Mucinous Cystic Neoplasm (Mucinous Cystadenocarcinoma of Low-Grade Malignant Potential) of the Pancreas

Abstract

Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon tumors. The classification and biologic potential of these neoplasms remain the subject of controversy. Attempts to classify these tumors in a similar manner to ovarian MCNs remains controversial, as even histologically benign-appearing pancreatic MCNs metastasize and are lethal. One hundred thirty cases of MCNs were identified in the files of the Endocrine Pathology Tumor Registry of the Armed Forces Institute of Pathology from the years 1979 to 1993. The pathologic features, including hematoxylin and eosin staining, histochemistry, immunohistochemistry (IHC), cell cycle analysis, and K-ras oncogene determination were reviewed. These findings were correlated with the clinical follow-up obtained in all cases. There were 130 women, aged 20-95 years (mean age at the outset, 44.6 years). The patients had vague abdominal pain, fullness, or abdominal masses. More than 95% of the tumors were in the pancreatic tail or body and were predominantly multilocular. The tumors ranged in size from 1.5 to 36 cm in greatest dimension, with the average tumor measuring >10 cm. A spectrum of histomorphologic changes were present within the same case and from case to case. A single layer of bland-appearing, sialomucin-producing columnar epithelium lining the cyst wall would abruptly change to a complex papillary architecture, with and without cytologic atypia, and with and without stromal invasion. Ovarian-type stroma was a characteristic and requisite feature. Focal sclerotic hyalinization of the stroma was noted. This ovarian-type stroma reacted with vimentin, smooth muscle actin, progesterone, or estrogen receptors by IHC analysis. There was no specific or unique epithelial IHC. K-ras mutations by sequence analysis were wild type in all 52 cases tested. Ninety percent of patients were alive or had died without evidence of disease (average follow-up 9.5 years), irrespective of histologic appearance; 3.8% were alive with recurrent disease (average 10 years after diagnosis); and 6.2% died of disseminated disease (average 2.5 years from diagnosis). Irrespective of the histologic appearance of the epithelial component, with or without stromal invasion, pancreatic MCNs should all be considered as mucinous cystadenocarcinomas of low-grade malignant potential. Pancreatic MCNs cannot be reliably or reproducibly separated into benign, borderline, or malignant categories.

Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays

“…More than 90% arise in females (Thompson et al, 1999;Zamboni et al, 1999). Pancreatic MCNs were first distinguished from serous cystic neoplasms by Compagno and Oertel (1978).…”

“…In addition, better knowledge of the molecular alterations that give rise to MCNs could help in the management of patients with these neoplasms. Because MCNs are uncommon and usually only contain a small number of neoplastic cells, molecular studies are difficult and as a result information about these neoplasms has largely been derived from immunohistochemical studies of proteins such as p53 (Thompson et al, 1999;Zamboni et al, 1999;Yoshizawa et al, 2002), mucin proteins (Luttges et al, 2002), markers of gastric or intestinal differentiation (Zamboni et al, 1999), as well as protein expression patterns within the 'ovarian-type' stroma (Fukushima and Mukai, 1997;Izumo et al, 2003). In contrast, much more is known about the genetic and epigenetic alterations involved in the development of pancreatic ductal adenocarcinomas, IPMNs and pancreatic intraepithelial neoplasms (PanINs).…”

Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently Involve KRAS Mutations and Malignant Progression

“…In the most recent World Health Organization (WHO) Classification of Tumours of the Digestive System (2010) (2), MCN was classified as a distinct entity of cystic neoplasms in both pancreas and liver, and it has been defined as "a cyst-forming epithelial neoplasm, usually showing no communication with the ductal system, composed of cuboidal to columnar, variably mucin-producing epithelium, and associated with ovarian-type subepithelial stroma" (3)(4)(5). MCNs tend to occur most often in middle-aged women and are regarded as pre-malignant lesions with significant potential for invasion and metastasis.…”

Biliary cystic tumors with bile duct communication: a cystic variant of intraductal papillary neoplasm of the bile duct

“…8 In contrast, IPMN-P, which does not have ovarianlike stroma, occurs in both genders and has a communication to the pancreatic ductal system. 9 That is, most cases previously reported as pancreatic mucinous cystic neoplasms with a luminal communication to the pancreatic duct or occurring in male patients are now thought to be IPMN-P. 14,15 Recently, great attention is being drawn to intraductal biliary tumors. In 2001, we reported a characteristic intraductal papillary tumor of the bile duct associated with hepatolithiasis as a biliary counterpart of IPMN-P (intraductal papillary neoplasm of the bile duct: IPN-B).…”