Hypervascular pancreatic “lesions”: a pattern-based approach to differentiation
Hypervascular pancreatic lesions/masses can arise due to a variety of causes, both benign and malignant, leading to a wide differential diagnosis. Accurate differentiation of these lesions into appropriate diagnoses can be challenging; however, this is important for directing clinical management. This manuscript provides a multimodality imaging review of hypervascular pancreatic lesion, with emphasis on an imaging-based algorithmic approach for differentiation of these lesions, which may serve as a decision support tool when encountering these uncommon lesions. Additionally, we stratify these lesions into three categories based on malignant potential, to help guide clinical management.
KeywordsPancreas Hypervascular masses Decision support Neuroendocrine tumor Pancreatic neoplasm
A broad variety of conditions can manifest as hypervascular pancreatic masses on contrast-enhanced cross-sectional imaging, and differentiation into specific diagnoses can be challenging due to overlapping morphologies and appearances. These lesions include primary pancreatic tumors, metastatic tumors to the pancreas, as well as lesions arising from structures which can mimic intrinsic pancreatic processes.
Pancreatic hypervascular lesions can be broadly classified into three categories based on malignant potential, which is beneficial in guiding clinical management of these lesions. Lesions with no-risk for malignancy include intra-/peripancreatic vascular anomalies, and intrapancreatic accessory spleen. Lesions with low risk for malignancy include solid pseudopapillary tumors and solid-appearing serous cystadenomas. Lesions with high risk for malignancy include pancreatic neuroendocrine tumors (pancreatic NETs), acinar pancreatic carcinomas, and hypervascular pancreatic metastases. Pancreatic NETs are further discussed based on the presence or absence of clinically significant manifestation of hormone secretion, and on the basis of associated syndromic states.
“No-risk for malignancy” lesions
Based on the flowchart-based approach, a hypervascular pancreatic lesion should first be assessed for its relationship with any adjacent vascular structures (Fig. 1). If a lesion is directly arising from a vascular structure, this is consistent with a vascular process adjacent to the pancreas, rather than a true pancreatic lesion. This initial identification is crucial, so as to prevent inadvertent biopsy or workup of a non-malignant vascular entity. The use of multiphasic reformatted CT or MR imaging can be helpful in determining relationships between these “lesions” and adjacent vessels. Vascular structures appearing as pancreatic vascular masses can be further divided based on arterial or venous origin (Fig. 1).
Pseudoaneurysms differ from true aneurysms by lacking one or more of the normal three vascular wall layers. While differentiation between pseudoaneurysms and true aneurysms can be challenging, the former arise secondary to erosion of the arterial adventitia, and typically should be considered in the setting of pancreatitis or trauma . Pseudoaneurysms can appear as peripancreatic or intrapancreatic. Pseudoaneurysms occur in up to 10% of patients with pancreatitis and most commonly involve the splenic artery (40%), gastroduodenal artery (30%), and pancreaticoduodenal arteries (10%) .
Intrapancreatic accessory spleen
Based on the flowchart-based algorithm, intrapancreatic accessory spleen should be considered in cases where there is no direct vascular connection involving the lesion, the patient does not present with clinical features of neuroendocrine tumors, and in which the lesion specifically involves the pancreatic tail (Fig. 1). Accessory splenic tissue, in all locations, is common and occurs in 10–30% of the population [11, 12]. Intrapancreatic accessory spleens are relatively less frequent with an autopsy series reporting a prevalence of 17% .
Intrapancreatic accessory spleens are benign, and no further invasive workup or treatment is needed, if the diagnosis can be confidently made on the basis of imaging alone. Lesions which remain indeterminate on imaging may require further evaluation with endoscopic ultrasound and fine needle aspiration .
“Low-risk for malignancy” lesions
Solid pseudopapillary tumors (SPT)
When following the proposed flowchart-based algorithm, solid pseudopapillary tumors should be considered in cases where there is no vascular connection with the lesion, the patient does not present with clinical features of neuroendocrine tumors, and in which there is no known history of primary hypervascular malignancy (Fig. 1). Solid pseudopapillary tumors are benign or low-grade malignant tumors that occur almost exclusively in young females [3, 20]. These are well-circumscribed masses which can occur anywhere in the pancreas with variable solid and cystic components.
These lesions can be detected incidentally or present with abdominal pain. Management is typically with surgical resection .
Solid-appearing serous cystadenomas
Following the flowchart-based algorithm, solid-appearing serous cystadenomas should be considered in cases where there is no vascular connection with the lesion, the patient does not have with clinical features of neuroendocrine tumors, and in whom there is no history of primary hypervascular malignancy (Fig. 1). Solid-appearing serous cystadenomas are rarely malignant and typically occur in asymptomatic elderly women [3, 21]. While the most common subtype of these lesions is the microcystic variant, which appears cystic on CT, these lesions can also rarely appear solid, due to enhancement of closely opposed walls and septa of cystic spaces, and can be mistaken for an alternative solid-enhancing pancreatic mass such as a neuroendocrine tumor .
Management of these lesions is typically conservative and with periodic surveillance .
“High risk for malignancy” lesions
Pancreatic acinar cell carcinoma
Pancreatic acinar cell carcinomas should be considered in cases where there is no vascular communication with the lesion, the patient does not have clinical features of neuroendocrine tumors, and where there is no history of a primary hypervascular malignancy (Fig. 1). Acinar cell carcinoma of the pancreas is a rare primary pancreatic malignancy, most commonly seen in elderly males . These tumors typically present as larger (> 4 cm) hypervascular pancreatic masses, arising from the exocrine pancreas . A characteristic paraneoplastic syndrome associated with these lesions is polyarthritis, eosinophilia, fat necrosis, and subcutaneous nodules, due to systemic secretion of pancreatic enzymes by these tumors.
Pancreatic acinar cell carcinoma most commonly appear on CT as exophytic well-defined masses with homogeneous enhancement and variable cystic components [3, 25]. MRI is beneficial in showing that these are solid-enhancing intrapancreatic masses. Tissue sampling, is necessary to distinguish these lesions from other similarly appearing entities, such as non-functioning neuroendocrine tumors.
Management of these lesions is with surgical resection, in the absence of metastatic disease .
Hypervascular pancreatic metastases
Metastases to the pancreas are relatively rare and account for 2–5% of pancreatic malignancies [26, 27]. The prevalence of metastatic disease to the pancreas ranges between 1.6 and 11% based on autopsy data [26, 28]. The most common primary malignancies to metastasize to the pancreas are renal cell carcinomas, followed by breast, lung, colorectal, and melanoma [29, 30].
Pancreatic metastases are most often incidentally detected, as a part of routine follow-up imaging . Though the time to metastasis is variable, long periods of latency have been shown between the initial treatment of renal cell carcinoma and the development of pancreatic metastases . In the setting of isolated “pauci-metastatic” pancreatic metastases from renal cell carcinoma, studies have shown a survival benefit to the resection of these lesions [29, 32].
Pancreatic neuroendocrine tumors (pancreatic NETs) are pancreatic tumors arising from the endocrine pancreas with variable behavior, ranging from slow-growing indolent lesions to aggressively metastasizing lesions [33, 34]. These have previously been called islet cell tumors, although these tumors arise from the pluripotent pancreatic ductal epithelium rather than pancreatic islet cells [3, 35]. These tumors all secrete hormones, but are subdivided as functional and non-functional tumors based on the presence or absence of a clinically significant syndromic state related to hormone secretion [3, 35, 36]. Classically, neuroendocrine tumors are described as solid hypervascular masses without associated ductal obstruction [36, 37]. While previously size was thought to be the primary indicator of tumor aggressiveness, tumors are now subdivided into low-, intermediate-, and high-grade lesions based on mitotic activity and percentage of nuclear antigen Ki-67 [34, 35, 38].
Functional neuroendocrine tumors
Following the flowchart-based algorithm, functional neuroendocrine tumors should be considered in cases where the patient has clinical symptoms suggestive of a neuroendocrine tumor (Fig. 1). Subsequently, these entities can be confirmed with either tissue sampling or confirmatory nuclear medicine imaging using somatostatin receptor agents [36, 39].
On contrast-enhanced CT, pancreatic neuroendocrine tumors appear as hypervascular pancreatic masses. Increased vascularity of these structures is secondary to a rich capillary network . Smaller lesions tend to enhance more homogeneously, whereas larger lesions may show more heterogeneity in enhancement, due to internal necrosis or calcification . Both arterial and portal venous phase images are complimentary in the detection of these lesions [41, 42].
MRI has been reported as having a sensitivity of 74–94% and specificity of 78–100% for the detection of neuroendocrine tumors . Neuroendocrine tumors on MRI, classically show intrinsic T1-hypointensity, T2-hyperintensity, and restricted diffusion on MRI, relative to normal pancreatic parenchyma . These lesions are typically vascular on both arterial and venous phase imaging with heterogeneity of enhancement increasing with lesion size . Conspicuity of lesions between arterial and venous phase is variable, with both phases serving in a complimentary capacity to optimize lesion detection [40, 42, 44].
Pancreatic neuroendocrine tumors and associated metastases can be localized by nuclear medicine imaging due to the presence of somatostatin receptors on these tumors. The most widely used test for this purpose is the planar In-111 octreotide scan, with single photon emission computed tomography . The sensitivity of this method, while dependent on tumor size and histology, is 80% . Newer somatostatin analogues bound to positron-emitting isotopes, such as Ga-68 DOTATATE, in conjunction with PET/CT have yielded greater diagnostic accuracy with sensitivity of 93% and specificity of 96% and are now being used more frequently [45, 46, 47].
Non-functional neuroendocrine tumors
The CT and MRI appearance of these tumors is similar to that of functional neuroendocrine tumors, described above. MRI is helpful to confirm the solid nature of these tumors. However, due to the absence of suggestive clinical features, these lesions can be difficult to definitively diagnose on the basis of imaging alone, and tissue sampling is often required.
Syndromic states associated with neuroendocrine tumors
There are a spectrum of diagnoses associated with hypervascular pancreatic lesions and it is important for the radiologist to lead clinicians towards the correct diagnosis, in order to appropriately guide management and direct patient care. While there are additional less common hypervascular pancreatic lesions, not presented in this review, (i.e., pancreatoblastomas, solitary fibrous tumors of the pancreas, and pancreatic hamartomas) these diagnoses are often reached by histology. The flowchart-based approach presented in this manuscript is a helpful decision support tool for both trainees and practicing radiologists who may not encounter hypervascular pancreatic lesions on a regular basis.
Compliance with ethical standards
No funding was received for this study.
Conflict of interest
All authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
Statement of informed consent was not applicable since the manuscript does not contain any patient data.
- 14.Coquia SF, Kawamoto S, Zaheer A, et al. (2014) Intrapancreatic accessory spleen: possibilities of computed tomography in differentiation from nonfunctioning pancreatic neuroendocrine tumor. J Comput Assist Tomogr 38(6):874–878. doi: 10.1097/rct.0000000000000127 CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Nihei K, Sakamoto K, Suzuki S, Mishina T, Otaki M (2016) A case of pancreatic metastasis of renal cell carcinoma. Gan Kagaku Ryoho Cancer Chemother 43(12):2274–2276Google Scholar
- 38.Cho JH, Ryu JK, Song SY, et al. (2016) Prognostic validity of the American Joint Committee on Cancer and the European Neuroendocrine Tumors Staging classifications for pancreatic neuroendocrine tumors: a retrospective nationwide multicenter study in South Korea. Pancreas 45(7):941–946. doi: 10.1097/mpa.0000000000000586 CrossRefPubMedGoogle Scholar
- 45.Mojtahedi A, Thamake S, Tworowska I, Ranganathan D, Delpassand ES (2014) The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature. Am J Nucl Med Mol Imaging 4(5):426–434PubMedPubMedCentralGoogle Scholar