Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review

Germinal predisposition to malignancy is found in approximately 10% of oncological pediatric patients. As awareness of cancer risk factors associated with germline mutations increases, and with advancements in molecular techniques, more carefully selected patients are being tested. This approach ena...

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Main Authors: Jakub Czarny, Dominika Galli, Agnieszka Wziątek, Agata Pastorczak, Bartosz Szmyd, Borys Przybyszewski, Anna Raciborska, Katarzyna Jończyk-Potoczna, Katarzyna Derwich
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1514697/full
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author Jakub Czarny
Dominika Galli
Agnieszka Wziątek
Agata Pastorczak
Bartosz Szmyd
Borys Przybyszewski
Anna Raciborska
Katarzyna Jończyk-Potoczna
Katarzyna Derwich
author_facet Jakub Czarny
Dominika Galli
Agnieszka Wziątek
Agata Pastorczak
Bartosz Szmyd
Borys Przybyszewski
Anna Raciborska
Katarzyna Jończyk-Potoczna
Katarzyna Derwich
author_sort Jakub Czarny
collection DOAJ
description Germinal predisposition to malignancy is found in approximately 10% of oncological pediatric patients. As awareness of cancer risk factors associated with germline mutations increases, and with advancements in molecular techniques, more carefully selected patients are being tested. This approach enables the identification of new variants—both those that are clearly linked to tumorigenesis and candidates, which biological role needs to be functionally verified. Pathogenic variants within cancer-predisposing genes not only increase nearly eightfold the risk of secondary cancers but also may be associated with excessive toxicity of antineoplastic treatment. We present the case of a girl who developed classical Hodgkin lymphoma at the age of 8 years and secondary Ewing sarcoma at the age of 16 years. Her father was diagnosed with classical Hodgkin lymphoma at the age of 27 years. Genetic testing revealed the carriership of a germline heterozygous variant in the PALB2 gene (NM_024675.4:c.110G>A, p.Arg37His) in both the patient and her father. Since the patient was exposed to chemotherapy due to lymphoma prior to the development of secondary malignancy and the variant is classified as an aberration of unknown significance, the causative role of the PALB2 variant remains uncertain. Nevertheless, the presented case may indicate the possible interplay between inherited genetic predisposition and the exposure to cytostatic drugs, which both are involved in promoting secondary cancers in pediatric patients.
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spelling doaj-art-81d721bfe9ca4287a53c8a83f27eb1b32025-08-20T02:43:16ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-02-011510.3389/fonc.2025.15146971514697Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature reviewJakub Czarny0Dominika Galli1Agnieszka Wziątek2Agata Pastorczak3Bartosz Szmyd4Borys Przybyszewski5Anna Raciborska6Katarzyna Jończyk-Potoczna7Katarzyna Derwich8Faculty of Medicine, Poznan University of Medical Sciences, Poznan, PolandFaculty of Medicine, Poznan University of Medical Sciences, Poznan, PolandDepartment of Pediatric Oncology, Hematology and Transplantology, Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, PolandDepartment of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, PolandDepartment of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, PolandDepartment of Oncology and Surgical Oncology for Children and Youth, Institute of Mother and Child, Warsaw, PolandDepartment of Oncology and Surgical Oncology for Children and Youth, Institute of Mother and Child, Warsaw, PolandDepartment of Pediatric Radiology, Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, PolandDepartment of Pediatric Oncology, Hematology and Transplantology, Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, PolandGerminal predisposition to malignancy is found in approximately 10% of oncological pediatric patients. As awareness of cancer risk factors associated with germline mutations increases, and with advancements in molecular techniques, more carefully selected patients are being tested. This approach enables the identification of new variants—both those that are clearly linked to tumorigenesis and candidates, which biological role needs to be functionally verified. Pathogenic variants within cancer-predisposing genes not only increase nearly eightfold the risk of secondary cancers but also may be associated with excessive toxicity of antineoplastic treatment. We present the case of a girl who developed classical Hodgkin lymphoma at the age of 8 years and secondary Ewing sarcoma at the age of 16 years. Her father was diagnosed with classical Hodgkin lymphoma at the age of 27 years. Genetic testing revealed the carriership of a germline heterozygous variant in the PALB2 gene (NM_024675.4:c.110G>A, p.Arg37His) in both the patient and her father. Since the patient was exposed to chemotherapy due to lymphoma prior to the development of secondary malignancy and the variant is classified as an aberration of unknown significance, the causative role of the PALB2 variant remains uncertain. Nevertheless, the presented case may indicate the possible interplay between inherited genetic predisposition and the exposure to cytostatic drugs, which both are involved in promoting secondary cancers in pediatric patients.https://www.frontiersin.org/articles/10.3389/fonc.2025.1514697/fullPALB2Hodgkin lymphomaEwing’s sarcomagenetic predispositiontumorigenesis
spellingShingle Jakub Czarny
Dominika Galli
Agnieszka Wziątek
Agata Pastorczak
Bartosz Szmyd
Borys Przybyszewski
Anna Raciborska
Katarzyna Jończyk-Potoczna
Katarzyna Derwich
Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review
Frontiers in Oncology
PALB2
Hodgkin lymphoma
Ewing’s sarcoma
genetic predisposition
tumorigenesis
title Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review
title_full Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review
title_fullStr Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review
title_full_unstemmed Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review
title_short Hodgkin lymphoma and Ewing sarcoma in pediatric patient carrying germline PALB2 variant: a case report and literature review
title_sort hodgkin lymphoma and ewing sarcoma in pediatric patient carrying germline palb2 variant a case report and literature review
topic PALB2
Hodgkin lymphoma
Ewing’s sarcoma
genetic predisposition
tumorigenesis
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1514697/full
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