539927
research-article2014
HICXXX10.1177/2324709614539927Journal of Investigative Medicine High Impact Case ReportsKato et al
Article
Hepatic Dysfunction as a Paraneoplastic Manifestation of Metastatic Prostate Adenocarcinoma
Journal of Investigative Medicine High Impact Case Reports 1–3 © 2014 American Federation for Medical Research DOI: 10.1177/2324709614539927 hic.sagepub.com
David Kato, MD1, Chinemerem Okwara, Christopher Moreland, MD, MPH1, and Allan Parker, MD1
Abstract Cholestasis is a general feature of intrahepatic or extrahepatic biliary obstruction by various mechanisms including cirrhosis, stricture, choledocholithiasis, hepatitis, and neoplasms. Neoplasms can directly impinge on the hepatobiliary tree resulting in bile stasis. Stauffer’s syndrome is another variant of this neoplastic process that can cause cholestasis and liver enzyme elevation without any direct hepatobiliary obstruction, and is thus categorized as a paraneoplastic syndrome of unclear pathophysiology. We report a first case of metastatic prostate adenocarcinoma with features of Stauffer’s syndrome that reversed completely on androgen deprivation therapy. This is in contrast to a previously reported case of Stauffer’s syndrome due to metastatic prostate adenocarcinoma, which reversed partially to androgen deprivation therapy. Our case demonstrates the importance of early recognition of Stauffer’s syndrome and underlying neoplasms in patients who present with cholestasis without clear evidence of intrahepatic or extrahepatic biliary obstruction, which may lead to early initiation of treatment. Keywords Stauffer’s syndrome, metastatic prostate adenocarcinoma, androgen deprivation therapy
Case Report A 60-year-old African American man presented to our hospital with a 6-month history of progressively worsening fatigue, 30-pound weight loss, jaundice, pruritis, dark urine, and straining on urination. He reported no previous intravenous drug use. His physical exam revealed nontender lymphadenopathy involving the anterior cervical, axillary, and inguinal areas. The rectal exam revealed irregularity of the left prostatic border. Initial laboratory results were significant for hyperbilirubinemia (9.3 mg/dL) with direct bilirubin predominance (7.9 mg/dL), as well as elevated aspartate aminotransferase (200 IU/L), alanine aminotransferase (169 IU/L), and alkaline phosphatase (1803 IU/L) with predominant hepatic origin evidenced by elevated liver isoenzyme (1352 IU/L) and γ-glutamyltransferase (2152 IU/L). Hepatitis, HIV, autoimmune, and acetaminophen toxicity evaluations were negative. Prostate-specific antigen was elevated (41.4 ng/mL). Computed tomography of the chest, abdomen, and pelvis showed markedly enlarged prostate glands with metastases involving the bones, lungs, and lymph nodes but sparing the hepato-cholangio-pancreatic organs. Magnetic resonance cholangiopancreatography revealed normal liver morphology with multiple hypointense T1/hyperintense T2-weighted
signal intensity lesions scattered throughout the liver, thought to represent hepatic cysts, with no intrahepatic or extrahepatic biliary duct dilatation to suggest obstruction. The patient underwent fine needle aspiration of the left external iliac lymph nodes; pathology revealed malignant cells consistent with metastatic adenocarcinoma of prostatic origin. Immunostaining for prostate-specific antigen (Figure 1A) and CD-10 (Figure 1B) were positive. Following oncology consultation, the patient began androgen deprivation therapy for inoperable metastatic prostate cancer. He took bicalutamide, an androgen receptor blocker, for 4 days during the hospitalization but stopped for the next 23 days since he failed to pick up the medications. Bicalutamide was restarted on treatment day 28. Additionally, he received leuprolide, a GnRH analog, on treatment day 49 and day 71. The patient responded well to the treatment as the liver function tests normalized over time (Figure 2). Improvement in laboratory values paralleled 1
University of Texas Health Science Center, San Antonio, TX, USA
Corresponding Author: David Kato, University of Texas Health Science Center San Antonio, 4502 Medical Dr, San Antonio, TX 78229, USA. Email: [email protected]
2
Journal of Investigative Medicine High Impact Case Reports
Figure 1. Immunostain of left external iliac lymph nodes: (A) Positive prostate-specific antigen stain; (B) Positive CD-10 stain.
clinical improvement, as the lymph nodes became nonpalpable and jaundice and pruritus completely resolved.
Discussion
Figure 2. Liver function response to androgen deprivation therapy.
Bicalutamide was given daily except for between day 4 and day 28. Leuprolide was given on day 49 and day 71. (A) Rapid decline in total bilirubin and alkaline phosphatase after treatment day 4 and day 28, respectively. (B) Rapid decline in aspartate aminotransferase and alanine aminotransferase after treatment day 28.
Stauffer’s syndrome, a paraneoplastic syndrome resulting in liver enzyme derangement, was initially introduced by Dr Maurice H. Stauffer, who witnessed a reversal of hepatic dysfunction following a resection of renal cell carcinoma.1 Since its original discovery, more literature has emerged supporting Stauffer’s syndrome in various types of neoplasms. Thus far, there are only 6 reported cases of adenocarcinoma as a source of Stauffer’s syndrome.2-7 Only one case of metastatic prostate adenocarcinoma demonstrated partial resolution of hepatic dysfunction with androgen deprivation therapy.2 Our case is the first report, to our knowledge, of metastatic prostate adenocarcinoma with CD-10-positive stain that responded to androgen deprivation therapy, resulting in a complete reversal of hepatic dysfunction in all measured categories. Of note, the total bilirubin level reversed early in his course, despite interruption of androgen deprivation therapy, which may be explained by bicalutamide’s long half-life of 6 days. The pathophysiology of Stauffer’s syndrome remains largely unexplained, but interleukin-6 is thought to play a crucial role.8 Overall, Stauffer’s syndrome is a rare complication of many types of cancer; however, liver dysfunction without obvious cause in the presence of concomitant neoplasm must be readily recognized as a possible paraneoplastic process.
Kato et al Authors’ Note Dr Kato and Okwara contributed equally to this work and should be considered co–first authors.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Stauffer MH. Nephrogenic hepatosplenomegaly. Gastroenterology. 1961;40:694. 2. Karakolios A, Kasapis C, Kallinikidis T, Kalpidis P, Grigoriadis N. Cholestatic jaundice as a paraneoplastic manifestation of prostate adenocarcinoma. Clin Gastroenterol Hepatol. 2003;1:480-483.
3 3. Reddy AN, Grosberg SJ, Wapnick S. Intermittent cholestatic jaundice and nonmetastatic prostatic carcinoma. Arch Intern Med. 1977;137:1616-1618. 4. Morís de la Tassa J, Claros González I, García-Alcalde Fernández ML, Antuña Egocheaga A, Argüelles Toraño M. Cholestasis and prostatic carcinoma. Description of a case and review of paraneoplastic cholestasis. Med Clin (Barc). 1991;96(1):22-25. 5. Koruk M, Büyükberber M, Savas C, Kadayifci A. Paraneoplastic cholestasis associated with prostate carcinoma. Turk J Gastroenterol. 2004;15:53-55. 6. Shah SH. Paraneoplastic liver dysfunction in prostate cancer. J Pain Symptom Manage. 2006;32:511-513. 7. Nguyen V, Gurney H, Van der Poorten D. Paraneoplastic hepatic dysfunction in metastatic prostate cancer: the role of cytokine dysregulation. J Clin Oncol. 2011;29(2): e21-e23. 8. Blay JY, Rossi JF, Wijdenes J, et al. Role of interleukin-6 in the paraneoplastic inflammatory syndrome associated with renal-cell carcinoma. Int J Cancer. 1997;72: 424-430.
research-article2014
HICXXX10.1177/2324709614539927Journal of Investigative Medicine High Impact Case ReportsKato et al
Article
Hepatic Dysfunction as a Paraneoplastic Manifestation of Metastatic Prostate Adenocarcinoma
Journal of Investigative Medicine High Impact Case Reports 1–3 © 2014 American Federation for Medical Research DOI: 10.1177/2324709614539927 hic.sagepub.com
David Kato, MD1, Chinemerem Okwara, Christopher Moreland, MD, MPH1, and Allan Parker, MD1
Abstract Cholestasis is a general feature of intrahepatic or extrahepatic biliary obstruction by various mechanisms including cirrhosis, stricture, choledocholithiasis, hepatitis, and neoplasms. Neoplasms can directly impinge on the hepatobiliary tree resulting in bile stasis. Stauffer’s syndrome is another variant of this neoplastic process that can cause cholestasis and liver enzyme elevation without any direct hepatobiliary obstruction, and is thus categorized as a paraneoplastic syndrome of unclear pathophysiology. We report a first case of metastatic prostate adenocarcinoma with features of Stauffer’s syndrome that reversed completely on androgen deprivation therapy. This is in contrast to a previously reported case of Stauffer’s syndrome due to metastatic prostate adenocarcinoma, which reversed partially to androgen deprivation therapy. Our case demonstrates the importance of early recognition of Stauffer’s syndrome and underlying neoplasms in patients who present with cholestasis without clear evidence of intrahepatic or extrahepatic biliary obstruction, which may lead to early initiation of treatment. Keywords Stauffer’s syndrome, metastatic prostate adenocarcinoma, androgen deprivation therapy
Case Report A 60-year-old African American man presented to our hospital with a 6-month history of progressively worsening fatigue, 30-pound weight loss, jaundice, pruritis, dark urine, and straining on urination. He reported no previous intravenous drug use. His physical exam revealed nontender lymphadenopathy involving the anterior cervical, axillary, and inguinal areas. The rectal exam revealed irregularity of the left prostatic border. Initial laboratory results were significant for hyperbilirubinemia (9.3 mg/dL) with direct bilirubin predominance (7.9 mg/dL), as well as elevated aspartate aminotransferase (200 IU/L), alanine aminotransferase (169 IU/L), and alkaline phosphatase (1803 IU/L) with predominant hepatic origin evidenced by elevated liver isoenzyme (1352 IU/L) and γ-glutamyltransferase (2152 IU/L). Hepatitis, HIV, autoimmune, and acetaminophen toxicity evaluations were negative. Prostate-specific antigen was elevated (41.4 ng/mL). Computed tomography of the chest, abdomen, and pelvis showed markedly enlarged prostate glands with metastases involving the bones, lungs, and lymph nodes but sparing the hepato-cholangio-pancreatic organs. Magnetic resonance cholangiopancreatography revealed normal liver morphology with multiple hypointense T1/hyperintense T2-weighted
signal intensity lesions scattered throughout the liver, thought to represent hepatic cysts, with no intrahepatic or extrahepatic biliary duct dilatation to suggest obstruction. The patient underwent fine needle aspiration of the left external iliac lymph nodes; pathology revealed malignant cells consistent with metastatic adenocarcinoma of prostatic origin. Immunostaining for prostate-specific antigen (Figure 1A) and CD-10 (Figure 1B) were positive. Following oncology consultation, the patient began androgen deprivation therapy for inoperable metastatic prostate cancer. He took bicalutamide, an androgen receptor blocker, for 4 days during the hospitalization but stopped for the next 23 days since he failed to pick up the medications. Bicalutamide was restarted on treatment day 28. Additionally, he received leuprolide, a GnRH analog, on treatment day 49 and day 71. The patient responded well to the treatment as the liver function tests normalized over time (Figure 2). Improvement in laboratory values paralleled 1
University of Texas Health Science Center, San Antonio, TX, USA
Corresponding Author: David Kato, University of Texas Health Science Center San Antonio, 4502 Medical Dr, San Antonio, TX 78229, USA. Email: [email protected]
2
Journal of Investigative Medicine High Impact Case Reports
Figure 1. Immunostain of left external iliac lymph nodes: (A) Positive prostate-specific antigen stain; (B) Positive CD-10 stain.
clinical improvement, as the lymph nodes became nonpalpable and jaundice and pruritus completely resolved.
Discussion
Figure 2. Liver function response to androgen deprivation therapy.
Bicalutamide was given daily except for between day 4 and day 28. Leuprolide was given on day 49 and day 71. (A) Rapid decline in total bilirubin and alkaline phosphatase after treatment day 4 and day 28, respectively. (B) Rapid decline in aspartate aminotransferase and alanine aminotransferase after treatment day 28.
Stauffer’s syndrome, a paraneoplastic syndrome resulting in liver enzyme derangement, was initially introduced by Dr Maurice H. Stauffer, who witnessed a reversal of hepatic dysfunction following a resection of renal cell carcinoma.1 Since its original discovery, more literature has emerged supporting Stauffer’s syndrome in various types of neoplasms. Thus far, there are only 6 reported cases of adenocarcinoma as a source of Stauffer’s syndrome.2-7 Only one case of metastatic prostate adenocarcinoma demonstrated partial resolution of hepatic dysfunction with androgen deprivation therapy.2 Our case is the first report, to our knowledge, of metastatic prostate adenocarcinoma with CD-10-positive stain that responded to androgen deprivation therapy, resulting in a complete reversal of hepatic dysfunction in all measured categories. Of note, the total bilirubin level reversed early in his course, despite interruption of androgen deprivation therapy, which may be explained by bicalutamide’s long half-life of 6 days. The pathophysiology of Stauffer’s syndrome remains largely unexplained, but interleukin-6 is thought to play a crucial role.8 Overall, Stauffer’s syndrome is a rare complication of many types of cancer; however, liver dysfunction without obvious cause in the presence of concomitant neoplasm must be readily recognized as a possible paraneoplastic process.
Kato et al Authors’ Note Dr Kato and Okwara contributed equally to this work and should be considered co–first authors.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Stauffer MH. Nephrogenic hepatosplenomegaly. Gastroenterology. 1961;40:694. 2. Karakolios A, Kasapis C, Kallinikidis T, Kalpidis P, Grigoriadis N. Cholestatic jaundice as a paraneoplastic manifestation of prostate adenocarcinoma. Clin Gastroenterol Hepatol. 2003;1:480-483.
3 3. Reddy AN, Grosberg SJ, Wapnick S. Intermittent cholestatic jaundice and nonmetastatic prostatic carcinoma. Arch Intern Med. 1977;137:1616-1618. 4. Morís de la Tassa J, Claros González I, García-Alcalde Fernández ML, Antuña Egocheaga A, Argüelles Toraño M. Cholestasis and prostatic carcinoma. Description of a case and review of paraneoplastic cholestasis. Med Clin (Barc). 1991;96(1):22-25. 5. Koruk M, Büyükberber M, Savas C, Kadayifci A. Paraneoplastic cholestasis associated with prostate carcinoma. Turk J Gastroenterol. 2004;15:53-55. 6. Shah SH. Paraneoplastic liver dysfunction in prostate cancer. J Pain Symptom Manage. 2006;32:511-513. 7. Nguyen V, Gurney H, Van der Poorten D. Paraneoplastic hepatic dysfunction in metastatic prostate cancer: the role of cytokine dysregulation. J Clin Oncol. 2011;29(2): e21-e23. 8. Blay JY, Rossi JF, Wijdenes J, et al. Role of interleukin-6 in the paraneoplastic inflammatory syndrome associated with renal-cell carcinoma. Int J Cancer. 1997;72: 424-430.
