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Mod Pathol. 2019 Jul 8. doi: 10.1038/s41379-019-0317-6. [Epub ahead of print]

Histomorphology of pancreatic cancer in patients with inherited ATM serine/threonine kinase pathogenic variants.

Author information

1
Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
3
Department of Surgery, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
4
Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
5
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
6
Department of Medicine, University of Pittsburgh Medical Center Health System, Pittsburgh, PA, USA.
7
Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, PA, USA.
8
Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. nrobert8@jhmi.edu.
9
Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. nrobert8@jhmi.edu.
10
Department of Pathology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. rhruban@jhmi.edu.
11
Department of Oncology, the Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA. rhruban@jhmi.edu.

Abstract

Germline pathogenic variants in the ATM serine/threonine kinase (ATM) gene are associated with an increased risk of pancreatic ductal adenocarcinoma. It is important to identify germline ATM pathogenic variants in pancreatic cancer patients because these alterations are potentially targetable with chemotherapeutic drugs and/or radiation and have implications for other family members. As germline pathogenic variants in other genes have been associated with distinct histologic subtypes of pancreatic cancer, we studied the histomorphology of pancreatic cancer in 23 patients with germline ATM pathogenic variants. The histologic subtype was ductal adenocarcinoma in 19/23 (83%) of the patients, adenosquamous carcinoma in 1/23 (4%), and colloid (mucinous non-cystic) carcinoma in 3/23 (13%). The percentage of colloid (mucinous non-cystic) carcinomas is higher than we have previously observed in patients with familial and sporadic pancreatic cancer (1 and 2% in prior reports, pā€‰<ā€‰0.01 and pā€‰<ā€‰0.01, respectively). Three carcinomas (2 colloid carcinomas, 1 ductal adenocarcinoma) arose in association with intraductal papillary mucinous neoplasms. Among the resected pancreata, non-invasive precursor lesions, including pancreatic intraepithelial neoplasia and incipient intraductal papillary mucinous neoplasms, were identified in 83%. We conclude that pancreatic cancers in patients with germline ATM pathogenic variants are more frequently of colloid (mucinous non-cystic) morphology but are overall morphologically diverse supporting the utility of universal germline genetic testing for patients with pancreatic cancer.

PMID:
31285527
DOI:
10.1038/s41379-019-0317-6

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