Kevin Shopsowitza, Zeid Hamadehb, Ryan Stubbinsa, Hayley Merkeleya, Helene Bruyerea, Mohammad Bahmanyara, Eric McGinnisa
aUniversity of British Columbia, Vancouver, BC, Canada; bVancouver General Hospital, Vancouver, BC, Canada
Rearrangements leading to constitutive PDGFRB activity are a rare cause of myeloid/lymphoid neoplasms, usually presenting as myelodysplastic/myeloproliferative neoplasms with prominent eosinophilia. These rearrangements are generally detectable by conventional karyotyping and are important to identify as they typically confer sensitivity to imatinib. Here we report a unique case of a myeloid/lymphoid neoplasm with cryptic PDGFRB rearrangement that presented as an unusual combination of T-lymphoblastic lymphoma (T-LBL) and systemic mastocytosis (SM). Notably, a novel PDGFRB fusion partner (JAKMIP2) was identified in this case by optical genome mapping (OGM). The patient presented to medical attention with an enlarging neck mass and was diagnosed with T-LBL. The staging bone marrow biopsy was negative for T-LBL but unexpectedly revealed SM positive for KIT D816V mutation. At the time of assessment the patient had mild monocytosis without eosinophilia. Bone marrow cytogenetic analysis showed a normal karyotype; however, interphase FISH detected a cryptic PDGFRB rearrangement with metaphase FISH suggesting an intrachromosomal chromosome 5 rearrangement. The same PDGFRB rearrangement was subsequently identified on the lymph node, demonstrating a clonal relationship between the patient’s T-LBL and SM. OGM revealed a tandem duplication event at chromosome 5q32 spanning chr5:147,629,580-150,098,238 (hg38) with breakpoints disrupting PDGFRB and JAKMIP2, resulting in a previously undescribed JAKMIP2::PDGFRB fusion. To date, the patient has shown a sustained cytogenetic and clinical response to imatinib therapy. This case highlights how OGM enables characterization of cryptic and novel genomic rearrangements, with great potential for improving classification and enabling appropriately targeted treatment of patients with diverse hematologic malignancies.