Complex glandular pattern is an aggressive morphology that predicts poor prognosis of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, with a 5-year survival rate of only 10 % for all cases, and 39 % for localized cases [1]. PDACs are subdivided into conventional PDACs and some histological subtypes. The World Health Organization (WHO) classification lists adenosquamous carcinoma, colloid carcinoma, hepatoid carcinoma, medullary carcinoma, invasive micropapillary carcinoma, signet-ring cell (poorly cohesive cell) carcinoma, and undifferentiated carcinoma as histological subtypes of PDAC that have distinct histology and prognosis [2]. Conventional PDACs are generally classified as well to poorly differentiated adenocarcinomas based on the degree of glandular formation and cytologic pleomorphism, but the tumor differentiation is not as strong prognostic factor as pathological stage. It is, therefore, of great significance to understand the histologic patterns of conventional PDACs in the correlation with prognosis of the patients.

Cribriform architecture is a growth pattern that is frequently encountered in invasive carcinomas of various organs. It has been reported as a highly aggressive pattern with adverse clinical outcomes in prostatic [3], [4], colorectal [5], and pulmonary adenocarcinomas [6]. The reported significances of cribriform architecture in PDACs differed variously [7], [8], [9]. The cribriform architecture in conventional PDACs often appears as the incomplete nests with ill-defined borders, which is intermingled with fused glands or irregular formed nest with a few small lumens.

The complex glandular pattern has been proposed for pulmonary adenocarcinoma [10], [11], [12], and this term was also introduced in the latest WHO classification of the thoracic tumors [13]. The complex glandular pattern originally encompasses not only the cribriform architecture but also fused-gland and poorly formed-gland architectures [12]. It was noted in pulmonary adenocarcinomas that the complex glandular pattern is associated with adverse clinical outcomes even if it exists as a minor component [12]. The significance of the complex glandular pattern has not yet been evaluated in PDACs. In this study, we analyzed the clinicopathological, immunohistochemical, and prognostic features of conventional PDACs with predominant complex glandular pattern.

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