Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from malignant (or premalignant) neoplasms?

Abstract

Objective: To determine whether the long-term behavior of cystic mucinous neoplasms of the pancreas could be predicted using a novel, precisely defined classification of benign mucinous cystadenomas, noninvasive proliferative cystic mucinous neoplasms, and invasive mucinous cystadenocarcinomas. The primary interest was to obtain long-term follow-up after complete resection to determine the recurrence rates based on this objective classification.

Background: Current understanding is that all cystic mucinous neoplasms of the pancreas are potentially malignant and that mucinous cystadenomas, when completely removed, are biologically benign. Cystadenocarcinomas are thought to be less aggressively malignant than ordinary ductal adenocarcinoma, but reported recurrence rates vary widely and are unpredictable.

Methods: All patients who underwent "curative" resection for cystic mucinous neoplasms at Mayo Clinic Rochester from 1940 to 1997 were identified. All available pathology slides, gross specimens, and clinical records were reviewed, eliminating patients with inadequate documentation. Neoplasms were reclassified as mucinous cystadenomas, noninvasive proliferative mucinous cystic neoplasms, or invasive cystadenocarcinomas based on specific histologic criteria.

Results: Of 84 patients (70 women, 14 men) with cystic mucinous neoplasms of the pancreas, 54 were classified as cystadenomas, 23 as noninvasive proliferative cystic mucinous neoplasms, and only 7 as cystadenocarcinomas. Recurrent disease developed in none of the 77 patients without invasion, but 5 of the 6 patients surviving resection for cystadenocarcinomas died of recurrent cystadenocarcinoma within 5 years.

Conclusions: When the neoplasm is completely resected and subjected to adequate histopathologic examination based on these objective criteria, absence of tissue invasion predicts a curative operation and detailed follow-up may be unnecessary. In contrast, a histologic diagnosis of invasive cystadenocarcinoma portends a dismal prognosis, similar to that of typical ductal adenocarcinoma of the pancreas.

Figure 1. Cystic mucinous neoplasms of pancreas, resection specimens. (A) Cystadenoma: multiple, large (>2 cm) cysts with thin walls and no obvious or prominent solid component. (B) Proliferative cystic mucinous neoplasm: more granular appearance and a solid component; walls of individual cystic areas appear thicker.

Figure 2. Mucinous cystadenoma of the pancreas, histologic features. Monotonously regular, single layer of benign-appearing mucinous epithelial cells.

Figure 3. Proliferative cystic mucinous neoplasms of the pancreas, spectrum of histologic changes. (A) Irregular papillary epithelial growth. Epithelial cells heaped up; nuclei mildly atypical. (B) Papillary epithelial fronds with low-grade nuclear dysplasia. (C) High-grade nuclear dysplasia and papillary/polypoid intracystic growth.

Figure 4. Mucinous cystadenocarcinoma, histologic features. Small irregular glands and single cells with high-grade nuclear dysplasia invading the stroma and eliciting a desmoplastic stromal response (i.e., proliferating fibroblast surrounding infiltrating malignant epithelium).