Background: Renal medullary carcinoma (RMC) is a rare and aggressive renal tumor, typically affecting young patients with sickle cell trait. It is often diagnosed at a metastatic stage and is associated with a poor prognosis. Case Presentation: A 31-year-old male with no known hemoglobinopathy presented with macroscopic hematuria, right flank pain, and cachexia. Hemoglobin electrophoresis confirmed the absence of sickle-cell trait or disease. Imaging revealed a large right renal mass with extensive metastases to the liver, lymph nodes, peritoneum, lungs, and bone. Histopathological analysis and immunohistochemistry confirmed SMARCB1 (INI1)-deficient RMC. Baseline laboratory values at diagnosis were: creatinine 0.9 mg/dL, eGFR 95 mL/min/1.73 m2, hemoglobin 10.5 g/dL, LDH 320 U/L, with ECOG performance status 1. First-line chemotherapy with cisplatin (75 mg/m2, Day 1) and gemcitabine (1000 mg/m2, Days 1 and 8) every 21 days resulted in disease progression after four cycles. Second-line therapy with paclitaxel (175 mg/m2, Day 1) and zoledronic acid (4 mg IV, Day 1) every 21 days was initiated; the patient died after a single cycle. Conclusion: This case underscores the aggressive nature and poor therapeutic response of metastatic RMC. Diagnosis hinges on SMARCB1 loss, and outcomes remain poor despite systemic chemotherapy. Early recognition, accurate diagnosis, and referral to clinical trials are crucial for improving prognosis.
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