RESUMEN
We report the case of a 7-month-old female patient who developed acute megakaryoblastic leukemia 6 months after the appearance of skull bone lesions. Initial evaluation and diagnosis of this patient were challenging and only achieved thanks to genomic analysis by NGS (next generation sequencing). It is unusual for the initial manifestation of acute megakaryoblastic leukemia to be a skull bone lesion. Extramedullary acute myeloid leukemia (eAML), also known as myeloid sarcoma (MS), often occurs simultaneously with acute myeloid leukemia (AML), although it may precede AML. Genomic analysis based on a NGS panel (Oncomine Childhood Cancer Research Assay) detected a RBM15::MKL1 fusion, a consequence of a t (1;22)(p13;q13) translocation, establishing the diagnosis of acute megakaryoblastic leukemia and enabling disease follow-up by qPCR. A diagnosis of eAML is built up from various findings in radiological, histological, immunophenotypic and genomic studies; when the tumor appears de novo, diagnosis is more complicated. We emphasize the importance of a multidisciplinary team in the initial approach to rare tumors and the use of genomic studies to contribute to the knowledge of these neoplasms, risk stratification and treatment planning.
RESUMEN
Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing's sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.
RESUMEN
Rothmund-Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted.
RESUMEN
Hereditary spherocytosis arises from alterations in the genes encoding red blood cell membrane proteins. Although its diagnosis is mostly clinical, recent advances in next-generation sequencing (NGS) technologies have allowed for a faster cost-effective gene-based diagnosis. We report the case of a boy with spherocytic anemia and development delay in whom a de novo 2.84-Mb deletion at chromosome 14 including SPTB (ß-spectrin gene) was identified by array-based comparative genomic hybridization. This alteration, consistent with de novo spherocytosis, was missed by a NGS gene panel. When associated with other symptoms, especially neurologic, NGS may not be appropriate to genetically diagnose spherocytic anemia.
