A mismatch repair-deficient and HPV-negative anorectal squamous cell carcinoma

  • Kun JiangEmail author
  • Brian Martens
  • Logan Meyer
  • Kim Truong
  • Gregory Y. Lauwers
Brief Report


Invasive primary squamous cell carcinomas involving the anorectal region are challenging to manage. Microsatellite instability has been shown to impact clinical courses and outcomes of patients affected by many types of carcinomas. To the best of our knowledge, there are no reports on microsatellite instability in anorectal squamous cell carcinomas. Here, we report a HPV-negative anorectal squamous cell carcinoma which, despite cisplatin-based chemoradiation therapy, showed progression. Interestingly, after identification of its mismatch repair-deficiency (MLH1/PMS2-absent, MSH2/MSH6-intact), pembrolizumab-based immunotherapy was initiated, leading to a marked clinical response. This unique case illustrates that microsatellite instability testing and immunotherapy targeting immune checkpoint blockade should be considered for managing anorectal squamous cell carcinomas that fail conventional chemoradiation therapies or when patients are non-surgical candidates. This report provides the first evidence of microsatellite instability in anorectal squamous cell carcinomas and supports the role for microsatellite instability testing in this cancer type to optimize patient management.


Squamous cell carcinoma Anorectal Microsatellite instability Immune checkpoint blockade 



We sincerely thank Dr. Bruce Wenig at Moffitt Cancer Center Pathology department for his expertise opinion and suggestions during the preparation of this manuscript.

Author’s contributions

Dr. Jiang conceived and designed the study, and wrote, edited, and reviewed the manuscript. Drs. Martens, Meyer, Truong, and Lauwers researched the data and edited and reviewed the manuscript. All authors gave the final approval for publication. Dr. Jiang takes full responsibility for the work, including the study design, access to data, and the decision to submit and publish the manuscript.

Compliance with ethical standards

This is a brief report on a novel and unique case of diagnostic interest; it is not a research project; there is no Human or Animal participant(s). Informed consent was acquired although no confidential personal information was cited or disclosed in this brief report.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PathologyH. Lee Moffitt Cancer CenterTampaUSA
  2. 2.University of South Florida Morsani College of MedicineTampaUSA
  3. 3.Department of RadiologyH. Lee Moffitt Cancer CenterTampaUSA

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