Synchronous T-lymphoblastic lymphoma and neuroblastoma in a 3-yr-old with novel germline SMARCA4 and EZH2 variants
- Pauline Tibout1,
- Joel Livingston1,
- Nisha Kanwar2,
- Kyoko E. Yuki2,
- Adam Shlien2,3,
- Bo Ngan4,
- Meredith S. Irwin1,5,
- Daniel A. Morgenstern1,5,
- Johann Hitzler1,5,
- Anita Villani1,5 and
- Sarah Cohen-Gogo1,3
- 1Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1E8, Canada;
- 2Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario M5G 1E8, Canada;
- 3Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, M5G 1E8 Canada;
- 4Division of Pathology, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario M5G 1E8, Canada;
- 5Department of Pediatrics, University of Toronto, Toronto, Ontario M5R 0A3, Canada
- Corresponding author: sarah.cohen-gogo{at}sickkids.ca
Abstract
T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.
- Received April 17, 2023.
- Accepted October 4, 2023.
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
