Longitudinal analysis of cell-free DNA. A. L265P MYD88 mutation was detectable prior to a definite diagnosis of intravascular large B-cell lymphoma (IVL2). White squares with solid black line represent MYD88 in cell-free DNAs; Black triangles represent MYD88 in tissue-derived DNAs prepared from bone marrow cells; A black circle represents MYD88 in tissue-derived DNAs prepared from a skin FFPE sample; Blue X-marks with dotted line represent levels of soluble interleukin-2 receptor. VAF, Variant allele frequencies; BM, Bone marrow; sIL2R, soluble interleukin-2 receptor; BMB, bone marrow biopsy; RSB, random skin biopsy; FDG PET/CT, 18F-fluorodesoxyglucose positron emission tomography/computed tomography; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; CR: complete response; ND, Not detected. B. L265P MYD88 mutation was detectable prior to relapse as extranodal diffuse large B-cell lymphoma of the cecum in a patient (IVL1). White squares with solid black line represent L265P MYD88 mutation in cell-free DNAs; Blue X-marks with dotted line represent levels of soluble interleukin-2 receptor. VAF, Variant allele frequencies; sIL2R, soluble interleukin-2 receptor; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; PD, progressive disease; R-ESHAP, rituximab, etoposide, cytarabine, cisplatinum, and methylprednisolone; ASCT, autologous stem cell transplantation; CR, complete response; ND: not detected. C. Y196C CD79B and PRDM1 mutations were detectable prior to relapse in a patient (IVL5). White circles with solid black line represent PRDM1 mutation in cell-free DNAs; Red triangles with dashed line represent Y196C CD79B in cell-free DNAs; Blue X-marks with dotted line represent levels of soluble interleukin-2 receptor. VAF, Variant allele frequencies; sIL2R, soluble interleukin-2 receptor; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; CR, complete response; IVLBCL, intravascular large B-cell lymphoma; ND, Not detected. D. L199P CD79B and PRDM1 mutations were detectable prior to relapse as extranodal diffuse large B-cell lymphoma of the central nervous system (IVL6). White circles with solid black line represent PRDM1 mutation in cell-free DNAs; Red triangles with dashed line represent L199P CD79B in cell-free DNAs; Blue X-marks with dotted line represent levels of soluble interleukin-2 receptor. VAF, Variant allele frequencies; sIL2R, soluble interleukin-2 receptor; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; CR, complete response; CNS, central nervous system; ND, Not detected.