Pathology and diagnosis of follicular lymphoma and related entities

Follicular lymphoma (FL) is an indolent, mature B-cell neoplasm classically characterised by the t(14;18)(q32;q21) with constitutive overexpression of the anti-apoptotic protein, BCL2. Most cases present in older adults with slowly progressive lymphadenopathy and follow an indolent clinical course. Typical morphology shows an expansile follicular proliferation with tumour expression of germinal centre markers, and bone marrow involvement at diagnosis is frequent. However, in the recent past, efforts to understand the biological and clinical heterogeneity of FL has effected significant change to the diagnostic approach. While morphological grade, assessed by enumerating large 'centroblasts' in the neoplastic follicles, generally correlates with outcome in systemic nodal FL, variants with high-grade morphology but indolent clinical behaviour have been identified. Given the clinical implications of these FL variants, knowledge of their clinical and histopathological defining features is of paramount importance to the pathologist. Furthermore, as with many areas of diagnostic oncology, precursors to FL have been identified and described with measurable rates of progression to bona fide lymphoma. Accurate diagnosis of these early lesions can often prevent unnecessary therapy and guide appropriate monitoring for disease progression. This review aims to summarise these key pathological and diagnostic features of FL. We further highlight the biological underpinnings of FL that will likely affect the classification, diagnosis, and treatment of patients with lymphoma.