Pancreatic cancer is high aggressive malignant neoplasm with very poor prognosis and about only 5% a five-year survival. It is the fourth leading cause of cancer death in USA, as well in Serbia, although in terms of the incidence of this disease the mortality is rising and it takes seventh place. Speaking about the southern Backa, the mortality rate is slightly lower and it is the fifth place, according to the available literature. This can be explained by the lack of highly specific and sensitive diagnostic tests, which makes pancreatic cancer most often detected by an advanced, inoperable stage of the disease (>60%), although surgical resection is the only curative therapy. Analogous to other carcinomas, there is a gradual progression of the pancreatic duct epithelial cells, so every invasive carcinoma arises from the previous intraepithelial neoplasia. There are three different types of common precancerous lesions known for pancreatic cancer which clinical detection and treatment can stop the progression to invasive cancer and reduce mortality. The first one is Pancreatic Intraepithelial Neoplasia (PanIN), and the other two types of precancerous lesions are both larger fluid-filled types- Intraductal Papillary Mucinous Neoplasms (IPMNs) and Mucinous Cystic Neoplasms (MCNs). PanIN is an asymptomatic, small (usually <5 mm in diameter), nonfluid flat or papillary lesion arising in the small intralobular pancreatic ducts. It is the most common and important precursor of invasive pancreatic carcinoma. Histologically, it’s consisted of columnar to cuboidal cells with varying amounts of mucin. Accordingly to different degrees of cytological and architectural atypia, PanIN is classified into three grades- low, intermediate and high grade. PanIN-1A (flat) and PanIN-1B (papillary) are low grade lesions with minimal atypia, while PanIN-2 belongs to intermediate lesion showing mild to moderate atypia with frequent papillae. PanIN-3, also referred as “carcinoma in situ”, is characterized by severe cytological and architectural atypia amd it can be flat, papillary or cribriform pattern. The immunohistochemical profile of PanINs vary with the grade of dysplasia. Low grade lesions show positivity for gastric foveolar mucin MUC5AC, pyloric gland mucin MUC6, while MUC1 is almost exclusively expressed by high grade PanINs lesions. Among fluid-filled types of precancerous pancreatic lesions, IPMNs are the most common lesions. IPMNs vary in their location and size within the pancreas size, and these two features correlate with how dangerous they are. Because they can be detected by imaging procedures, it is possible to detect them before they become cancer. They are most often detected in patients who are routinely monitored due to a high familial risk, or incidentally in people who were imaged for another reason. Those lesions belong to group of the heterogeneous group of cystic pancreatic lesions because papillary epithelial proliferation and mucin production lead to cystic dilatation of involved ducts. SPECIJALNA SESIJA: KATEDRA ZA PATOLOGIJU MEDICINSKOG FAKULTETA, UNIVERZITETA NOVI SAD, SRBIJA 29 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. Those lesions are slightly more common in the head and uncinate process (55%) compared with the body and the tail of the pancreas and about 30% of them are multifocal. IPMNs are subdivided into main duct IPMN (MD-IPMN) which are localized in the main pancreatic duct and measured ≥5 mm, while the other branch duct type (BD-IPMN) is >5 mm in diameter andcommunicates with the main pancreatic duct but it is uninvolved by the process. Mixed IPMN combines both types. Microscopically, the lining epithelial component is represented by tall mucin producing columnar cells but lack the “ovarian-type” seen in mucinous cystic neoplasms. Like PanINs, IPMNs are graded on the basis of the greatest degree of dysplasia into low grade, moderate and high grade dysplasia or carcinoma in situ and IPMN with associated invasive carcinoma. Many studies have showed that approximately one-third of patients with IPMN are associated with invasive carcinoma, so precise basement membrane micro analysis is an imperative. Accordingly to their histological characteristics there are intestinal, pancreatobiliary, oncocytic and gastric subtype of IPMN with different immunohistochemical profiles. Intestinal-type IPMN is characterized by tall columnar cells with elongated nuclei and amphophilic cytoplasm and MUC2, MUC5AC, MUC4 and CDX-2 positivity. In contrast, pancreatobiliary subtype of IPMN is characterised by branched papillae with high grade intraepithelial neoplasms and MUC1 And MUC5AC immuno positivity. The third are oncocytic type, predominantly occurs in main duct and presented with a complex branched papillary structures covered by oncocytic cells mixed with goblet cells and mucin-containing cells. This type shows diffuse positivity for MUC5AC, MUC6 and focal positivity for MUC1 or MUC2. The gastric subtype is low grade lesions mainly found in branched ducts and characterised by papillae covered by foveolar glandular epithelium with MUC5AC and sometimes MUC6 positivity. The last and the most infrequent type of pre-cancerous pancreatic lesions are MCNs. The principle difference between IPMNs and MCNs is how they look under a microscope, and how they behave in the patient. These cystic lesions are almost solitary, typically located in the pancreatic body and tail. Grossly, this lesion can grow very large, it is usually septated and with fibrous pseudocapsule often with calcifications. Histologically, the epithelium og noninvasive MCN is consisted of columnar cells with varying degree of dysplasia (low grade, moderate and high grade dysplasia) and underlying ovarian-like stroma. Immunohistochemically, thode epithelial cells are EMA, CEA, MUC5AC, MUC2, cytokeratins 7, 8/18 and 19 positive, while the underlying ovarian-like stroma shows ER, PR, vimentin and SMA immune reactivity. Precancerous lesions of the pancreas are important changes whose visualization and detection in a significant number would reduce the incidence of pancreatic cancer and, consequently, the mortality of this highly aggressive neoplasm with an unfavorable therapy outcome.

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