Case report: Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, associated with a germline mutation in PMS2

Abstract

Most tumors, including brain tumors, are sporadic. However, a small subset of CNS tumors are associated with hereditary cancer conditions like Lynch Syndrome (LS). Here, we present a case of an oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and LS with a germline pathogenic PMS2 mutation. To our knowledge, this has only been reported in a few cases in the literature. While the family history is less typical of LS, previous studies have indicated the absence of a significant family history in patient cohorts with PMS2 mutations due to its low penetrance. Notably, only a handful of studies have worked on characterizing PMS2 mutations in LS, and even fewer have looked at these mutations in the context of brain tumor development. This report aims to add to the limited literature on germline PMS2 mutations and oligodendrogliomas. It highlights the importance of genetic testing in neuro-oncology.

Keywords: CNS; IDH-mutant and 1p/19q-codeleted; PMS2; lynch syndrome; oligodendroglioma.

Figure 1

Timeline of the disease history and management. TMZ, Temozolomide.

Figure 2

Diagnosis of an oligodendroglioma, IDH-mutant and 1p/19q co-deleted, CNS WHO grade 3 by (A) MRI before the most recent tumor resection; (B) H&E staining (20X) and (C) DNA methylation profiling of the tumor sample from the most recent tumor resection.

Figure 3

(A) PMS2 mutation found in the proband (c.251-2A>T); (B) Immunohistochemistry staining of MMR proteins, including MLH1, MSH6, MSH2, and PMS2 (20X) using the tumor sample from the most recent tumor resection.

Figure 4

Three-generation family history pedigree.