Clinical meaning of the World Health Organization morphologic classification (flat vs. tumoral) of gallbladder intraepithelial neoplasm as a prognostic factor in gallbladder cancer

BACKGROUND: In the World Health Organization (WHO) classification, gallbladder (GB) intraepithelial lesions are grouped as flat or tumoral, according to their morphological features. The purpose of this study was to investigate the relationship between the morphologies and clinical features of GB cancer (GBC) and to examine the feasibility of using morphologic classification as a prognostic factor. METHODS: From January 2000 to December 2012, the available pathologic slide reviews of 381 patients were analyzed at the Seoul National University Hospital. All pathologic slides were evaluated by two pancreato-biliary tract pathology experts. GBCs were categorized into eight groups (Flat: F1-2, Borderline, Tumoral: Tu1-5), according to the thickness of the mucosal lesion, histologic patterns of the mucosa under microscopy, invasion extent, and patient history of premalignant lesions. According to the morphologic classification, clinical features were compared and survival analysis was performed. RESULTS: In three groups, flat lesions comprised 179 (46.9%) cases and borderline and tumoral comprised 97 (25.4%) and 105 (27.5%) cases, respectively. More favorable pathologic and clinical results were found within the tumoral group. The borderline group had an intermediate tendency between flat and intraluminal in clinicopathologic parameters. In the curative resected T2 stage group, the borderline group demonstrated an intermediate trend compared to that of the flat and tumoral groups, but this was statistically insignificant (P=0.08). CONCLUSIONS: Flat type GBCs show worse prognosis than tumoral GBCs. The morphological classifications between flat and tumoral on the basis of 1 cm and by papillary feature is feasible. Tumor morphology can be used as a reference while deciding the treatment plan, especially in T2 GBC.