carcinoma on two different patients. Patient A (a-b). 99m-Tc-MDP bone scan (a) and whole-body contrast-enhanced magnetic resonance imaging (MRI), T1 weighted images (DCE) (b). MRI demonstrates improved visualization of metastatic lesions involving the left iliac bone (blue arrow) and clear visualization tiny bone metastases in the spine (red arrows). Patient B (c-f). Visualization of small bone metastases. Axial contrast-enhanced computed tomography (CT) at the level of L1 shows single lytic metastases in the right aspect of the vertebral body (orange arrow) (c). Axial contrast-enhanced MRI, T1 weighted images (DCE) (d), axial MRI diffusion-weighted sequence (e), and axial MRI, T2 weighted images (f) can detect additional small spinal metastases, which are not visualized on CT (green arrows).

Figure 11

Imaging in MEN syndrome. 18F-FDG PET/CT (a) and 18F-FDOPA PET/CT (b) in MEN2B syndrome with metastatic pheochromocytoma (fractionated norepinephrine: 994 pg/ml, normal: 18-112 pg/ml; fractionated metanephrine: 1099 pg/ml, normal: 12-61 pg/ml) and metastatic medullary carcinoma (calcitonin: 5575, normal: < 8 pg/ml). In this case, the primary pheochromocytoma is seen in all images (yellow arrow); however, metastatic lesions are best visualized on 18F-FDOPA PET/CT (red arrows). Imaging cannot differentiate between medullary carcinoma metastases and metastases originating from pheochromocytoma.