Cystic neoplasms are diverse tumors that range from harmless benign cysts to invasive, potentially lethal, cancers. Approximately 5% to 15% of all pancreatic cysts are neoplastic; these constitute less than 5% of all pancreatic neoplasms. Some of these are almost always benign (e.g., serous cystadenoma); others, such as mucinous cystic neoplasms, can be benign or malignant.
Serous cystadenomas account for approximately 25% of all pancreatic cystic neoplasms; they are composed of glycogen-rich cuboidal cells surrounding small cysts containing clear, straw-colored fluid (
Fig. 17.5 ). The tumors typically manifest in the seventh decade of life with nonspecific symptoms such as abdominal pain; the female-to-male ratio is 2:1. These tumors are almost uniformly benign, and surgical resection is curative in the vast majority of patients. Most serous cystadenomas carry somatic loss of function mutations of the von Hippel-Lindau (VHL) tumor suppressor gene, which you will recall is a negative regulator of hypoxia-inducible factor 1 alpha (HIF-1-alpha) (Chapter 6).
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Fig. 17.5 Serouscystadenoma.(A)Cross-sectionthroughaserouscystad-enoma.Onlyathinrimofnormalpancreaticparenchymaremains.Thecystsarerelativelysmallandcontainclear,straw-coloredfluid.(B)Thecystsarelinedbycuboidalepitheliumwithoutatypia.
In contrast to serous cystic tumors, close to 95% of mucinous cystic neoplasms arise in women, usually in the body or tail of the pancreas, and manifest as painless, slow-growing masses. The cystic spaces are filled with thick, tenacious mucin, and the cysts are lined by a columnar mucinous epithelium with an associated densely cellular stroma resembling that of the ovary (
Fig. 17.6 ). Based on the degree of cytologic and architectural atypia in the epithelial lining, noninvasive mucinous cystic neoplasms are classified as harboring low-grade, moderate, or severe dysplasia. Up to one-third of these cysts can be associated with an invasive adenocarcinoma, another important difference from the serous tumors. Distal pancreatectomy for noninvasive mucinous cysts typically is curative, even in the setting of severe dysplasia.
In contrast with mucinous cystic neoplasms, intraductal papillary mucinous neoplasms (IPMNs) occur more frequently in men than in women and more frequently involve the head of the pancreas. IPMNs arise in the main pancre-atic ducts, or one of its major branch ducts, and lack the cellular stroma seen in mucinous cystic neoplasms (
Fig.
17.7 ). As with mucinous cystic neoplasms, the epithelia of noninvasive IPMNs harbor various grades of dysplasia, and a subset of lesions is associated with invasive adenocarcinoma. In particular, “colloid” carcinomas of the pancreas, which are adenocarcinomas associated with abundant extracellular mucin production, nearly always represent malignant transformation of an IPMN. Up to two-thirds of IPMNs harbor oncogenic mutations of GNAS on chromosome 20q13, which encodes the alpha subunit of a stimulatory G-protein, Gs (Chapter 20). Constitutive activation of this G-protein is predicted to result in an intracellular cascade that promotes cell proliferation.