A pediatric bithalamic high grade glioma with concomitant H3K27M and EGFR mutations

Background. Despite many treatment approaches, survival rates in high grade glial tumors are still not at the desired level. One of the cause of this failure might be that although having similar histologic features, they may display different biological behaviors depending on molecular heter...

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Main Authors: Buket Kara, Ayça Ersen Danyeli, Mehmet Öztürk, Kübra Ertan, Yavuz Köksal
Format: Article
Language:English
Published: Hacettepe University Institute of Child Health 2022-08-01
Series:The Turkish Journal of Pediatrics
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Online Access:https://turkjpediatr.org/article/view/206
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author Buket Kara
Ayça Ersen Danyeli
Mehmet Öztürk
Kübra Ertan
Yavuz Köksal
author_facet Buket Kara
Ayça Ersen Danyeli
Mehmet Öztürk
Kübra Ertan
Yavuz Köksal
author_sort Buket Kara
collection DOAJ
description Background. Despite many treatment approaches, survival rates in high grade glial tumors are still not at the desired level. One of the cause of this failure might be that although having similar histologic features, they may display different biological behaviors depending on molecular heterogeneity. Case. A 10-year-old girl presented with sudden onset left sided hemiparesis, headache, and ataxia. Physical examination was normal except for left sided hemiparesis and ataxia. A hyperintense mass lesion involving the bilateral thalamus was detected in the axial T2-weighted and coronal FLAIR sequences on brain MRI. There was no enhancement in axial T1-weighted contrast-enhanced sequences. Due to the size and location of the tumor, the patient was considered inoperable. Intensity modulated radiotherapy was intended for curative treatment to the patient because the radiological findings suggested a low-grade glial tumor. Tumor was unresponsive to radiotherapy but biopsy could be performed. The histopathological examination revealed a diffuse glial tumor with increased cellularity, mild nuclear atypia and rare mitosis. Due to the infiltrative pattern of the tumor, it was accepted as a high grade diffuse glial tumor. A chemotherapy protocol including cisplatin and etoposide in the first cycle, vincristine and cyclophosphamide in the second cycle, and carboplatin and vincristine in the third cycle were instituted to the patient. After the third cycle of chemotherapy, the tumor progressed radiologically. H3.1 K27M c.83A > T (HIST1H3C p.Lys28Met), ATRX c.2169_2170del (p.Glu723AspfsTer9), TP53 c.338T > C (p.Phe113Ser), and EGFR c.2300_2308dup (p.Ala767_va1769dup) were detected in the genetic assessment of tumor tissue. The patient`s treatment was changed to vincristine, temozolomide, and irinotecan. Unfortunately, MRI showed progression after three cycles of second-line chemotherapy. The patient`s family refused any further treatment, and the patient died with progressive disease in a short time. Conclusions. EGFR mutation along with H3.1 K27M mutation is extremely rare in children to our knowledge. It should be kept in mind that if there is a possibility of targeted therapy, there may be a treatment option in this malignant disease with a poor prognosis.
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publisher Hacettepe University Institute of Child Health
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series The Turkish Journal of Pediatrics
spelling doaj-art-91720bda21924c7ba8014e329f3946942025-08-20T02:55:21ZengHacettepe University Institute of Child HealthThe Turkish Journal of Pediatrics0041-43012791-64212022-08-0164410.24953/turkjped.2021.1140A pediatric bithalamic high grade glioma with concomitant H3K27M and EGFR mutationsBuket Kara0Ayça Ersen Danyeli1Mehmet Öztürk2Kübra Ertan3Yavuz Köksal4Departments of Pediatric Hematology and Oncology, Selçuk University Faculty of Medicine, Konya, Turkey.Department of Pathology, Acıbadem University School of Medicine, İstanbul, Turkey.Departments of Radiology, Selçuk University Faculty of Medicine, Konya, Turkey.Departments of Pediatrics, Selçuk University Faculty of Medicine, Konya, Turkey.Departments of Pediatric Hematology and Oncology, Selçuk University Faculty of Medicine, Konya, Turkey. Background. Despite many treatment approaches, survival rates in high grade glial tumors are still not at the desired level. One of the cause of this failure might be that although having similar histologic features, they may display different biological behaviors depending on molecular heterogeneity. Case. A 10-year-old girl presented with sudden onset left sided hemiparesis, headache, and ataxia. Physical examination was normal except for left sided hemiparesis and ataxia. A hyperintense mass lesion involving the bilateral thalamus was detected in the axial T2-weighted and coronal FLAIR sequences on brain MRI. There was no enhancement in axial T1-weighted contrast-enhanced sequences. Due to the size and location of the tumor, the patient was considered inoperable. Intensity modulated radiotherapy was intended for curative treatment to the patient because the radiological findings suggested a low-grade glial tumor. Tumor was unresponsive to radiotherapy but biopsy could be performed. The histopathological examination revealed a diffuse glial tumor with increased cellularity, mild nuclear atypia and rare mitosis. Due to the infiltrative pattern of the tumor, it was accepted as a high grade diffuse glial tumor. A chemotherapy protocol including cisplatin and etoposide in the first cycle, vincristine and cyclophosphamide in the second cycle, and carboplatin and vincristine in the third cycle were instituted to the patient. After the third cycle of chemotherapy, the tumor progressed radiologically. H3.1 K27M c.83A > T (HIST1H3C p.Lys28Met), ATRX c.2169_2170del (p.Glu723AspfsTer9), TP53 c.338T > C (p.Phe113Ser), and EGFR c.2300_2308dup (p.Ala767_va1769dup) were detected in the genetic assessment of tumor tissue. The patient`s treatment was changed to vincristine, temozolomide, and irinotecan. Unfortunately, MRI showed progression after three cycles of second-line chemotherapy. The patient`s family refused any further treatment, and the patient died with progressive disease in a short time. Conclusions. EGFR mutation along with H3.1 K27M mutation is extremely rare in children to our knowledge. It should be kept in mind that if there is a possibility of targeted therapy, there may be a treatment option in this malignant disease with a poor prognosis. https://turkjpediatr.org/article/view/206EGFR mutationH3K27M mutationbithalamic high grade gliomachildren
spellingShingle Buket Kara
Ayça Ersen Danyeli
Mehmet Öztürk
Kübra Ertan
Yavuz Köksal
A pediatric bithalamic high grade glioma with concomitant H3K27M and EGFR mutations
The Turkish Journal of Pediatrics
EGFR mutation
H3K27M mutation
bithalamic high grade glioma
children
title A pediatric bithalamic high grade glioma with concomitant H3K27M and EGFR mutations
title_full A pediatric bithalamic high grade glioma with concomitant H3K27M and EGFR mutations
title_fullStr A pediatric bithalamic high grade glioma with concomitant H3K27M and EGFR mutations
title_full_unstemmed A pediatric bithalamic high grade glioma with concomitant H3K27M and EGFR mutations
title_short A pediatric bithalamic high grade glioma with concomitant H3K27M and EGFR mutations
title_sort pediatric bithalamic high grade glioma with concomitant h3k27m and egfr mutations
topic EGFR mutation
H3K27M mutation
bithalamic high grade glioma
children
url https://turkjpediatr.org/article/view/206
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