Integrated histomolecular approach to discriminate primary cutaneous follicle centre and marginal zone lymphoma of the scalp.

Overlapping features between follicular lymphomas (FLs) and marginal zone lymphomas (MZLs) have been described, especially in their paediatric forms. Although adult primary cutaneous follicle centre lymphoma (PCFL) and primary cutaneous marginal zone lymphoma (PCMZL) of the scalp appear to display overlapping histological and molecular features, these entities have never been studied. The aim of this study was to describe the clinical, histological, and mutational profiles of PCFL and PCMZL of the scalp and to highlight possible overlapping features. From 2011 to 2023, 38 patients with PCFL or PCMZL of the scalp from two centres were retrospectively included. In each case, a histological review, immunohistochemistry with additional immunostaining for myeloid cell nuclear differentiation antigen, BCL2 fluorescence in situ hybridisation, and targeted next-generation sequencing were performed. Among the 23 PCFL (60%) and 15 PCMZL (40%) cases included, 10 had a difficult initial diagnosis based on histological data alone. The most frequent pathogenic variants in PCFL cases were TNFRSF14 (15%), BCL2 (11%), SOCS1 (11%), and CREBBP (6%). The most frequent pathogenic variants in PCMZL cases were TNFAIP3 (24%), KMT2D (14%), CARD11 (10%), and ITPKB (10%). The integrated histomolecular approach helped reclassify five PCMZL cases into PCFL and showed plasmacytic differentiation in 12% of PCFL cases. This study highlights the histological and molecular overlaps between PCFL and PCMZL of the scalp and underscores the interest of an integrated histomolecular diagnosis to discriminate between these entities.