ReviewMultimodality preoperative imaging of pancreatic insulinomas
Introduction
Pancreatic insulinomas are a rare tumour of the islet cells of the pancreas. They account for the majority of functional neuroendocrine tumours of the pancreas (Table 1). The incidence is about one case per 250,000 patient-years, and there is a slight female predominance with a female-to-male ratio of 3:2.1 The median age at diagnosis is about 50 years, except when patients with insulinoma have associated multiple endocrine neoplasia type 1 (MEN 1), in whom the median age drops to the mid 20s. Insulinomas are characteristically small with approximately 66% being less than 2 cm at presentation.2 Even though these tumours tend to be small, the functionality of these lesions causes their early presentation. There is often a typical history of recurrent hypoglycaemic collapse and dizzy spells. These symptoms combined with biochemical evidence of fasting hyperinsulinaemia often allow the diagnosis to be made. Insulinomas are usually solitary (95%) and the vast majority (98%) are intra-pancreatic in location. Most insulinomas are benign (90%) with metastatic disease being rare.3 They are generally very vascular lesions, may be cystic, and may rarely calcify. Insulinomas are the most common cause of hypoglycaemia resulting from endogenous hyperinsulinism. Insulinomas continue to pose a diagnostic challenge to physicians, surgeons and radiologists alike. The role of imaging is to detect and provide precise anatomical localization and staging of tumours prior to surgery. Due to their small size at clinical presentation, they are notoriously difficult to localize radiologically, and specifically designed protocols are necessary to aid detection. In this review, we present an overview of the imaging of insulinomas in current day practice and describe the options available for preoperative localization.
Section snippets
Clinical presentation
The symptoms and features of patients with insulinomas are largely related to excessive release of insulin into the bloodstream from the tumour. Up to 85% of patients present with diplopia, blurred vision, palpitations, or weakness.4 Other symptoms include abnormal behaviour, confusion and amnesia. Grand mal seizures occur in 12% of patients. Hunger may be a prominent symptom and weight gain occurs in about 30% of patients. Symptoms caused by mass effects of local tumour mass are very rare as
Biochemical presentation
The presence of hypoglycaemia in the face of inappropriately elevated levels of insulin is the key to diagnosis of an insulinoma.5 The calculation of an abnormal ratio of insulin to plasma glucose is diagnostic. During a monitored fast, a low blood glucose level and high serum insulin level enable diagnosis to be made. In healthy individuals, the islet cells of the pancreas secrete equal amounts of insulin and C-peptide into the bloodstream. These molecules are derived from the same inactive
Overview
Imaging to localize insulinomas should only take place once the diagnosis has been confirmed biochemically.7 It must be remembered that the role of imaging is not to diagnose insulinomas, but to identify and localize the tumour.8 As tumours are usually less than 2 cm in size, they may be invisible on conventional imaging and specific dedicated sequences need to be employed to detect small lesions. Two fundamental features of these tumours aid radiological detection: (a) most insulinomas are
Abdominal ultrasound (Fig. 1)
Abdominal ultrasound was one of the first imaging techniques available in this field, but has a poor to moderate detection rate, with figures ranging from 0–66%. One study quoted a sensitivity of 79%, but this has not been reproduced elsewhere.10 Accurate imaging is limited by the small size of the tumour, interference by other intra-abdominal organs, and obese patients. Tumours located in the body and tail of the pancreas are particularly difficult to visualize. Ultrasound is also operator
Endoscopic ultrasound (EUS; Fig. 2)
The advent of EUS brought preoperative imaging to a new level comparable with that of intra-operative. Sensitivities of 80—90% have consistently been described, detecting tumours as small as 2 mm.11 It enables visualization of the pancreas with an accurate analysis of the relationship of the tumour to vital structures such as the biliary and pancreatic ducts. Local metastases and invasion may be detected. It also potentially facilitates a preoperative tissue diagnosis by means of fine-needle
CT (Figs. 3—5)
CT is safe, simple to perform and operator independent. CT imaging visualizes the exact location of tumour, its relationship to vital structures, and the presence of metastases. As insulinomas are highly vascular in the arterial phase, modern contrast-enhanced imaging has focused on this property to aid detection. Precise bolus timing is critical in optimizing visualization. However, initial results using CT to visualize insulinomas were disappointing, with reported sensitivities as low as 21%.
MRI (Fig. 6)
Currently there is strong evidence emerging for the use of MRI in imaging insulinoma.20 Like CT, it is safe, non-invasive, rapid and facilitates the detection of metastases. Limitations include the standard contra-indications to MRI. More specifically, there are difficulties with motion artefact, low signal-to-noise ratio, and poor contrast of tumour against normal parenchyma. An early study demonstrated a sensitivity of only 7%,18 but the most recent literature reports sensitivities of over
Selective arteriography and hepatic venography (Fig. 7)
Selective arteriography of the coeliac axis and pancreatic arterial supply is felt by some experts to be the best overall preoperative localization procedure. Sensitivities of up to 66% have been described,25, 26 however, there is a false-positive rate of 5%. Combining arteriography with CT has been tried but does not significantly increase sensitivity.10 Arteriography with catheterization of small arterial branches of the celiac system combined with calcium injections (which stimulate insulin
Functional imaging (Figs. 8—10)
More recently, functional imaging with radiolabelled isotopes such as octreotide adds a further tool in the evaluation and detection of insulinomas.28 The sensitivity of somatostatin receptor scintigraphy is 60%, although some insulinomas lack somatostatin receptor subtype 2 for successful identification.29
Positron emission tomography plays only a limited role. It may detect the presence of a neuroendocrine tumour, and may have a limited role in the evaluation of operability of malignant
Treatment and prognosis
In the vast majority of cases, surgical excision provides a cure and is the treatment of choice.30 Simple enucleation is the procedure of choice in insulinomas in the pancreatic head. Total pancreatectomy is usually avoided because of its high morbidity and mortality. As most tumours are benign, complete cure occurs in up to 90% of patients. Patients with malignant insulinoma have a much better prognosis compared with those with a pancreatic ductal malignancy, and pancreatic resection with
Conclusion
Insulinomas are rare islet cell functional neuroendocrine tumours of the pancreas. They typically present when they are small in size due to their symptomatic release of insulin causing hypoglycaemic effects. The diagnosis is therefore often suggested clinically with biochemical testing confirming the diagnosis. The role of imaging is predominantly used to identify the tumour and assess its location within the pancreas and relationship to other structures. The combination of modern imaging
Acknowledgements
Courtesy of Dr Wai Lup Wong, Mount Vernon Hospital, London.
References (31)
- et al.
Recent advances in the diagnosis and treatment of insulinomas
Surg Clin North Am
(1979) - et al.
Neuroglycopenic and other symptoms in patients with insulinomas
Am J Med
(1999) - et al.
Is preoperative localization of insulinomas necessary?
Ann Chir
(2001) - et al.
Endoscopic ultrasound in the localisation of pancreatic islet cell tumours
Best Pract Res Clin Endocrinol Metab
(2005) - et al.
Imaging islet cell tumours
Clin Radiol
(1994) - et al.
MRI in insulinomas: Preliminary findings
Eur J Radiol
(1992) - et al.
Malignant islet-cell tumors of the pancreas
World J Surg
(1984) - et al.
Surgical approach to insulinomas. Assessing the need for preoperative localization
Arch Surg
(1992) Insulinoma
Neuroendocrinology
(2004)- et al.
Preoperative localization and intraoperative glucose monitoring in the management of patients with pancreatic insulinoma
Surg Gynecol Obstet
(1986)
Localization of hormonally active gastrointestinal tumors
Contrast-enhanced ultrasonographic detection of small pancreatic insulinoma
J Ultrasound Med
Value of abdominal sonography and MR imaging at 0.5 T in preoperative detection of pancreatic insulinoma: A comparison with dynamic CT and angiography
Abdom Imaging
Endoscopic ultrasonography for the preoperative localization of insulinomas
Pancreas
CT, endoscopic sonography, and a combined protocol for preoperative evaluation of pancreatic insulinomas
AJR Am J Roentgenol
Cited by (89)
Imaging of Insulinoma by Targeting Glucagonlike Peptide-1 Receptor
2021, PET ClinicsMultimodality Imaging of the Pancreatic Neuroendocrine Tumors
2019, Seminars in Ultrasound, CT and MRIMR Imaging of Pancreatic Neuroendocrine Tumors
2018, Magnetic Resonance Imaging Clinics of North AmericaCitation Excerpt :CT is often used for initial evaluation of patients with abdominal pain or to identify suspected functioning tumors, as it is widely available, fast, and has excellent resolution. A range of sensitivities has been reported for CT, ranging from 30% to 80% for small tumors, with significantly higher sensitivities reaching up to 95% for larger lesions.21–23 The role of MR imaging in PNET evaluation is expanding.
Pancreatic insulinoma misdiagnosed as atrial fibrillation: A case report from Iraq
2023, Medicine (United States)