Simultaneous Occurrence of Multiple Neoplasms in Children with Cancer Predisposition Syndromes: Collaborating with Abnormal Genes

Abstract

The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, juvenile xanthogranuloma, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nephroblastoma, in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play significant roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are important for improving outcomes in these individuals.

Keywords: cancer predisposition syndromes; genetic abnormalities; neoplasms; pediatric cancers; personalized treatment; simultaneous occurrence; tumor suppressor genes.

Figure 1

A diagram showing the analysis and workflow. CPS—cancer predisposition syndrome.

Figure 2

Photographs of the first patient, taken in January 2021, showing left-sided hemihypertrophy (a) and café-au-lait spots on the right thigh (b).

Figure 3

Timeline illustrating the disease course of Case 1.

Figure 4

Pelvic MRI scan illustrating a large vaginal tumor (indicated by arrow) in the second patient presented.

Figure 5

Peripheral blood smear showing leukocytosis with monocytosis, left-shifted neutrophils and immature cells, dysplastic granulocytes with pseudo Pelger cells and pycnotic nuclei, and 6% blasts.

Figure 6

Bone marrow smear showing reduced cell content, absence of megakaryocytes, monocytosis with dysplastic and immature monocytes, very dysplastic myelopoiesis with pseudo Pelger cells, and aplastic erythropoiesis. Additionally, 13% blasts are observed.

Figure 7

Timeline illustrating the disease course of Case 2.

Figure 8

Timeline illustrating the disease course of Case 3.