Teaching Case

A 62-year-old woman was referred with a neck ultrasound performed elsewhere, showing an enlarged and heteroechoic left lobe of the thyroid gland, and fine needle aspiration cytology demonstrating medullary carcinoma of the thyroid. The patient's serum calcitonin was 520pg/ml. A ⁶⁸Ga-DOTANOC PET/CT scan was performed to rule out metastases.

Fig 1a shows ⁶⁸Ga-DOTANOC hybrid fused PET/CT whole body scan at the level of the thyroid gland showing well defined focal intense avidity in the left lobe. The normal right lobe shows no avidity. No avid cervical lymph nodes detected. No other suspicious areas were identified to suggest distant metastasis.
Fig 1b is the corresponding non contrast axial CT image showing an enlarged, hypodense mass replacing the left lobe of the thyroid.
Fig 1c shows a Maximum Intensity Projection(MIP) image with focal intense uptake in the left lobe of the thyroid gland.
Fig 1d shows whole body MIP image with focal intense avidity in the site of left lobe of thyroid gland and no other abnormal foci. Normal physiological uptake in the pituitary, kidneys, spleen, bladder.

Background

Medullary carcinoma of the thyroid (MTC) is a rare neuroendocrine tumour (NET) that expresses somatostatin receptors (SSTR) on the cell membrane and secretes calcitonin(Ctn). Despite treatment with total thyroidectomy and modified neck lymphnode dissection, approximately 50% of patients have persistent/recurrent disease [1]. Imaging of recurrent MTC is difficult, posing a major management problem. Ctn forms the most sensitive preoperative marker for MTC, monitoring effectiveness of treatment, and for detecting recurrence. Unfortunately, the rise in calcitonin carries no clue to the site of the disease and this obstacle may delay surgery. With ¹⁸F-FDG PET reportedly showing low sensitivity in Ctn <1000pg/ml, the introduction of ⁶⁸Ga-DOTANOC/DOTATATE PET/CT has significantly improved the detection of NET and has been reported as a valuable adjunct in the localization of metastatic spread of MTC [1].

Clinical Perspective

The most frequent sites of MTC metastasis are cervical and mediastinal lymph nodes, lungs, liver and bone. The American Thyroid Association recommends neck ultrasound (US) in all cases. Contrast-enhanced Computed Tomography (CECT) of the neck and chest, CECT or contrast-enhanced Magnetic Resonance Imaging (MRI) of the liver, and bone scintigraphy are recommended in patients with extensive neck disease or metastases, and when Ctn > 500 pg/mL. FDG-PET/CT is not recommended to detect the presence of distant metastases [2].

Imaging Perspective

Because of the small lesion size and low metabolic rate, conventional imaging is often difficult in MTC. CT, US, and MRI may fail to characterize or detect lesions. Therefore, functional imaging plays a crucial role in management [3].

⁶⁸Ga-DOTANOC is injected intravenously and PET/CT performed after 1 hour. With the short half life of ⁶⁸Ga, excellent radiolabelling chemistry and fast background clearance, high resolution PET images are produced. ⁶⁸Ga-DOTANOC binds to SSTR overexpressed on NET cells. A positive scan is reported as active disease or recurrence/relapse when at least one focus of abnormal intense uptake with high SUV measurement is observed [4].

Outcome

Surgery is the primary curative modality, done only when diagnosis is timely, so there is a high rate of persistent and recurrent disease indicated by elevated Ctn. This patient underwent total thyroidectomy and central lymph node dissection. Histopathology confirmed MTC. Successful management of recurrence requires accurate localisation with cross sectional and functional imaging.

Take Home Message

⁶⁸Ga-DOTANOC/DOTATATE PET/CT is a promising diagnostic method for the evaluation of patients with recognised/suspected MTC, with reportedly high sensitivity for localising metastatic spread, and may be used in staging, re-staging, and in regular follow up [2].