Assessment of tumor growth in pancreatic neuroendocrine tumors in von Hippel Lindau syndrome

Background The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing, but only a subset of these heterogeneous tumors will progress to malignant disease, which is associated with a poor prognosis. Currently, there are limited data on the natural history of these tumors and it is difficult to determine which patients require surgical intervention because the risk of metastatic disease cannot be accurately determined. Study Design We conducted a prospective study of 87 patients with von Hippel Lindau syndrome-associated solid pancreatic lesions to determine the natural history of these tumors with biochemical testing, follow-up anatomic and functional imaging, and advanced imaging analysis, with a median follow-up of 4 years. Results Approximately 20% of consecutive tumor measurements during follow-up were decreased in size and 20% showed no change. This included 2 of 4 surgically proven malignant tumors, which had a net decrease in tumor size over time. Tumor volume, as derived from greatest diameter and volumetric measurements, showed good correlation to pathology tumor measurement of surgically resected tumors (Spearman rank correlation ρ = 0.72, p = 0.0011, and ρ = 0.83, p < 0.0001, respectively). Tumor density measurement had an inverse relationship with tumor size (Spearman rank correlation -0.22, p = 0.0047). A tumor density cutoff of 200 was 75% specific for malignant tumors. Conclusions Pancreatic neuroendocrine tumors demonstrate a nonlinear growth pattern, which includes periods of no growth and apparent decrease in size by imaging. These growth patterns are variable and are not associated with tumor grade and malignancy. Tumor density, as measured in this cohort, may offer a specific diagnostic tool for malignant disease.