Systemic Presentation of Somatic TET2 Mutated B-Cell Lymphoma in a Child With Kabuki Syndrome and a Germline KMT2D Variant

Abstract Objectives Kabuki syndrome (KS) is a rare congenital malformation syndrome associated with germline KMT2D mutations. Recurrent somatic mutations in KMT2D have frequently been observed in B-cell lymphoma, but limited studies are available that evaluate the genetic landscape of B-cell lymphomas in the setting of KS. Methods We describe a unique case of B-cell lymphoma that illustrates histologic features of pediatric-type follicular lymphoma (FL) in a young patient with KS and autoimmune disease who showed a systemic presentation of widespread lymphadenopathy and clonal lymphocytosis. Results We present the first reported case of a young patient with KS harboring a germline KMT2D variant and presenting with a systemic CD10-positive, BCL2-negative B-cell lymphoma of follicle center origin illustrating histologic features of pediatric-type FL. Targeted next-generation sequencing of the B-cell lymphoma showed somatic TET2 and subclonal CXCR4 variants. These findings suggest that abnormal epigenetic regulation caused by alterations in KMT2D and TET2 may have played critical roles in promoting lymphomagenesis in this patient. Conclusions This unique case presentation highlights the importance of close clinical monitoring and the value of clinical context in the diagnosis of pediatric FL-like lesions in patients with KS.