False positive localisation of C-11 methionine in a colloid nodule

INTRODUCTION

A diagnosed case of carcinoma of the left breast planned for neoadjuvant chemotherapy underwent both 18F-Fluorodeoxyglucose (FDG) and 11C-methionine (MET) positron emission tomography/computed tomography (PET/CT). Both studies demonstrated intense focal tracer uptake in a nodule in the left lobe of thyroid. Cytopathology revealed it to be a colloid nodule. Thyroid lesions are frequently detected in patients undergoing FDG PET/CT. Some studies have reported that the incidence of thyroid incidentalomas with increased FDG uptake is 1.2-2.5% on PET examinations.[1–4] The risk of malignancy in these studies ranged from 26.7-50%. With an increasing utility of amino acid tracers such as C-11 MET for oncological indications, non-oncological causes[5] of uptake of this tracer should be kept in mind to avoid misinterpretation of the study.

CASE REPORT

A 45-year-old female presented with a left breast swelling since past 5 months. The swelling was single, painless, not fixed to the chest wall, and was associated with palpable left axillary lymphadeopathy. On histopathology, it was diagnosed as a case of infiltrating ductal cell carcinoma. As a part of protocol evaluating the utility of F-18 FDG and C-11 MET for prediction of response to neoadjuvant chemotherapy in locally advanced breast carcinoma the patient underwent the two studies on consecutive days. 222 MBq of FDG was injected intravenously and the patient was rested for 60 min followed by the PET/CT acquisition on a Discovery STE 16 camera (GE). 3D PET emission scan from head to thigh at 2 min per incremental bed position was acquired. C-11 MET PET/CT was done the next day 30 min after injecting 555 MBq of tracer followed by a two bed 3D PET acquisition for 10 min per bed position, with the axilla and chest in the acquisition field. Images were reconstructed using 3D VUE algorithm and viewed on a Xeleris workstation (GE) using the volumetrix protocol. On evaluation of the maximum intensity projection (MIP) image, abnormal FDG [Figure 1a] and MET [Figure 2a] accumulation was noted in the left breast and left axillary region and also in the left side of the neck. The transaxial fused PET/CT images [Figures 1b and 2b] localised this uptake to a well-defined solitary hypodense nodule in the left lobe of thyroid. On retrospective examination, a nodule, soft to firm in consistency and moving with deglutition was palpable in the left lobe of thyroid. The patient was referred for a FNAC prior to starting chemotherapy, which revealed features of a simple colloid nodule. Neoadjuvant chemotherapy with cyclophosphamide, adriamycin, and 5-flurouracil was started the next day.

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Figure 1a Maximum intensity projection (MIP) FDG-PET image showing abnormal tracer accumulation in the left side of neck (arrow), the primary in the–breast and –axillary nodes can also be seen

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Figure 1b Transaxial fused FDG PET/CT image showing the abnormal localization in a nodule (arrow) in the left lobe of thyroid

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Figure 2a Maximum intensity projection (MIP) MET-PET image showing abnormal tracer accumulation in the left side of neck (arrow head), the primary in the –breast and –axillary nodes can also be seen

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Figure 2b Transaxial fused MET PET/CT image showing the abnormal localization in a nodule (arrow head) in the left lobe of thyroid

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DISCUSSION

Thyroid nodules with abnormal increased tracer accumulation may be incidentally discovered on the FDG PET/CT study for other oncological indications. Increased FDG uptake can be observed in thyroid carcinoma and metastatic nodules due to augmented expression of glucose transport proteins such as GLUT-1, enhanced glycolysis, and increased cellular proliferation.[6–8] However, FDG also accumulates non-specifically in infectious, inflammatory diseases, or simply benign thyroid nodules secondary to lymphoid tissue activation, increased metabolic activity, and rapid iodine turnover.[910] The lack of specificity of FDG has prompted the use of radiolabeled amino acids such as C-11 methionine.

MET follows metabolic pathways of methionine and is a potential tracer to image altered amino acid metabolism in cancer. Methionine is needed for protein synthesis and as a precursor of S-adenosylmethionine, which is the most important biological methyl group donor in several biochemical reactions (e.g., methylation of DNA) in vivo.[1112] However, recent studies have suggested that tissue accumulation of methionine is primarily related to active transport of amino acids rather than to protein synthesis rate.[13] The increased utilization of methionine can be measured by PET using radiolabeled MET as the tracer. Uptake of MET in tumor tissue is rapid, and it has been evaluated for use in brain tumors, breast cancer, and pelvic malignancies. The recent advent of MET imaging in oncology has brought its own specific pitfalls and artefacts.[5] Knowledge of these potentially false positive causes of uptake is crucial to avoid misinterpretation of images. The possibility of MET accumulation in benign thyroid pathologies such as a colloid nodule has not been reported so far, but should be kept in mind while reporting the MET study in oncology and confirmatory cytopathology is recommended.