The Molecular Landscape and Other Distinctive Features of Primary Cutaneous Follicle Center Lymphoma.

Primary cutaneous follicle center lymphoma (PCFCL) is distinguished from other follicular lymphomas (FL) based on its clinicopathologic features including diminished CD10 and frequent lack of BCL2 rearrangements(R). Whether newer germinal center-associated markers would also be less commonly expressed and whether mutational studies would support its segregation from classic FL and FL subsets, including those which also typically lack BCL2R, are uncertain. To address these questions, 22 PCFCL were stained for MEF2B and HGAL, and targeted next generation sequencing was performed with results compared to a meta-analysis of FL, pediatric-type FL (PTFL), low stage FL (LSFL) and other FL subsets. Selected FISH studies were also performed. While 27% of cases lacked CD10, all tested were MEF2B+ and HGAL+. The most common somatic mutations in the 12 to 19 analyzable PCFCL were TNFRSF14 (40%, plus 10% with 1p36 deletions), followed by CREBBP, TNFAIP3, KMT2D, SOCS1, EP300, STAT6 and FOXO1 (17-25%). Three of the most commonly mutated genes in FL (KMT2D, CREBBP and BCL2) were significantly less commonly mutated in PCFCL than in FL and TNFAIP was more commonly mutated with no difference for TNFRSF14 between PCFCL and FL or PTFL. CREBBP was also less frequently mutated than in LSFL but more frequently mutated than in PTFL. MAP2K1 mutations were much more common in PTFL (44% versus 0%). 2/22 of the PCFCL had a BCL2 rearrangement and 0/12 BCL6 rearrangement. These findings, while showing well-recognized and new shared features between PCFCL and other FL, highlight a distinctive mutational profile further supporting its recognition as a distinct entity.