Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes

Abstract

Objective: Invasive cancers arising from intraductal papillary mucinous neoplasm (IPMN) are recognised as a morphologically and biologically heterogeneous group of neoplasms. Less is known about the epithelial subtypes of the precursor IPMN from which these lesions arise. The authors investigate the clinicopathological characteristics and the impact on survival of both the invasive component and its background IPMN.

Design and patients: The study cohort comprised 61 patients with invasive IPMN (study group) and 570 patients with pancreatic ductal adenocarcinoma (PDAC, control group) resected at a single institution. Multivariate analyses were performed using a stage-matched Cox proportional hazard model.

Results: The histology of invasive components of the IPMN cohort was tubular in 38 (62%), colloid in 16 (26%), and oncocytic in seven (12%). Compared with PDAC, invasive IPMNs were associated with a lower incidence of adverse pathological features and improved mortality by multivariate analysis (HR 0.58; 95% CI 0.39 to 0.86). In subtype analysis, this favourable outcome remained only for colloid and oncocytic carcinomas, while tubular adenocarcinoma was associated with worse overall survival, not significantly different from that of PDAC (HR 0.85; 95% CI 0.53 to 1.36). Colloid and oncocytic carcinomas arose only from intestinal- and oncocytic-type IPMNs, respectively, and were mostly of the main-duct type, whereas tubular adenocarcinomas primarily originated in the gastric background, which was often associated with branch-duct IPMN. Overall survival of patients with invasive adenocarcinomas arising from gastric-type IPMN was significantly worse than that of patients with non-gastric-type IPMN (p=0.016).

Conclusions: Tubular, colloid and oncocytic invasive IPMNs have varying prognosis, and arise from different epithelial subtypes. Colloid and oncocytic types have markedly improved biology, whereas the tubular type has a course that resembles PDAC. Analysis of these subtypes indicates that the background epithelium plays an equally, if not more, important role in defining the biology and prognosis of invasive IPMNs.

Figure 1

Epithelial subtypes of intraductal papillary mucinous neoplasm: (A) gastric; (B) intestinal; (C) oncocytic; (D) pancreatobiliary.

Figure 2

Histological subtypes of intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma: (A) tubular adenocarcinoma which resembles pancreatic ductal adenocarcinoma and consists predominantly of infiltrating tubular neoplastic glands associated with a desmoplastic stroma devoid of significant stromal mucin; (B) colloid carcinoma characterised by extensive (>80%) stromal mucin pools, containing relatively scant neoplastic cells; (C) low-power and (D) high-power magnifications of oncocytic carcinoma, showing infiltrating tubules and/or nests composed of oncocytic cells (invading into the duodenal mucosa in this case).

Figure 3

(A) Overall survival after resection of intraductal papillary mucinous neoplasm (IPMN)-associated invasive adenocarcinoma (IPMN) was significantly better than conventional pancreatic adenocarcinoma (PDAC) (median survival, 58 vs 18 months). (B) Overall survival curves after resection of IPMN-associated invasive adenocarcinoma (IPMN) and conventional ductal adenocarcinoma (PDAC) stratified by nodal status. The favourable survival of invasive IPMN compared with PDAC was noted in patients with node-negative disease (LN (−): median survival, 89 vs 26 months), but not in those with node-positive disease (LN (+): median survival, 18 vs 16 months). (C) Overall survival curves after resection of IPMN-associated invasive adenocarcinoma (IPMN) and conventional ductal adenocarcinoma (PDAC) stratified by histological grade of tumour. The favourable survival of invasive IPMN compared with PDAC was seen in patients with low histological grade (median survival, 89 vs 20 months), but not in those with high histological grade (median survival, 16 vs 16 months). (D) Overall survival curves after resection of IPMN-associated invasive adenocarcinoma based on histological subtype and conventional ductal adenocarcinoma (PDAC). Compared with patients with PDAC, those with oncocytic carcinoma and colloid carcinoma experienced significantly improved outcomes (p<0.0001, median survival, 18 vs 95 and 132 months, respectively), but those with tubular adenocarcinoma did not, upon multivariate analysis (p=0.76, median survival, 18 vs 35 months).