Abstract

Background: Prostate-specific membrane antigen (PSMA) imaging is increasingly used in the evaluation and management of prostate cancer. However, PSMA expression can also occur in non-prostatic malignancies and benign tissues, presenting diagnostic challenges.

Case presentation: We report a 70-year-old male with metastatic prostate adenocarcinoma who underwent serial Ga-68 PSMA PET/CT imaging before and after six cycles of Lu-177 PSMA therapy. While initial imaging revealed multiple PSMA-avid lesions in the prostate and skeletal system and a mildly PSMA-avid thyroid nodule, post-therapy PET/CT demonstrated resolution of most metastatic sites with notable increase in PSMA uptake in the left thyroid nodule. Fine-needle aspiration biopsy of the thyroid lesion revealed papillary carcinoma, Hürthle cell variant. Total thyroidectomy was performed, and histopathology confirmed the diagnosis. The patient subsequently received radioiodine therapy for residual thyroid tissue.

Discussion: This case highlights a rare but clinically significant scenario of increased PSMA uptake in a thyroid nodule following Lu-177 PSMA therapy, leading to the diagnosis of Hürthle cell variant papillary thyroid carcinoma. PSMA expression in thyroid neoplasms is uncommon but should be recognized as a potential pitfall during PSMA-targeted imaging in prostate cancer patients. The findings also suggest a possible influence of Lu-177 PSMA therapy on subsequent PSMA expression in non-prostatic tissues.

Conclusion: Increased PSMA uptake in thyroid nodules after Lu-177 PSMA therapy can indicate underlying malignancy, as in this rare case of Hürthle cell variant papillary carcinoma. Awareness of this potential finding is essential to avoid misinterpretation and to ensure prompt and accurate diagnosis.

Key words: Ga-68 PSMA PET/CT, Lu-177 PSMA therapy, thyroid nodule, Hürthle cell variant, papillary thyroid carcinoma, prostate cancer.