J Pathol Transl Med.  2022 Mar;56(2):92-96. 10.4132/jptm.2021.10.15.

An unusual case of microsatellite instability–high/deficient mismatch repair (MSI-H/dMMR) diffuse large B-cell lymphoma revealed by targeted gene sequencing

• Han B
• Kim S
• Koh J
• Bae JM
• Yun H
• Jeon YK

• KMID: 2527193
• DOI: http://doi.org/10.4132/jptm.2021.10.15

Abstract

Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status has been approved as a tissue-agnostic biomarker for immune checkpoint inhibitor therapy in patients with solid tumors. We report the case of an MSI-H/dMMR diffuse large B-cell lymphoma (DLBCL) identified by targeted gene sequencing (TGS). A 90-year-old female who presented with vaginal bleeding and a large mass in the upper vagina was diagnosed with germinal center-B-cell-like DLBCL, which recurred at the uterine cervix at 9 months after chemotherapy. Based on TGS of 121 lymphoma-related genes and the LymphGen algorithm, the tumor was classified genetically as DLBCL of EZB subtype. Mutations in multiple genes, including frequent frameshift mutations, were detected by TGS and further suggested MSI. The MSI-H/dMMR and loss of MLH1 and PMS2 expression were determined in MSI-fragment analysis, MSI real-time polymerase chain reaction, and immunohistochemical tests. This case demonstrates the potential diagnostic and therapeutic utility of lymphoma panel sequencing for DLBCL with MSI-H/dMMR.

Keyword

Diffuse large B-cell lymphoma; Microsatellite instability; Deficient mismatch repair; Targeted gene sequencing

Figure

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  Fig. 1 Microscopy and immunohistochemical findings. (A) Atypical lymphoid cells show a centroblastic morphology and diffuse growth pattern. Atypical lymphoid cells are positive for CD20 (B), CD10 (C), and BCL6 (D) and are negative for MUM1 (E), BCL2 (F), and C-MYC (G). The Ki-67 labeling index was 80% (H). Scattered small CD3+ cells (I) and CD8+ cells (J) are observed. Programmed death-ligand 1 is expressed mainly in tumor-associated macrophages and occasionally in tumor cells (insert, about 5% of tumor cells in the whole slide) (K). Immunohistochemistry reveals mismatch repair proteins and loss of expression of MLH1 (L) and PMS2 (M) but intact expression of MSH6 (N) and MSH2 (O).

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  Fig. 2 Microsatellite instability (MSI) test results. MSI was detected in all five quasi-monomorphic markers using the U-TOP MSI detection test, revealing the MSI-high (MSI-H) status of the tumor. Genomic DNA from HeLa cells was used as a negative control.

Reference

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