The clinicopathological and genetic features of ovarian diffuse large B-cell lymphoma

Abstract

Ovarian lymphoma, whether a primary or secondary condition, is very rare. Little is known about its genetic aberrations. Here, we reviewed the clinical, morphological and immunohistochemical characteristics of nine ovarian diffuse large B-cell lymphoma (DLBCL) cases and performed fluorescence in situ hybridisation (FISH) analysis to detect MYC, BCL2 and BCL6 translocations. We also performed whole exome sequencing analysis to determine their genomic features compared with those of conventional extranodal DLBCL. The results showed that six of nine cases were bilateral and three cases were left-sided. Histologically, the tumour cells were homogeneous and a starry-sky pattern was very common in ovarian DLBCL (Burkitt-like). Immunohistochemically, most of the cases (7/9) were germinal centre B-cell-like (GCB) subtype, and dual expression of MYC and BCL2 was found in three cases of ovarian DLBCL. A double-hit (involving MYC and BCL6) phenotype was found in one case of ovarian DLBCL (GCB subtype). Sequencing analysis revealed that NOTCH4, NCOR2, BCL10 and CARD11 were frequently mutated both in ovarian DLBCL and conventional extranodal DLBCL. COL27A1, PRKCB, HLA-A, NOTCH3 and HDAC4 mutations were found only in ovarian DLBCL but not in conventional DLBCL, and NOTCH3 and HDAC4 mutations were only identified in the GCB subtype. Furthermore, several signalling pathways including the B-cell receptor, Epstein-Barr virus infection, HTLV-1 infection, Notch, PI3K-AKT and mTOR were found to be involved in ovarian DLBCL. Our results broaden the understanding of the clinicopathological and molecular characteristics of ovarian DLBCL and compare their genetic features to those of conventional extranodal DLBCL for the first time.