Synchronous Periampullary Tumors in a Patient With Pancreas Divisum and Neurofibromatosis Type 1

Cleandra Gregório; Clévia Rosset; Laura da Silva Alves; Cristina Brinkmann Oliveira Netto; Simone Marcia Dos Santos Machado; Vivian Pierri Bersch; Alessandro Bersch Osvaldt; Patricia Ashton-Prolla

doi:10.3389/fgene.2020.00395

Synchronous Periampullary Tumors in a Patient With Pancreas Divisum and Neurofibromatosis Type 1

Front Genet. 2020 Apr 28:11:395. doi: 10.3389/fgene.2020.00395. eCollection 2020.

Authors

Affiliations

¹ Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
² Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
³ Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
⁴ Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁵ Serviço de Patologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁶ Serviço de Cirurgia do Aparelho Digestivo, Grupo de Vias Biliares e Pâncreas, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
⁷ Grupo do Pâncreas, Serviço de Cirurgia do Aparelho Digestivo, Hospital Moinhos de Vento, Porto Alegre, Brazil.
⁸ Programa de Pós-graduação em Medicina: Ciências Cirúrgicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Abstract

Introduction: In this study, we describe for the first time a Neurofibromatosis type 1 patient with pancreas divisum, multiple periampullary tumors and germline pathogenic variants in NF1 and CFTR genes.

Case report: A 62-year-old female NF1 patient presented with weakness, choluria, nausea, and diffuse abdominal pain to an emergency room service. Magnetic resonance imaging revealed an abdominal mass involving the periampullary region and pancreas divisum. After surgical resection, three synchronous neoplasms were detected including two ampullary tumors (adenocarcinoma of the major ampulla and a neuroendocrine tumor of the minor ampulla) and a gastrointestinal stromal tumor (GIST). Germline multigene panel testing (MGPT) identified two pathogenic heterozygous germline variants: NF1 c.838del and CFTR c.1210-34TG[12]T[5].

Conclusion: This is the first report of a Neurofibromatosis type 1 patient with pancreas divisum and multiple periampullary tumors harboring pathogenic germline variants in NF1 and CFTR genes. The identification of two germline variants and a developmental anomaly in this patient may explain the unusual and more severe findings and underscores the importance of comprehensive molecular analyses in patients with complex phenotypes.

Keywords: CFTR pathogenic variant; GIST; NF1 pathogenic variant; neurofibromatosis type 1; pancreas divisum; periampullary tumors; synchronous neoplasms.