Brain Tumor Res Treat.  2024 Jan;12(1):70-74. 10.14791/btrt.2023.0042.

Lynch Syndrome-Associated Glioblastoma Treated With Concomitant Chemoradiotherapy and Immune Checkpoint Inhibitors: Case Report and Review of Literature

• Nakase K
• Matsuda R
• Sasaki S
• Nakagawa I

• KMID: 2552343
• DOI: http://doi.org/10.14791/btrt.2023.0042

Abstract

Lynch syndrome (LS) is an autosomal dominant disorder caused by mutations in mismatch repair (MMR) genes and is also known to be associated with glioblastomas. The efficacy of immunotherapy for LS-associated glioblastomas remains unknown. Herein, we report a rare case of LS-associated glioblastoma, treated with chemotherapy using immune checkpoint inhibitors (ICI). A 41-year-old female patient presented with headaches and sensory disturbances in the right upper limb for 6 weeks. She had been treated for rectal cancer and had a family history of LS. MRI revealed two ring-enhancing lesions in the left precentral gyrus. She underwent subtotal resection, leading to a pathological diagnosis of isocitrate dehydrogenase wild-type glioblastoma. She received daily administration of (temozolomide, 75 mg/m ² ) and concurrent radiotherapy (60 Gy) postoperatively. However, the tumor recurred 1 year after the initial treatment. A molecular genetic study showed high microsatellite instability (MSI), and she was treated with pembrolizumab therapy. Disease progression occurred despite six cycles of pembrolizumab therapy and radiotherapy at the dose of 40 Gy. She died due to glioblastoma progression 19 months after the initial treatment. The present case demonstrates that some LS-associated glioblastomas may be resistant to ICI despite high MSI, possibly because of intratumor heterogeneity related to MMR deficiency.

Keyword

Lynch syndrome; Glioblastomas; Immunotherapy

Figure

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  Fig. 1 Patient brain neuroimaging. A: Pedigree showing affected and unaffected members of the patient’s family. B-G: MRI showing two lesions. The lesions are hyperintense on axial T2-weighted images (B and E) and ring-enhancing on contrast-enhanced T1-weighted images (C and F). Postoperative contrast-enhanced T1-weighted image shows subtotal resection (white arrow) (D and G).

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  Fig. 2 Histopathological findings showing glioblastoma feature, including poorly differentiated pleomorphic tumor cells with marked nuclear atypia and brisk mitotic activity, focal necrosis with pseudopalisades, and microvascular proliferation. The tumor cells were negative for isocitrate dehydrogenase (IDH)-1. P53 staining showed strong positivity in about 30% of the tumor cells. The lesion was diagnosed as glioblastoma, IDH wild type (A and B: H&E staining, ×100; C: IDH, ×200; D: p53, ×200).

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