A novel hyperplasia-neoplasia sequence in pancreatic endocrine tumors: Glucagon cell adenomatosis

Pancreatic neuroendocrine neoplasms: Updates on genomic changes in inherited tumour syndromes and sporadic tumours based on WHO classification

“…In contrast, the disease mechanisms are still unclear in patients without GCGR mutations. The disorder seems to be unrelated to MEN1 and VHL [70,71]. Although GCHN has generally followed a benign clinical course, one of the patients with wild-type GCGR showed lymph node micro-metastases [70].…”

“…The patient's parents also showed an identical but heterozygous GCGR mutation [70]. Loss of the GCGR genes may lead to the development of islet glucagon cell hyperplasia, glucagon cell microadenomas, macroadenomas and/or increased serum glucagon level [70,72]. The patients with GCGR mutations exhibited numerous tumours (could >600) and larger tumour size (up to 80 mm) than tumours from patients with wild-type GCGR [70].…”

“…GCHN, also known as glucagon cell adenomatosis (GCA), is a recently recognised inherited autosomal-recessive disorder caused by germline mutations in GCGR located on chromosome 17q25 [67][68][69][70][71][72]. The GCGR germline mutations were found in 50% of patients, which was homozygous GCGR mutations or at least two heterozygous mutations leading to premature stop codons or probably deficient protein expression [70]. The patient's parents also showed an identical but heterozygous GCGR mutation [70].…”

“…The GCGR germline mutations were found in 50% of patients, which was homozygous GCGR mutations or at least two heterozygous mutations leading to premature stop codons or probably deficient protein expression [70]. The patient's parents also showed an identical but heterozygous GCGR mutation [70]. Loss of the GCGR genes may lead to the development of islet glucagon cell hyperplasia, glucagon cell microadenomas, macroadenomas and/or increased serum glucagon level [70,72].…”

“…Loss of the GCGR genes may lead to the development of islet glucagon cell hyperplasia, glucagon cell microadenomas, macroadenomas and/or increased serum glucagon level [70,72]. The patients with GCGR mutations exhibited numerous tumours (could >600) and larger tumour size (up to 80 mm) than tumours from patients with wild-type GCGR [70]. In contrast, the disease mechanisms are still unclear in patients without GCGR mutations.…”