MNDA-positive Follicular Lymphoma is a heterogeneous disease: a case series study of 19 patients.

CONTEXT: Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein involved in key cellular processes. It is expressed in 78% of marginal zone lymphomas (MZLs), but only in 2.6-19% of follicular lymphomas (FLs). The role and implications of MNDA expression in the FL context remain poorly understood. OBJECTIVE: To characterize, for the first time, the morphological, immunophenotypic, molecular, and clinical features of MNDA-positive FLs. DESIGN: We retrospectively analysed a series of 19 MNDA-expressing FLs. Histopathological features, immunohistochemistry, cytogenetic rearrangements, and mutational profiles were assessed. Clinical data, including disease grade and relapse patterns, were also reviewed. RESULTS: All the 19 MNDA-positive FLs showed a follicular growth pattern, and 57.9% were low-grade. MNDA expression appeared at relapse in four initially negative cases. Marginal zone or plasmacytic differentiation was seen in 26.1% of cases. All cases were BCL6-positive; 21% were P53-positive, and 63% showed high Ki67 (> 40%). BCL2 rearrangements were found in 57.9% andBCL6 in 44.4% of the individuals. BCL2-rearranged cases had a distinct mutational profile from non-rearranged individuals. TP53mutations were present in three BCL6-rearranged cases, two of which also featured BCL2-rearrangements. Marginal/plasmacytic characteristics were not associated with specific mutations. Extra nodal recurrence occurred in 21% of cases, including one located in the colon. CONCLUSION: FLs can express MNDA, giving rise to a biologically heterogeneous subgroup of FL cases with diverse clinical, morphological, and genetic characteristics. Further studies are needed to characterize them better.