Misleading IL-18 Elevation in Sarcoidosis: Renal Cell Carcinoma Masquerading as Renal Sarcoidosis

Introduction: Interleukin-18 (IL-18) is a proinflammatory cytokine within the interleukin-1 family, playing a key role in both innate and adaptive immunity through the stimulation of interferon-gamma (IFN-γ). Elevated IL-18 levels have been associated with inflammatory and autoimmune diseases, including Sarcoidosis. Moreover, elevated IL-18 has been observed in certain malignancies, including renal cell carcinoma (RCC). This case highlights the diagnostic challenge of elevated IL-18 in a patient with both sarcoidosis and a renal mass. Case Description: A 67-year-old man with a history of diabetes mellitus, chronic kidney disease stage G3a, pulmonary sarcoidosis, and prostate cancer underwent surveillance PET-CT, which revealed an incidental 5.2 cm solid left kidney mass, that was confrimed on A CT. Cytokine profile demonstrated a markedly elevated IL-18 level of 819 pg/mL, other cytokines were normal. Given the elevated IL-18 both urology and pulmonary teams initially suspected a sarcoid-related granulomatous inflammation. Accordingly, the patient was referred to nephrology for preoperative renal function assessment and evaluation of possible renal sarcoidosis. Laboratory testing showed stable kidney function with a serum creatinine of 1.4 mg/dL consistent with his baseline. Despite the working impression of renal sarcoidosis, concern for malignancy persisted due to the size and radiologic features of the lesion. A DMSA renal scan demonstrated symmetric function (49% right, 51% left), and the patient proceeded with left radical nephrectomy. Discussion: Histopathology confirmed papillary RCC, with no histologic evidence of sarcoidosis. Postoperatively, the patient’s serum creatinine peaked at 2.58 mg/dL but gradually improved to a nadir of 1.13 mg/dL without the need for dialysis. IL-18 is a pro-inflammatory cytokine involved in Th1 activation and IFN-γ production, commonly elevated in sarcoidosis. It is also elevated in malignancies such as RCC, where it may correlate with tumor progression and prognosis. In this case, despite elevated IL-18 and a history of sarcoidosis, the renal mass was ultimately diagnosed as papillary RCC. This highlights the importance of interpreting IL-18 within a comprehensive clinical context—alongside imaging and histopathology—to avoid misdiagnosis and ensure appropriate management.