Metastatic prostatic adenocarcinoma presenting as generalized lymphadenopathy unmasked by a COVID booster vaccine

KEY CLINICAL MESSAGE: Lymphadenopathy following recent immunization is usually regional. Generalized lymphadenopathy should arouse suspicion for alternative underlying pathology. Prostate adenocarcinoma should be considered in the differential diagnosis for malignancy in an elderly male patient. Metastatic prostate adenocarcinoma can have good prognostic outcomes if treatment is started promptly, even in the setting of widespread disease. ABSTRACT: Generalized lymphadenopathy is commonly attributed to infectious causes or malignancy, often lymphoproliferative disorders. We present a rare case of metastatic prostate cancer diagnosed after initially presenting as generalized lymphadenopathy following a coronavirus disease 2019 (COVID) booster vaccination. A 70‐year‐old Hispanic male presented with left lower quadrant abdominal pain, nausea, headache, myalgia, severe constipation, and a right‐sided neck swelling that had been increasing in size since the day of his vaccination. Computed tomography (CT) scans of soft tissue neck, chest, abdomen, and pelvis with contrast showed extensive lymphadenopathy. Ultrasound‐guided biopsy results of the enlarged right supraclavicular node and prostate revealed histopathology consistent with that of prostate acinar adenocarcinoma. He started on bicalutamide for 4 weeks, transitioned to gonadotropin releasing hormone analogue (leuprolide) injections every 3 months and oral androgen receptor signaling inhibitor (abiraterone with prednisone daily). PSA level declined from 121 ng/mL at diagnosis to 1.3 ng/mL after 3 months of therapy, and repeat imaging showed marked improvement in the size of his mediastinal, retroperitoneal, and pelvic lymphadenopathy. To the best of our knowledge, this is the first case reported of a COVID vaccine booster uncovering lymphadenopathy leading to the diagnosis of metastatic prostate cancer.