PURPOSE: Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. METHODS: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2. RESULTS: Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months. CONCLUSIONS: dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.
PURPOSE:Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. METHODS: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2. RESULTS: Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months. CONCLUSIONS:dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.
Authors: Aung Ko Win; Noralane M Lindor; Joanne P Young; Finlay A Macrae; Graeme P Young; Elizabeth Williamson; Susan Parry; Jack Goldblatt; Lara Lipton; Ingrid Winship; Barbara Leggett; Katherine M Tucker; Graham G Giles; Daniel D Buchanan; Mark Clendenning; Christophe Rosty; Julie Arnold; A Joan Levine; Robert W Haile; Steven Gallinger; Loïc Le Marchand; Polly A Newcomb; John L Hopper; Mark A Jenkins Journal: J Natl Cancer Inst Date: 2012-08-28 Impact factor: 13.506
Authors: Dung T Le; Jennifer N Uram; Hao Wang; Bjarne R Bartlett; Holly Kemberling; Aleksandra D Eyring; Andrew D Skora; Brandon S Luber; Nilofer S Azad; Dan Laheru; Barbara Biedrzycki; Ross C Donehower; Atif Zaheer; George A Fisher; Todd S Crocenzi; James J Lee; Steven M Duffy; Richard M Goldberg; Albert de la Chapelle; Minori Koshiji; Feriyl Bhaijee; Thomas Huebner; Ralph H Hruban; Laura D Wood; Nathan Cuka; Drew M Pardoll; Nickolas Papadopoulos; Kenneth W Kinzler; Shibin Zhou; Toby C Cornish; Janis M Taube; Robert A Anders; James R Eshleman; Bert Vogelstein; Luis A Diaz Journal: N Engl J Med Date: 2015-05-30 Impact factor: 91.245
Authors: Christine M Ribic; Daniel J Sargent; Malcolm J Moore; Stephen N Thibodeau; Amy J French; Richard M Goldberg; Stanley R Hamilton; Pierre Laurent-Puig; Robert Gryfe; Lois E Shepherd; Dongsheng Tu; Mark Redston; Steven Gallinger Journal: N Engl J Med Date: 2003-07-17 Impact factor: 91.245
Authors: Hari Nathan; Timothy M Pawlik; Christopher L Wolfgang; Michael A Choti; John L Cameron; Richard D Schulick Journal: J Gastrointest Surg Date: 2007-09-05 Impact factor: 3.452
Authors: Winston Wong; Maeve A Lowery; Michael F Berger; Yelena Kemel; Barry Taylor; Ahmet Zehir; Preethi Srinivasan; Chaitanya Bandlamudi; Joanne Chou; Marinela Capanu; Anna Varghese; Kenneth H Yu; Christine A Iacobuzio-Donahue; Jinru Shia; David S Klimstra; William R Jarnagin; Zsofia K Stadler; Eileen M O'Reilly Journal: Cancer Date: 2019-01-08 Impact factor: 6.860
Authors: T Peter Kingham; Victoria G Aveson; Alice C Wei; Jason A Castellanos; Peter J Allen; Daniel P Nussbaum; Yinin Hu; Michael I D'Angelica Journal: Curr Probl Surg Date: 2020-06-30 Impact factor: 1.909
Authors: Richard Gallon; Peter Gawthorpe; Rachel L Phelps; Christine Hayes; Gillian M Borthwick; Mauro Santibanez-Koref; Michael S Jackson; John Burn Journal: Cancers (Basel) Date: 2021-01-22 Impact factor: 6.639