Classification of Tumoral Intraepithelial Neoplasms of the Gallbladder under a Unified Category of Intracholecystic Papillary Tubular Neoplasms (ICPN) with 4 Subsets Discernible by Correlation of Morphology and Immunophenotype.
Kee-Taek Jang, Nevra Dursun, Olca Basturk, Juan Carlos Roa, Oscar Tapia, Paul Terry, NVolkan Adsay. SMC, Seoul, Korea; Emory, GA; MSKCC, NY; UFRO, Temuco, Chile
Background: In the WHO-2010, tumoral intraepithelial neoplasms (TIN) of gallbladder are classified under 7 different names, some based on cell lineage (pyloric, foveolar, intestinal, biliary), some by growth pattern (tubulopapillary), and others by degree of dysplasia (non-invasive papillary ca).
Design: 87 cases >1 cm were evaluated by correlation of morphology with IHC for cell lineage markers MUC1 (biliary), MUC2/CDX2 (intestinal), MUC6 (pyloric) and MUC5AC (foveolar), CK7 and CK20.
Results: I. Hybrid and mixed lineages were very common. 49 (56%) had cellular morphology difficult to classify into an established lineage, and this group also showed a complex IHC profile: MUC1 55%; MUC5AC 53%; MUC6 26%, MUC2 14%, and CK20 20%. 74% had recognizable foci of different lineages within the given tumor, 52% with corresponding expected IHC profile. These mixed types were mostly biliary-foveolar type (n=44), 41 of which expressed non-foveolar markers. 22 with intestinal-like features were negative for MUC2/CDX2. II. Correlation of morphology with IHC allowed the delineation of 4 subtypes. 1. Biliary (n=68): Papillary/tubulopapillary; most with HG dysplasia; consistent MUC1/CK7; common foci with pyloric or foveolar features (MUC5AC or MUC6) some with pleomorphic clear cells; some with intestinal-like morphology but MUC2/CDX2 (-). 2. Pyloric complex-tubular (n=13): Nodular, pedunculated lesions composed of complex tightly-packed small tubular units with cuboidal nuclei; uniform/diffuse MUC6; 6 with focal MUC1 highlighting the higher grade or biliary type areas; 2 with Brunner-gland and 2 with foveolar features. 3. Foveolar (n=3): Tubulopapillary; abundant apical, pale, MUC5AC (+) cytoplasm. 4. Intestinal (n=3): Papillary/tubulopapillary; all the characteristics of a colonic-type adenoma; MUC2/CDX2 (+).
Conclusions: There are significant phenotypic overlaps, variable growth patterns and intratumoral heterogeneity in TINs of GB, warranting their unification under one category of ICPN. Correlation of IHC with morphology allows the recognition of 4 subtypes of ICPNs, the vast majority of the cases falling into the biliary category, followed by pyloric complex-tubular, and rarely, foveolar or intestinal. Papillary vs tubular patterns and degree of dysplasia are trans-categorical and thus not applicable in the classification. We believe that this definition of ICPN and its subtypes is a more accurate reflection of the TINs of GB.
Category: Liver & Pancreas
Monday, February 28, 2011 1:45 PM
Platform Session: Section D, Monday Afternoon