Cystic Lesions of the Pancreas

Residents Section Pattern of the Month w668 04.29.11 Khan et al. Residents Section Pattern of the Month Residents inradiology tif Khan 1 Faisal Khosa Ronald L. Eisenberg Khan, Khosa F, Eisenberg RL Keywords: CT, cystic lesions, MRI, pancreas DOI:10.2214/JR.10.4378 Received February 2, 2010; accepted after revision October 27, 2010. 1 ll authors: Department of Radiology, eth Israel Deaconess Medical Center, Harvard Medical School, 330 rookline ve, oston, M 02115. ddress correspondence to R. L. Eisenberg (rleisenb@bidmc.harvard.edu). WE This is a Web exclusive article. JR 2011; 196:W668 W677 0361 803X/11/1966 W668 merican Roentgen Ray Society C ystic lesions of the pancreas are a diverse group of lesions, ranging from benign processes to invasive malignant tumors, and often can be morphologically differentiated on CT and MRI on the basis of characteristic features. This is important because a precise diagnosis determines the treatment and surgical approach. Pancreatic cysts can be morphologically classified into four categories: 1. Unilocular cysts (cysts without septation or a solid component) pancreatic pseudocyst, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystadenoma. Pseudocyst and IPMN are the two most common entities in this category, but there are other possibilities, such as oligocystic serous cystadenoma, lymphoepithelial cyst, and cystic islet cell neoplasm. 2. Microcystic lesions (collection of microcysts) serous cystadenoma. 3. Macrocystic lesions (multilocular cysts with fewer compartments, each > 2 cm) mucinous cystadenoma, IPMN, and lymphoepithelial cyst. 4. Cysts with solid components, i.e., mucinous cystic neoplasm (mucinous cystadenoma and mucinous cystadenocarcinoma) IPMN, solid and papillary epithelial neoplasm, and solid neoplasms that may show cystic degeneration (adenocarcinoma and islet cell tumors). The demographics and distinguishing features of most common pancreatic cystic tumors are listed in Table 1. In general cystic lesions are hypodense on unenhanced CT unless there are hemorrhagic, proteinaceous, or mucinous components when the density is determined by the relative amounts of the various components. On contrast-enhanced CT, the enhancement characteristics also vary depending on the type of lesion. In an uncomplicated case, the cystic components are hypodense and do not enhance. If hemorrhage is present, the lesion may be hyperdense, isodense, or hypodense depending on the type of blood products. Similarly, uncomplicated cystic lesions on MRI show low signal intensity relative to normal pancreatic parenchyma on unenhanced T1-weighted sequences and high signal intensity on T2-weighted images, although this also can vary if there are hemorrhagic, proteinaceous, or mucinous components within these lesions. On contrast-enhanced MRI, the enhancement characteristics also vary depending on the type of lesion. The most common cystic lesions of the pancreas seen on imaging are pseudocysts, serous cystadenoma, mucin-containing lesions (IPMN, mucinous cystadenoma, or cystadenocarcinoma), and solid papillary epithelial neoplasm. Other rare pancreatic cystic lesions include true epithelial cysts, cystic islet cell tumors, and adenocarcinoma with cystic degeneration. Pseudocyst Overall, pseudocysts are the most common cystic lesions of the pancreas. pancreatic pseudocyst is a sharply marginated unilocular or multilocular fluid-filled structure that is often best delineated after contrast administration. These pancreatic or peripancreatic collections are encapsulated by fibrous tissue and usually form after inflammation, necrosis, or hemorrhage related to acute pancreatitis or trauma. There are no vascularized or enhancing soft-tissue elements within uncomplicated pseudocysts. In acute pancreatitis, there usually is associated mesenteric edema and peripancreatic stranding, whereas in chronic pancreatitis, there may be associated pancreatic parenchymal calcifications. Older cysts tend to have thicker walls that may contain calcium. The primary mimic of a pseudocyst is mucinous cystadenoma, and there may be significant overlap of imaging features between these two entities. In such cases, the patient history may be helpful. If not, then serial follow-up imaging is useful W668 JR:196, June 2011

TLE 1: Imaging and Demographic Features of Most Common Pancreatic Cystic Tumors Lesion Features Occurrence ge (y) Sex ffected Pseudocyst Unilocular or multilocular, associated with pancreatitis, ny age oth located anywhere in or along the pancreas Serous cystadenoma Central scar with calcification is a characteristic appearance, > 60 Women microcystic and commonly located in the pancreatic head, smooth lobulated contour, minimal wall enhancement Mucinous cystic neoplasm Unilocular or multilocular, septated cystic lesion, usually 50 Women located in the body and tail of pancreas, distinguishing pathologic feature is surrounding ovarian type stroma Intraductal papillary mucinous neoplasm Classified according to whether the disease process involves 40 Men more than women the main pancreatic duct, isolated side branches, or a combination of both; these communicate with the pancreatic ductal system Solid and papillary epithelial neoplasm Heterogeneous appearance with mixed cystic and solid components, can undergo hemorrhagic degeneration and shows progressive accumulation of contrast agent, usually located in the tail 35 Exclusively women because pancreatic pseudocysts often evolve over short intervals whereas mucinous cystadenoma often persists without a significant interval change. These cysts can be located anywhere within the pancreas but predominantly involve the body or tail of the organ. Unenhanced CT usually shows a pancreatic pseudocyst as a round or oval hypodense lesion. If the pseudocyst contains hemorrhage, it appears as areas of increased attenuation within the lesion. On contrast-enhanced CT, the wall of a pseudocyst enhances but not the fluid within it (Fig. 1). ecause of its ability to image the entire body, CT may show pseudocysts that have dissected superiorly to the mediastinum or to other ectopic locations, such as the lumbar or inguinal region. pseudocyst appears hyperintense on T2-weighted sequences and has homogeneous bright internal signal intensity, a characteristic feature that confirms that the lesion is a fluidfilled structure (Fig. 2). On unenhanced T1-weighted MR images, the lesion is hypointense unless it contains hemorrhagic elements that are hyperintense. On contrast-enhanced T1- weighted images, the fibrous capsule may show contrast enhancement (Fig. 2). Serous Cystadenoma Serous cystadenomas are benign cystic neoplasms of the pancreas that occur frequently in older women. They are composed of numerous small cysts, typically < 1 cm, which are conjoined in a honeycomb-like pattern. The cysts are lined by glycogen-rich epithelium and separated by fibrous septa that radiate from a central scar, which may be calcified. These lesions have a slight predominance for the pancreatic head and are often diagnosed incidentally. These lesions, instead of invading surrounding structures, usually displace adjacent organs. trophy of pancreatic tissue and dilatation of pancreatic and biliary ducts proximal to the lesion are uncommon. Serous cystadenomas occur frequently in von-hippel-lindau disease. On CT, a serous cystadenoma commonly has a lobular shape and appears hypodense on unenhanced scans because of its water density nature (Fig. 3). The fibrous portion of the lesion enhances after contrast administration. Calcified areas usually appear hyperdense and are generally arranged in a characteristic stellate pattern in the center of the lesion (Fig. 4). The characteristic spongelike or irregular honeycomb appearance is seen Fig. 1 CT of pancreatic pseudocyst. xial contrastenhanced CT image of abdomen shows homogeneously low-density nonenhancing cystic collection (arrows) in pancreatic tail in patient with prior episode of acute pancreatitis. JR:196, June 2011 W669

Khan et al. Fig. 2 MRI of pancreatic pseudocyst., xial T2-weighted HSTE image shows homogeneously hyperintense cystic lesion (arrows) in pancreatic tail., Dynamic T1-weighted contrast-enhanced liver acquisition with volume acceleration (LV) (GE Healthcare) image shows nonenhancing homogeneously hypointense lesion (arrows) in pancreatic tail, consistent with uncomplicated pancreatic pseudocyst. Fig. 3 CT of serous cystadenoma. and, xial () and coronal () contrast-enhanced CT images show serous cystadenoma (arrow, ) at junction of head and body of pancreas with classic appearance of lobulated outline, fine internal septation, lack of vascular encasement, and central scar (best depicted on coronal image). Fig. 4 CT of serous cystadenoma. and, xial () and coronal () contrast-enhanced CT images show serous cystadenoma in pancreatic head with classic appearance of lobulated outline, fine internal septation, lack of vascular encasement, and calcification in central scar (arrows). in only 20% of cases. In general, the appearance of a serous microcystic adenoma depends on the number of fibrous septa and their degree of enhancement. Tumors with less fibrous septation may continue to have attenuation equal to that of fluid even after contrast administration. The presence of large numbers of microcysts may produce a solid appearance with increased contrast enhancement on CT, but the finding of a cluster of small fluid-containing cysts at MRI is usually diagnostic. W670 JR:196, June 2011

Fig. 5 MRI of serous cystadenoma., Heavily T2-weighted coronal thick slab MRCP image shows high-signal-intensity lesion (arrows) at junction of head and body of pancreas (cluster of small cysts). Internal septation is best depicted on MRCP image (also incidental hepatic cysts)., Dynamic delayed coronal reconstruction image after gadolinium injection shows that lesion (arrow) has homogeneous low signal with rim enhancement and contains fine enhancing internal septations. t MRI, a serous cystadenoma appears as a cluster of small cysts on T2-weighted images. The cystic components of a serous cystadenoma are hyperintense, and the fibrous elements are hypointense (Fig. 5). There is no visible communication between the cysts and the pancreatic duct. On unenhanced T1-weighted images, the cystic portions of the tumor are hypointense, although prior hemorrhage within the lesion can make it appear hyperintense. The fibrous components are hypointense on all unenhanced sequences. fter contrast administration, enhancement of the fibrous elements may be detected on early and late imaging, with persistent enhancement of the central scar on delayed dynamic imaging (Fig. 5). Calcification appears hypointense on both T1- and T2-weighted sequences. The high sensitivity of MRI in detecting fluid makes this modality of special importance in diagnosing tumors with small microcysts. The visualization of four of the following five CT and MRI features has been reported to aid in making the diagnosis of serous cystadenoma: location in the pancreatic head, wall thickness < 2 mm, lobulated contour, lack of communication with the pancreatic duct, and minimal wall enhancement. Mucinous Cystadenoma Mucinous cystadenoma is rare, comprising 2.5% of exocrine tumors of the pancreas. They vary from benign slow-growing cystic adenomas (67%) to aggressive and invasive mucinous cystadenocarcinomas (33%). These cystic lesions often have thickened walls that are lined with mucin-producing columnar epithelium. The distinguishing pathologic feature is the presence of surrounding ovarian-type stroma similar to that seen in biliary cystadenomas. Unlike IPMNs, mucinous cystadenomas do not communicate with the pancreatic ductal system. ecause benign tumors can transform into invasive carcinomas at any time, all mucinous cystic tumors are considered surgical lesions. Most (> 95%) mucinous cystadenomas have been found in women and typically involve the body and tail of the pancreas. They frequently are clinically silent and can therefore attain sizes greater than 10 cm before becoming palpable. On CT, mucinous cystadenomas are well-defined smooth lesions that are hypodense to surrounding pancreatic parenchyma (Fig. 6). The cystic contents have fluid density. Contrastenhanced scans show enhancement of the cyst wall and accentuate any septations and mural nodules. The presence of mural nodules or septal thickening and calcification strongly suggests a malignant lesion. Distal to the tumor, the pancreas may show such changes of chronic pancreatitis as atrophy, duct dilatation, coarse calcification, and areas of decreased enhancement, although such changes are not specific for mucinous neoplasms. It is essential to search for evidence of local invasion to surrounding organs. t MRI, a mucinous cystadenoma commonly manifests as a unilocular or minimally septated cystic lesion. lthough the cyst fluid is typically mucin filled, the most common MRI JR:196, June 2011 W671

Khan et al. Fig. 6 CT of mucinous cystadenoma. xial contrastenhanced CT image shows well-circumscribed nonenhancing low-density lesion (arrows) in distal body tail of pancreas. characteristics are those of simple fluid, with homogeneous high signal intensity on T2- weighted images (Fig. 7) and homogeneous low signal intensity on unenhanced T1- weighted images (Fig. 7). fter contrast administration, the cyst wall, septations, and areas of nodularity may become apparent (Fig. 7C). lthough not a specific finding; concomitant obstructive pancreatitis may show atrophic changes in the gland, with compensatory ductal dilatation and areas of decreased signal intensity on fat-saturated unenhanced T1-weighted images that show heterogeneous enhancement on delayed contrast-enhanced images. Calcification, when present, appears hypointense on all sequences. s with CT, the presence of mural nodules or septal thickening and calcification strongly suggests a malignant lesion. When invasive or enhancing nodular components are present in a mucinous cyst with a surrounding ovarian-type stroma, the lesion is a mucinous cystadenocarcinoma (Fig. 8). Mural nodules and septa are better depicted with MRI, whereas calcification is better depicted with CT. Intraductal Papillary Mucinous Neoplasm IPMN is a mucin-producing tumor of the pancreas that is clinically and histopathologically distinct from mucinous cystadenoma. These are most frequently seen in men (mean age, 60 years) and are characterized by mucinous transformation of the pancreatic ductal epithelium. IPMNs can be classified according to whether the disease process involves the main pancreatic duct, isolated side branches, or a combination of both. They may also be characterized according to whether they produce a diffuse pattern of ductal dilatation or a segmental cystic appearance. The location of the tumor is very important for the prognosis. Main duct IPMNs are highly likely to have malignant transformation (70%), whereas approximately Fig. 7 MRI of mucinous cystadenoma., xial fat-suppressed T2-weighted image shows well-circumscribed hyperintense lesion (arrows) in distal body tail of pancreas that does not show communication with pancreatic duct. and C, Mass (arrows) has low signal intensity on unenhanced T1-weighted image () and does not show internal complexity or enhancement after contrast administration (C). On contrast-enhanced image, there is subtle delayed enhancement of surrounding wall. C W672 JR:196, June 2011

15 20% of side-branch lesions show foci of malignancy according to the surgical literature. lthough diffuse ductal dilatation may also be seen in cases of advanced chronic pancreatitis, there are almost always associated pancreatic parenchymal changes, i.e., atrophy, loss of lobulated contour and loss of inherent T1 hyperintensity of pancreatic parenchyma, or delayed uptake of contrast agent due to fibrosis. IPMN varies from a slow-growing localized lesion to an invasive and metastatic tumor. It typically occurs in older patients and is more common in men. The imaging diagnosis of IPMN depends on identifying the relationship of the lesion to the pancreatic duct, especially in the case of side-branch types. These tumors dilate the affected side branch with mucin, producing the appearance of a pleomorphic cystic pancreatic mass that communicates with the main duct. This communication is a key feature in the diagnosis of IPMN on radiologic imaging because other neoplastic cystic lesions (mucinous cystadenoma and serous cystadenoma) may have an otherwise similar appearance. On CT, a side-branch IPMN typically appears as a hypodense nonenhancing pleomorphic lesion. It is classically located in the uncinate process and in close relation to a nondilated main pancreatic duct. Multiplanar reformatted images show communication between the lesion and the duct that may not be well visualized on axial images. Main pancreatic duct lesions can be classified depending on whether they produce diffuse or segmental duct dilatation. On contrast-enhanced CT scans, any internal enhancing elements may also be seen. MRCP has shown significant promise as a noninvasive technique for providing multiplanar perspectives of the pancreatic ductal system (Fig. 9). Main pancreatic duct IPMN produces dilatation of the entire duct without a discrete intraductal obstructing lesion. Sidebranch lesions have a pleomorphic appearance and are hyperintense on T2-weighted sequences and hypointense on unenhanced T1-weighted images. The overall relation between a side- Fig. 8 MRI of mucinous cystadenocarcinoma., xial fat-suppressed T2-weighted image shows well-circumscribed hyperintense mass in distal body tail of pancreas that does not show communication with pancreatic duct. Mass has subtle area of low signal intensity within it (arrow). and C, Mass shows homogeneous low signal intensity (arrow, ) on unenhanced T1-weighted image () and enhancing nodule (arrow, C) after contrast administration (C). Fig. 9 Intraductal papillary mucinous neoplasm. Heavily T2-weighted thick-slab MRCP image shows innumerable cystic lesions (arrows) within pancreatic parenchyma, which are connected to otherwise unremarkable main pancreatic duct. C JR:196, June 2011 W673

Khan et al. Fig. 10 Side-branching intraductal papillary mucinous neoplasm. xial HSTE image shows pancreatic tail lesion (arrows) as unilocular cyst in communication with pancreatic ducts. Fig. 11 Solid and papillary epithelial neoplasm. xial contrast-enhanced CT image shows 10-cm hypovascular, well-circumscribed mass in body and tail of pancreas (arrow) with internal branching papillae (arrowhead). branch IPMN and the main pancreatic duct is best visualized on MRCP; the nodular components and degree of wall thickening are best appreciated on contrast-enhanced images (Fig. 10). Findings worrisome for malignancy in an IPMN include enhancing solid components, involvement of the main pancreatic duct, main pancreatic duct dilatation of more than 10 mm, size of more than 3.5 cm, and extension beyond the gland. Solid and Papillary Epithelial Neoplasm Solid and papillary epithelial neoplasm is a rare tumor that usually occurs in the tail of the pancreas. It occurs exclusively in young women (mean age, 35 years) and primarily in those of frican and sian descent. Solid and papillary epithelial neoplasm is usually a benign or a low-grade malignant tumor with a slow growth pattern; it is generally asymptomatic and may be diagnosed as an incidental finding. s the lesion progresses, it may produce a mass effect on the surrounding structures but does not invade them. On CT, solid and papillary epithelial neoplasm appears as a large encapsulated mass with cystic and solid components. Cystic components are secondary to tumor degeneration. The solid tissue elements are situated peripherally, with central areas of hemorrhage and cystic degeneration with internal branching papillae (Fig. 11). The solid components and capsule enhance after contrast administration. MRI shows solid and papillary epithelial neoplasm as a well-defined mass that most commonly has a heterogeneous appearance due to hemorrhage and necrosis on both T1- and T2- weighted sequences. reas of intratumoral hemorrhage are hyperintense on unenhanced T1- weighted images and hypointense on T2-weighted scans. n important diagnostic feature of solid and papillary epithelial neoplasm is the presence of a hypointense fibrous capsule, which most probably develops as a reaction to the expansile tumor. The enhancement pattern shows a gradual accumulation of contrast agent within the tumor, differentiating it from neuroendocrine tumors which show early arterial enhancement. True Epithelial Cyst true epithelial cyst of the pancreas appears on CT as a single small fluid-filled structure with an imperceptible wall. The cyst contains no internal septa and shows no contrast enhancement. There is strong association between true epithelial cysts of the pancreas and von Hippel-Lindau disease, in which multiple unilocular cysts are scattered throughout a healthy pancreas on contrastenhanced CT scans. MRI shows a unilocular lesion that is hyperintense on T2-weighted sequences (Fig. 12), is hypointense on T1-weighted sequences, and shows no internal complexity or enhancement. The lesion is without internal septations and does not communicate with the pancreatic duct. Cystic Neuroendocrine Tumors Cystic neuroendocrine tumors are an uncommon subset of pancreatic neuroendocrine neoplasm. They most often occur in adults and have no sex predilection. enign cystic degeneration is rare in neuroendocrine neoplasms; most cyst formation within these lesions is secondary to tumor degeneration (Figs. 13 and 13). Identification of a cystic neuroendocrine tumor is W674 JR:196, June 2011

challenging and relies on identifying the highly vascularized soft-tissue components. Correlation with clinical history is essential because these neoplasms are more frequent in patients with multiple endocrine neoplasia syndrome. On CT and MRI, the diagnosis of cystic neuroendocrine tumor may be suggested by a rim of highly vascularized tissue that shows avid enhancement in the early arterial phase, a feature that correlates with the histologic finding of neoplastic neuroendocrine cells lining the periphery of the cyst (Figs. 13C and 13D). Fig. 12 Epithelial cyst. xial HSTE image shows well-circumscribed lesion (circle) in body of pancreas that appears hyperintense without internal complexity and does not communicate with pancreatic duct. Ductal denocarcinoma With Cystic Degeneration Ductal adenocarcinoma is the most dreaded cancer of the pancreas, with high morbidity and mortality. Depending on its location, this tumor presents as an infiltrative lesion with resultant obstruction of the pancreatic duct (Fig. 14), common bile duct, or both. Ductal carcinoma may also invade the surrounding vasculature (Fig. 14). The tumor is predominantly solid, but cystic degeneration is a rare imaging presentation (Fig. 14). On CT and MRI, pancreatic ductal adenocarcinoma appears as a hypovascular infiltrative soft-tissue mass (Fig. 14C). Complex cystic areas representing internal tumor necrosis or side-branch ductal obstruction may be seen. The tumor usually causes vascular invasion and pancreatic ductal obstruction at an early stage and thus is well depicted on cross-sectional imaging. Miscellaneous Neoplasms Other pancreatic neoplasms may manifest as cysts containing a solid component, solid tumors associated with a cystic component, or cystic degeneration. These include metastasis, cystic teratoma, sarcoma, hemangioma, lymphangioma, and paraganglioma. C D Fig. 13 MRI of cystic islet cell tumor. and, xial T2-weighted image () and heavily T2-weighted, thick-slab MRCP image () show well-circumscribed hyperintense lesion (arrows) in body of pancreas that does not show communication with pancreatic duct. C and D, Lesion has low signal intensity on unenhanced T1-weighted image (C) and shows avid rim enhancement (arrow) in early arterial phase image (D). JR:196, June 2011 W675

Khan et al. Fig. 14 CT of adenocarcinoma with cystic degeneration., xial contrast-enhanced CT image shows infiltrative lesion in head of pancreas (arrows) involving superior mesenteric artery and superior mesenteric vein. There is also obstructed dilated pancreatic duct (arrowhead). and C, xial T2-weighted () and contrastenhanced T1-weighted (C) images show infiltrative hypoenhancing mass (arrows) with internal cystic components that are T2 hyperintense. rrowhead indicates obstructed dilated pancreatic duct. Management Cystic pancreatic lesions comprise a wide range of benign and malignant pathologic entities; many of these have specific features that are well visualized by cross-sectional imaging. oth CT and MRI allow optimal evaluation of internal architecture and enhancement characteristics of these lesions. The decision to follow rather than resect a pancreatic lesion is a matter of clinical judgment on the basis of the age of the patient, comorbidities, and estimation of the cancer risk in the lesion. Ideally, the imaging modality at baseline and follow-up should provide adequate information regarding the size of the lesion and the main pancreatic duct as well as the presence of intramural nodules. These criteria can be assessed satisfactorily by using noninvasive imaging studies, such as CT or MRI, or by more invasive tests, such as endoscopic ultrasound. The management of benign and low-grade malignant tumors (serous cystadenoma and solid and papillary epithelial neoplasm, respectively) depends on the clinical symptoms. If detected incidentally in an asymptomatic patient, the lesion can be followed with imaging at intervals that vary according to institutional protocol. When the lesion is symptomatic or diagnosis is in question, surgical resection is undertaken. Mucinous lesions (mucinous cystadenoma and IPMN) have malignant potential. ccording to international guidelines, the estimated risk of prevalence of invasive cancer is 30% in symptomatic side-branch IPMN and 0 5% in asymptomatic lesions. On the basis of limited available data from multiple studies, it appears that there is a low risk of near-term progression to invasive cancer in asymptomatic cystic lesions without main duct dilatation (> 6 mm) and without mural nodules and those < 30 mm. The interval between follow-up examinations for these lesions remains to be determined. However, until definitive studies are performed to answer this question, it would appear reasonable to do yearly follow-up if the lesion is < 10 mm; 6- or 12-month follow-up for lesions between 10 and 20 mm; and 3- or 6-month followup for lesions > 20 mm. On follow-up studies, indications for resection include the development of symptoms attributable to the cyst (e.g., pancreatitis), presence of intramural nodules, cyst size > 30 mm, and dilation of the main pancreatic duct (> 6 mm). fter 2 years of stability, the follow-up interval may be lengthened. Patients with branch duct IPMN who are symptomatic should be treated with resection, not only to alleviate the symptoms but also because of a higher likelihood of malignancy. It is important to emphasize that the decision to treat should be individualized on the basis of patient preference and willingness to undergo followup studies. Unless there are contraindications to surgery, all mucinous cystic lesions should be resected. C W676 JR:196, June 2011

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