Staufferʼs Syndrome: Another Protean Manifestation of the “Internistʼs Tumor”

Abstract

Purpose: A 46 yr man with no past medical history presented with fatigue, left flank pain and 60 lb weight loss for 8 months. He denied any recent alcohol, illicit drug or medication use. Physical examination revealed a palpable mass in the left flank. Most prominent laboratory abnormality were elevated alkaline phosphatase (Alk P) at 731(50- 120 U/l) and γ-glutamyltransferase (GGT) at 261 (3-60 U/l). Serum bilirubin and aminotransferases were normal. Total serum protein was 8.2 g/dl, albumin 2.2 g/dl and total cholesterol 163 mg/dL. Microcytic anemia, thrombocytosis and mildly deranged coagulation parameters were also present. Proteinuria and hematuria were noted on urinalysis. MRI abdomen showed a 17 cm heterogeneous left renal mass involving the left renal vein with para aortic lymphadenopathy suggestive of renal cell carcinoma. Mild hepatosplenomegaly with no focal lesions was noted. There was no intra or extrahepatic biliary dilatation or any evidence of cirrhosis. Immunologic investigations revealed the absence of rheumatoid factor and antineutrophil cytoplasmic, antimitochondrial and antismooth muscle antibodies. Hepatitis and HIV viral serologies were negative, serum free thyroxine was normal and polyclonal gammopathy was observed on protein electrophoresis. The cholestasis was diagnosed as a paraneoplastic phenomenon associated with renal cell cancer (Stauffer's syndrome) and a left radical nephrectomy was attempted. Intraoperatively, the mass was inoperable due to involvement of great vessels. Histopathological examination confirmed the diagnosis of poorly differentiated renal adenocarcinoma. The patient then elected for home hospice. Nonmetastatic nephrogenic hepatic dysfunction syndrome (Stauffer's syndrome) is a unique paraneoplastic manifestation of renal cell carcinoma that usually presents as anicteric cholestasis, though a variant presenting with jaundice has also been described. It is characterized by elevated Alk P, ESR, a-2-globulin, and GGT with thrombocytosis, prolongation of prothrombin time, and hepatosplenomegaly, in the absence of hepatic metastasis. The underlying pathophysiology of this paraneoplastic manifestation is assumed to be from interleukin-6 overexpression by the primary tumor. The cholestasis reverses spontaneously after resection of the tumor. This phenomenon has also been reported with leiomyosarcoma, angiosarcoma, malignant histiocytoma, prostate carcinoma, and bronchial adenocarcinoma. It may occasionally be the initial presentation of the underlying neoplasm and if suspected may be lead to an early diagnosis. We conclude that paraneoplastic syndromes especially from renal cell carcinoma should be kept in the differential in evaluating unexplained cholestasis.