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Case report
Pancreatic cancer ‘mismatch’ in Lynch syndrome
  1. Andrew E Hendifar1,
  2. Brent K Larson2,
  3. Rebecca Rojansky2,
  4. Michelle Guan1,
  5. Jun Gong1,
  6. Veronica Placencio1,
  7. Richard Tuli3,
  8. Megan Hitchins4
  1. 1 Department of Gastrointestinal Malignancies, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
  2. 2 Department of Pathology, Stanford University, Stanford, California, USA
  3. 3 Department of Radiation Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
  4. 4 Cancer Genetics and Prevention Program, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
  1. Correspondence to Dr Andrew E Hendifar; Andrew.Hendifar{at}cshs.org

Abstract

Objective Immune therapy with the PD1 inhibitor pembrolizumab has been approved to treat unresectable/metastatic solid tumours exhibiting mismatch repair (MMR) deficiency. Lynch syndrome (LS), caused by autosomal dominant germline mutations of a MMR gene, predisposes to the development of MMR-deficient cancers. We report a case of MSH2-LS with an MMR-intact pancreatic ductal adenocarcinoma (PDAC) ineligible for treatment with pembrolizumab.

Design Immunohistochemistry of MMR proteins was performed in each malignancy developed in a MSH2-LS patient to determine MMR status.

Results The patient carried a pathogenic MSH2 germline mutation and had a history of LS-type cancers, including endometrial carcinoma, colorectal adenocarcinoma, urothelial carcinoma of the bladder and PDAC. Three malignancies (endometrial, colorectal, urothelial) lacked MSH2 and MSH6 expression, consistent with MSH2-associated tumorigenesis. However, MSH2 and MSH6 expression were intact in the PDAC, suggesting the sporadic occurrence of the pancreatic tumour unrelated to the germline MSH2 mutation. These inconsistent MMR statuses among the tumours rendered the patient ineligible for the immunotherapy pembrolizumab.

Conclusion Testing for MMR protein expression is recommended for each tumour in patients with LS, especially pancreatic, as discordant results may have profound effects on treatment opportunities. To our knowledge, this is the first documented case of MMR-intact PDAC in a patient with MSH2-LS.

  • DNA Microsatellite Instability
  • Cancer Genetics
  • Cancer Syndromes
  • Pancreatic Cancer
  • Gastrointestinal Cancer

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjgast-2019-000274

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    Footnotes

    • Contributors AEH wrote the manuscript, performed literature searches, cared for the patient, obtained consent for images to be used herein and provided the case history. BKL and RR prepared the figures and analysed the histological images. MG contributed to parts of the manuscript and performed literature searches. JG, VP, RT and MH edited the manuscript prior to submission.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent Not required.

    • Ethics approval Obtained from institution.

    • Provenance and peer review Not commissioned; externally peer reviewed.