Evolving paradigm for managing small nonfunctional incidentally discovered pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PNETs), although rare, have been increasing in incidence over the last two decades (1). Their biological behavior encompasses a spectrum from slow-growing and indolent to aggressive, with the potential to spread to distant sites resulting in death. Studies have documented that the risk of spread and distant disease is often related directly to tumor size (2) and inversely to incidental detection (3). Broadly, PNETs can be classified as functional or nonfunctional. Functional tumors are defined by the production and release into the circulation of hormones, such as insulin, that have biological activity and can result in significant morbidity. Management of these functional PNETs is surgical resection when technically feasible, and this recommendation is generally agreed upon. The best approach for the management of incidentally discovered nonfunctional PNETs is not as straightforward. Nonfunctional tumors are often silent and asymptomatic, discovered only when detected by imaging studies often ordered to work-up unrelated conditions or complaints. Unlike their functional counterparts, the sole reason for managing asymptomatic nonfunctional PNETs is to prevent their spread to distant sites and any subsequent impact on the patient’s survival. With the improvement in cross-sectional imaging techniques, an increasing number of small ( 2.0 cm) asymptomatic PNETs are being discovered. The so-called “incidental” PNET is the subject of a natural history study published in the current issue of the JCEM (4). Gaujoux et al (4) report on an over 10-year experience diagnosing, managing, and following nonfunctioning PNETs less than 2.0 cm in size in 46 patients at two institutions. All patients that were followed had at least 18 months of serial imaging or follow-up after resection. Median overall follow-up for all patients was 34 months, with maximum follow-up of 52 months. As the authors point out in their introduction, there is a paucity of level 1 data available to guide management decisions for the asymptomatic patient found to have a less than 2.0-cm PNET. The authors considered patients for inclusion in their retrospective study based on the following criteria: 1) they must be over 18 years old; 2) they must have been diagnosed with a nonfunctioning PNET, defined according to the European Neuroendocrine Tumor Society guidelines by the absence of clinical symptoms of hormonal hypersecretion (http://www.enets.org); 3) the tumor must be smaller than 2.0 cm in diameter on imaging at initial diagnosis (in multifocal lesions, only the largest lesion was measured); 4) patients must be free of main pancreatic duct or biliary dilatation on imaging; 5) tumors must be of sporadic origin (and with multiple endocrine neoplasia type 1 [MEN1]-negative genetic testing if tumors were multiple); 6) tumors must have been incidentally discovered (ie, defined as lesions detected during abdominal imaging done for nonpancreatic-related reasons); 7) tumors must present without local invasion, node, or distant metastasis on imaging; 8) patients must have a proven diagnosis (ie, positive fine-needle aspiration [FNA], biopsy under endoscopic ultrasound, or positive somatostatin receptor imaging); 9) patients should have a Ki-67 2% when available; 10) patients should not have past or present specific treatment of their PNET (including somatostatin analogs); 11) tumor should be initially nonresected or resected after at least 18 months of radiological follow-up; and 12) tumor should have at least two serial cross-sectional images available.