Lynch syndrome-associated chordoma with high tumor mutational burden and significant response to immune checkpoint inhibitors

Brain Tumor Pathol. 2023 Jul;40(3):185-190. doi: 10.1007/s10014-023-00461-w. Epub 2023 Apr 22.

Abstract

Chordoma is a rare malignant bone tumor arising from notochordal tissue. Conventional treatments, such as radical resection and high-dose irradiation, frequently fail to control the tumor, resulting in recurrence and re-growth. In this study, genetic analysis of the tumor in a 72-year-old male patient with refractory conventional chordoma of the skull base revealed a high tumor mutational burden (TMB) and mutations in the MSH6 and MLH1 genes, which are found in Lynch syndrome. The patient and his family had a dense cancer history, and subsequent germline genetic testing revealed Lynch syndrome. This is the first report of a chordoma that has been genetically proven to be Lynch syndrome. Chordomas usually have low TMB; however, this is an unusual case, because the TMB was high, and immune checkpoint inhibitors effectively controlled the tumor. This case provides a basis for determining the indications for immunotherapy of chordoma based on the genetic analysis. Therefore, further extensive genetic analysis in the future will help to stratify the treatment of chordoma.

Keywords: Clival chordoma; Immune-checkpoint inhibitor; Immunotherapy; Lynch syndrome; Tumor mutational burden.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Chordoma* / genetics
  • Chordoma* / therapy
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / therapy
  • Genetic Testing
  • Humans
  • Immune Checkpoint Inhibitors
  • Male
  • Mutation

Substances

  • Immune Checkpoint Inhibitors