Primary central nervous system lymphomas (PCNSL) are aggressive non-Hodgkin lymphomas
affecting the central nervous system (CNS). Although immunophenotyping studies suggested
an uniform activated B-cell (ABC) origin, more recently a spectrum of ABC and germinal
center B-cell (GC) cases has been proposed, with the molecular subtypes of PCNSL still
being a matter of debate. With the emergence of novel therapies demonstrating different
efficacy between the ABC and GC patient groups, precise assignment of molecular subtype
is becoming indispensable. To determine the molecular subtype of 77 PCNSL and 17 secondary
CNS lymphoma patients, we used the NanoString Lymphoma Subtyping Test (LST), a gene
expression-based assay representing a more accurate technique of subtyping compared
with standard immunohistochemical (IHC) algorithms. Mutational landscapes of 14 target
genes were determined using ultra-deep next-generation sequencing. Using the LST-assay,
a significantly lower proportion (80% vs 95%) of PCNSL cases displayed ABC phenotype
compared with the IHC-based characterization. The most frequently mutated genes included
MYD88, PIM1, and KMT2D. In summary, we successfully applied the LST-assay for molecular
classification of PCNSL, reporting higher proportion of cases with GC phenotype compared
with IHC analyses, leading to a more precise patient stratification potentially applicable
in the diagnostic algorithm of PCNSL.
