Atypical Metastatic Disease in Thyroid from Pancreatic Neuroendocrine Tumor and its Response to [¹⁷⁷Lu]Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT): A Promising Therapeutic Option for Somatostatin Receptor Expressing Unusual Metastatic Sites

Abstract

There are no standardized treatment guidelines for this condition with atypical sites of metastatic disease in neuroendocrine tumors (NETs). We present a patient of pancreatic NET with liver metastasis and incidentally detected thyroid gland metastasis, a rare site of metastasis in the context of NETs. After two cycles of [¹⁷⁷Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT), the metastatic thyroid lesion exhibited a remarkable response, as evidenced by neck ultrasonography and post-PRRT single photon emission computed tomography/computed tomography scan. This case upholds the fact that PRRT can demonstrate an excellent response at the atypical metastatic sites, thereby avoiding the necessity for surgical treatment and preventing morbidity associated with other therapeutic options.

 

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Keywords

[¹⁷⁷Lu]Lu-DOTATATE - peptide receptor radionuclide therapy (PRRT) - neuroendocrine tumors (NET) - thyroid metastasis - atypical metastatic sites

Introduction

Neuroendocrine tumors (NETs) are a rare type of tumors that can occur throughout the body, while they are most frequently observed in the gastroenteropancreatic organs. NET of gastroenteropancreatic origin typically metastasize to abdominal lymph nodes and the liver. Metastasis to the thyroid is extremely uncommon in gastroenteropancreatic NETs (GEP-NET).[1] [¹⁷⁷Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is an approved treatment for the metastatic, advanced GEP-NET. Nevertheless, due to the scarcity of data on atypical site metastases in NET, there are no standardized treatment guidelines. We present an unusual case of thyroid metastasis originating from a pancreatic NET (PNET), which was treated with [¹⁷⁷Lu]Lu-DOTATATE therapy and demonstrated an excellent response to PRRT.

 

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Case Report

A 52-year-old female known case of well-differentiated grade II (Ki-67 index of 5%) PNET with liver metastasis was referred to our center for consideration of PRRT. Clinically, baseline symptoms before starting PRRT were multiple episodes of sharp pricking pain in the left hypochondriac and epigastric region and loss of appetite. As part of the pre-PRRT workup, the patient underwent [⁶⁸Ga]Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT), which showed somatostatin receptor (SSTR) expressing primary pancreatic lesion (maximum standardized uptake value [SUVmax]: 30) and multiple metastatic liver lesions (SUVmax: 23). Focal increased SSTR-based tracer uptake (SUVmax: 10) was noted in the isthmus of thyroid as shown in [Fig. 1A], which was localized to a well-defined hypodense nodule (7 × 8mm) in the isthmus of thyroid as shown in [Fig. 1B]. Ultrasonography (USG)-guided fine-needle aspiration cytology (FNAC) from the nodule in the isthmus showed metastatic NET involvement. The patient was asymptomatic for thyroid metastasis. The patient received two cycles of [¹⁷⁷Lu]Lu-DOTATATE (cumulative dose of 12.3 GBq). Post-PRRT scans after 1st and 2nd cycle showed good tracer concentration in primary pancreatic lesion, metastatic liver lesions, and focal tracer uptake in metastatic thyroid nodule in the isthmus as shown in [Fig. 1C] and [D], respectively. Pre-PRRT USG neck showed an ill-defined solid hypoechoic anteroposterior × width dimension (7 × 8 mm) in the isthmus as shown in [Fig. 1E] and post-PRRT USG neck showed reduction in size of the nodule (5.3 × 6.3 mm), as illustrated in [Fig. 1F] indicative of favorable response to PRRT. This is also evidenced from post-PRRT regional single photon emission CT/CT scan done after the 3rd cycle of PRRT as shown in [Fig. 1G] and [H]. Clinical response post-two cycles of PRRT as communicated by the patient was reduction in pain frequency from multiple episodes daily to once every 4 to 5 days, 75% reduction in the intensity of pain, and gain of appetite. The patient tolerated PRRT very well without any side effects and was planned for further cycles of PRRT.

Fig. 1 [⁶⁸Ga]Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) maximum intensity projection image (A) showed intense somatostatin receptor (SSTR) expressing primary pancreatic lesion, multiple metastatic liver lesions, and focal moderate SSTR expression in the isthmus of the thyroid gland (red arrow). [⁶⁸Ga]Ga-DOTATATE PET/CT (B) showed focal SSTR expressing a well-defined hypodense nodule in the isthmus (yellow arrows). Post-[¹⁷⁷Lu]Lu-DOTATATE therapy scans after 1st (C) and 2nd (D) cycles of peptide receptor radionuclide therapy (PRRT) showed good tracer concentration in the primary pancreatic lesion, metastatic liver lesions and adequate uptake in the isthmus lesion of thyroid (green arrows). Pre-PRRT ultrasonography (USG) neck (E) showed an ill-defined solid hypoechoic (7 × 8 mm) nodule in the isthmus (blue arrows) and post-PRRT USG neck (F) showed reduction in size of nodule (5.3 × 6.3 mm) indicative of favorable response to PRRT. Post-[¹⁷⁷Lu]Lu-DOTATATE therapy regional single photon emission computed tomography/computed tomography (SPECT/CT) scan after 3rd PRRT with axial CT (G) showing reduction in size (white arrow) and fused (H) images demonstrating good [¹⁷⁷Lu]Lu-DOTATATE uptake in the thyroid metastatic lesion.

 

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Discussion

Incidental focal SSTR uptake in a thyroid lesion on SSTR PET/CT imaging in a known case of neoplasia is observed in several circumstances, including metastasis from NET, primary medullary thyroid carcinoma (MTC), and thyroid malignancies of follicular origin. SSTR PET/CT is unable to differentiate between these tumors.[2] FNAC can facilitate precise diagnosis and differentiate metastatic NET from more prevalent conditions. Fortunately, NET metastasis to the thyroid is exceedingly uncommon, with only a limited number of case reports and series documented in the literature.[3] [4] [5] [6] Total thyroidectomy is the standard treatment for primary follicular cell thyroid malignancy and MTC, and it has even been advocated as a treatment for metastatic disease in primary tumors found elsewhere. Nonetheless, it is associated with significant morbidity and adversely affects patient's quality of life.[1] The efficacy of PRRT has been demonstrated in SSTR-expressing GEP-NET with metastatic disease at conventional locations. The efficacy of PRRT has neither been examined nor established for the treatment of atypical site metastases in NET.[7] In this case of PNET with liver metastasis, we identified an incidental focal SSTR expressing thyroid lesion, which was confirmed as metastatic disease from NET, and the patient received two cycles of PRRT as per the standard treatment plan. The thyroid lesion exhibited an excellent response following PRRT, thereby averting the need for surgical treatment with a total thyroidectomy, thereby preventing morbidity and also enhancing the overall quality of life.

 

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Conclusion

In the present report, [¹⁷⁷Lu]Lu-DOTATATE PRRT proved as a highly effective treatment option for atypical metastatic site in NET. It demonstrated an excellent response in treating both atypical and conventional metastatic sites, thereby preventing the morbidity associated with other alternative treatment for atypical sites and finally, enhancing quality of life. This case description will be helpful in formulating future guidelines for the treatment of atypical metastatic sites in the context of NET.

 

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Conflict of Interest

None declared.

• References

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Publikationsverlauf

Artikel online veröffentlicht:
26. Juni 2025