Pancreatic Imaging Mimics: Part 2, Pancreatic Neuroendocrine Tumors and Their Mimics

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1 Integrative Imaging Pictorial Essay Raman et al. Mimics of Pancreatic Neuroendocrine Tumors Integrative Imaging Pictorial Essay CME SM Pancreatic Imaging Mimics Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved FOCUS ON: Siva P. Raman 1 Ralph H. Hruban 2 John L. Cameron 3 Christopher L. Wolfgang 3 Elliot K. Fishman 1 Raman SP, Hruban RH, Cameron JL, Wolfgang CL, Fishman EK Keywords: CT, islet cell tumor, neuroendocrine tumor, pancreas DOI: /JR Received January 26, 2012; accepted after revision February 23, Department of Radiology, Johns Hopkins University, JHOC 3251, 601 N Caroline St, altimore, MD ddress correspondence to S. P. Raman (srsraman3@gmail.com). 2 Johns Hopkins Medical Institutions, Johns Hopkins University, altimore, MD. 3 Department of Surgery, Johns Hopkins Hospital, altimore, MD. CME/SM This article is available for SM/CME credit. JR 2012; 199: X/12/ merican Roentgen Ray Society Pancreatic Imaging Mimics: Part 2, Pancreatic Neuroendocrine Tumors and Their Mimics OJECTIVE. This pictorial essay reviews the imaging appearance of pancreatic neuroendocrine tumors, as well as a number of mimics on CT. CONCLUSION. Pancreatic neuroendocrine tumors have a distinct appearance, typically characterized by a well-defined hypervascular mass best visualized on arterial phase images. However, a number of other lesions can mimic the CT appearance of pancreatic neuroendocrine tumors, including pancreatic metastases, acinar cell carcinoma, pancreatoblastoma, solitary fibrous tumor, pancreatic hamartoma, serous adenoma, intrapancreatic splenules, exophytic gastrointestinal stromal tumors, and peripancreatic paragangliomas. T he appearance of pancreatic neuroendocrine tumors is relatively distinct, characterized by their hypervascularity and conspicuity on arterial phase images. s CT technology has improved over the last decade, it has become increasingly common to incidentally discover hypervascular lesions in the pancreas, which overwhelmingly represent small pancreatic neuroendocrine tumors. lthough these small lesions are usually nonfunctional and nonaggressive in their behavior, they are increasingly resulting in surgical resection [1]. However, we have encountered a number of incidentally discovered hypervascular lesions in and around the pancreas that can mimic the CT appearance of pancreatic neuroendocrine tumors (Table 1). lthough a prospective diagnosis is not always possible, knowledge of these entities is important, because certain imaging features can rarely allow an alternative diagnosis when confronted with an incidentally discovered hypervascular pancreatic mass. Pancreatic Neuroendocrine Tumors Pancreatic neuroendocrine tumors (i.e., islet cell tumors) are pancreatic masses composed of well-differentiated endocrine cells (which normally compose < 5% of the pancreas). lthough these tumors were once classified as functioning or nonfunctioning, it is now understood that all pancreatic neuroendocrine tumors secrete hormones (e.g., insulin, glucagon, vasoactive intestinal peptide, gastrin, or somatostatin) to some degree. Neu- roendocrine tumors can be either sporadic or associated with a number of different syndromes, including multiple endocrine neoplasia type 1, von Hippel Lindau syndrome, and tuberous sclerosis [2]. The behavior of these tumors can range from benign to malignant (a differentiation that is difficult to make on the basis of histologic analysis), with the best predictor of aggressive behavior or distant metastatic disease being tumor size. Neuroendocrine tumors usually appear as a solid avidly enhancing mass that can arise in any portion of the pancreas. These neoplasms are usually intraparenchymal and are typically best seen in the arterial phase of enhancement, because smaller lesions can be very difficult to visualize on venous or delayed imaging (Fig. 1). However, a few atypical appearances of neuroendocrine tumors have also been described, including masses that are pedunculated or exophytic from the pancreatic parenchyma and lesions that are better visualized on the portal venous phase images compared with the arterial phase [3]. In rare cases, islet cell tumors can be cystic or centrally necrotic in appearance (Fig. 1). Classically, because these lesions do not arise from the pancreatic ductal epithelium, pancreatic ductal obstruction and dilatation have not been considered typical features of neuroendocrine tumors, except in those cases with very large masses that obstruct the duct secondary to mass effect. However, it has become increasingly clear that even small neuroendocrine tumors can produce JR:199, ugust

2 Raman et al. Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved ductal obstruction, ductal dilatation, and upstream pancreatic atrophy. It is thought that these small tumors secrete serotonin and other related metabolites, which cause fibrotic stricturing of the main pancreatic duct [4]. Those tumors that are associated with clinical findings and appreciably elevated hormone levels ( functioning ) tend to be small (< 3 cm), whereas those unassociated with symptoms ( nonfunctioning ) tend to be appreciably larger and more heterogeneous [2]. Pancreatic Metastases Metastases to the pancreas are rare (2 4% of pancreatic masses), with the most common tumors including renal cell carcinoma, melanoma, sarcoma, colon cancer, lung cancer, and breast cancer [5]. lthough most metastases occur within a few years of initial presentation, renal cell carcinoma is known for metastasizing to the pancreas as long as 20 years after initial presentation [6]. The appearance of most pancreatic metastases is not particularly specific, although renal cell carcinoma metastases are usually highly vascular and can resemble neuroendocrine tumors [6] (Figs. 2 and 3). In these cases, a history of a primary malignancy (particularly renal cell carcinoma) should strongly raise the possibility of a pancreatic metastasis. Peripancreatic Gastrointestinal Stromal Tumor Gastrointestinal stromal tumors are submucosal neoplasms found throughout the gastrointestinal tract but most commonly are in the stomach. When found in the proximal small bowel, they are most common in the second portion of the duodenum [7]. lthough originating from the submucosal layer of the bowel, these lesions can grow outward exophytically from the stomach or duodenum toward the pancreas, making distinction from a primary pancreatic mass very difficult. Moreover, these masses can show avid enhancement on arterial phase imaging and can become necrotic and cystic in appearance as they grow larger, features that can be very suggestive of a pancreatic neuroendocrine tumor (Figs. 4 and 5). ccurate diagnosis is contingent on identifying a fat plane between the mass and the pancreas and delineating the neoplasm s origin from the adjacent stomach or bowel [7]. Peripancreatic Paraganglioma Paragangliomas are neuroendocrine tumors arising from the chromaffin cells of the autonomic nervous system. These tumors typical present in young and middle-aged adults, and patients with a retroperitoneal paraganglioma do not usually present with symptoms due to hormone secretion but more typically present with abdominal pain. Up to 33% of these lesions are malignant, eventually developing metastatic disease [8]. In some cases (< 25 cases in the extant literature), retroperitoneal paragangliomas arise in close proximity to the pancreas, making differentiation from a primary pancreatic lesion very difficult. Moreover, like other paragangliomas, peripancreatic paragangliomas tend to be hypervascular and avidly enhancing, sometimes showing internal heterogeneity and necrosis when large [8] (Figs. 6 8). However, when a fat plane is identified between the mass and the adjacent pancreas, this diagnosis can be suggested. cinar Cell Carcinoma n uncommon tumor of the pancreas (< 1% of pancreatic neoplasms), acinar cell carcinoma is typically encountered in men older than 50 years [9 11]. In 15% of cases, these lesions hypersecrete lipase, resulting in a syndrome characterized by fat necrosis, bone infarcts, fevers, and polyarthritis ( lipase hypersecretion syndrome ) [6, 12]. lthough up to 50% of patients initially present with metastatic disease (liver and lymph nodes), acinar cell carcinoma still has a slightly better prognosis than ductal adenocarcinoma, with a 5-year survival rate of 50% [10, 12]. Given the tumor s rarity, it is difficult to establish any classic imaging findings. Nevertheless, a few characteristic imaging features have been described (Figs. 9 12): cinar cell carcinomas tend to be large, averaging 6 cm in size, and are usually exophytic and well circumscribed, often with an enhancing capsule. These neoplasms do not usually cause ductal obstruction, despite their large size [9]. Internal hemorrhage, necrosis, and cystic change are common [13] (Figs ). Given this constellation of findings, acinar cell carcinomas are often prospectively mistaken for pancreatic neuroendocrine tumors, even though they are usually not overtly hypervascular. Intrapancreatic Splenule (ccessory Spleen) ccessory spleens represent a congenital anomaly arising from aberrant splenic embryologic fusion, resulting in the ectopic deposition of normal splenic tissue in abnormal sites. ccording to autopsy reports, the second most common location for accessory spleens is in the tail of the pancreas (Fig. 13). ecause of their relatively high density and enhancement, accessory spleens in this location can be easily mistaken for a primary pancreatic mass, particularly a neuroendocrine tumor [14]. Most intrapancreatic splenules are located at the tip of the pancreatic tail and should not be more than 3 cm from the tail. lesion located closer to the pancreatic body is TLE 1: Pancreatic Neuroendocrine Tumor Mimics and Important Points in the Differential Diagnosis Entity Renal cell carcinoma metastases Intrapancreatic accessory spleen Gastrointestinal stromal tumor Peripancreatic paraganglioma cinar cell carcinoma Solid serous adenoma Solitary fibrous tumor Pancreatic hamartoma Pancreatoblastoma Key Diagnostic Features Hypervascular mass in a patient with a history of renal cell carcinoma Tail of the pancreas mass that follows the attenuation of the spleen on all phases Fat plane between the mass and pancreas; origin from the stomach or duodenum Fat plane between the mass and pancreas, as well as with the adjacent bowel Exophytic well-circumscribed mass with an enhancing capsule; typically not overtly hypervascular Can be indistinguishable from neuroendocrine tumor; on MRI, possibly T2 signal bright with septations Large exophytic hypervascular mass; cannot be reliably differentiated from neuroendocrine tumor Variable appearance; hypervascular lesions cannot be differentiated from neuroendocrine tumors Variable appearance; usually in pediatric population 310 JR:199, ugust 2012

3 Mimics of Pancreatic Neuroendocrine Tumors Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved unlikely to represent a splenule. Moreover, accessory splenules derive their arterial supply from the splenic artery and their venous drainage from the splenic vein and should have enhancement characteristics identical to those of the spleen on all phases. This is particularly useful during the arterial phase, because a splenule should mimic the serpiginous heterogeneous enhancement pattern of the spleen. In cases where the accessory spleen is small, distinguishing it from a neuroendocrine tumor according to its enhancement pattern may still be difficult. In those cases, the use of a 99m Tc-labeled sulfur colloid scan or 9m Tc-labeled heat-damaged RC scan (both of which are typically taken up by splenic tissue) can be useful to distinguish these entities [14]. Solid Serous denoma Serous cystadenomas ( microcystic adenoma), which account for roughly 20% of all pancreatic cystic lesions, are typically associated with a honeycomb pattern (multiple internal cysts) and a central scar with dystrophic calcification. However, certain subtypes of serous tumors can have a very different appearance: Serous adenoma, a type of serous neoplasm without an appreciable cystic component on histologic analysis, appears completely solid on CT. s a result of the highly vascularized stroma common to all serous neoplasms, these lesions avidly enhance on arterial phase images, and like other serous lesions, will not usually result in pancreatic ductal obstruction [15] (Figs ). lthough they are histologically indistinguishable from more typical serous cystic neoplasms, these masses cannot be differentiated from pancreatic neuroendocrine tumors on CT. Some series have suggested that MRI may be helpful, because lesions that are fundamentally cystic (but appear solid on CT) should be T2 hyperintense and show subtle septations on T2- weighted images. However, the utility of MRI for those serous tumors that are truly histologically solid is less certain [15]. Solitary Fibrous Tumor n unusual tumor of the pancreas, solitary fibrous tumors are typically benign but can rarely be locally aggressive or frankly malignant. Very few reports of the CT appearance of this tumor exist in the literature, but these lesions are usually large exophytic well-circumscribed hypervascular masses that cannot be reliably differentiated from neuroendocrine tumors [16] (Fig. 17). Pancreatic Hamartoma benign lesion with fewer than 10 reported cases in the literature, pancreatic hamartomas represent a disorganized combination of tissue normally found in the pancreas, such as fat, fibrous tissue, smooth muscle, and benign pancreatic endocrine or exocrine cells. The few reported CT cases have ranged from primarily cystic tumors to lesions that are solid and avidly enhancing [17] (Fig. 18). Pancreatoblastoma Pancreatoblastoma is a neoplasm usually found in children 1 8 years old, although a few cases have been described in neonates and adults (Fig. 19). It is an aggressive tumor, with a 5-year survival rate of only 60%, and 15% of patients initially present with metastatic disease [18, 19]. The imaging findings are nonspecific and can resemble either ductal adenocarcinoma or a neuroendocrine tumor. These neoplasms tend to be large and heterogeneous, often containing internal calcification. s they grow larger, necrosis and internal hemorrhage are common, and vascular invasion has been described [19]. However, because of their relatively soft consistency, these lesions usually do not obstruct the biliary or pancreatic ducts [6]. Conclusion Neuroendocrine tumors have a relatively distinct CT appearance characterized by avid enhancement on arterial phase images. s CT technology has improved, it has become increasingly common to identify incidental hypervascular lesions in the pancreas, most of which represent small nonfunctional pancreatic neuroendocrine tumors with relatively nonaggressive behavior [1]. However, as this pictorial essay has illustrated, a number of pancreatic and peripancreatic lesions can mimic the CT appearance of neuroendocrine tumors. Close attention to certain key imaging features can allow an alternative diagnosis in some cases. References 1. Vagefi P, Razo O, Deshpande V, et al. Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms. rch Surg 2007; 142: Horton KM, Hruban RH, Yeo C, Fishman EK. Multi-detector row CT of pancreatic islet cell tumors. RadioGraphics 2006; 26: Fidler JL, Fletcher JG, Reading CC, et al. Preoperative detection of pancreatic insulinomas on multiphasic helical CT. JR 2003; 181: Kawamoto S, Shi C, Hruban RH, et al. Small serotonin-producing neuroendocrine tumor of the pancreas associated with pancreatic duct obstruction. JR 2011; 197:663; [web]w482 W Du X, Zhao Y, Zhang T, et al. Primary pancreatic lymphoma: a clinical quandary of diagnosis and treatment. Pancreas 2011; 40: Low G, Panu, Millo N, Leen E. Multimodality imaging of neoplastic and non-neoplastic solid lesions of the pancreas. RadioGraphics 2011; 31: Xue HD, Liu W, Xiao Y, et al. Pancreatic and peripancreatic lesions mimic pancreatic islet cell tumor in multidetector computed tomography. Chin Med J (Engl) 2011; 124: Singhi D, Hruban RH, Fabre M, et al. Peripancreatic paraganglioma: a potential diagnostic challenge in cytopathology and surgical pathology. m J Surg Pathol 2011; 35: Hsu MY, Pan KT, Chu SY, Hung CF, Wu RC, Tseng JH. CT and MRI features of acinar cell carcinoma of the pancreas with pathological correlations. Clin Radiol 2010; 65: Mortenson MM, Katz MH, Tamm EP, et al. Current diagnosis and management of unusual pancreatic tumors. m J Surg 2008; 196: utturini G, Pisano M, Scarpa, D Onofrio M, uriemma, assi C. ggressive approach to acinar cell carcinoma of the pancreas: a single institution experience and a literature review. Langenbecks rch Surg 2011; 396: Matos JM, Schmist CM, Turrini O, et al. Pancreatic acinar cell carcinoma: a multi-institutional study. J Gastrointest Surg 2009; 13: Raman SP, Hruban RH, Cameron JL, Wolfgang CL, Kawamoto S, Fishman EK. cinar cell carcinoma of the pancreas: computed tomography features a study of 15 patients. bdom Imaging 2012 [Epub ahead of print] 14. Kawamoto S, Johnson PT, Hall H, Cameron JL, Hruban RH, et al. Intrapancreatic accessory spleen: CT appearance and differential diagnosis. bdom Imaging 2011 [Epub ahead of print] 15. Sun HY, Kim SH, Kim M, Lee JY, Han JK, Choi I. CT imaging spectrum of pancreatic serous tumors based on new pathologic classification. Eur J Radiol 2010; 75:e45 e Sugawara Y, Sakai S, ono S, et al. Solitary fibrous tumor of the pancreas. Jpn J Radiol 2010; 28: McFaul CD, Vitone LJ, Campbell F, et al. Pancreatic hamartoma. Pancreatology 2004; 4: ien E, Godzinksi J, Dall Igna P, et al. Pancreatoblastoma: a report from the European cooperative study group for pediatric rare tumors (EXPeRT). Eur J Cancer 2011; 47: Yang X, Wang X. Imaging findings of pancreatoblastoma in 4 children including a case of ectopic pancreatoblastoma. Pediatr Radiol 2010; 40: JR:199, ugust

4 Raman et al. Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig. 1 Examples of pancreatic neuroendocrine tumors in two different patients., 62-year-old man. Image shows avidly enhancing mass (arrow) arising from and extending exophytically from pancreatic head, confirmed to be neuroendocrine tumor at surgery., 65-year-old woman. Image shows small nonfunctional islet cell tumor (solid arrow) that is predominantly cystic but shows hypervascularity at its margin (open arrow). Fig year-old woman with recent history of right nephrectomy for renal cell carcinoma. xial arterial phase CT image shows avidly enhancing small mass (arrow) in pancreatic head, representing small metastasis. Lesion was not visible on venous phase images (not shown). Fig year-old man who presented with diffuse pancreatic metastases 17 years after his initial right nephrectomy. and, xial () and coronal () arterial phase CT images show innumerable renal cell carcinoma (clear cell type) metastases (arrows) to pancreas. Notably, although pancreas appears globally enlarged on venous phase imaging (not shown), discrete enhancing lesions are visible on arterial phase images only. 312 JR:199, ugust 2012

5 Mimics of Pancreatic Neuroendocrine Tumors Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old man with enhancing mass near third portion of duodenum. and, xial () and coronal () CT images show enhancing mass (arrows) closely abutting pancreatic head and duodenum. Prospectively, it was unclear whether this represented primary duodenal gastrointestinal stromal tumor or pancreatic neuroendocrine tumor. However, mass was discovered to be duodenal gastrointestinal stromal tumor at surgery. Fig year-old woman with enhancing mass (arrow) immediately between duodenum and pancreatic head on coronal contrast-enhanced CT image. This mass was prospectively believed to be neuroendocrine tumor but was found to be duodenal gastrointestinal stromal tumor at surgery. Fig year-old man with large retroperitoneal mass. and, xial () and coronal volume-rendered () arterial phase images show large avidly enhancing mass (arrows) extending from near pancreatic head downward into retroperitoneum. However, fat plane was identified between pancreatic head and mass, and retroperitoneal paraganglioma was favored over pancreatic neuroendocrine tumor. Diagnosis of retroperitoneal paraganglioma was confirmed at surgery. JR:199, ugust

6 Raman et al. Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old man with retroperitoneal mass. and, xial () and coronal () arterial phase images show enhancing mass (arrows) with central necrosis in close proximity to pancreatic head. However, mass was thought to be distinct from pancreatic head, and retroperitoneal paraganglioma was favored over pancreatic neuroendocrine tumor. Diagnosis of retroperitoneal paraganglioma was confirmed at surgery. Fig year-old woman with pancreatic head mass. and, xial () and coronal () images show avidly enhancing mass (arrows) near pancreatic head. Mass was not thought to be separate from pancreas and was prospectively thought to represent pancreatic neuroendocrine tumor. However, peripancreatic paraganglioma was identified at surgery. Fig year-old man with acinar cell carcinoma of pancreatic tail. and, xial () and coronal volume-rendered () contrast-enhanced images show relatively homogeneous mass (arrows), which was originally thought to represent pancreatic neuroendocrine tumor. 314 JR:199, ugust 2012

7 Mimics of Pancreatic Neuroendocrine Tumors Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old man with acinar cell carcinoma of pancreatic body and tail., xial contrast-enhanced CT image shows tubular cystic mass (solid arrow) with internal mural nodularity. In addition, mass is bilobed in shape (open arrow)., Coronal CT image nicely shows bilobed shape of mass (arrow). Fig year-old woman with acinar cell carcinoma of pancreatic tail. xial CT image shows well-circumscribed hypodense lesion (arrow) with minimal internal heterogeneity arising from upstream pancreatic body and tail. Lesion was originally thought to represent neuroendocrine tumor. Fig year-old man with acinar cell carcinoma. xial contrast-enhanced arterial phase CT image shows large necrotic mass (solid arrow) arising from tail of pancreas with irregular peripheral enhancement (open arrow). This lesion was originally thought to represent mucinous cystadenocarcinoma or necrotic islet cell tumor. JR:199, ugust

8 Raman et al. Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig. 13 Examples of intrapancreatic splenules in two different patients., 50-year-old woman. xial contrast-enhanced arterial phase image shows intrapancreatic splenules (arrow). Diagnosis of splenule was made prospectively only in this case., 67-year-old man. xial contrast-enhanced arterial phase image shows intrapancreatic splenules (arrow). Fig year-old woman with incidentally discovered pancreatic mass. and, xial () and coronal () contrast-enhanced arterial phase CT images show solid hypervascular mass (arrows) arising from pancreatic tail. Mass was thought to represent pancreatic neuroendocrine tumor but was found to be solid serous adenoma after surgery. Fig year-old man with incidentally discovered pancreatic mass. and, xial () and coronal () contrast-enhanced arterial phase CT images show solid hypervascular mass (solid arrows, and ) arising from pancreatic tail with central calcification (open arrow, ). Mass was thought to represent pancreatic neuroendocrine tumor but was found to be solid serous adenoma after surgery. 316 JR:199, ugust 2012

9 Mimics of Pancreatic Neuroendocrine Tumors Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old woman with incidentally discovered pancreatic mass., xial contrast-enhanced arterial phase CT image shows mixed cystic and solid hypervascular mass (arrow) arising from pancreatic head., Coronal maximum-intensity-projection image nicely shows marked neovascularity (arrow) associated with mass. Mass was thought to represent pancreatic neuroendocrine tumor but was found to be serous cystadenoma after surgery. Fig year-old man with solitary fibrous tumor of pancreas and liver metastasis. and, Coronal () and axial () CT images show large mixed cystic and solid mass in pancreatic head (arrow, ) and vascular mass in liver (arrow, ). This was originally thought to represent neuroendocrine tumor with metastasis. Fig year-old man with pancreatic hamartoma of pancreatic body. xial contrast-enhanced CT in portal venous phase shows well-circumscribed enhancing mass (arrow). Notably, lesion was not visible on arterial phase images (not shown). This mass was originally thought to represent neuroendocrine tumor. Fig year-old man with pancreatoblastoma of pancreatic body and tail. xial CT image shows ill-defined hypodense soft-tissue mass (solid arrow) in pancreatic body and tail, with upstream pancreatic atrophy and ductal dilatation (open arrow). JR:199, ugust

10 Raman et al. Downloaded from by on 01/03/18 from IP address Copyright RRS. For personal use only; all rights reserved FOR YOUR INFORMTION This article is part of a self-assessment module (SM). Please also refer to Pancreatic Imaging Mimics: Part 1, Imaging Mimics of Pancreatic denocarcinoma, which can be found on page 301. Each SM is composed of two journal articles along with questions, solutions, and references, which can be found online. You can access the two articles at and the questions and solutions that comprise the Self-ssessment Module by logging on to clicking on JR (in the blue Publications box), clicking on the article name, and adding the article to the cart and proceeding through the checkout process. The merican Roentgen Ray Society is pleased to present these SMs as part of its commitment to lifelong learning for radiologists. Continuing medical education (CME) and SM credits are available in each issue of the JR and are free to RRS members. Not a member? Call (from the U.S. or Canada) or to speak to an RRS membership specialist and begin enjoying the benefits of RRS membership today! 318 JR:199, ugust 2012