Applicability and Prognostic Relevance of Ampullary Carcinoma Histologic Typing as Pancreatobiliary Versus Intestinal
S Balci, GE Kim, N Ohike, T Tajiri, I Coban, A Krasinskas, S Bandyopadhyay, O Basturk, A Dolgun, D Kooby, C Staley, NV Adsay. Hacettepe U, Ankara, Turkey; UCSF, CA; Emory U, GA; Showa U, Yokohama, Japan; U of Pittsburgh, PA; WSU, MI; NYU, NY
Background: Ampullary carcinomas (ACs) show cell-lineage towards the epithelial lining located in this region. A lineage-based classification as pancreatobiliary (PB) or intestinal (IN) has been proposed, and treatment protocols are being designed accordingly; however, the applicability and prognostic relevance of this system has yet to be verified.
Design: 5 observers independently classified 232 stringently-defined invasive ACs, based on their resemblance to pancreatic or colonic carcinomas, as: pure PB, pure IN, mixed (MX) and others (OT). MX group was further divided, based on the predominant pattern, as MXPB vs MXIN. For incidence and prognostic analysis, 3 of 5 were considered as consensus diagnosis.
Results: The incidences of cases that were classified as pure PB and pure IN was 32% and 6%; remainder were MX (41%) or OT (12%). Agreement among the observers for these categories was "fair" (Kappa=0.3850; Z score=28.80; p<0.001), with only 23% agreed by all 5. The high incidence of MX category was attributed to tumor heterogeneity, mostly along the advancing carcinoma edge that often displayed PB pattern in an otherwise IN tumor. However, when the predominant-pattern based classification was evaluated (by combining MXPBs to pure PB and MXINs to pure IN), "moderate" agreement was obtained (Kappa=0.4402; Z=28.09; p<0.0001) with 59% classified as PB, 25% as IN and 15% as OT. The PB-predominant (pure PB + MXPB) group had a significantly lower median survival (41 mos) than that of IN-predominant (pure IN+MXIN) tumors (80 mos; p=0.026) with a 1.78 times higher risk of death (p=0.028). However, this survival correlation was not independent of established prognostic parameters in multivariate analysis.
Conclusions: As a transitional region, ACs often show hybrid phenotypes between PB and IN epithelium, producing substantial subjectivity of histologic type designation. Tumor heterogeneity is common, particularly along the advancing edge with morphologic transformation. If the predominant-pattern approach is employed, PB vs IN classification has moderate agreement and good prognostic value; however, the differences in survival is by no means analogous to that of pancreatic vs colonic adenocarcinoma. Other prognosticators are necessary to appropriately stratify ACs.
Category: Liver & Pancreas
Tuesday, March 23, 2010 2:30 PM
Platform Session: Section C, Tuesday Afternoon