First case of primary CNS lymphoma in a patient with severe combined immunodeficiency carrying a novel ZAP70 mutation: a case report.

INTRODUCTION

Zeta-chain-associated protein kinase 70 () is a tyrosine kinase that plays a crucial role in T-cell activation via the T-cell receptor/CD3 complex and contributes to B-cell signaling. variants can cause a range of immunodeficiencies with variable clinical presentations, including infections and malignancies.

CASE PRESENTATION

A 4-year-old boy presented with chronic cough, dyspnea, recurrent chest infections, and failure to thrive. Chest radiography revealed diffuse bilateral opacities, suggesting a diagnosis of diffuse familial bronchiectasis. Immunological workup at 18 years of age showed CD4 and CD8 T-cell lymphopenia, and genetic analysis revealed a homozygous pathogenic splice-site mutation (c.402 + 2 T>C). The patient then developed headaches, dizziness, and double vision, and Epstein-Barr virus (EBV) polymerase chain reaction (PCR) testing revealed a viral load of 700 IU/mL. Magnetic resonance imaging (MRI) revealed three brain lesions, and brain biopsy confirmed EBV-positive CD20 + diffuse large B-cell lymphoma (DLBCL). Despite aggressive chemotherapy and palliative radiotherapy, the patient's condition deteriorated, resulting in death.

DISCUSSION

To our knowledge, this is the first known case of primary central nervous system DLBCL in a patient with a novel variant. deficiency is typically associated with combined immunodeficiency and rarely with malignancies such as leukemia or lymphoma. Genetic screening at earlier stages could have potentially identified this underlying immunodeficiency sooner and altered the management course.

CONCLUSION

This case underscores the diagnostic challenges and aggressive course of -related disease and highlights the need for increased clinical suspicion, immunologic surveillance, early genetic screening, and development of targeted therapies.