95. Genomic profiling of a t(14;19) small B-cell lymphoma using whole exome sequencing

Aly Abdelkareem

Shiva Sathyanarayana

I am Shiva Sathyanarayana working as a senior molecular fellow at Clinical Genomics and Advanced Technology (CGAT) Laboratory at Dartmouth Hitchcock Medical Center, New Hampshire. I am an accomplished biologist with ten plus years of research and four years of industry experience. I love using my technical and application expertise in clinical and molecular tests, including new assays and technology evaluations we conduct routinely at our CGAT laboratory. I did my M.Sc. and Ph.D. in Genetics from the University of Mysore, India. Outside of my regular lab work, I have been actively involved in community service, volunteering for different organizations and fundraising events for charitable causes. I am an enthusiastic hiker and a runner.


Shivaprasad Sathyanarayana, Joel Lefferts, Wahab Khan, Prabhjot Kaur, Jeremiah Karrs

Dartmouth Hitchcock Medical Center, Lebanon, NH, United States

Small B-cell lymphomas are a diverse group of Non-Hodgkin lymphomas representing a clonal expansion of neoplastic B-cells. As molecular techniques evolve in clinical laboratories, this diverse group of tumors divides into more specific entities. Examples include MYD88 in lymphoplasmacytic lymphoma (LPL), t(14;18) in follicular lymphoma, and t(11;14) in mantle cell lymphoma. Less defined genetic changes include unusual translocations such as t(14;19), which has been reported in different subtypes of small B-cell lymphomas. Here, we present the clinical, morphological, cytogenetic, and whole exome sequencing (WES) findings in a B-cell lymphoma with t(14;19). This patient was a 54-year-old female with isolated cervical neck adenopathy who underwent lymph node biopsy. Conventional pathologic assessment, cytogenetic studies, B-cell clonality, and whole-exome sequencing were performed. Histology showed partial effacement of the architecture by a polymorphous infiltrate. The infiltrating B-cells were CD20+, CD5+(subset), and cyclin D1. Metaphase chromosome analysis revealed a complex karyotype, including a t(14;19)(q32;q13). FISH showed negative for BCL2 rearrangement. B-cell gene rearrangement studies showed a clonal pattern. WES analysis detected pathogenic variants in CXCR4 (p.S339CfsTer4) and TNFAIP3 (p.E388LfsTer2). We performed, to our knowledge, the first WES of a t(14;19) small B-cell lymphoma which detected variants in CXCR4 and TNFAIP3. CXCR4 variants have been described in LPL, but nearly always occur in conjunction with MYD88 variants. So, while our genomic profiling did not illicit a currently defined lymphoma by WHO criteria, it does raise the possibility that t(14;19) may have unique molecular signatures and clinical phenotypes. This work merits sequencing of additional cases of t(14;19).