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The new revised WHO classification of tumors of the pancreas includes both exocrine and endocrine neoplasms in one classification (Table 1.1) . This chapter will briefly review the major exocrine tumors, which are covered in more detail in subsequent chapters. A more detailed discussion of the classification of precursor pancreatic ductal lesions and pancreatic neuroendocrine tumors of the pancreas will also be provided in this chapter.
Classification of solid exocrine tumors of the pancreas
Ductal adenocarcinoma and its variants make up more than 90% of all malignant exocrine pancreatic tumors. About two thirds of ductal adenocarcinomas occur in the head of the gland; the rest occur in the body or tail, or diffusely throughout the pancreas. They are characterized by an intense desmoplastic reaction in which duct-like structures of varying degrees of differentiation are seen. It comprises extracellular matrix together with a number of different host cell types, including fibroblasts, small endothelial-lined vessels, residual normal epithelia, and a variety of inflammatory cells which are both locally derived and recruited from the circulation . The interplay between all these cells types and the pancreatic cancer cells influences new blood vessel formation, invasion, metastases, and evasion of the host immune system . Because of their proximity to the intrapancreatic portion of the common bile duct, tumors in the head usually produce jaundice since they compress and obstruct the bile duct as they grow. They often obstruct the pancreatic duct as well, and although steatorrhea may result, there may not be any obvious symptoms. Tumors of the head of the pancreas are usually at least 2 cm in diameter when they are first diagnosed. Most tumors that are resected have a median diameter of 2.5–3.5 cm. Tumors of the body and tail commonly are larger (5–7 cm) and more advanced when they are discovered because they do not produce symptoms as early as head tumors do. The symptoms from tumors in the body and tail are usually caused by malignant infiltration of the retroperitoneal structures and nerves, which produces pain. By the time the diagnosis is made, almost all are unresectable. Nevertheless, there is evidence that resectable body tumors have a similar prognosis to resectable tumors in the head of the gland. Approximately 70–80% of adenocarcinomas of the head of the pancreas have metastasized to regional lymph nodes by the time they are discovered, which worsens the prognosis but does not preclude cure. These tumors also commonly invade lymphatic channels and perineural spaces. The prognosis is also influenced by the degree of tumor differentiation and by the presence of invasion of the retroperitoneal tissues adjacent to the cancer. The best outcome is seen in patients who have well-differentiated neoplasms, without retroperitoneal invasion or lymph node metastases. Distant metastases (e.g., lung) may occur, but pancreatic cancer typically infiltrates locally into the adjacent structures (e.g., stomach, duodenum, colon, transverse mesocolon, portal and superior mesenteric veins, superior mesenteric artery). The liver is the most common site of intraabdominal metastasis, and peritoneal seeding of the tumor is also seen. In patients without distant spread, vascular invasion by tumor is the most common reason for unresectability.
Table 1.1. WHO histologic classification of tumors of the exocrine and endocrine pancreas
- Epithelial tumors
- Serous cystadenoma
- Mucinous cystadenoma
- Intraductal papillary-mucinous adenoma
- Mature teratoma
- Borderline (uncertain malignant potential)
- Mucinous cystic neoplasm with moderate dysplasia
- Intraductal papillary-mucinous neoplasm with moderate dysplasia
- Solid-pseudopapillary neoplasm
- Ductal adenocarcinoma
- Mucinous noncystic carcinoma
- Signet ring cell carcinoma
- Adenosquamous carcinoma
- Undifferentiated (anaplastic) carcinoma
- Undifferentiated carcinoma with osteoclast-like giant cells
- Mixed ductal–endocrine carcinoma
- Serous cystadenocarcinoma
- Mucinous cystadenocarcinoma
- Intraductal papillary mucinous carcinoma
- Acinar cell carcinoma
- Acinar cell cystadenocarcinoma
- Mixed acinar–endocrine carcinoma
- Solid-pseudopapillary carcinoma
- Ductal adenocarcinoma
- Nonepithelial tumors
- Mesenchymal tumors
- Solitary fibrous tumor
- Ewing sarcoma
- Desmoplastic small round cell tumor
- Perivascular epithelioid cell neoplasm
- Diffuse large B-cell lymphoma (DLBCL)
- Secondary tumors
- Mesenchymal tumors
- Pancreatic neuroendocrine microadenoma
- Neuroendocrine tumor G1 (NET G1)/Carcinoid
- Neuroendocrine tumor G2 (NET G2)
- Neuroendocrine carcinoma
- Large cell neuroendocrine carcinoma
- Small cell neuroendocrine carcinoma
- Functional PNET
- Gastrinoma, malignant
- Glucagonoma, malignant
- Insulin-producing carcinoma (insulinoma)
- Somatostatinoma, malignant
- Vipoma, malignant
- Epithelial tumors
The most widely accepted staging system for pancreatic cancer is the American Joint Committee on Cancer (in cooperation with the TNM committee of the International Union Against Cancer), which is shown in Table 1.2 . Although this system is prognostic for overall survival, it is not particularly useful in guiding treatment, because some patients with advancedstage disease (i.e., stage IVA) may be candidates for surgical resection, whereas others may not. For this reason, pancreatic cancer patients are generally classified by physicians as having resectable, locally advanced, or metastatic disease. Other histologic variants of pancreatic ductal adenocarcinoma have been described, including mucinous noncystic carcinoma, signet ring cell carcinoma, adenosquamous carcinoma, undifferentiated (anaplastic) carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, and mixed ductal–endocrine carcinoma.
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