I n t e g r a t i ve I m a g i n g P i c t o r i a l E s s ay

Coakley et al. Mimics of Pancreatic Adenocarcinoma Integrative Imaging Pictorial Essay

CME SAM

Pancreatic Imaging Mimics

Pancreatic Imaging Mimics: Part 1, Imaging Mimics of Pancreatic Adenocarcinoma

OBJECTIVE. The purpose of this article is to describe the imaging features of diseases that may closely simulate pancreatic adenocarcinoma, either radiologically or pathologically. CONCLUSION. Neoplastic and inflammatory diseases that can closely simulate pancreatic adenocarcinoma include neuroendocrine tumor, metastasis to the pancreas, lymphoma, groove pancreatitis, autoimmune pancreatitis, and focal chronic pancreatitis. Atypical imaging findings that should suggest diagnoses other than adenocarcinoma include the absence of significant duct dilatation, incidental detection, hypervascularity, large size (> 5 cm), IV tumor thrombus, and intralesional ducts or cysts. he accurate diagnosis of pancreatic adenocarcinoma is of critical importance, because the disease has a high mortality and its treatment has substantial morbidity. Several lines of evidence suggest that misdiagnosis, either radiologically or pathologically, may be relatively common. Published false-negative rates for the pathologic misdiagnoses of pancreatic adenocarcinoma range from 1.6% to 30% [1]. In a study of 25 patients who survived more than 5 years after surgical resection for adenocarcinoma, 13 failed to show the typical pathologic characteristics of adenocarcinoma on retrospective analysis [2]. In a series of 186 patients diagnosed with adenocarcinoma who underwent resection, 12 had their diagnosis changed on further pathologic review [2]. The American Cancer Society 5-year survival rate of 6% is discordant with the much lower 5-year survival rate of 1.8% reported at Memorial Sloan-Kettering Cancer Center, where the histologic diagnosis might be less subject to error [2, 3]. Anecdotally, we have encountered several patients said to have pancreatic adenocarcinoma on the basis of erroneous radiologic or histopathologic interpretations in whom atypical imaging findings were critical in establishing the correct diagnosis. These considerations suggest that the diagnosis of pancreatic cancer should be treated more like breast cancer, with multidisciplinary involvement of both radiologists and pathologists to review cases of discordance or uncertainty.

Fergus V. Coakley 1 Katryana Hanley-Knutson John Mongan Ramon Barajas Matthew Bucknor Aliya Qayyum
Coakley FV, Hanley-Knutson K, Mongan J, Barajas R, Bucknor M, Qayyum A

FOCUS ON:

The purpose of this pictorial essay is to describe the imaging features of diseases that may closely simulate pancreatic adenocarcinoma, either radiologically or pathologically. Neoplastic Mimics of Pancreatic Adenocarcinoma Neuroendocrine Tumors Pancreatic neuroendocrine tumors account for 5% of pancreatic tumors and may be associated with von HippelLindau disease, neurofibromatosis-1, tuberous sclerosis, and multiple endocrine neoplasia type 1 syndrome. The 5-year survival rate of 81% for pancreatic neuroendocrine tumor [4] is significantly higher than that for pancreatic adenocarcinoma. On CT or MRI, pancreatic neuroendocrine tumor most commonly presents as a hypervascular mass of variable size, best seen on early arterial phase imaging. Unlike adenocarcinoma, such tumors are often wellcircumscribed and duct obstruction is uncommon [5] (Fig. 1). Duct obstruction, when present, appears to be a feature of small welldifferentiated serotonin-producing tumors and may reflect the local fibrogenic effect of serotonin [6] (Fig. 2). They are often larger than adenocarcinomas, and IV tumor thrombus may be seen [7] (Fig. 3). Liver metastases may be present; findings that suggest metastases from neuroendocrine tumor rather than adenocarcinoma include hypervascularity, T2 hyperintensity, large size, intralesional hemorrhage or necrosis, or positive somatostatin receptor scintigraphy [8].

Keywords: CT, imaging mimics, pancreatic adenocarcinoma DOI:10.2214/AJR.11.7907 Received September 6, 2011; accepted after revision February 15, 2012. J. Mongan was supported by the National Institutes of Biomedical Imaging and Bioengineering (T32 training grant 1 T32 EB001631).
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All authors: Department of Radiology, University of California San Francisco, Box 0628, M-372, 505 Parnassus Ave, San Francisco, CA 94143-0628. Address correspondence to F. V. Coakley (Fergus.Coakley@radiology.ucsf.edu).

CME/SAM This article is available for SAM/CME credit. AJR 2012; 199:301308 0361803X/12/1992301 American Roentgen Ray Society

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Coakley et al. Metastasis to the Pancreas Metastases to the pancreas are relatively uncommon, but the pancreas is a recognized site of spread for both renal cell and lung cancer. Renal cell cancer is the single most common primary site in cases of metastases to the pancreas, accounting for 30% of such lesions, but they are usually hypervascular at CT and so are unlikely to be confused with pancreatic adenocarcinoma, which is generally hypovascular [9]. In addition, the diagnosis of renal cell cancer is usually clear because of changes related to prior nephrectomy or ablation. Interestingly, in a recent MRI study, 50% of renal cell carcinoma metastases to the pancreas were found to be hypovascular on MRI [10]. Lung cancer is the second most common primary site in cases of metastases to the pancreas, accounting for 23% of such lesions, and these tumors are frequently hypovascular. The finding of a hypovascular pancreatic head mass without significant biliary or pancreatic duct dilatation should prompt consideration of metastasis from a primary bronchogenic carcinoma, and imaging of the chest may be useful (Figs. 47). Metastases to the pancreas are often well circumscribed, another finding that would be atypical for primary pancreatic adenocarcinoma [10]. Pancreatic Lymphoma Primary pancreatic lymphoma accounts for less than 0.5% of pancreatic masses but can potentially be cured, which is one reason why it is important to diagnose correctly [11]. Primary pancreatic lymphoma is often bulky and encases the vasculature but does not occlude it. Ductal dilatation and cystic changes are rare [12] (Figs. 8 and 9). Adenocarcinoma Arising in Intraductal Papillary Mucinous Neoplasm Adenocarcinoma arising in the setting of intraductal papillary mucinous neoplasm may not strictly constitute an imaging mimic of de novo adenocarcinoma, because both represent primary epithelial malignancy of the pancreas, but invasive cancer derived from intraductal papillary mucinous neoplasm has a 5-year survival rate of 34%, compared with 9% for standard adenocarcinoma [13], and the radiologic appearances are distinctive. As such, a brief description of the cross-sectional findings appears appropriate in this essay. The natural history and frequency of malignant degeneration in intraductal papillary mucinous neoplasms are not well established, but it is known that cancer arises more frequently in the main duct than in branch duct intraductal papillary mucinous neoplasms [14]. A main pancreatic duct diameter of over 6 mm, a mural nodule greater than 3 mm in size, or abnormal attenuation in the adjacent pancreatic parenchyma suggest malignancy in main duct intraductal papillary mucinous neoplasm (Figs. 10 and 11). Solid nodules, thick enhancing walls or septations, a connection more than 1 cm in diameter between a dilated side branch and the main pancreatic duct, or a tumor larger than 3 cm suggest malignancy in branch duct intraductal papillary mucinous neoplasm. Inflammatory Pseudotumors Groove Pancreatitis This condition is a form of focal chronic pancreatitis that often occurs in the groove between the pancreatic head, common bile duct, and the duodenum and is most commonly seen in middle-aged alcoholic men [15]. Groove pancreatitis presents as a poorly enhancing mass on CT or MRI. Unlike adenocarcinoma, ductal dilatation is uncommon, and small intralesional ducts or cysts may be present [16] and are often best appreciated on MRI. Imaging changes related to cystic dystrophy in the duodenal wall, which likely reflect a duodenal response to chronic or repeated inflammation, may be superimposed [17]. Autoimmune Pancreatitis Autoimmune pancreatitis, also known as lymphoplasmacytic (sclerosing) pancreatitis, is often associated with other autoimmune conditions [18]. On CT, autoimmune pancreatitis presents with either diffuse or focal enlargement that is isodense or slightly hypodense, most commonly in the head of the pancreas. There may be irregular wall thickening, narrowing of the main pancreatic duct, peripancreatic stranding (halo sign), and enhancement of the gallbladder and common bile duct [18] (Fig. 12). Extrapancreatic abnormalities associated with IgG4-related systemic disease may be seen, including salivary gland uptake on PET, retroperitoneal fibrosis, periaortitis, inflammatory renal pseudotumors, and autoimmune cholangiopathy. In addition to these extrapancreatic features, the lack of pancreatic duct dilatation is a key feature that distinguishes autoimmune pancreatitis from adenocarcinoma. Focal Chronic Pancreatitis Focal chronic pancreatitis is most commonly related to alcohol abuse. On imaging, chronic pancreatitis may present with pancreatic tail atrophy and ductal dilatation (Fig. 13). Focal parenchymal sparing may mimic a mass. Contrast-enhanced power Doppler ultrasound and diffusion-weighted MRI may provide help in differentiating the two entities, with greater enhancement and apparent diffusion coefficient values seen in adenocarcinoma [19, 20]. The visualization of an unobstructed main pancreatic duct penetrating a pancreatic mass has been reported as a useful sign that favors the diagnosis of an inflammatory pseudotumor over pancreatic adenocarcinoma [21]. Conclusion Neoplastic and inflammatory diseases that can simulate pancreatic adenocarcinoma include neuroendocrine tumor, metastasis to the pancreas, lymphoma, groove pancreatitis, autoimmune pancreatitis, and focal chronic pancreatitis. Atypical findings that should suggest diagnoses other than adenocarcinoma include the absence of significant duct dilatation, incidental detection, hypervascularity, large size (> 5 cm), venous invasion, and intralesional ducts or cysts. References
1. Bellizzi AM, Frankel WL. Pancreatic pathology: a practical review. Lab Med 2009; 40:417426 2. Conlon KC, Dougherty E, Klimstra DS, Coit DG, Turnbull AD, Brennan MF. The value of minimal access surgery in the staging of patients with potentially resectable peripancreatic malignancy. Ann Surg 1996; 223:134140 3. American Cancer Society. Cancer facts & figures 2010. Atlanta, GA: American Cancer Society, 2010 4. Sarmiento JM, Farnell MB, Que FG, et al. Pancreaticoduodenectomy for islet cell tumors of the head of the pancreas: long-term survival analysis. World J Surg 2002; 26:12671271 5. Sheth S, Hruban RK, Fishman EK. Helical CT of islet cell tumors of the pancreas: typical and atypical manifestations. AJR 2002; 179:725730 6. Kawamoto S, Shi C, Hruban RH, et al. Small serotonin-producing neuroendocrine tumor of the pancreas associated with pancreatic duct obstruction. AJR 2011; 197:663; [web]W482W488 7. Rockall AG, Reznek RH. Imaging of neuroendocrine tumours (CT/MR/US). Best Pract Res Clin Endocrinol Metab 2007; 21:4368 8. Debray MP, Geoffroy O, Laissy JP, et al. Imaging appearances of metastases from neuroendocrine tumours of the pancreas. Br J Radiol 2001; 74:10651070 9. Klein KA, Stephens DH, Welch TJ. CT characteristics of metastatic disease of the pancreas. RadioGraphics 1998; 18:369378

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10. Takeuchi M, Matsuzaki K, Kubo H, Nishitani H. High-b-value diffusion-weighted magnetic resonance imaging of pancreatic cancer and massforming chronic pancreatitis: preliminary results. Acta Radiol 2008; 49:383386 11. Grimison PS, Chin MT, Harrison ML, Goldstein D. Primary pancreatic lymphoma: pancreatic tumours that are potentially curable without resectiona retrospective review of four cases. BMC Cancer 2006; 6:117 12. Jayanthi V, Randhir J, Rajesh N. Problems in diagnosing lymphoma of the pancreas with computed tomography: a case report. J Gastrointestin Liver Dis 2007; 16:101103 13. Woo SM, Ryu JK, Lee SH, et al. Survival and prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas: comparison with pancreatic ductal adenocarcinoma. Pancreas 2008; 36:5055 14. Pedrosa I, Boparai D. Imaging considerations in intraductal papillary mucinous neoplasms of the pancreas. World J Gastrointest Surg 2010; 2:324330 15. Itoh S, Yamakawa K, Shimamoto K, Endo T, Ishigaki T. CT findings in groove pancreatitis: correlation with histopathological findings. J Comput Assist Tomogr 1994; 18:911915 16. Thomas H, Marriott P, Portmann B, Heaton N, Rela M. Cystic dystrophy in heterotopic pancreas: a rare indication for pancreaticoduodenectomy. Hepatobiliary Pancreat Dis Int 2009; 8:215217 17. Blasbalg R, Baroni RH, Costa DN, Machado MCC. MRI features of groove pancreatitis. AJR 2007; 189:7380 18. Sahani DV, Sainani NI, Deshpande V, Shaikh MS, Frinkelberg DL, Fernandez-del Castillo C. Autoimmune pancreatitis: disease evolution, staging, response assessment, and CT features that predict response to corticosteroid therapy. Radiology 2009; 250:118129 19. Scialpi M, Di Maggio A, Midiri M, Loperfido A, Angelelli G, Rotondo A. Small renal masses: assessment of lesion characterization and vascularity on dynamic contrast-enhanced MR imaging with fat suppression. AJR 2000; 175:751757 20. Scialpi M, Midiri M, Bartolotta TV, et al. Pancreatic carcinoma versus chronic focal pancreatitis: contrast-enhanced power Doppler ultrasonography findings. Abdom Imaging 2005; 30:222227 21. Ichikawa T, Sou H, Araki T, et al. Duct-penetrating sign at MRCP: usefulness for differentiating inflammatory pancreatic mass from pancreatic carcinomas. Radiology 2001; 221:107116 22. Coakley FV. Pitfalls and pseudotumors in abdominal imaging. In: Kruskal J, Anderson S, Soto J, eds. 2012 Categorical course: pitfalls in clinical imaging. Leesburg, VA: American Roentgen Ray Society, 2012

Fig. 167-year-old man with vague abdominal discomfort. Axial contrastenhanced CT image shows hypervascular mass (arrow) in head of pancreas. No biliary or pancreatic ductal dilatation was present (not shown). Resection confirmed diagnosis of neuroendocrine tumor.

Fig. 245-year-old woman with intermittent nausea and vomiting. Axial curved planar reformatted image through pancreas shows isodense pancreatic mass (white arrows) with associated upstream pancreatic atrophy and ductal dilatation (black arrow). Tumor was positive at somatostatin scintigraphy, and resection confirmed well-differentiated pancreatic neuroendocrine tumor. Duct-obstructive pancreatic neuroendocrine tumor appears to reflect serotonin production, causing local fibrosis and stricturing.

Fig. 377-year-old man with newly diagnosed myasthenia gravis. Axial contrastenhanced CT image shows infiltrative mass (arrow) in pancreatic tail, with tumor thrombus extending into splenic vein. CT-guided biopsy of mass performed at outside institution was interpreted as showing adenocarcinoma. Patient remained alive and well without treatment 18 months later. This clinical course was considered discordant with initial biopsy result. Biopsy was repeated at our institution and revealed neuroendocrine tumor.

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Fig. 455-year-old woman with abdominal pain, weight loss, and 84 pack-year smoking history. A, Axial curved planar reformatted contrast-enhanced CT image shows ill-defined 3-cm mass (arrow) in pancreatic head. Absent biliary and minimal pancreatic ductal dilatation is atypical for pancreatic adenocarcinoma, suggesting alternative diagnosis such as lung cancer metastatic to pancreas. Chest CT was suggested. B, Axial contrast-enhanced chest CT image shows 2-cm spiculated mass (arrow) in left upper lobe. Biopsy confirmed diagnosis of nonsmall cell lung cancer.

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Fig. 547-year-old woman who presented with epigastric pain and vomiting. A, Axial curved planar reformatted contrast-enhanced CT image shows 4-cm low-attenuating heterogeneous rim enhancing mass (white arrow) in junction of head and body of pancreas. Additional lesions are present in pancreatic tail (vertical black arrow) and right paraspinal musculature (horizontal black arrow). Pancreatic duct is mildly dilated. B, Coronal enhanced curved planar reformatted CT image shows absence of biliary dilatation. This should raise suspicion of diagnosis other than pancreatic adenocarcinoma. This patient was subsequently diagnosed with metastatic nonsmall cell lung cancer to pancreas. (Reprinted from [22]).

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Fig. 670-year-old man. A, Axial curved planar reformatted contrast-enhanced CT image shows 1.5-cm low-attenuating pancreatic head mass (arrow) with minimal pancreatic ductal dilatation. Lack of marked ductal dilatation suggests diagnosis other than adenocarcinoma. (Fig. 6 continues on next page)

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Fig. 6 (continued)70-year-old man. B, Axial abdominal ultrasound image shows that pancreatic head mass (arrow) is echogenic. C, Axial fused image from 18F-FDG PET/CT scan shows pancreatic head mass is intensely FDG-avid. D, Axial image from FDG PET scan shows intensely FDG-avid primary lung cancer and intramuscular metastasis. Diagnosis of metastatic small cell lung cancer was confirmed histologically. (Reprinted from [22]).

Fig. 750-year-old man with abdominal pain and 75 pack-year smoking history. A, Axial curved planar reformatted contrast-enhanced CT image shows that large 6-cm pancreatic head mass (arrow) is not associated with biliary dilatation. Large size and lack of biliary duct dilatation suggests that pancreatic mass is not primary pancreatic adenocarcinoma. B, Axial CT image of chest shows large right perihilar mass, and diagnosis of small cell lung cancer was confirmed histopathologically.

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Fig. 850-year-old man 2 years after liver transplant for hepatitis Brelated cirrhosis. A, Axial curved planar reformatted contrast-enhanced CT image. Low-density 5-cm pancreatic head mass (arrow) is not associated with biliary dilatation, making adenocarcinoma less likely diagnosis. Fine-needle aspiration was done on mass and interpreted as pancreatic adenocarcinoma. Six cycles of chemotherapy were administered, and mass resolved. Surgical exploration and repeat biopsy showed no evidence of adenocarcinoma. According to atypical surgical and imaging findings, final presumptive clinical diagnosis of posttransplant lymphoproliferative disorder was made. B, Coronal CT image shows mass (arrow) is not causing biliary dilatation. (Reprinted from [22]).

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Fig. 968-year-old woman with recurrent epigastric pain, weight loss, and elevated lipase levels. A, Axial contrast-enhanced CT image shows mass (arrow) in pancreatic head associated with circumferential wall thickening of descending duodenum. Other images (not shown) showed absence of biliary dilatation. Initial radiologic diagnosis of pancreatic adenocarcinoma was suggested. Patient was referred to our institution for possible resection, where large size and lack of biliary dilatation were considered to be atypical for pancreatic adenocarcinoma. Biopsy was performed and revealed lymphoma. B, Axial T1-weighted gadolinium-enhanced fat-saturated image shows mass (arrow) is hypovascular. C, Axial single-shot rapid acquisition with refocused echoes T2-weighted image shows mass (arrow) is of intermediate T2 signal intensity. (Fig. 9 continues on next page)

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Fig. 9 (continued)68-year-old woman with recurrent epigastric pain, weight loss, and elevated lipase levels. D, Transverse abdominal ultrasound image shows mass (arrow) is heterogeneously hypoechoic.

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Fig. 1077-year-old man with painless jaundice. A, Axial contrast-enhanced CT image shows moderate biliary dilatation and gross pancreatic duct dilatation (arrow). Latter suggests main duct intraductal papillary mucinous neoplasm. B, Axial contrast-enhanced CT image shows large intracystic solid nodule (arrow) in dilated main pancreatic duct, consistent with malignancy arising in main duct intraductal papillary mucinous neoplasm. Diagnosis was confirmed at surgery. (Reprinted from [22]).

Fig. 1156-year-old man with history of alcohol abuse. Axial curved planar reformatted contrast-enhanced CT image shows infiltrative hypodense 3-cm mass (arrow) in pancreatic head. Fine-needle biopsy was initially interpreted as adenocarcinoma, and patient received four cycles of chemotherapy. Of note, mass was detected incidentally at CT performed for ureteral colic. No significant pancreatic or biliary ductal dilatation is present, and small intralesional cysts are visible. After recognition of these atypical imaging features, cytologic reinterpretation was requested and established final diagnosis of groove pancreatitis.

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Fig. 1277-year-old man who presented with pneumonia and weight loss and was found to have serum CA-19-9 level of 325 U/mL (normal, < 36 U/mL), prompting presumptive clinical diagnosis of adenocarcinoma. A, Axial curved planar reformatted CT image shows diffusely enlarged pancreas. However, no discrete mass is visible. Hypodense capsule or peripancreatic halo (area between arrows) is present, and no biliary or pancreatic ductal dilatation is seen. B, Axial image from 18F-FDG PET/CT scan shows diffusely FDG-avid pancreas. Constellation of incidental detection, peripancreatic halo, absence of duct dilatation, and diffuse uptake of FDG on PET were considered highly suggestive of autoimmune pancreatitis. Steroids were administered and peripancreatic halo resolved on follow-up, which was clinically considered as confirming diagnosis of autoimmune pancreatitis. Fig. 1357-year-old man with recurrent epigastric pain and history of heavy alcohol use. On axial curved planar reformatted contrast-enhanced CT image, marked dilatation of pancreatic duct can be traced to level of hypovascular mass (arrow) in pancreatic head. No biliary dilatation was seen. Biopsy of mass was interpreted as adenocarcinoma. Patient remained alive and well 3 years later. Specimen was reexamined and reinterpreted as showing inflammatory cells only, and mass was ultimately considered most likely due to focal chronic pancreatitis.

F O R YO U R I N F O R M AT I O N

This article is part of a self-assessment module (SAM). Please also refer to Pancreatic Imaging Mimics: Part 2, Pancreatic Neuroendocrine Tumors and Their Mimics, which can be found on page 309. Each SAM is composed of two journal articles along with questions, solutions, and references, which can be found online. You can access the two articles at www.ajronline.org, and the questions and solutions that comprise the Self-Assessment Module by logging on to www.arrs.org, clicking on AJR (in the blue Publications box), clicking on the article name, and adding the article to the cart and proceeding through the checkout process. The American Roentgen Ray Society is pleased to present these SAMs as part of its commitment to lifelong learning for radiologists. Continuing medical education (CME) and SAM credits are available in each issue of the AJR and are free to ARRS members. Not a member? Call 1-866-940-2777 (from the U.S. or Canada) or 703-729-3353 to speak to an ARRS membership specialist and begin enjoying the benefits of ARRS membership today!

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