title: Pancreatic acinar cell carcinomas with prominent ductal differentiation: Mixed acinar ductal carcinoma and mixed acinar endocrine ductal carcinoma.
abstract: BACKGROUND
  Pancreatic acinar cell carcinomas (ACCs) are clinically and pathologically distinct from pancreatic ductal adenocarcinomas (PDAs). Whereas endocrine differentiation has been well shown in ACCs, significant ductal components are rare. This paper reviews the clinicopathologic features of a series of ACCs with prominent ductal differentiation.
  
  
  METHODS
  Cases of pancreatic ACCs with significant ductal differentiation were identified in the surgical pathology databases of 2 academic centers. Patient clinical information, gross and histologic features, and histochemical and immunohistochemical (IHC) results were recorded. Cases were tested for KRAS2 mutations.
  
  
  RESULTS
  Eleven cases were identified (10 men and 1 woman; age range 52 to 79 y). Four patients presented with jaundice. At last follow-up, 7 patients died of disease and 2 others had recurrences. Tumors measured between 2 and 5.5 cm and were ill-defined, nodular, and multilobulated. Ten were located in the head of the pancreas. All but 2 exhibited extrapancreatic invasion. All cases showed significant evidence of both acinar and ductal differentiation, estimated to be at least 25% of the neoplastic cells, and 3 cases in addition had endocrine differentiation in more than 25% of cells. Five cases were predominately acinar with intracellular and sometimes extracellular mucin ("mucinous acinar cell carcinoma" pattern). Six cases seemed more mixed with areas recapitulating typical PDAs whereas the other portions of the tumors seemed akin to typical acinar cell carcinomas ("combined acinar and ductal" pattern). IHC positive staining results were as: trypsin (92%), chymotrypsin (92%), monoclonal carcinoembryonic antigen (100%), CK19 (100%), B72.3 (73%), CA19.9 (73%), CD56 (18%), synaptophysin (36%), and chromogranin (36%). One case showed p53 over-expression aznd none showed DPC4/Smad4 loss. Two cases had KRAS2 mutations.
  
  
  CONCLUSIONS
  Despite the early embryologic divergence of acinar and ductal cell lineages, rare pancreatic tumors have both acinar and ductal differentiation, usually predominantly the former. The clinical course is highly aggressive.
authors.affiliation: Deparment of Pathology, University of Virginia, Charlottesville, USA.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Stelow
authors.forename: Ruthy
authors.initials: R
authors.lastname: Shaco-Levy
authors.forename: Fei
authors.initials: F
authors.lastname: Bao
authors.forename: Joaquin
authors.initials: J
authors.lastname: Garcia
authors.forename: David S
authors.initials: DS
authors.lastname: Klimstra
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018267:Carcinoma, Acinar Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018273:Carcinoma, Islet Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D009154:Mutation; D009378:Neoplasms, Multiple Primary; D009518:New York / Q000453:epidemiology; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D014768:Virginia / Q000453:epidemiology; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D009077:Mucins; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins