Morphological, immunohistochemical and molecular analysis of follicular dendritic cell sarcomas: L1CAM as a new diagnostic marker

Aims: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm exhibiting morphological and immunophenotypical features of follicular dendritic cells. Given its rarity and broad morphological spectrum, diagnosis can be challenging. Knowledge of the molecular basis of this rare tumour is still limited. To further refine the biological and diagnostic characteristics of these neoplasms, we performed a comprehensive morphological, immunohistochemical and molecular analysis. Methods and results: As well as histopathological and immunohistochemical analysis, we performed molecular analysis by next-generation panel sequencing of 15 tissue samples from 13 patients diagnosed with FDCS. In the histomorphological analysis of this FDCS series, we observed a morphological spectrum with a mixture of spindled and epithelioid cells (six of 13), but also cases with predominant epithelioid cytomorphology (seven of 13). We identified the L1 cell adhesion molecule (L1CAM) as a novel immunomarker of FDCS, as it was variably expressed in all cases. Sequencing led to the identification of 170 variants (classes 3, 4 and 5) in 112 genes. The most frequently detected (likely) pathogenic mutations affected NFKBIA (five of 13), leading to activation of nuclear factor kappa B (NFκB) signalling. Notably, deleterious NFKBIA mutations were only found in cases with predominant epithelioid morphology (five of seven). Furthermore, TP53 mutations were detected in two cases with epithelioid morphology and high proliferation rate, and one of these cases relapsed twice. Conclusions: The morphological and genetic landscape of FDCS in this series was heterogeneous. However, in line with previous data, we identified recurrent genetic alterations affecting NFkB signalling. The expression of the adhesion molecule L1CAM might aid in the diagnosis of this uncommon neoplasia.