CT and MR Imaging Findings of Pancreatic Paragangliomas

Abstract Previous studies on pancreatic paraganglioma, a rare neoplasm, have primarily reported its ultrasound and routine and contrast-enhanced computed tomography (CT) findings. To our knowledge, we are the first to report the contrast-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) sequence findings of pancreatic paraganglioma. A male patient, ages 41 years, was admitted to our hospital due to a pancreatic space-occupying lesion that had been present for more than 10 days. The patient had no obvious discomfort. He had a history of hypertension and hyperthyroidism. Physical examination revealed upper abdominal tenderness without a palpable mass. Routine and contrast-enhanced abdominal CT showed a soft tissue mass at the pancreatic head/uncinate process, with patchy calcification within the lesion. On a contrast-enhanced CT scan, severe enhancement of the mass in the arterial phase was noted, as was slightly reduced but still marked enhancement in the venous phase. The celiac trunk and superior mesenteric artery segment were wrapped by the tumor. Thickened, tortuous vessels were observed at the lesion edges, around which there were multiple enlarged lymph nodes. The main pancreatic duct was markedly dilated. Routine and contrast-enhanced pancreatic MRI demonstrated an abnormal nodular signal in the pancreatic head/uncinate process that was approximately 4.3 × 6.4 cm2 in size. T1-weighted imaging (T1WI) revealed hypointensity, whereas T2-weighted imaging (T2WI) revealed nonhomogeneous, slight hyperintensity. Patchy hypointensity on both T1WI and T2WI was observed within the lesion. DWI showed slight hyperintensity. Grossly heterogeneous enhancement of the mass was observed on a contrast-enhanced MRI scan, with the tumor wrapped around the adjacent vasculature, and multiple enlarged lymph nodes were observed peripherally. After preoperative preparation, the patient underwent pancreatoduodenectomy. Histopathology and immunohistochemistry of the resected tumor indicated pancreatic paraganglioma. After surgery, the patient recovered well, without presenting any recurrence or metastasis during short-term follow-up. For hypervascular pancreatic tumors on contrast-enhanced CT or MRI, and particularly those occurring in the pancreatic head, with a clear display of draining veins, the possibility of pancreatic paraganglioma should be considered. These tumors usually exhibit necrosis or cystic changes and are occasionally accompanied by calcification.

plasm, have primarily reported its ultrasound and routine and contrastenhanced computed tomography (CT) findings. To our knowledge, we are the first to report the contrast-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) sequence findings of pancreatic paraganglioma.
A male patient, ages 41 years, was admitted to our hospital due to a pancreatic space-occupying lesion that had been present for more than 10 days. The patient had no obvious discomfort. He had a history of hypertension and hyperthyroidism. Physical examination revealed upper abdominal tenderness without a palpable mass. Routine and contrast-enhanced abdominal CT showed a soft tissue mass at the pancreatic head/uncinate process, with patchy calcification within the lesion. On a contrast-enhanced CT scan, severe enhancement of the mass in the arterial phase was noted, as was slightly reduced but still marked enhancement in the venous phase. The celiac trunk and superior mesenteric artery segment were wrapped by the tumor. Thickened, tortuous vessels were observed at the lesion edges, around which there were multiple enlarged lymph nodes. The main pancreatic duct was markedly dilated. Routine and contrast-enhanced pancreatic MRI demonstrated an abnormal nodular signal in the pancreatic head/uncinate process that was approximately 4.3 Â 6.4 cm 2 in size. T1-weighted imaging (T1WI) revealed hypointensity, whereas T2-weighted imaging (T2WI) revealed nonhomogeneous, slight hyperintensity. Patchy hypointensity on both T1WI and T2WI was observed within the lesion. DWI showed slight hyperintensity. Grossly heterogeneous enhancement of the mass was observed on a contrast-enhanced MRI scan, with the tumor wrapped around the adjacent vasculature, and multiple enlarged lymph nodes were observed peripherally. After preoperative preparation, the patient underwent pancreatoduodenectomy. Histopathology and immunohistochemistry of the resected tumor indicated pancreatic paraganglioma. After surgery, the patient recovered well, without presenting any recurrence or metastasis during short-term follow-up.
For hypervascular pancreatic tumors on contrast-enhanced CT or MRI, and particularly those occurring in the pancreatic head, with a clear display of draining veins, the possibility of pancreatic paraganglioma should be considered. These tumors usually exhibit necrosis or cystic changes and are occasionally accompanied by calcification.

INTRODUCTION
P araganglioma is a type of tumor derived from neural crest cells. During the development of paraganglioma, neural crest cells, which are distributed in a scattered pattern in the body, aggregate to form paraganglia. Most paragangliomas associated with the parasympathetic system occur in the cranial base, neck, and anterior mediastinum, including the vagal paraganglia, carotid body paraganglion, and jugulotympanic paraganglia. The most common paragangliomas are carotid body tumors and glomus jugulare tumors; such tumors have a chemoreceptor function. 1 Paragangliomas associated with the sympathetic system can occur in any part of the sympathetic chain, such as the posterior mediastinum and thoracolumbar paravertebral region, including Zuckerkandl's body; the latter is more common, and these tumors are considered to have functions similar to those in the adrenal medulla. 1 The adrenal medulla is a special type of paraganglion. Paragangliomas originating in the adrenal medulla have a specific name, pheochromocytomas, whereas those occurring in other parts of the adrenal medulla are called extra-adrenal paragangliomas. Approximately 1-quarter of sporadic pheochromocytoma patients may have related gene mutations, including mutations of the RET gene (associated with multiple endocrine neoplasia type 2), VHL gene (associated with von Hippel-Lindau disease), succinate dehydrogenase subunit B gene (SDHB), and succinate dehydrogenase subunit D (SDHD) gene. 2 In addition, extra-adrenal paraganglioma patients are considered to have a potential genetic predisposition. 2 To our knowledge, paragangliomas rarely occur in the pancreas; indeed, there are thus far only 26 cases of pancreatic paragangliomas reported in the English-language literature. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Here, we report a case of pancreatic paraganglioma with complete clinical and imaging data. Additionally, we are the first to report its contrastenhanced magnetic resonance imaging (MRI) and diffusionweighted imaging (DWI) sequence findings.

CONSENT
The patient signed the necessary documents to consent to the use of his data for teaching and publication. more than 10 days. Ten days prior, the patient had gone to a local hospital for medical examination, and a duodenal ampullary mass had been found on abdominal ultrasound examination. Routine and contrast-enhanced pancreatic MRI at the local hospital had shown a space-occupying lesion in the pancreatic head, and the possibility of malignancy with celiac truncal and superior mesenteric arteriovenous involvement had been considered. The patient had no abdominal pain, abdominal distension, nausea, vomiting, chills, or fever at that time and did not receive treatment. At the most recent presentation, the patient had no discomfort, such as chills, fever, dizziness, headache, nausea, or vomiting, and was visiting our hospital for further diagnosis and treatment. The patient had an 8-month history of hypertension, with his highest blood pressure being 210/120 mm Hg. He was taking antihypertensive drugs, such as oral nifedipine and metoprolol, and claimed that his blood pressure was well controlled. The patient had a >10-year history of hyperthyroidism, had previously received I 131 isotope therapy and was taking oral euthyrox for treatment. He denied a family history of related diseases. On physical examination, the abdomen was flat and soft, and upper abdominal tenderness was noted, without rebound tenderness or a palpable mass. Routine blood tests revealed a slightly elevated neutrophil count (77.0% [normal range: 50.0-70.0%]) and reduced lymphocyte and eosinophil counts (13.4% [normal range: 20.0-40.0%] and 0.3% [normal range: 0.5-5.0%], respectively), whereas the remaining indices were generally within normal ranges. The liver function index, that is, the alanine aminotransferase level, was mildly elevated, to 49 U/L (normal range: 5-40 U/L), whereas the remaining liver, kidney, and electrolyte indices were all generally within normal ranges. The ferritin index had risen to 360.7 ng/mL (normal range: 7.0-323.0 ng/mL), whereas the remaining tumor markers, including a-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, and total prostate-specific antigen, were all within the normal ranges. Hepatitis B surface antigen, hepatitis C antigen, anti-HIV antibody, and anti-Treponema pallidum antibodies were all negative.
Routine and contrast-enhanced abdominal computed tomography (CT) showed a markedly enlarged pancreatic head/ uncinate process, within which extension of an irregular mass to the top of the horizontal duodenal segment along the retroperitoneal space was observed, with an average density of approximately 48.9 Hounsfield units (HU). Patchy calcification was observed within the lesion. On a contrast-enhanced CT scan, heterogeneous enhancement of the mass was noted, with an average arterial phase density of approximately 176.6 HU and an average venous phase density of approximately 106.1 HU (Figure 1). The adjacent celiac trunk and initial segment of the superior mesenteric artery were wrapped by the tumor. Multiple thickened, tortuous vascular shadows were observed at the tumor margins, around which there were multiple enlarged lymph nodes. These enlarged lymph nodes were also grossly enhanced. The main pancreatic duct was markedly dilated. Routine and contrast-enhanced pancreatic MRI demonstrated an irregularly shaped mass in the pancreatic head/uncinate process that was approximately 4.3 Â 6.4 cm 2 in size. T2weighted imaging (T2WI) revealed nonhomogeneous, slight hyperintensity, whereas T1-weighted imaging (T1WI) revealed hypointensity. Patchy hypointensity on both T1WI and T2WI were observed within the lesion. DWI showed slight hyperintensity. Severe heterogeneous enhancement of the mass was observed on a contrast-enhanced scan (Figure 2), and the mass wrapped around the proximal part of the adjacent superior mesenteric artery. Multiple enlarged lymph nodes were observed around the mass. The possibility of a malignant neuroendocrine neoplasm was considered preoperatively.
After preoperative preparation, the patient underwent pancreatoduodenectomy. Intraoperatively, the mass was observed to be located in the pancreatic uncinate process. This mass was approximately 4 Â 6 cm 2 in size, hard in texture, and wrapped around the superior mesenteric artery and vein. Multiple enlarged, hard lymph nodes were noted at the superior border of the pancreas along the mesenteric vessels. The blood supply around the tumor was abnormally rich. Surgical specimens showed that the mass was located in the pancreatic uncinate process and that the stomach, duodenum, pancreas, and bile duct margins were negative. Immunohistochemistry showed CK (pan) (À), Melan-A (À), CgA (þ), Syn (þ), S-100 (þ), Ki-67 (2%), CD56 (þ), and b-catenin (membrane þ) (Figure 3). The diagnosis was finalized as pancreatic paraganglioma. Because the tumor in our case grew invasively, the biological behavior was suggested to be malignant. No tumor cells were observed within the submitted lymph nodes. After surgery, the patient recovered well and presented no tumor recurrence on ultrasound reexamination 1 month postoperatively.
The histopathological feature of paragangliomas is welldefined cell nests (''Zellballen''). Cell nests are mainly composed of chief cells, within which there are many catecholamine-containing granules that are surrounded by a thin layer of sustentacular cells. 24 Paraganglioma is a hypervascular lesion in which the chief cells are also closely associated with fenestrated capillaries. 1 Therefore, paragangliomas always appear as hypervascular masses on imaging.
In 2012, Higa and Kapur 16 reported the first case of malignant pancreatic paraganglioma. However, due to the lack of specific pathological characteristics, no consensus has been reached on diagnostic criteria for malignant paraganglioma. Low reactivity for neuropeptides and high division are considered to be associated with malignant paraganglioma, whereas the presence of pleomorphism, mitosis, and vascular invasion is not necessarily related to the poor clinical course and prognosis. 16 Kimura et al 25 attempted to evaluate the biological characteristics of paraganglioma using a scoring system; however, in the well-differentiated and moderately differentiated categories, 13% and 63% cases, respectively, still presented with malignancy. Currently, lymph node metastasis and metastases in other organs are still definite evidence for the confirmation of malignant paraganglioma. 26 Among the previously reported 3 cases of malignant pancreatic paragangliomas, 2 cases showed only 1 lymph node metastasis, whereas the remaining case presented with multiple intrahepatic metastases. 16,17,19 In the case report by Al-Jiffry et al, 17 CT failed to detect any enlarged lymph nodes, despite the pathological confirmation of lymph node metastasis. By contrast, in our case, markedly enlarged lymph nodes were detected on both CT and MRI, suggesting lymph node metastasis, but the histopathology findings were negative. Therefore, caution is needed in the imaging evaluation of lymph nodes for pancreatic paragangliomas due to the presence of false negatives and false positives. Nevertheless, CT can detect the metastases of malignant paragangliomas in other organs as well as tumor recurrence. 17,19 Surgical resection, including simple mass resection and pancreaticoduodenectomy, is the preferred treatment for pancreatic paraganglioma. 17,21 For functional pancreatic paragangliomas, the preoperative administration of a-adrenergic receptor blockers contributes to successful surgical procedures. 19 One patient with functional pancreatic paraganglioma lost the chance for surgical resection due to intraoperative hypertension. 19 Most described pancreatic paraganglioma patients had good surgical outcomes and were alive during 14-month to 5-year follow-ups. 6,7,9,12,14,16 -19,22 Two pancreatic paraganglioma patients died, 1 of whom was a patient with malignant pancreatic paraganglioma and multiple liver metastases who had received chemotherapy and lived for 4 years. 8,19 In our case, although the patient had peripheral tumor invasion, no recurrence or metastasis was found on short-term reexamination.

CONCLUSIONS
Paraganglioma of the pancreas is a rare neoplasm. Most pancreatic paragangliomas are nonfunctional paragangliomas that occur in people in their 50s and more frequently in women; pancreatic paragangliomas also often lack specific clinical symptoms. Most tumors are located in the pancreatic head. Imaging findings include hypervascular masses with draining veins on contrast-enhanced CT or MRI, often accompanied by necrosis or cystic changes and occasionally by calcification. Surgical resection is the preferred treatment for pancreatic paraganglioma, which has a good prognosis.