From the Guidelines
Stauffer syndrome is a paraneoplastic condition characterized by signs of cholestasis unrelated to tumor infiltration of the liver or intrinsic liver disease, which typically resolve after kidney tumor resection, as noted in the 2019 ESMO clinical practice guidelines for renal cell carcinoma diagnosis, treatment, and follow-up 1. This condition is primarily associated with renal cell carcinoma and is considered one of the paraneoplastic syndromes that can occur in patients with this type of cancer. Key features of Stauffer syndrome include:
- Liver dysfunction without evidence of liver metastases
- Elevated liver enzymes
- Jaundice
- Hepatomegaly
- Abnormal liver function tests
- Resolution of liver abnormalities after surgical removal of the primary kidney tumor The exact mechanism behind Stauffer syndrome is not fully understood but is believed to involve inflammatory cytokines released by the tumor that affect liver function, as suggested by the presence of systemic symptoms such as fever, weight loss, and fatigue in some patients 1. While the primary association is with renal cell carcinoma, similar paraneoplastic syndromes have been reported with other malignancies. Treatment of Stauffer syndrome focuses on addressing the underlying cancer, with nephrectomy being a common approach for renal cell carcinoma, which often leads to the normalization of liver function, highlighting the importance of early diagnosis and treatment of the primary tumor 1.
From the Research
Definition and Characteristics of Stauffer Syndrome
- Stauffer syndrome is a rare paraneoplastic syndrome classically associated with renal cell carcinoma (RCC) 2, 3, 4, 5, 6.
- It is characterized by a reversible anicteric elevation of liver enzymes, alkaline phosphatase, erythrocyte sedimentation rate (ESR), thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly in the absence of direct hepatobiliary obstruction or jaundice 2.
- A rare atypical variant of this syndrome with jaundice has been described in the literature 2, 3, 6.
Association with Malignancies
- Stauffer syndrome is associated with various malignancies, particularly renal cell carcinoma 2, 3, 4, 5, 6.
- It has also been described in lymphoproliferative diseases, prostate cancer, and broncogenic tumors 6.
Diagnostic Challenges
- Stauffer syndrome poses diagnostic challenges, and it is essential to consider both the icteric and anicteric variants in the differential diagnosis of unexplained cholestasis in the absence of hepatic metastasis 2.
- The syndrome may precede other manifestations of renal cell carcinoma, and underlying renal cell carcinoma should be excluded by focused investigations in cases of unexplained abnormal liver function 4.
Clinical Implications
- Early recognition and treatment of Stauffer syndrome are crucial, as proper treatment of the baseline disease can enable the reversal of paraneoplastic signs and symptoms 3, 6.
- The size of the renal mass may not influence the development of Stauffer syndrome, and the entity should always be considered in patients with liver dysfunction and jaundice with a suspicion or confirmed diagnosis of a renal mass 3.