Page 214 - 2022_01-Haematologica-web

R.J. Leeman-Neill et al.
ABC
DE
F
GHI
JKL
Figure 2. Immunophenotypic features of post-transplant plasmablastic lymphomas. (A) Hematoxylin and eosin (H&E)-stained section of tissue from case 2 showing plasmablasts, which are (B) partially positive for CD138 and (C) diffusely positive for MUM1 and display variable (D) PAX5 and (E) CD56 expression and evidence of (F) EBV infection by in situ hybridization for EBER. (G) H&E-stained section of case 9 showing plasmablasts, which are (H) partially positive for CD79a, (I) diffusely positive for MUM1 and display (J) aberrant CD10 expression, (K) P53 overexpression, and (L) moderate (30%) MYC expression.
While HIV-related PBL and PT-PBL appear to exhibit over- lapping genomic changes, some differences are evident.
In our series of PT-PBL, mutations in epigenetic modifiers were among the most frequent alterations (73%). Inactivating mutations of the KMT2/MLL family of histone H3 methyltransferases, which were most common, pro- mote neoplasia via modification of global transcriptional activity.20 These mutations, particularly in KMT2D, have also been identified in monomorphic PTLD (DLBCL) (39%) and immunocompetent DLBCL (30-43%) and occur in 6- 10% of cases of MM.21-26 Infrequent KMT2A mutations (6%), but no KMT2D mutations, have been reported in HIV- related PBL.7 Recurrent loss-of-function mutations were also observed in the methylcytosine dioxygenase TET2 (27%),
which have been shown to alter gene transcription via wide- spread DNA hypermethylation, a process important in the pathogenesis of PTLD.27 TET2 mutations are frequent in immunocompetent DLBCL and MM22,23,25,26,28 and occur in 9% of HIV-related PBL.7 In contrast to their common occur- rence in EBV+ DLBCL, in our cohort TET2 mutations were exclusively seen in EBV– PBL.29 Other epigenetic modifiers recurrently mutated in HIV-related PBL include EP300, which was mutated in one PT-PBL, as well as TRRAP and HDAC6, which were not in our sequencing panel.7,11
Alterations (mutations and copy number changes) in DNA damage response and repair pathway genes were detected in 82% of our cohort, with chromosome 17/TP53 abnormalities being the most common recurrent events
206
haematologica | 2022; 107(1)