deletions in the q arm of chromosome 1 at position 36, [60-70% of cases]) that lead to lose of TNFAIP3 (encodes tumor necrosis factor, alpha-induced protein 3 which inhibits the activation of NF-κB, blocks cell death due to apoptosis, and regulates lymphocyte-based immune responses through its ubiquitin ligase activity); 3) mutations in PRDM1 (encodes the PR domain zinc finger protein which promotes the maturation and proliferation of B-cells); and 4) the same mutations seen in ISFL including KMT2D (85-90% of cases), CREEBP (40-65% of cases), BCL2 (40-65% of cases), and EZH2 (20-30% of cases) as well as other mutations such as those in the histone-modifying gene HIST1H1E (20-30% of cases), the RRAGC gene (~17% of cases) which regulates cell growth, survival, death, and proliferation, and, in ≤15% of cases several other genes including MEF2B, STAT6, EP300, ARID1A, SLC22A2, CARD11, FOXO1, GNA12, B2M (i.e. the gene for beta-2 microglobulin), and SGK1. Except for the t(14:18)(q32:q21.3) translocation and EZH2 mutations which lead to gains in the expression and function, respectively, of their products, the genetic alterations generally lead to a loss in the production or function of the cited genes products. However, the exact roles, if any, of these genomic abnormalities in promoting the progression of ISFL to FL are unclear.
Grade 2: follicles have 6 to 15 centroblasts per hpf. Grade 3: follicles have >15 centroblasts per hpf. Grade 3A: Grade 3 in which the follicles contain predominantly centrocytes. Grade 3B: Grade 3 in which the follicles consist almost entirely of centroblasts.Grades 1 and 2 are regarded as low grade FL; Grade 3A is usually also regarded as low grade FL although some studies have regarded it as high grade FL; and Grade 3B is regarded as a highly aggressive FL in the t-FL category.In addition to grade 3B disease, histologic examinations may reveal other evidence of t-FL such as histologic findings consistent with FL and diffuse large cell lymphoma in the same tissue (referred to as composite lymphomas) or in separate tissues (referred to as (discordant lymphomas) or histologic findings similar to those found in Burkitt lymphoma, precursor B-cell lymphoblastic leukemia, plasmablastic lymphoma, the high grade subtype of B-cell lymphoma, Hodgkin lymphoma of the B-cell type, chronic lymphocytic leukemia/small cell lymphocytic lymphoma, or histiocytic sarcoma. Other findings indicating the presence of this transformation include rapid growth in size of lymph nodes, recently acquired or new B symptoms, recent development of FL lesions in non-nodal tissue, rapid rises in serum lactate dehydrogenase levels, and the presence of high levels of serum calcium. Differential diagnosis
FL may be confused with marginal zone B-cell lymphoma, mantle cell lymphoma, and the small lymphocytic lymphoma variant of chronic lymphocytic leukemia.