EnVision staining, 400 magnification

EnVision staining, 400 magnification. and fit patients as a consolidative treatment; however, the majority of the patients TD-198946 may not be qualified for this procedure. The HL-RS transformation has better outcomes than those of DLBCL-RS and can effectively be treated by the adriamycin, bleomycin, vinblastine, and dacarbazine regimen. Although novel agents are currently being investigated for RS, immunochemotherapy nevertheless remains a standard treatment for DLBCL-RS. analysis can be determined where such cases are regarded by some as being a true RS transformation. In the remaining 20% cases, the rearrangement differs from that of the CLL/SLL clone where such cases are defined as being clonally unrelated and resemble the occurrence of de novo DLBCL and have a significantly better prognosis, similar TD-198946 to that of de novo DLBCL.13C15 Open in a separate window Figure 1 CLL transformation into DLBCL. Notes: Rabbit polyclonal to Neuron-specific class III beta Tubulin (A) Large cells of DLBCL (lower left) next to infiltration by small CLL cells (upper right) HE, 200 magnification. (B) DLBCL with centroblastic morphology (upper right); few small CLL cells (lower left); HE staining, 400 magnification. (C) DLBCL cells reveal stronger membrane CD20 expression than that of CLL cells. (D) MIB1 staining in 80% of the DLBCL cells and in 3% of the CLL cells. (E) CD23 membrane expression in CLL cells; DLBCL cells are negative. (F) BCL6 nuclear expression in DLBCL cells; CLL is negative; EnVision staining, 400 magnification. Abbreviations: CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; HE, hematoxylin and eosin. Open in a separate window Figure 2 Morphological and phenotypic spectrum of CLL transformation into HL may strongly differ upon histopathological examination. Notes: Type I C CLL with Hodgkin transformation (ACC). (A) ReedCSternberg cells are sparsely dispersed in the background of small CLL cells; HE staining. (B) CD15 membrane and dot-like expression in HRS cell. (C) CD23 expression in CLL cells; the ReedCSternberg cell is negative. EnVision staining, 400 magnification. Type II C CLL transformation in HL (DCF). (D) The numerous HRS cells among histiocytes, eosinophils, and small lymphocytes in the background; a few CLL cells in TD-198946 the lower right; HE staining, 200 magnification. The HRS cells reveal membrane CD30 expression (E) and dot-like expression of CD15 (F); EnVision staining, 400 magnification. Abbreviations: CLL, chronic lymphocytic leukemia; HE, hematoxylin and eosin; HL, Hodgkins lymphoma; HRS cell, Hodgkin and ReedCSternberg cell. Clonal relationships between the underlying CLL and the diagnosed DLBCL-RS are mostly diagnosed by sequencing immunoglobulin genes.16 The introduction of novel sequencing and molecular methods has allowed a better understanding of DLBCL-RS pathogenesis while also addressing the issue of its clonal evolution. It is recognized that most of the genetic alterations occur in a particular dominant CLL clone at the time of disease transformation, so giving a rise to a linear transformation model.4,13,15 A minority of DLBCL-RS cases develop from a common precursor cell that had acquired alterations early on, possibly leading to the rise of separate CLL and DLBCL-RS clones. Such a branched transformation model is a characteristic feature of leukemic RS cases and is associated with loss.4,17 Interestingly, although de novo DLBCL and DLBCL-RS present similar morphologies upon histopathological examination, significant genetic and epigenetic differences have been noted.15,17 Most molecular events associated with DLBCL-RS lead to the deregulation of cell cycle control, proliferation, and damage to DNA repair and target genes via somatic mutations of (60%C80%), (30%), or itself (30%) or by affecting their regulatory functions, eg, (30%) and (10%).17C22 Furthermore, DLBCL-RS lacks the typical recurrent mutations of de novo DLBCL affecting nuclear factor-B (eg, are rarely observed in DLBCL-RS, whereas in de novo DLBCL they are observed in over 50% of the analyzed cases.15,20 Besides the gene mutations, recurrent copy number alterations have also been reported comprising deletions of 7q31, 8p, 14q, and trisomy 12 and amplifications of 8q21, 13q, and 18q.19,28,29 The analysis of genetic alterations between CLL and DLBCL-RS has led to the proposal of existence of two main genetic pathways responsible for transformation. The first transformation route, in over 50% cases, was found to be associated with and mutations. The second is regarded to be associated with trisomy 12 and mutations in almost one third of instances.17 For the remaining DLBCL-RS cases, no clear genetic transformation profile could be distinguished. It is therefore suggested that B-cell receptor (BCR) signaling and cellCcell interactions may also be key factors leading to the development of DLBCL-RS. The BCR on CLL cells of the rare subset, #8, bearing the unmutated configuration mutations or trisomy 12 and possess an increased risk of transforming into DLBCL.30C34.