Benign Mimics & Physiologic Uptake on PSMA PET

In this video case series, Dr. Louis Mazzarelli, Director of Molecular Imaging at Lawrence Memorial and Westerly Hospitals, focuses on one of the most critical challenges in prostate cancer imaging: distinguishing true metastatic disease from physiologic uptake and benign mimics on PSMA PET.

Dr. Mazzarelli systematically reviews normal patterns of physiologic PSMA uptake, including the salivary and lacrimal glands, liver, spleen, kidneys, bowel, urinary tract, and autonomic ganglia. He emphasizes that recognizing these predictable patterns is essential to avoiding false-positive interpretations. The session then highlights common benign mimics of prostate cancer metastases, including fibrous dysplasia, healing fractures, Paget disease, degenerative bone changes, sarcoidosis, and hepatic hemangiomas.

Through multiple case examples, Dr. Mazzarelli demonstrates how benign lesions may show low-level or even focal PSMA uptake, occasionally mimicking metastatic disease. He reinforces the importance of correlating PSMA PET findings with CT and MRI morphology, reviewing prior imaging for stability, and assessing uptake intensity, symmetry, and anatomic distribution. Special attention is given to ganglia, which can appear asymmetric and nodal in location but lack true malignant features.

The overarching teaching point is that PSMA PET accuracy depends on context. Careful integration of molecular signal with cross-sectional imaging, clinical history, PSA kinetics, and prior studies is essential to prevent overcalling disease. This case underscores best practices for interpretation, improves reader confidence, and reinforces a systematic approach to PSMA PET reporting in prostate cancer care.