Histopathologic Basis for the Favorable Survival after Resection of Intraductal Papillary Mucinous Neoplasm-Associated Invasive Adenocarcinoma of the Pancreas

Abstract

Objective To identify pathologic features that may account for the favorable survival after resection of invasive pancreatic adenocarcinoma arising in the setting of intraductal papillary mucinous neoplasm (IPMN) compared with standard pancreatic ductal adenocarcinoma (PDA) in the absence of IPMN. Summary Background Data The 5-year survival after resection of IPMN-associated invasive adenocarcinoma is reported to be between 40% and 60%, which is superior to the 10–25%, typically cited after resection of standard PDA. It remains unclear whether this represents distinct biology or simply a tendency for earlier presentation of IPMN-associated invasive adenocarcinoma. Methods A single institution’s prospective pancreatic resection database was retrospectively reviewed to identify patients with invasive pancreatic adenocarcinoma who underwent pancreatectomy with curative intent. Log rank and Cox regression analysis were used to identify factors associated with survival. Results From 1995 to 2006, 1260 consecutive patients were identified, 132 (10%) with IPMN-associated invasive adenocarcinoma and 1128 (90%) with standard PDA. Actuarial 5-year survival was 42% after resection for IPMN-associated versus 19% for standard PDA (P < 0.001). However, compared with standard PDA, invasive adenocarcinoma arising within an IPMN was associated with a lower incidence of (1) advanced T stage (T2–T4, 96% vs. 73%, P < 0.001); (2) regional lymph node metastasis (78% vs. 51%, P < 0.001); (3) poor tumor differentiation (44% vs. 26%, P < 0.001); (4) vascular invasion (54% vs. 33%, P < 0.001); (5) perineural invasion (92% vs. 63%, P < 0.001); and (6) microscopic margin involvement (28% vs. 14%, P < 0.001). Specifically, in the presence of any one of the aforementioned adverse pathologic characteristics, outcomes after resection for IPMN-associated and standard PDA were not significantly different. Conclusion The favorable biologic behavior of IPMN-associated compared with standard PDA is based on its lower rate of advanced T stage, lymph node metastasis, high tumor grade, positive resection margin, perineural, and vascular invasion. In the presence of any one of the aforementioned adverse pathologic characteristics, however, survival outcomes after resection of IPMN-associated and after resection of standard pancreatic adenocarcinoma are similar.

Adjuvant Radiotherapy in the Treatment of Invasive Intraductal Papillary Mucinous Neoplasm of the Pancreas: an Analysis of the Surveillance, Epidemiology, and End Results Registry

“…6,7,9,10,12,15,16,33,37,38 In our population-based study of 972 patients, the 5-year OS for patients with and without adjuvant RT was 24%, which is on the lower end of previously reported survival. Our findings, however, suggest that certain subgroups may benefit from RT following surgical resection.…”

“…An emerging body of evidence suggests that IPMN and pancreatic adenocarcinoma, in fact, have a different natural history and prognosis. 6,9,10,15,16,[36][37][38][39] Most studies to date of adjuvant RT have been single-center and pooled multisite series of adjuvant chemotherapy (with or without RT) in a limited number of patients with invasive pancreatic IPMN. 6,9,12 Using SEER, we were able to identify a large cohort of cases and, accordingly, achieve sufficient statistical power to estimate subgroup differences according to provision of adjuvant RT.…”

“…13,14 Recent evidence suggests that invasive IPMN in the setting of lymph node involvement, advanced tumor stage and grade, tumor size [2 cm, and positive resection margins is associated with poor outcomes comparable to pancreatic adenocarcinoma. 15,16 Adjuvant chemoradiotherapy has been recommended for many patients with pancreatic adenocarcinoma due to a survival advantage compared with treatment with surgical resection alone, though results from the European Study Group for Pancreatic Cancer (ESPAC) ESPAC-1 trial suggested that adjuvant RT may not be of benefit. [17][18][19][20][21][22][23] However, the role of adjuvant RT in the treatment of invasive IPMN has not been well studied.…”

Comparison of guidelines for intraductal papillary mucinous neoplasm: What is the next step beyond the current guidelines?

“…Disease‐specific survival of patients with recurrent lesions remains low 35, 36, 37, 38. Therefore, it is reasonable to carry out postoperative surveillance for invasive IPMN as done for PDAC.…”

Intraductal Papillary Mucinous Tumors of the Pancreas: Biology, Diagnosis, and Treatment

“…For invasive intestinal IPMN, the invasive component corresponds to mucinous (colloid) carcinoma and is characterized by extensive stromal pools of extraluminal mucin, containing single cells or strands of neoplastic glandular epithelium or even a small component of signet ring cells [24,26,30]. Patients with these colloid carcinomas have a higher 5-year survival rate than those with ductal (tubular) adenocarcinomas (57% versus 37%) [31].…”