Intraepithelial involvement of non-neoplastic glands in papillary preinvasive neoplasms of the biliary tract: a potential diagnostic pitfall.

Intracholecystic papillary neoplasms of the gallbladder (ICPN) and intraductal papillary neoplasms of the bile duct (IPNB) show intramural neoplastic growths in addition to intraluminal papillary or polypoid neoplastic growth. Such intramural growths include intraepithelial involvement of non-neoplastic glands by preinvasive neoplastic epithelia (glandular involvement) as well as stromal invasive carcinoma. A total of 29 ICPN cases and 84 IPNB cases were pathologically examined for their glandular involvement. Glandular involvement was characterized by intramural neoplastic glands (1) showing cytological and phenotypical similarities to intraluminal preinvasive papillary neoplasms and (2) showing reminiscent configurations of non-neoplastic glands, such as (i) a mixture of preinvasive neoplastic epithelia and non-neoplastic epithelia within the same glands, (ii) neoplastic glands close to or within clustered non-neoplastic glands, or (iii) continuous growth of intraluminal preinvasive neoplastic glands into the walls. Such glandular involvement was found in 16 of 29 ICPN and 48 of 84 IPNB, and 15 of the former and 28 of the latter were not associated with invasive carcinoma. Non-invasive ICPN and IPNB with glandular involvement showed a favorable postoperative overall survival (OS). Glandular involvement by preinvasive neoplastic epithelia was frequently found in ICPN and IPNB. Such lesions may be diagnostic pitfalls in ICPN and IPNB referring to invasion. Glandular involvement without invasive carcinoma was not associated with an unfavorable postoperative OS in ICPN and IPNB. Recognition of glandular involvement may thus prevent overestimation of invasive carcinoma in ICPN and IPNB.