Second-look ultrasound with positron emission tomography (PET) for evaluating recurrent lesions of medullary thyroid cancer: a case description

Background

Medullary thyroid cancer (MTC) accounts for 1–2% of thyroid cancers; MTC can be sporadic (75%) or familial (25%) (1). After surgical resection, sporadic MTC clinically or incidentally manifests as advanced disease with regional and distant metastasis rates at presentation of 35% and 13%, respectively (2). Thus, sporadic MTC has poor overall survival at 10 years (3).

In MTC, the basal level of serum calcitonin (Ct) is a prognostic factor and indicator of remission. Failure to achieve postoperative biochemical remission is defined as serum Ct not normalizing, and postoperative basal or stimulated Ct greater than 10 ng/mL (4). In metastatic or recurrent MTC, lesion detection using imaging modalities is crucial for disease management. Elevated Ct and carcinoembryonic antigen (CEA) levels are indicative of recurrence. Recurrent or metastatic lesions need to be localized before an effective treatment plan can be developed.

Functional or metabolic imaging with 68Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) has become increasingly useful in identifying obscure recurrent and metastatic lesions (5). However, PET is expensive, takes about an hour to complete, and is not widely available in some countries or regions. Ultrasound (US) is an alternative imaging method for assessing persistent/recurrent locoregional lesions in patients with thyroid cancer, in whom lymph node metastasis is common. However, the sensitivity of US in evaluating lateral lymph node metastases is relatively low at 27% (6,7). When recurrent/persistent MTC occurs after initial cervical surgery, the rate of false-negative US findings increases to more than 40% (8). However, US is easy to perform and radiation free, and thus can be used for the multiple follow-up monitoring of recurrent lesions. Moreover, US can be used for further interventional procedures to obtain pathological results.

In this article, we present the case of a patient with MTC who failed to achieve postoperative biochemical remission after two operations even though his cervical US results were negative. 18F-DOPA PET/CT/68Ga-DOTATATE PET/CT showed a 0.3-cm lesion with slightly increased radioactivity uptake. The patient underwent second-look US, which revealed a lymph node (0.9 cm × 0.3 cm in size) behind the lateral border of the internal jugular vein.

Case presentation

A 22-year-old man presented with a right neck mass one year ago. Thyroid US showed a 1.1-cm thyroid nodule in the right lobe with multiple lymphadenopathies (right level II/III/IV/VI lymph nodes), classified as TR5 under the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) classification (9). The patient’s preoperative serum Ct was 292 pg/mL, and adrenal CT results were negative. His blood calcium and parathyroid hormone were within the normal range. The patient underwent thyroidectomy.

Postoperative pathology showed MTC invading the striated muscle tissue and the blood vessel wall and metastatic lymph nodes (right level II/III/IV/V/VI lymph nodes). The molecular pathological examination showed a missense mutation in RET exon 16. After surgery, the patient was treated with euthyrol. At 3 months after surgery, lymph node metastasis in the right level II was found by US re-examination. US-guided fine needle aspiration of the lymph node revealed tumour cells, and the Ct of the puncture fluid was >1,535 pg/mL. Lymph node dissection was performed, and metastatic lymph nodes were confirmed by pathology.

On postoperative monitoring, the patient’s Ct did not return to normal (53 pg/mL), and the patient was treated with Octreotide for four courses to monitor the fluctuation in Ct at 91–110 pg/mL. His cervical US results were negative. 68Ga-DOTATATE PET-CT showed a 0.3-cm lesion with slightly increased radioactivity uptake behind the left internal jugular vein, and a maximum standardized uptake (SUVmax) value of 1.9; 18F-DOPA PET/CT showed a lesion with slightly increased radioactivity uptake behind the left internal jugular vein, and a SUVmax value of 2.0, indicating metastatic lesions. The patient underwent second-look US, which revealed a lymph node (0.9×0.3 cm in size) with loss of the fatty hilum behind the lateral border of the internal jugular vein (Figure 1).

Figure 1 The second-look ultrasound showed a lymph node (0.9×0.3 cm in size) with loss of the fatty hilum behind the lateral border of the internal jugular vein (A,C). The colour Doppler ultrasound image of the lymph node revealed a local abundant blood flow signal (B,D). The thick arrows mark the lymph nodes; the thin arrow marks the internal jugular vein.

The history of past illness showed that the patient had suffered from hypertension 8 years earlier, after appendectomy. The patient was generally in good health and denied other diseases. On the physical examination, a surgical scar was observed on the patient’s neck.

The patient was ultimately diagnosed as MTC (pT4aN1bM0 stage IVA) with suspicion of lymph node metastasis behind the left internal jugular vein. In this case, recurrence/metastasis of MTC occurred within a short time of the second operation, indicating a poor prognosis and a complex and difficult condition. The patient was treated with the tyrosine kinase inhibitor (TKI) drug Anluotini. At the 2-month follow-up, his serum Ct was 92 pg/mL. There were no other signs of tumour recurrence.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this article and any accompanying images. A copy of the written consent form is available for review by the editorial office of this journal.

Discussion

MTC is a neuroendocrine tumour derived from thyroid parafollicular cells. In differential diagnosis, MTC needs to be differentiated from multiple endocrine neoplasia type 2 (MEN-2). Clinical manifestations of MEN-2 (in addition to those of MTC) include pheochromocytoma or hyperparathyroidism. No family members of the patient in this case had MTC, and the patient did not experience paroxysmal headaches, palpitations, or sweating in the course of the disease. No abnormal adrenal changes were observed in the previous abdominal imaging and PET-CT. The patient was thus diagnosed with sporadic MTC.

At 3 months after radical thyroidectomy, US revealed multiple enlarged lymph nodes in the right neck, and neck lymph node dissection was performed. The patient’s serum CEA and Ct levels did not return to normal after the second operation, and the Ct and CEA doubling times were short. In MTC, Ct levels above 500 pg/mL are highly indicative of failure to achieve biochemical remission (10). The doubling times of Ct and CEA post-operatively are sensitive indicators of metastatic MTC progression and aggressiveness (11,12). This led to a further imaging examination to identify any recurrences or metastases. However, in this case, the cervical US was negative. PET/CT showed a 0.3-cm lesion with a low uptake of 68Ga-DOTATATE and 18F-DOPA, indicating metastatic lesions. The second-look US detected a recurrent or metastatic lymph node (0.9×0.3 cm in size). Due to the small size of the lesion and the proximity of the jugular vein, it would have been difficult to operate on the lesion. In the case of reoperation, the lesion might not have been completely removed, and recurrence might have occurred. Thus, TKI drugs were chosen for this patient for the follow-up treatment.

In patients with MTC, the detection of recurrent or metastatic lesions is crucial for effective treatment. Despite its limited sensitivity, US is the preferred method for the long-term monitoring of locoregional lesions due to its consistency and ease of use. US is non-radiative, and it is used to guide interventional procedures. There have been reports of PET imaging with a sensitivity range of 44–80% in the literature (13). Additionally, the cholecystokinin-2 receptor (CCK-2R) has been shown to be overexpressed in most MTC cells; thus, CCK-2R ligands can be used for the imaging or radioligand therapy of MTC (14). However, these techniques are not widely available, and they require expensive materials, longer time, and experienced personnel to operate. For the follow-up monitoring of recurrent lesions, second-look targeted US has become the tool of choice to monitor lesions detected by PET.

Conclusions

Based on this case, we report that the combination of US-PET/CT is a reliable and feasible imaging strategy that can significantly improve both the detection rate of additional enhancing lesions and the number of US-guided procedures. The US-PET/CT combination may be a valuable tool for second looks, and may also help doctors to select the most appropriate treatment plan and patient management approach.

Acknowledgments

Funding: This work was supported by the National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-B-066) and the Fundamental Research Funds for the Central Universities (No. 3332023011).

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-720/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this article and any accompanying images. A copy of the written consent form is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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