Systematic comparison of sporadic and syndromic pancreatic islet cell tumors

Abstract

Pancreatic islet cell tumors (ICTs) occur as sporadic neoplasias or as a manifestation of multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau disease (VHL). Molecular classification of ICTs is mandatory for timely diagnosis and surveillance. Systematic comparison of VHL-ICTs and sporadic ICTs has been lacking. Our registry-based approaches used the German NET-Registry with 259 patients with neuroendocrine tumors (NETs), who were primarily diagnosed with NETs, and the German VHL-Registry with 485 molecular genetically confirmed patients who had undergone magnetic resonance imaging or computed tomography of the abdomen. All patients provided blood DNA for testing of the MEN1 and VHL genes for intragenic mutations and large deletions. In the NET-Registry, 9/101 patients (8.9%) with ICTs had germline mutations, 8 in MEN1 and 1 in VHL. In the VHL-Registry, prevalence of NETs was 52/487 (10.6%), and all were ICTs. Interestingly, of those with VHL p.R167W, 47% developed ICTs, compared to 2% of those with p.Y98H. In total, there were 92 truly sporadic, i.e. mutation-negative ICT patients. Comparing these with the 53 VHL-ICT patients, the statistically significant differences were predominance of female gender (PZ0.01), multifocal ICTs (PZ0.0029), and lower malignancy rate (P!0.001) in VHL-ICTs compared to sporadic cases. VHL was prevalent in !0.5% of NETs, while NETs occur in w10% of VHL, virtually exclusively as ICTs, which are rarely the first presentation. Patients with NETs should not be subjected to genetic testing of the VHL gene, unless they have multifocal ICTs, other VHL-associated tumors, and/or a family history for VHL.

Transcriptional alterations in hereditary and sporadic nonfunctioning pancreatic neuroendocrine tumors according to genotype

“…The pathways involved in cilium and microtubule formation, both of which are part of the cell's spindle‐cell apparatus and are crucial to cell division, were upregulated in sporadic NFPanNETs, which could explain the reported aggressive behavior and rapid growth of sporadic tumors compared with their hereditary counterparts (Fig. ) . Gene enrichment in pathways comprising ion channel activity and neuron development, both of which reportedly are upregulated in PanNETs, were most prevalent in MEN1‐associated NFPanNETs only (Fig.…”

“…3). 28 Gene enrichment in pathways comprising ion channel activity and neuron development, both of which reportedly are upregulated in PanNETs, were most prevalent in MEN1-associated NFPanNETs only (Fig. 4).…”

von Hippel–Lindau disease: A clinical and scientific review

“…33,34 Pancreatic tumours with cystic components are microcystic cystadenomas. 35 Other features Endolymphatic sac tumours (ELST) can be detected by MRI or CT imaging in up to 11% of patients. 36 Bilateral ELSTs are considered pathognomonic for VHL disease.…”

Network Oncology (NO) - a Clinical Cancer Register for Health Services Research and the Evaluation of Integrative Therapeutic Interventions in Anthroposophic Medicine

“…They comprise a group of hospitals or outpatient practices with fewer cases, which are basically not representative for a population. Cancer entity specific registers like the German registers for neuroendocrine tumors [4,5] or gastrointestinal stromal tumors [6] record cases in more detail, using also pathological and therapeutic data to develop tumor classifications and new therapeutic strategies [7]. However, none of these registers records complementary or integrative therapy methods that are internationally summarized as complementary and alternative medicine (CAM) [8,9].…”