Abstract
Introduction
Cholangiocarcinoma (CCA) is very often an adulthood disease with primary sclerosing cholangitis (PSC) as one of the risk factors. It is rarely seen in the pediatric population, and when it is diagnosed before adulthood, it can be associated with PSC as well as HIV infection, biliary atresia, radiation therapy, and choledochal cyst. Although there have been some case reports of pediatric CCA, cases of childhood CCA associated with PSC are still relatively rare.
Aim
To describe the clinical and pathologic features of CCA in pediatric patients with previously diagnosed PSC.
Methods
Retrospective study
Results
Four patients with PSC (age range 15–18, mean 17 years) were included in this study. All patients underwent ERCP for diagnosis. Tissue samples obtained included routine cytology and FISH. ERCP was used to target sites for tissue acquisition in all patients. 3/4 of patients have inflammatory bowel disease (two Crohn’s disease and one ulcerative colitis). Alkaline phosphatase was elevated in 3/4 patients, aspartate aminotransferase/alanine aminotransferase were elevated in 2/4 patients, and total bilirubin/direct bilirubin were elevated in 2/4 patients. 4/4 patients had positive FISH studies, and 3/4 patients had brush cytology concerning for CCA. 2/4 patients received chemotherapy, one patient underwent orthotopic liver transplant, and one patient underwent Whipple procedure. Two patients died soon after being diagnosed.
Conclusions
Young patients with PSC can develop CCA. This finding has implications for both screening and surveillance for cancer in pediatric patients with PSC.
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References
Shaib YH, El-Serag HB, Davila JA, et al. Risk factors of intrahepatic cholangiocarcinoma in the United States: a case–control study. Gastroenterology. 2005;128:620–626.
Welzel TM, Graubard BI, El-Serag HB, et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case–control study. Clin Gastroenterol Hepatol. 2007;5:1221–1228.
Mangeya N, Mafukidze AT, Pascoe M, et al. Cholangiocarcinoma presenting in an adolescent with vertically acquired HIV infection. Int J STD AIDS. 2008;19:717–718.
Kulkarni PB, Beatty E. Cholangiocarcinoma associated with biliary cirrhosis due to congenital biliary atresia. Am J Dis Child. 1977;131:442–444.
Cunningham JJ. Cholangiocarcinoma occurring after childhood radiotherapy for Wilm’s tumor. Hepatogastroenterology. 1990;37:395–397.
Bismuth H, Krissat J. Choledochal cystic malignancies. Ann Oncol. 1990;10:94–98.
Tanaka S, Kubota M, Yagi M, et al. An 11-year-old male patient demonstrating cholangiocarcinoma associated with congenital biliary dilatation. J Pediatr Surg. 2006;41:e15–e19.
Hayward AR, Levy J, Facchetti F, et al. Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM. J Immunol. 1997;158:977–983.
Saikusa N, Naito S, Iinuma Y, Ohtani T, Yokoyama N, Nitta K. Invasive cholangiocarcinoma identified in congenital biliary dilatation in a 3-year-old boy. J Pediatr Surg. 2009;44:2202–2205.
Bjornsson E, Angulo P. Cholangiocarcinoma in young individuals with and without primary sclerosing cholangitis. Am J Gastroenterol. 2007;102:1677–1682.
Deneau M, Adler DG, Schwartz JJ, et al. Cholangiocarcinoma in a 17-year-old boy with primary sclerosing cholangitis and inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2011;52:617–620.
Broome U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38:610–615.
Tischendorf JJ, Hecker H, Kruger M, et al. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol. 2007;102:107–114.
Bergquist A, Glaumann H, Persson B, et al. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case–control study. Hepatology. 1998;27:311–316.
de Groen PC. Cholangiocarcinoma in primary sclerosing cholangitis: who is at risk and how do we screen? Hepatology. 2000;31:247–248.
Rosen CB, Nagorney DM, Wiesner RH, et al. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg. 1991;213:21–25.
Suarez-Munoz MA, Fernandez-Aguilar JL, Sanchez-Perez B, et al. Risk factors and classifications of hilar cholangiocarcinoma. World J Gastrointest Oncol. 2013;5:132–138.
Awadallah NS, Chen YK, Piraka C, Antillon MR, Shah RJ. Is there a role for cholangioscopy in patients with primary sclerosing cholangitis? Am J Gastroenterol. 2006;101:284–291.
Moreno Luna LE, Kipp B, et al. Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology. 2006;131:1064–1072.
Barr Fritcher EG, Kipp BR, Voss JS, et al. Primary sclerosing cholangitis patients with serial polysomy fluorescence in situ hybridization results are at increased risk of cholangiocarcinoma. Am J Gastroenterol. 2011;106:2023–2028.
Belchacz BG. Tumors of the bile ducts, gallbladder, and ampulla. In: Feldman M, ed. Sleisenger and Fortran’s Gastrointestinal and Liver Disease, vol. 1. 9th ed. Philadelphia: Saunders; 2010:1171–1176.
Barr Fritcher EG, Voss JS, Jenkins SM, et al. Primary sclerosing cholangitis with equivocal cytology: fluorescence in situ hybridization and serum CA 19-9 predict risk of malignancy. Cancer Cytopathol. 2013. Epub. 02/01/2014.
Vasilieva LE, Papadhimitriou SI, Alexopoulou A, et al. An extended fluorescence in situ hybridization approach for the cytogenetic study of cholangiocarcinoma on endoscopic retrograde cholangiopancreatography brushing cytology preparations. Hum Pathol. 2013;44:2173–2179. doi:10.1016/j.humpath.2013.04.012.
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Liu, R., Cox, K., Guthery, S.L. et al. Cholangiocarcinoma and High-Grade Dysplasia in Young Patients with Primary Sclerosing Cholangitis. Dig Dis Sci 59, 2320–2324 (2014). https://doi.org/10.1007/s10620-014-3152-0
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DOI: https://doi.org/10.1007/s10620-014-3152-0