Intrahepatic Cholestasis in the Setting of Recurrent Prostate Cancer: A Paraneoplastic Syndrome

Abstract

Through well-known mechanisms such as bile duct obstruction and hepatic infiltration, malignancies can cause cholestasis and intrahepatic symptoms and signs. Through unclear mechanisms, and in the absence of infection, obstruction, and infiltration, paraneoplastic syndromes may also cause intrahepatic cholestasis and jaundice. Though usually described in association with renal cell carcinoma (known as Stauffer's syndrome), cholestasis and jaundice may occur in association with other malignancies, including prostate cancer. We present a rare variant of Stauffer's syndrome involving recurrent prostate cancer. A 72-year-old man who had undergone prostatectomy for prostate cancer 8 years prior presented with back pain and jaundice. The patient was found to have recurrent prostate cancer with metastatic disease to the bone. Laboratory values (Table 1) included elevations in prostate specific antigen (PSA), bilirubin, aspartate aminotransferase, alkaline phosphatase. Hepatitis profile and HIV screen were negative. Liver ultrasound and magnetic resonance cholangiopancreatography (Figure 1) demonstrated no obstruction or masses. Liver biopsy, negative for metastatic prostate cancer, revealed intrahepatic cholestasis and extensive extramedullary hematopoeisis (Figure 2). We prescribed ursodiol and pentoxifylline, and planned hormonal therapy for prostate cancer.Figure 1Figure 2Table 1: Select Laboratory Findings on AdmissionThe patient was discharged in good condition and followed up with gastroenterology and oncology as an outpatient. The patient began leuprolide injections every 3 months. Liver function tests dramatically decreased and, with the exception of alkaline phosphatase, returned to normal limits (Table 2). Stauffer's syndrome variant seen with prostate cancer is rare with only 6 reported cases in the literature. Case reports of cholestasis attributed to prostate cancer-related paraneoplastic syndromes have documented improvement in cholestasis following treatment of the underlying malignancy. Therefore, we have reason to believe that our patient's cholestasis and jaundice resolved due to treatment of the underlying malignancy. We theorize the alkaline phosphatase remains elevated secondary to bony metastasis. This case illustrates the importance of considering malignancy during evaluation of unexplained cholestasis and jaundice. Through paraneoplastic syndromes, malignancies can produce symptoms at locations far from the primary lesion or metastases, and by mechanisms other than direct organ infiltration or local obstruction. In the proper clinical setting, patients who present with nonobstructive cholestatic jaundice should be evaluated for nongastrointestinal malignancies, including prostate cancer.Table 2: Select Laboratory Findings 5 Months After Therapy with Leuprolide