Pancreatic Intraepithelial Neoplasia (PanIN) as a Morphologic Marker of Pancreatobiliary Type of Ampullary Carcinoma

The classification of ampullary adenocarcinoma into intestinal and pancreatobiliary sub-types has been found to be important in predicting prognosis and determining therapeutic strategy. Due to considerable inter-observer variability in sub-typing based solely on morphology, higher frequency of poorly differentiated cancers and low incidence of the disease, the histomorphologic classification of ampullary adenocarcinoma remains one of the grey zones in surgical pathology. Pan-IN is a well recognized precursor to pancreatic adenocarcinoma. Three studies have shown concurrent Pan-IN in patients with ampullary carcinoma, but their association with the two sub-types has not yet been reported. Fourteen cases of surgical resection for ampullary adenocarcinoma were retrieved from the archives. The cases were classified into two groups based on the presence or absence of concomitant Pan-IN. All the cases were stained for CK7, CK 20, Villin and CDX 2 and were classified as intestinal or pancreatobiliary types based on the staining pattern. All the 10 cases with Pan-IN stained negative for CDX2 and were classified as pancreatobiliary type (p = 0.01). Of the cases without Pan-IN, 3 were classified as intestinal sub-type based on morphology and CDX2 positivity and 1 was classified as pancreatobiliary type. Concomitant Pan-IN was present in 91% of pancreatobiliary type of ampullary adenocarcinoma. The grade of Pan-IN did not influence the grade or stage of the adenocarcinoma (p > 0.05). The co-occurrence of Pan-IN in a high percentage of the pancreatobiliary sub-type and its complete absence in the intestinal sub-type may serve as a strong differentiator between the two sub-types.