Composite B‑cell lymphoma and extranodal natural killer/T‑cell lymphoma presenting with distinct clone evolution and tumor microenvironment: A report of two cases

Composite lymphoma containing both B-cell lymphoma and extranodal natural killer/T-cell lymphoma (ENKTL) is extremely rare. Clonal evolution and tumor microenvironment (TME) features have not been reported previously. The present study reports one case of the heterochronous occurrence of follicular lymphoma (FL) and ENKTL and one case of the simultaneous occurrence of diffuse large B-cell lymphoma (DLBCL) and ENKTL. The results of targeted DNA sequencing demonstrated the genetic features and dynamic clonal evolution of each component. Notably, in the case of ENKTL secondary from FL, predominant clones harbored in ENKTL were already present at the initial diagnosis of FL and expanded to full clonal prevalence afterward in ENKTL. In the case of synchronous DLBCL and ENKTL, predominant clones in ENKTL were exclusive to those clones dominating in DLBCL. Multiple immunofluorescence and CIBERSORT analyses depicted TME features and showed that CD68⁺ macrophages were abundant in FL, DLBCL and ENKTL. The present report could broaden our understanding of composite lymphoma.