Pancreas Ductal Adenocarcinoma and its Mimics: Review of Cross-sectional Imaging Findings for Differential Diagnosis

Ductal adenocarcinoma is the most common pancreatic neoplasm. A variety of pancreatic lesions mimic pancreas ductal adenocarcinoma (PDAC), such as high-grade neuroendocrine tumors, small solid pseudopapillary tumors, metastases, focal autoimmune pancreatitis, and groove pancreatitis. These occasionally look similar in images, but they have differential diagnosis points. Familiarity with the imaging features of PDAC and its mimics is paramount for correct diagnosis and management of patients. In this essay, we describe imaging findings of PDAC and its mimics for differential diagnosis.


Introduction
Pancreas ductal adenocarcinoma (PDAC) accounts for 85-90% of all pancreatic neoplasms and is one of the leading causes of death worldwide [1,2]. Various other tumors and inflammatory lesions in the pancreas occasionally mimic PDAC. It is clinically important to differentiate PDAC from other pancreatic lesions because of different prognosis and treatment options [3][4][5]. PDAC commonly involves various major vessels around the pancreas and frequently accompanies distant metastases. As a result, less than 20% of patients with PDAC are eligible for resection at the time of diagnosis [6]. On the other hand, patients with neuroendocrine tumors (NETs) or solid pseudopapillary tumors (SPTs) are usually good candidates for surgical resection and show better prognosis than those with PDAC [3,7]. Moreover, most inflammatory lesions do not need surgical resection but rather conservative treatment [8,9]. Therefore, the objective of this article is to assist in differential diagnosis by describing imaging features of PDAC and its mimics.

Imaging Features of PDAC
Computed tomography (CT) is a useful modality for detecting and staging PDACs [10]. PDACs usually appear as low attenuating masses in the pancreatic and portal venous phases and typically accompany pancreatic duct dilatation with abrupt narrowing (Figures 1A, 1B, and 2A). Bile duct dilatation is occasionally combined with a dilated pancreatic duct in cases of pancreas head cancer; this is called the double duct sign ( Figure 1B) [11]. Vascular invasion is important for diagnosing PDAC and determining therapeutic options and is supposed when there is a vascular caliber change, irregular vessel wall, more than 180° of vessel is in contact with the tumor, or peritumoral fat infiltration is identified (Figures 1A, 2B, and 2C) [12,13]. Liver metastases from PDAC usually show hypovascularity ( Figure 2D).

High-grade neuroendocrine tumors
Pancreatic NETs originate from the islet cells of Langerhans and are divided into low-, intermediate-, and high-grade according to the World Health Organization classification [5]. High-grade NETs more frequently show vascular invasion, lymph node metastasis, and diffusion restriction compared with low-grade; therefore, highgrade NETs can mimic PDAC on images ( Figure 3A) [7,14,15]. However, high-grade NETs usually do not show pancreatic duct dilatation. In addition, they occasionally accompany tumor thrombus, which can be helpful in the differential diagnosis of high-grade NETs from PDAC ( Figure 3C) [16]. Liver metastases from NETs frequently reveal findings of hypervascularity and intralesional hemorrhage, in contrast to those from PDAC, which reveal hypovascularity ( Figure 3B and 3D) [17,18].

Small (≤3 cm) solid pseudopapillary tumors
SPTs are uncommon neoplasms with low malignancy potential, occurring predominantly in young women [3,19]. Calcification, cystic change, and internal hemorrhage due to weak vascular channels are characteristic features of SPT [20,21]. However, small (≤3 cm) SPTs show different imaging findings from larger ones, primarily a homogeneous nature. Small SPTs show a pure solid consistency, well-defined margin, and diffusion restriction on magnetic resonance (MR) imaging ( Figure 4A-D) [22,23]. After contrast infusion, small SPTs reveal an early heterogeneous nature, followed by a progressive enhancement pattern ( Figure 4E and 4F) [22,23].

Metastases
A previous study [24] reported that up to 11% of patients with malignancy have pancreatic metastases at autopsy. In patients with another malignancy who have pancreatic mass, lack of pancreatic duct dilatation usually suggests that pancreatic metastases are more likely than PDAC ( Figure 5) [25]. However, pancreatic ductal involvement can unfortunately occur in some pancreatic metastases. In those cases, the absence of adjacent vascular invasion may be a clue for differentiation of metastases from PDAC [24,26].

Focal autoimmune pancreatitis
Autoimmune pancreatitis (AIP) is an uncommon form of chronic pancreatitis caused by an autoimmune mechanism [27]. It is a challenge to distinguish focal AIP from PDAC because the two diseases show similar imaging    features, but several reports [28][29][30][31] have offered suggestions for discriminating between them. According to those studies, slightly lower or similar signal intensity compared with the spleen on unenhanced T1-weighted images, relatively homogeneous enhancement, signs of pancreatic duct penetration, smooth tapered narrowing of the pancreatic duct (icicle sign) or bile duct, multifocal stricture of the pancreatic duct, and a delayed enhancement pattern on dynamic enhanced images are features favoring AIP over PDAC (Figure 6). Another clue for diagnosis of AIP is involvement of an extra-pancreatic organ such as the biliary tree, retroperitoneum, salivary gland, or kidney (Figure 7) [8].

Groove pancreatitis
Groove pancreatitis is an uncommon type of pancreatitis affecting the pancreaticoduodenal groove, defined as the potential space between the pancreatic head, com-    mon bile duct, and duodenum [32]. This inflammatory lesion commonly develops in middle-aged men with a history of chronic alcoholism [32]. On imaging, groove pancreatitis presents as an ill-defined lesion between the pancreatic head and the duodenum, sometimes with bile and pancreatic duct narrowing; therefore, it can mimic PDAC (Figure 8) [9,25,33]. However, groove pancreatitis reveals a sheet-like curvilinear appearance and delayed enhancement. In addition, it is accompanied by cystic dystrophy in the duodenal wall and smooth bile duct narrowing ( Figure 8D) [9,33].

Conclusion
Neoplastic lesions such as high-grade NETs, small SPTs, and metastases and inflammatory lesions including focal AIP and groove pancreatitis can mimic PDAC. Abrupt narrowing of a dilated pancreatic duct is a usual imaging finding of PDAC. Although some mimics occasionally accompany pancreatic duct dilatation, they have points of differential diagnosis: presence of tumor thrombus and hypervascular liver metastases, absence of adjacent vascular invasion, and delayed enhancement pattern. In addition to these imaging findings, the shape of the narrowed pancreatic duct is a key imaging feature for discrimination of PDAC from other disease entities. Familiarity with the imaging features of PDAC and its mimics is paramount for managing patients in daily practice.

Funding Information
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. This work was supported by the Soonchunhyang University Research Fund.