High-Grade Transformation of Low-Grade Non-Hodgkin's Lymphomas: Mechanisms of Tumor Progression

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Abstract
In the natural history of low-grade non-Hodgkin's lymphomas (NHL) a prolonged indolent phase of the disease may be followed by clinical progression toward intermediate and high-grade disease. The abrupt appearance of diffuse large cell lymphoma (DLL) in patients with low-grade NHL is usually associated with an accelerated clinical course and shorter time of survival. The histologic transformation has been described for chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and lymphoma of mucosa-associated lymphoid tissue (MALT). Although the histological transformation of low-grade lymphomas are relatively frequent, the clonal relationship between the two neoplasms and pathogenetic mechanisms underlying the progression of the disease are widely debated. In this review, we will focus on the possible relationship between the low-grade and the transformed high-grade NHLs and genetic lesions that may be associated with the histologic transformation and clinical progression of the disease.