title: Mucinous carcinomas of the gallbladder: clinicopathologic analysis of 15 cases identified in 606 carcinomas.
abstract: BACKGROUND
  There are virtually no data in the literature regarding the incidence, patterns, and clinicopathologic characteristics of mucinous carcinomas (MCs) of the gallbladder (GB).
  
  
  OBJECTIVE
  To determine the incidence of mucinous differentiation in invasive GB carcinomas and the clinicopathologic characteristics of those that qualify as MC.
  
  
  METHODS
  Primary invasive GB carcinomas (n  =  606) were reviewed for mucinous differentiation. Some degree of mucin production was identified in 40 cases (6.6%); however, only 15 (2.5%) were qualified for the World Health Organization definition of MC (stromal mucin deposition constituting >50% of the tumor).
  
  
  RESULTS
  The mean age was 65 years, and the female to male ratio was 1.1 (versus 3.9 for conventional pancreatobiliary-type GB adenocarcinomas; P  =  .04). A significant proportion of the cases (8 of 12, 67%) presented with the clinical picture and intraoperative findings that were interpreted as acute cholecystitis. Mean and median tumor sizes were larger than those of conventional adenocarcinomas (4.8 and 3.4 cm versus 2.9 and 2.5 cm, respectively; P  =  .01). Most (13 of 15, 87%) cases presented with pT3 tumors (versus 48% for ordinary GB carcinomas; P  =  .01). Two cases had almost an exclusive colloid pattern (>90% composed of well-defined stromal mucin nodules that contained scanty carcinoma cells, most of which were floating within the mucin). Eight cases were of mixed-mucinous type, showing a mixture of colloid and noncolloid patterns. Five others had prominent signet-ring cells, both floating within the mucin (which constituted >50% of the tumor by definition) and infiltrating into the stroma as individual signet-ring cells in some areas. Immunohistochemical analysis performed on the 7 cases that had available tissue revealed CK7 in 4 of 7 (57%), CK20 in 2 of 7 (29%), MUC1 in 4 of 7 (57%), MUC2 in 6 of 7 (86%), CDX2 in 1 of 7 (14%), MUC5AC in 6 of 7 (86%), MUC6 in 0 of 7 (0%), and loss of E-cadherin in 6 of 7 (86%). The MLH1 and MSH2 were retained in 6 of 7 cases (100%). Follow-up information was available for 13 cases: 11 (85%) died of disease (1-37 months) and 2 (15%) were alive (23 months and 1 month). Overall survival of MCs was significantly worse than that of conventional adenocarcinomas (13 versus 26 months; P  =  .01); however, that did not seem to be independent of stage.
  
  
  CONCLUSIONS
  Mucinous carcinomas constitute 2.5% of GB carcinomas. They present with an acute cholecystitis-type picture. Most MCs are a mixed-mucinous, not pure colloid, type. They are typically large and advanced tumors at the time of diagnosis and thus exhibit more-aggressive behavior than do ordinary GB carcinomas. Immunophenotypically, they differ from conventional GB adenocarcinomas by MUC2 positivity, from intestinal carcinomas by an often inverse CK7/20 profile, from pancreatic mucinous carcinomas by CDX2 negativity, and from mammary colloid carcinomas by a lack of MUC6. Unlike gastrointestinal MCs, they appear to be microsatellite stable.
authors.affiliation: Department of Pathology, Istanbul Education and Research Hospital, Istanbul, Turkey.
authors.forename: Nevra
authors.initials: N
authors.lastname: Dursun
authors.forename: Oscar Tapia
authors.initials: OT
authors.lastname: Escalona
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Roa
authors.forename: Olca
authors.initials: O
authors.lastname: Basturk
authors.forename: Pelin
authors.initials: P
authors.lastname: Bagci
authors.forename: Asli
authors.initials: A
authors.lastname: Cakir
authors.forename: Jeanette
authors.initials: J
authors.lastname: Cheng
authors.forename: Juan
authors.initials: J
authors.lastname: Sarmiento
authors.forename: Hector
authors.initials: H
authors.lastname: Losada
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kong
authors.forename: Leslie
authors.initials: L
authors.lastname: Ducato
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
authors.forename: N Volkan
authors.initials: NV
authors.lastname: Adsay
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D005260:Female; D005706:Gallbladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055262:Mucin-2 / Q000378:metabolism; D055272:Mucin-6 / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D053554:Keratin-20; D053552:Keratin-7; C524625:MUC2 protein, human; C524734:MUC6 protein, human; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins