A 57-year-old male presented with exertional dyspnoea of 1-week duration without fever, night sweats and weight loss. He was admitted to the department of cardiac surgery of the First Affiliated Hospital of China Medical University (CMU) in April 2018 because of the right atrial mass revealed by echocardiography in a local hospital with a negative medical history. Physical examination showed no lymphadenopathy, and the liver and spleen were not palpable. Laboratory tests indicated that routine blood parameters, liver and renal function, and the coagulation index were normal, and the patient was negative for anti-HIV antibodies. The electrocardiogram (ECG) revealed sinus tachycardia and atrial premature beats. The computed tomographic angiography (CTA) of the coronary artery demonstrated a low-density bulk in the right atrium with dimensions of 70 mm X 52 mm infiltrating into both the superior vena cava (SVC) and inferior vena cava (IVC), oppressing the pulmonary vein (Figure 1). Increased uptake of FDP (SUV=25.8) was shown in the cardiac mass by positron emission tomography/computed tomography (PET/CT), and no extracardiac involvement was demonstrated. The patient underwent surgery for cardiac mass resection, which provided pathologic evidence of DLBCL. The cardiac mass was composed of a diffuse infiltrate of large lymphoid cells with round or oval nuclei and an altered nuclear-cytoplasmic ratio, as observed under microscopic examination. Immunohistochemical staining revealed that the lymphoid cells were positive for CD20, CD45, Pax-5, Bcl-6, Mum1, Bcl-2, and MYC; sporadic positive for CD21 and CD3; and negative for CD10, CK, CyclinD1, CD30, and CD5. The Ki67 index was 80% (Figure 1). Using a NGS platform (Hiseq X Ten, Illumina, San Diego, CA), the whole exome sequencing of 165 hematological tumour-associated genes (Table S1) was performed at Righton Biomedical technology Company Limited (Shanghai, China) using tumour DNA extracted from formalin-fixed paraffin-embedded (FFPE) block. The original data reads obtained from sequencing libraries were collated and evaluated according to the standard protocols, compared with the reference sequence (CRCh37/UCSC hg19), and the sequencing depth and coverage were counted. SNP and InDel mutation information were detected. Functional annotation (GO, Pathway) and conservative prediction and pathogenicity analysis (SIFT, Polyphen-2, GERP) of the mutation genes were performed. In order to get more detailed information, we screened the oncogene/suppressor gene/susceptible gene, analyzed the high-frequency mutation gene, as well as the mutation characteristics and frequency of NMF, and screened the known driving genes. A total of 13 point mutations involving 11 genes were demonstrated by NGS. Seven point mutations in TBL1XR1, CD79B, IGLL5, ZMYM3, MYD88, TMSB4X and PIM1 had previously been reported in DLBCL, while six point mutations in PIM1, BTK, NRXN3, CUX1 and CSMD1 were first reported in lymphoma. Detailed information on the gene mutated is provided in Table 1. DNA copy number variations (CNVs) and regions of homozygosity were identified using whole-genome hybridization at Kingmed Clinical Laboratory (Guangzhou, China). and the genomic locations were retrieved from the National Center for Biotechnology Information (NCBI) build 37 (hg 19) genome. Tumour DNA extracted from FFPE sample using Qiagen QIAamp DNA FFPE Tissue Kit (Qiagen Inc., Valencia, CA) was hybridized with the OncoScan CNV FFPE assay kit (Affymetrix, Santa Clara, CA, USA) according to the manufacturer's protocols. Copy number analysis was estimated utilizing the Chromosome Analysis Suite 3.0 (ChAS 3.0) software, which enabled us to view and summarize chromosomal aberrations across the genome including copy number gain or loss, or loss of heterozygosity. In total, 19 CNVs involving 13 chromosomes (1, 3, 5, 6, 7, 11, 12, 15, 17, 18, 19, X, and Y), including 11 chromosomal gain and eight chromosomal loss CNVs, and four copy-neutral loss of heterozygosity (CN-LOH) lesions were identified by SNP array karyotyping (Figure 2). Sixteen large chromosomal abnormalities with sizes greater than 5 Mb were observed with multiple chromosome involvement, for example, 1q+, 3p+, 3q+ 5p+, 6p-, 6q-, 7q+, +11, 15q-, 17q+, +18, 19q+, Xq+ and -Y. Four cryptic chromosomal aberrations (<=5 Mb), all of which were chromosomal loss, were recognized at 12q24.31, 17p13.1, 19p13.3 and 19q13.42q13.43. It is worth noting that some cancer-associated genes were located in these regions of genomic imbalance, for example, the tumour suppressor genes (TSGs) PRDM1 (6q21), TP53 (17p13.1), HLA-A, HLA-B, and HLA-C (6q22.1, 6q22.3, and 6q22.3, respectively) and the oncogenes Bcl-2 (18q21.3), Bcl-6 (3q27.3), and SPIB (19q33.33) (Table 2). In addition, using TP53/CSP17 Probe kit (17p13.1/17p11.1-q11) (Jinpujia medical technology Company Limited, Beijing, China), the deletion of 17p13.1 containing TP53 gene was confirmed by Fluorescence in situ hybridization (FISH) (Figure S1) which was in accordance with SNP array. The patient received 6 courses of chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, R-CHOP regimen) after surgery, achieved complete remission as evaluated by PET/CT and showed normal cardiac function by echocardiography. He is currently in remission as of July 2019.