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Pancreas ductal adenocarcinoma with cystic features on cross-sectional imaging: radiologic-pathologic correlation.

Pancreatic ductal adenocarcinoma (PDA) accounts for 90% of all pancreatic neoplasms and is the fourth leading cause of cancer-related death in the western world (1). PDA typically presents as an infiltrative hypovascular solid mass, frequently associated with pancreatic and/or common bile duct obstruction and local vascular invasion (2). However, PDAs may demonstrate intratumoral cystic features or accompany peritumoral non-neoplastic cystic lesions (2-5). Depending on histopathologic types of PDAs with cystic features, PDAs may mimic various types of cystic neoplasms on imaging. Therefore, radiologists should be aware of pathologic background and corresponding imaging findings of PDAs with cystic features. In this review, imaging findings and differential diagnosis of each pathologic type of PDA with cystic features are discussed.

Classification of PDAs with cystic features based on histopathologic types

There are several different histopathologic types of the cystic changes associated with PDAs (2-5). Cystic features of PDAs are largely divided into neoplastic cysts and non-neoplastic cysts. Neoplastic cystic changes include large-duct type cysts, neoplastic mucin cysts, and colloid carcinomas formed by neoplastic glands themselves and degenerative cystic changes usually caused by hemorrhagic necrosis of tumor. Non-neoplastic cystic changes include retention cysts caused by ductal obstruction and pseudocysts caused by tumor-associated pancreatitis.

Neoplastic cysts

PDAs with large-duct type cysts

Pathologically, conventional PDAs are composed of small, irregular shaped ductal elements infiltrating the desmoplastic stroma (6). Large-duct type is one of the morphologic variations of PDAs, which is characterized by more dilated malignant ducts forming a microcystic feature (3). The pathologic criteria are as follows: more than 50% of tumor sections available for examination contain infiltrative ducts with a diameter >5 mm or have macroscopically identifiable microcystic pattern (7). With these criteria, large-duct type ductal adenocarcinomas account for 7% of ductal adenocarcinomas in a review of 230 pancreatectomy specimens (7). Large-duct type PDAs manifest as a predominantly solid tumor with several small intratumoral cysts on imaging (Figs. 1, 2). The size of cysts is small, usually 0.5-0.7 cm in diameter, occasionally exceeding 1 cm (3, 4). Although rare, multiple small intratumoral cysts of large-duct type can show honeycomb-like appearance on cross-sectional images (Fig. 2) (8). PDA with cystic structures showing honeycomb-appearance may be mistaken with serous cystadenoma (Fig. 3) or branch duct type intraductal papillary mucinous neoplasm (IPMN) (2).

PDAs with neoplastic mucin cysts

Yoon et al. (4) proposed neoplastic mucin cyst as a new classification of intratumoral cystic lesion of PDA. Both neoplastic mucin cysts and large-duct cysts are lined by mucin-producing neoplastic cells. The difference between neoplastic mucin cysts and large-duct type cysts is the size of cyst and the amount of mucin secretion (5). The size of large-duct type cysts is small, usually <1 cm, but the size of neoplastic mucin cysts can be large, up to 7 cm. Neoplastic mucin cysts in PDAs (Fig. 4) have smooth margin and they are usually solitary, but occasionally a few cysts are seen (4).

PDA with neoplastic mucin cyst should be distinguished from IPMN with an associated invasive carcinoma. When a solid mass in the pancreatic parenchyma surrounding the dilated ducts appears, IPMN progressing to invasive carcinoma should be considered (9). PDA with neoplastic mucin cyst differs from invasive carcinoma of IPMN (Fig. 5), because neoplastic mucin cyst does not appear around a solid mass but within a solid mass (4).

Colloid carcinomas

According to the World Health Organization classification of pancreatic tumors, colloid carcinoma, also known as mucinous noncystic adenocarcinoma is a histologic variant of PDA, accounting for 1%-3% (5, 10). Colloid carcinoma is not a true cystic tumor, but this tumor shows predominantly cystic appearance on imaging due to abundant mucin. Pathologically, colloid carcinoma is defined as an infiltrating ductal epithelial neoplasm of pancreas characterized by the presence, in at least 50% of the neoplasm, of abundant extracellular stromal mucin pools and a scant amount of neoplastic cells floating in the center (5, 10). As the mucin pool acts as a physical barrier, colloid carcinoma has better prognosis than ordinary PDA (10).

Colloid carcinomas of the pancreas show poorly enhancing low attenuated mass on contrast-enhanced computed tomography (CT) and very high signal intensity on T2-weighted magnetic resonance imaging (MRI) due to abundant extracellular mucinous components (Fig. 6). On dynamic contrast-enhanced imaging, the colloid carcinomas show central poorly enhancing mucin pools with gradual peripheral and internal mesh-like enhancement of the intervening stroma (10).

Colloid carcinoma can be confused with mucinous cystic neoplasm (MCN) or IPMN with invasive carcinomas due to its predominantly cystic imaging features. MCN with an associated invasive carcinoma manifests as a large unilocular or septated cystic lesion with intracystic enhancing soft tissue (Figs. 7, 8). In contrast, colloid carcinomas show lobulated contours, indistinct margin and gradual internal enhancement. Intraductal papillary component, dilatation of the downstream pancreatic duct, or spillage of mucin from the ampulla of Vater at endoscopic retrograde cholangiopancreatography are the features of IPMNs, but not of colloid carcinomas (11).

PDAs with degenerative cystic changes

Pathologically, degenerative cystic change is formed by tumor necrosis containing necrotic and hemorrhagic tissue in the cavity. Degenerative cystic cavities in PDAs are usually characterized by a large solitary intratumoral cystic lesion with irregular margin and central location of the tumor (Fig. 9) (3, 4). The incidence of degenerative cystic change is increased in larger tumors, and most tumors tend to have a high proliferation rate and be classified as moderately or poorly differentiated adenocarcinomas (3, 12).

PDAs with degenerative cystic change should be differentiated from other pancreatic tumors with intratumoral cystic degeneration such as solid-pseudopapillary neoplasm and cystic neuroendocrine tumor (4). Solid pseudopapillary neoplasm is usually seen as a large well-defined predominantly solid mass with cystic components of variable size in young women. Well-circumscribed tumor margin and homogeneously enhancing soft-tissue components are clues to differentiate solid pseudopapillary neoplasms from PDA. Pancreatic neuroendocrine tumor (Fig. 10) is typically seen as a well-circumscribed hypervascular solid tumor, with cystic components reported in 17% (11). The solid component of neuroendocrine tumor shows intense arterial enhancement, which helps to differentiate neuroendocrine tumor from PDA.

Non-neoplastic cysts

PDAs with retention cysts

Obstruction of pancreatic duct by tumor may result in the formation of retention cysts in PDAs (8). Due to its mechanism of formation, retention cyst is located at the tumor periphery, not inside the tumor. Pathologically, retention cysts are lined by normal flat ductal epithelium without atypia (3). On CT or MRI, retention cysts have smooth margins and are located outside of the tumor in the pancreas (Figs. 11, 12). The cysts are usually unilocular and small (0.5-1.5 cm), but can be large, up to 10 cm. When a cyst suspected to be a retention cyst is observed, it is important to ensure carefully whether obstruction of the pancreatic duct is caused by a stone, stricture, or duct-obstructing tumor (13). Careful evaluation of the peripheral portion of the cyst may reveal poorly enhancing ductal adenocarcinoma near the retention cyst (Figs. 11, 12).

PDAs with attached pseudocysts

Idiopathic pancreatitis can be an initial presentation of pancreatic adenocarcinoma (14, 15). Tumor-related pancreatitis can occur by ductal obstruction due to PDA, which may result in pseudocyst formation. Histopathologically, pseudocyst is lined by necrotic tissue with hemorrhagic material and turbid fluid, which is surrounded by inflammatory tissue. Pseudocysts are usually unilocular and always located outside of the tumor or even outside of the pancreas on CT and MRI (Fig. 13). Pseudocysts are often irregularly marginated in the early stage of their formation, but gradually become well-defined with a thick enhancing wall formed by granulation tissue and a fibrous capsule over time. Internal blood products and necrotic debris are commonly noted as high signal intensity on T1-weighted images (11).

When acute pancreatitis occurs concurrently with PDA, overlapping clinical findings and confusing imaging findings often delay correct diagnosis and treatment. If there are no predisposing factors for acute pancreatitis in old-aged patients, hidden PDA should be considered in the differential diagnosis of pseudocyst.

Summary of imaging features

Depending on the histopathologic types of cystic features, PDAs demonstrate differences in number, size, location and margin of cysts on cross-sectional images (Fig. 14). Large-duct type cysts usually represent as several small cysts, while neoplastic mucin cysts, colloid carcinomas, and degenerative necrotic cysts usually present as a single cyst. Large-duct type cysts and neoplastic mucin cysts are characterized by well-defined margins. Colloid carcinomas and degenerative necrotic cysts are characterized by ill-defined margins. Retention cysts and pseudocysts are located outside the tumor and can be of variable sizes. Pseudocysts may even be located outside the pancreas.


Depending on the histopathologic types of cystic features, PDAs demonstrate different imaging findings. PDAs with large-duct type cyst usually show a predominantly solid tumor with several small intratumoral cysts. PDAs with neoplastic mucin cyst or colloid carcinoma may mimic mucinous cystic neoplasm or IPMN with an associated invasive carcinoma. PDAs with degenerative cystic change should be differentiated from solid pseudopapillary tumor and cystic neuroendocrine tumor. Combined retention cyst or pseudocyst may delay the diagnosis of PDA, because a small poorly enhancing solid tumor can be masked by the large cystic lesion. The radiologists should be aware that PDAs can show cystic features on imaging and PDA must be considered in the differential diagnosis of cystic pancreatic lesions.

Conflict of interest disclosure

The authors declared no conflicts of interest.


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Seo Yeon Youn

Sung Eun Rha

Eun Sun Jung

In Seok Lee

From the Departments of Radiology (S.Y.Y., S.E.R. [??], Hospital Pathology (E.S.J.), Internal Medicine (I.S.L.), Hepato-Biliary-Pancreatic Cancer Center (S.E.R., E.S.J., I.S.L.), Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea; Cancer Research Institute (S.E.R., E.S.J., I.S.L.), The Catholic University of Korea College of Medicine, Seoul, South Korea.

ORCID iDs of the authors: S.Y.Y. 0000-0002-7692-3413; S.E.R. 0000-0003-1514-929X; E.S.J. 0000-0002-8451-939X; I.S.L. 0000-0002-1127-1522.

Main points

* Pancreatic ductal adenocarcinomas (PDAs) may show intratumoral neoplastic cystic features or accompany peritumoral non-neoplastic cystic lesions, mimicking cystic pancreatic tumors.

* Neoplastic cystic changes include large-duct type cysts, neoplastic mucin cysts, colloid carcinomas and degenerative cystic cavities.

* Non-neoplastic cystic changes include retention cysts caused by ductal obstruction and pseudocysts caused by tumor-related pancreatitis.

* Depending on the histopathologic type of cystic features, PDAs may demonstrate different imaging findings in the number, size, location and margin of cysts on cross-sectional imaging.

Received 16 June 2017; revision requested 28 August 2017; last revision received 23 September 2017; accepted 28 October 2017.

DOI 10.5152/dir.2018.17250
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Title Annotation:PICTORIAL ESSAY
Author:Youn, Seo Yeon; Rha, Sung Eun; Jung, Eun Sun; Lee, In Seok
Publication:Diagnostic and Interventional Radiology
Article Type:Essay
Date:Jan 1, 2018
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