Double Duty: Complete Pathologic Response of Two Colonic Primaries with Mosaicism of a Novel MLH1 Mutation to Neoadjuvant Pembrolizumab

Beatrice Preti; Laila Schenkel; Matthew Cecchini; Tommaso Romagnoli; Michael Susmoy Sanatani; Karissa French; Patrick Colquhoun; Mark David Vincent

doi:10.3390/curroncol30100653

Double Duty: Complete Pathologic Response of Two Colonic Primaries with Mosaicism of a Novel MLH1 Mutation to Neoadjuvant Pembrolizumab

Curr Oncol. 2023 Oct 6;30(10):9039-9048. doi: 10.3390/curroncol30100653.

Authors

Beatrice Preti¹, Laila Schenkel², Matthew Cecchini³, Tommaso Romagnoli^{3

4}, Michael Susmoy Sanatani¹, Karissa French⁵, Patrick Colquhoun⁶, Mark David Vincent¹

Affiliations

¹ Division of Medical Oncology, Department of Oncology, Western University, London, ON N6A 3K7, Canada.
² Division of Molecular Diagnostics, Western University, London, ON N6A 3K7, Canada.
³ Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada.
⁴ Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada.
⁵ Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada.
⁶ Department of Surgery, Western University, London, ON N6A 3K7, Canada.

Abstract

We present a fascinating case of a 57-year-old male with a novel mutation in MLH1 (MLH1:c.1288G > T, p.(Glu430*)), who presented with two synchronous colonic tumours, initially deemed unresectable, and experienced a complete pathological response on neoadjuvant pembrolizumab. Extensive genetic testing revealed post-zygotic mosaicism from the novel mutation.

Keywords: MLH1; MSI-H; colon cancer; dMMR; immunotherapy.

Publication types

Case Reports

MeSH terms

Colonic Neoplasms* / drug therapy
Colonic Neoplasms* / genetics
Humans
Male
Microsatellite Instability
Middle Aged
Mosaicism*
MutL Protein Homolog 1 / genetics
Mutation
Neoadjuvant Therapy*

Substances

MLH1 protein, human
MutL Protein Homolog 1
pembrolizumab

Grants and funding

This research received no external funding.