Incidental nonfunctioning pancreatic endocrine tumors: clinical and surgical implications

Introduction: the widespread use of imaging techniques allowed increasing incidentally detection of asymptomatic non-functioning PNETs (NF-PNETs). Incidental non-functioning PNETs (I-NF-PETs) are usually smaller and lower in stage than symptomatic NF-PNETs (S-NF-PETs) and incidental detection seems to be an important favourable prognostic factor even after accounting for tumor stage, grade and location. There is a complete lack of data as regards of the admitted correct management of asymptomatic patients with potentially benign NF-PET. Aims:1) to define the biological behaviour of I-NF-PETs who underwent surgical resection and 2) to evaluate a follow-up policy in the management of I-NF-PNETs at stage I. Methods: All patients with a pathologically confirmed diagnosis of sporadic NF-PETs who underwent resection at the Departments of Surgery of the University of Verona and of Ospedale “Sacro Cuore – Don Calabria” of Negrar between 1990 and 2011 were included. A comparison of demographic, clinical and pathological characteristics between I-NF-PETs and S-NF-PETs was made. Statistical analyses were performed to identify differences in biological behavior between I-NF-PETs and S-NF-PETs. Results: A total of 131 patients (42.8%) had diagnosis of I-NF-PETs and the remaining 175 patients (57.2%) had diagnosis of S-NF-PETs. No sex predilection was observed (p=0.752). The median patient age was for male: 62 years (range 24 – 83) and 55 (range 17 – 78) with I-NF-PET and S-NF-PET diagnosis respectively; for female was 55 years (range 35 – 72) and 53 (range 25 – 74) with I-NF-PET and S-NF-PET (p= 0.223) respectively. The most common location of I-NF-PETs was in the body-tail of the pancreas (65 cases, 49.6%), whereas S-NF-PETs were most commonly founding both in the body-tail (56.6%) and in the head of the pancreas (38.3%) (p= <0.001). Clear surgical margins (R0) were obtained in 123 patients (93.9%) with I-NF-PET and in 131 patients (74.9%) with S-NF-PET (p<0.001). Median tumor size was lesser for I-NF-PETs with a median of 20 mm (range 7 – 120), than S-NF-PETs (median 35 mm; range 5 – 140); p= 0.016). Therefore T1 incidental tumors were mostly found than symptomatic PETs (p<0.001). Equally lymph-node metastases (N1) were identified in 44.6% of patients with S-NF-PET (78 cases) versus a 20.6% of patients with incidental tumor (27 cases); p<0.001. One patient with I-NF-PET on stage I was found to have malignant disease; this patient initially was classified as benign and underwent enucleation with clear surgical margins (R0), but had liver disease recurrence after 28 months after surgical resection. In this case preoperative imaging evaluation demonstraded the main pancreatic duct (MPD) obstruction (> 5 mm) and a serotonin immunoreactivity at the immunohistochemical evaluation. From September 2007 to September 2011 a total of 19 patients with I-NF-PNET diagnosis were enrolled. All cases was classified as NET-G1 and median size was 15 mm (range 9 – 20). In all cases, no MPD obstruction was confirmed at preoperative imaging. All this patients refused surgical resection. Currently Follow-Up was available for all patients, with a median follow-up of 22 months (range 6 – 48). All Patients were alive, asymptomatic and with tumor stable in size and no evidence of progression disease. Conclusions: this study shows that patients with incidentally detected NF-PETs represent about 40% of resectable NF-PETs and frequency of incidental diagnosis was increasing in last years. Incidental detection seems to be an important favorable prognostic factor for histopathological features, patients overall survival and disease free survival. Anyway pancreatic surgery have a recognized high rate of perioperative morbidities and for < 20 mm and carefully selected pancreatic neuroendocrine “incidentalomas” a clinical-laboratory and radiographic surveillance might be possible.