**2. Classification**

#### **2.1. Anatomic classification: involvement of the pancreatic ductal system**

Most IPMN arise from the pancreatic main duct or its branch ducts (**Figure 1**). Most of these tumors are unifocal, 20–30% are multifocal, and 5–10% of the IPMN diffusely affect the entire duct system of the pancreas. Depending on the involvement of the pancreatic duct, IPMNs are classified as either main duct IPMN (MD-IPMN) or branch duct IPMN (BD-IPMN). If both, main and branch ducts are involved together, then it is defined as combined-type IPMN (**Figure 2**). The clinical pathologic behavior of combined-type IPMN is similar to that of MD-IPMN. MD-IPMN is frequently more associated with this malignant transformation than is BD-IPMN, requiring surgical resection in more than a half of the patients, while most patients with BD-IPMN can be observed for a long time after the diagnosis.

**Figure 1.** Types of IPMN: MD-IPMN, BD-IPMN, mixed type-IPMN. Modified from: Bliss D (Illustrator) 2001. Pancreas, Duodenum, and Small Intestine [image]. Available at: https://visualsonline.cancer.gov/details.cfm?imageid=4364.

**Figure 2.** Differences between MD-IPMN and BD-IPMN.

#### **2.2. Histologic classification: IPMN subtype**

Biomarkers represent an interesting opportunity, but until they can be used on a regular clinical basis, we are obliged to say knowledgeable on new insights involving radiologic characteristics and potential malignancy prior to deciding, which is the best available indi-

Most IPMN arise from the pancreatic main duct or its branch ducts (**Figure 1**). Most of these tumors are unifocal, 20–30% are multifocal, and 5–10% of the IPMN diffusely affect the entire duct system of the pancreas. Depending on the involvement of the pancreatic duct, IPMNs are classified as either main duct IPMN (MD-IPMN) or branch duct IPMN (BD-IPMN). If both, main and branch ducts are involved together, then it is defined as combined-type IPMN (**Figure 2**). The clinical pathologic behavior of combined-type IPMN is similar to that of MD-IPMN. MD-IPMN is frequently more associated with this malignant transformation than is BD-IPMN, requiring surgical resection in more than a half of the patients, while most patients with BD-IPMN can be observed for a long time after the

**Figure 1.** Types of IPMN: MD-IPMN, BD-IPMN, mixed type-IPMN. Modified from: Bliss D (Illustrator) 2001. Pancreas, Duodenum, and Small Intestine [image]. Available at: https://visualsonline.cancer.gov/details.cfm?imageid=4364.

**2.1. Anatomic classification: involvement of the pancreatic ductal system**

vidualized option for each patient.

**Figure 2.** Differences between MD-IPMN and BD-IPMN.

**2. Classification**

72 Challenges in Pancreatic Pathology

diagnosis.

Immunohistochemical staining with mucin antibodies enables differentiation between tumors with different prognoses. Four subtypes of IPMNs have been characterized: gastric, intestinal, pancreatobiliary, and oncocytic. Most of BD-IPMNs are composed of gastric-type epithelium. However, intestinal type is more common in MD-IPMN. In a recent report, the four subtypes of IPMNs were associated with significant differences in survival. Patients with gastric-type IPMN had the best prognosis, whereas those with intestinal and pancreatobiliary type had a bad prognosis [1–6].

#### **2.3. World Health Organization (WHO)**

The World Health Organization (WHO) classified IPMNs into three subgroups according to degree of dysplasia: (I) IPMN with low- or intermediate-grade dysplasia; (II) IPMN with highgrade dysplasia (carcinoma in situ); and (III) IPMN with an associated invasive carcinoma. IPMN associated with PDAC (pancreatic ductal adenocarcinoma arising in association with an IPMN) was further classified into two subtypes: tubular adenocarcinoma, composed of predominantly gland-forming neoplastic cells with fibrotic stroma and absence of significant extracellular stromal mucin and colloid carcinoma (mucinous noncystic carcinoma), composed of sparsely populated strips, clusters, or individual neoplastic cells residing within extensive pools of extracellular mucin [6]. In case of IPMN with low- to intermediate-grade of dysplasia, dysplastic changes in the columnar cells are minimal or absent. The prognosis is usually favorable [7].
