B Lymphoproliferative Neoplasms of Uncertain Biological Significance: Report from the IV Workshop of the Italian Group of Hematopathology and Review of the Literature

Abstract

Lymphoproliferative neoplasms of uncertain biological significance are increasingly encountered due to widespread usage of immunophenotypic and molecular techniques. Considering that clearer biological criteria and patient management have been established for B-cell lymphoproliferative diseases of undetermined significance occurring in the peripheral blood, many issues are still obscure for early lesions detected in lymphoid tissues. Regardless that some categories of lymphoproliferative neoplasms of uncertain biological significance have been recognized by the 4th edition of the WHO, other anecdotal early lymphoproliferative lesions still remain fully undefined. Some early lesions frequently originate from the germinal center, including atypical germinal centers BCL2-negative, an early pattern of large B-cell lymphoma with IRF4 rearrangement, and “in situ” high-grade B lymphomas. Moreover, other early lymphoproliferative lesions arise outside the germinal center and include those developing within the setting of monocytoid B-cell hyperplasia, but they also can be directly or indirectly associated with chronic inflammations. This review aims to summarize the concepts discussed during the IV Workshop organized by the Italian Group of Hematopathology, focus on the state-of-the-art on B-cell lymphoproliferative neoplasms of uncertain biological significance, and offer operative insights to pathologists and clinicians in routine diagnostics.

Malignancy-like subtle histological changes and misdiagnosis pitfalls in reactive hyperplastic lymph nodes

“…Confirmation of FL by Bcl2 stain is crucial. Atypical GCs for Bcl-2 − usually have only clusters of large centroblasts with aberrant mitosis and are not expressed for Bcl-2 by immunostaining 35 . Several studies have shown that lymphoid clones can still be detected even in the context of normal reactive GC and benign hyperplastic marginal regions by immunoglobulin gene rearrangement [36][37][38][39] .…”

“…Flow cytometry results demonstrated that FLBUS was not misinterpreted as it could only reflect B cells similar to FL. Recently, FLBUS has been proposed to show that these cases are not lymphomas but only look like lymphomas 31, 35 . Consistent with concerns that overdiagnosis of lymphoma leads to a patient's pessimism and may result in unnecessary treatment.…”