The first pancreatic neuroendocrine tumor in Li-Fraumeni syndrome: a case report

Abstract

Background: Li-Fraumeni syndrome is a cancer predisposition syndrome caused by germline TP53 tumor suppressor gene mutations, with no previous association with pancreatic neuroendocrine tumors (PNETs). Here we present the first case of PNET associated with Li-Fraumeni syndrome. Case presentation: This is a 43-year-old female who underwent laparoscopic distal pancreatectomy at age 39 for a well-differentiated grade 2 cystic PNET. When the patient was 41 years old, her seven-year-old daughter was found to have an astrocytoma and a germline TP53 mutation. While undergoing surveillance with 68 Gallium-DOTATATE positron emission tomography/computed tomography for her PNET, the patient was found to have a large choroid plexus papilloma in her right temporal lobe. She underwent genetic counseling and testing that identified a germline pathogenic variant in TP53, leading to the diagnosis of Li-Fraumeni syndrome. Her PNET had a hemizygous pathogenic TP53 mutation with loss of the wild-type alternate allele, consistent with loss of heterozygosity and the two-hit hypothesis. She was enrolled in a Li-Fraumeni syndrome protocol and continues surveillance screening with our service. Conclusions: This is the first PNET reported in association with Li-Fraumeni syndrome. Pancreatic cancer risk is elevated in this syndrome, and our case highlights the need for vigilance in screening for pancreatic neoplasms in these patients.

Risk factors for pancreas and lung neuroendocrine neoplasms: a case–control study

“…Genes involved in familial susceptibility are well known for both lung and pancreas NEN. Heritable syndromes associating with NEN development include the multiple endocrine neoplasia type 1 syndrome and, less frequently, the von Hippel-Lindau, the neurofibromatosis type 1, the Cowden, the tuberous sclerosis and the Li-Fraumeni syndromes [ 26 , 27 ]. During the last three years also deep sequencing data on solid cancer unveiled unexpected germline gene aberrations in neuroendocrine neoplasia (e.g., MUTYH , CHEK2 , and BRCA2 genes in pancreas NEN) [ 28 , 29 ] together with a substantial absence of known cancer drivers [ 30 , 31 ].…”

Li–Fraumeni-associated pancreatic neuroendocrine tumour and XAF1 p.Glu134Ter risk modifier variant

“…Only one previous case of a pNET associated with LFS has been reported. The case was of a 43-year-old female with a G2 pNET and a rare TP53 PGVs on the residue 337, c.1009C > T, p.R337C, which was also found in her pNET tissue with an allele frequency of 93% [ 6 ]. Here we report the first case of a patient with pNET and TP53 p.R337H and XAF1 p.E134* germline variants.…”

Clinical Course, Genetic, and Immunohistochemical Characterization of Solid Pseudopapillary Tumor of the Pancreas (Frantz Tumors) in a Brazilian Cohort

“…To our knowledge, this is the first report evaluating germline genetic testing in SPN of the pancreas and describing this type of association. A variety of pancreatic neuroendocrine tumors are described in patients with Li-Fraumeni syndrome in some reports [ 40 ]. Furthermore, a different histology of pancreatic tumors consisting of adenocarcinomas are seven times more frequent in Li-Fraumeni patients [ 41 , 42 ].…”