Unusual presentation of pediatric precursor B-cell acute lymphoblastic leukemia with bulky mediastinal mass with <i>KRAS</i> mutation and <i>CDKN2A/2B</i> deletions: A case report

Superior mediastinal syndrome is a critical oncological emergency that poses significant therapeutic challenges, yet can yield favorable outcomes with timely intervention. Non-Hodgkin lymphoma is the most common malignant cause of mediastinal syndrome, which is followed by T-cell acute lymphoblastic lymphoma. However, B-cell acute lymphoblastic leukemia (B-ALL) rarely presents with a mediastinal mass. When molecular screening for B-ALL is negative, genome-wide technologies give valuable information about the nature of the disease and prognosis, and hence pave the way for effective management. We report the case of a 12-year-old male who presented with an anterior mediastinal mass, associated malignant pleural and pericardial effusions, and features of mediastinal syndrome. At the time of presentation, his functional status was significantly compromised, with a Lansky Play Performance Scale score of 20. Peripheral blood smear demonstrated the presence of blasts. Immunophenotyping of the peripheral blood confirmed the diagnosis of B-ALL. An intercostal drainage tube was placed on the right side of the chest to manage the pleural effusion. The patient was initiated on the modified Berlin–Frankfurt–Münster (BFM) induction regimen. Molecular analysis using polymerase chain reaction for common ALL-associated translocations was negative. Conventional cytogenetic studies revealed a normal karyotype. Next-generation sequencing (NGS) identified mutations in CDKN2A, CDKN2B, and KRAS , which are associated with high-risk disease biology. The patient showed a favorable response to induction therapy, achieving complete remission. He subsequently received high-risk consolidation chemotherapy as per the BFM protocol guidelines. He is currently on maintenance chemotherapy and continues to be monitored for disease status. B-ALL typically presents with bone marrow and peripheral blood involvement, and less commonly with extramedullary disease. In pediatric patients, anterior mediastinal masses are far more characteristic of T-cell ALL, given its frequent involvement of the thymus. Given the rarity of mediastinal involvement in pediatric B-ALL, this case contributes valuable insight to the limited body of literature on atypical presentations of the disease and highlights the importance of thorough diagnostic evaluation, even when clinical findings are suggestive of T-cell lineage.