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Published on: June 8, 2019
Glioma arising in the setting of mismatch repair deficiency-rare or are we missing it?
Aditi Goyal1, Shilpa Rao1, Karthik S Rishi2
1Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India.
Abstract:
Germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) can be mono-allelic or biallelic, resulting in a Lynch syndrome (LS) or constitutional mismatch repair deficiency (CMMRD) syndrome respectively. Glioma arising in the setting of MMR deficiency is uncommon. We describe two pediatric patients with high-grade glioma (HGG) and associated MMR protein deficiency. On histomorphology both cases showed HGG with astrocytic morphology and prominent multinucleated tumor cells. On immunohistochemistry, the first case was negative for IDH1 p.R132H showed loss of ATRX and p53 positivity. The second case was positive for IDH1 p.R132H and p53, but showed retained expression of ATRX. The histomorphology in both cases and additionally IDH mutation with retained ATRX in the second case, prompted us to test for MMR protein deficiency which was carried out by immunohistochemistry (IHC). One case revealed an immunostaining pattern suggestive of CMMRD while the other was suggestive of LS. Both the cases showed good response to surgery and radio-chemotherapy in the follow-up available. Our cases highlight the importance of testing for MMR proteins by simple IHC, in the setting of appropriate clinical scenario, histopathological and immunohistochemical findings. The recognition of these tumors is extremely important to guide further treatment and prompt family screening.
Insights
Mismatch repair deficiency is linked to rare pediatric high-grade gliomas. Identifying this deficiency through immunohistochemistry is crucial for guiding treatment and family screening.
Area of Science:
- Oncology
- Genetics
- Neuropathology
Background:
- Germline mutations in mismatch repair (MMR) genes cause Lynch syndrome (LS) or constitutional mismatch repair deficiency (CMMRD).
- High-grade gliomas (HGG) in the context of MMR deficiency are infrequent.
- This study examines two pediatric HGG cases with MMR protein deficiency.
Purpose of the Study:
- To report two pediatric cases of high-grade glioma with MMR protein deficiency.
- To highlight the diagnostic utility of immunohistochemistry for MMR proteins in HGG.
- To emphasize the importance of recognizing these rare tumors for treatment and family screening.
Main Methods:
- Histopathological examination of HGG with astrocytic morphology and multinucleated tumor cells.
- Immunohistochemistry (IHC) for MMR proteins, IDH1 p.R132H, ATRX, and p53.
- Clinical correlation of findings to differentiate between CMMRD and LS.
Main Results:
- Both cases presented as HGG with specific morphological features.
- One case showed MMR protein deficiency suggestive of CMMRD; the other suggested LS.
- Both patients responded well to standard treatments including surgery and radio-chemotherapy.
Conclusions:
- Testing for MMR protein deficiency via IHC is vital in specific clinical and histopathological scenarios.
- Early recognition of MMR-deficient HGG aids in appropriate treatment selection.
- Identifying MMR deficiency facilitates essential family screening for hereditary cancer syndromes.
