Complement Chaos: A Perplexing Case of C3G and Seminoma in a Young Man

Introduction: C3G represents a spectrum of glomerular diseases characterized by dysregulation of the alternative complement pathway. Concurrent presentation of solid tumors and C3GN is rare and yet to be reported. Here we present a case of C3G with partial resolution after radical orchiectomy of a seminoma, highlighting the novel interplay between testicular malignancy and complement-mediated injury. Case Description: A 38-year-old male presented with testicular swelling, severe hypertension, and renal dysfunction. Further evaluation revealed a testicular mass, elevated b-HCG, and histological changes suggestive of C3GN on renal biopsy. Work up for plasma cell dyscrasias and C3 Nephritic factor were unrevealing however, genetic testing revealed a heterozygous mutation in the CFH gene. Following radical orchiectomy for seminoma, renal function showed partial improvement. After initiation of mycophenolic acid and steroids, renal function and proteinuria continued to improve with normalization of C3 levels. Discussion: In addition to genetic mutations and autoantibodies, this case suggests a potential link between testicular seminoma and C3G. The interplay between testicular seminoma, CFH gene mutation, and complement activation may have contributed to renal dysfunction. Resection of the seminoma, combined with immunomodulatory therapy, likely mitigated immune dysregulation and led to the resolution of renal dysfunction. This highlights the need to consider malignancy as a potential trigger for complement-mediated renal injury in patients with C3G, warranting further investigation into the underlying mechanisms and optimal therapeutic strategies. - Test Initial evaluation Post-Orchectomy 6 months of IS therapy Cr (mg/dl) 3.6 2.1 1.4 C3 (mg/dl) N/A 69 143 Urine Protein-Cr ratio (mg/mg) N/A 7.2 3.6