title: Intra-pancreatic Distal Bile Duct Carcinoma is Morphologically, Genetically, and Clinically Distinct from Pancreatic Ductal Adenocarcinoma.
abstract: Differentiating intra-pancreatic distal bile duct carcinoma invading the pancreas from pancreatic ductal adenocarcinomas (PDAC) surrounding the distal common bile duct (CBD) can be challenging. Our aim is to identify clinical, morphological, and genetic features characteristic of intra-pancreatic distal bile duct carcinoma.
  
  
  
  Clinicopathologic data of 550 patients undergoing a pancreaticoduodenectomy between September 1990 and May 2008 were reviewed. KRAS status was assessed with mass-spectrometric genotyping.
  
  
  
  Ninety-seven patients with intra-pancreatic adenocarcinomas surrounding the CBD were identified; slides were available for 80. Two relationships with the CBD were recognized as follows: type I (n = 42): cancer grew concentrically around the CBD and type II (n = 38): cancer grew asymmetrically around the CBD. Type I adenocarcinomas were associated with high-grade biliary dysplasia (45 vs. 13 %; p = 0.003); type II were associated with high-grade pancreatic intra-epithelial neoplasia (PanIN-2 or -3) (39 vs. 9 %; p = 0.003). Type I tumors had a better median survival (46 months) compared to type II (23 months) or other PDAC (20 months) (p < 0.001). Mutated KRAS was identified in 3/26 (11 %) type I and 20/21 (95 %) type II cancers (p < 0.001). There may be poorer survival in the presence of a KRAS mutation than wild-type KRAS (22.9 vs. 41.6 months; p = 0.3).
  
  
  
  Distal periductal adenocarcinomas fall into two distinct groups with biologic, morphologic and genetic differences. Those growing symmetrically around the CBD are more likely to be intra-pancreatic distal bile duct carcinomas and are associated with improved survival whereas cancers with asymmetric growth are more likely to have KRAS mutations and to be PDACs. These findings facilitate a more accurate histopathological diagnosis, which could improve patient selection for therapeutic trials.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. vdeshpande@mgh.harvard.edu.
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Ioannis T
authors.initials: IT
authors.lastname: Konstantinidis
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Carlos Fernandez-Del
authors.initials: CF
authors.lastname: Castillo
authors.affiliation: Department of Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Aram F
authors.initials: AF
authors.lastname: Hezel
authors.affiliation: Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Haigis
authors.affiliation: Department of Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Ting
authors.affiliation: Department of Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Bardeesy
authors.affiliation: Department of Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Lipika
authors.initials: L
authors.lastname: Goyal
authors.affiliation: Department of Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Warshaw
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Ferrone
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D003138:Common Bile Duct Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Intra-pancreatic distal bile duct carcinoma; KRAS; Pancreatic ductal adenocarcinoma