Discordant bone marrow involvement in XXXX : comparative molecular analysis reveals a heterogeneous group of disorders.

@entity1 @entity588 @entity706 @entity5 @entity2225 @entity1072 @entity2282 @entity4042 @entity876 @entity1892 @entity982 @entity6492 @entity1893 @entity7513
Discordant bone marrow (BM) involvement in @entity1 with a diagnosis of large-cell @entity1893 ( @entity1893 ) is characterized by marrow infiltrates predominantly composed of small lymphoid cell, cytologically compatible with low-grade @entity1893 . Although this phenomenon is well described morphologically, molecular data concerning the relationship of the two lesions are lacking. The aim of the study was to investigate the clonal relationship of discordant @entity706 manifestations by using @entity7513 ( @entity7513 ), as well as @entity588 rearrangements, as molecular markers. @entity7513 rearrangements were amplified by PCR with consensus primers directed against framework regions 3 or 2 (FR3 and FR2), followed by automated fragment length analysis and sequencing in selected cases. Rearrangements of the @entity588 gene were identified with primers against the major breakpoint region. Small BM infiltrates were isolated by laser capture microdissection. In addition, immunohistochemistry was performed on paraffin sections using antibodies against CD3, @entity2282 , @entity2225 , @entity588 , @entity4042 , @entity876 , and the Ki67 antigen. @entity982 -embedded tissues of 21 cases diagnosed as @entity1892 ( @entity1892 ) with discordant BM involvement and no previous history of low-grade B-cell @entity1893 were analyzed. After review of immunohistochemical stains, 5 cases were excluded either as concordant BM infiltrates by @entity706 with abundant reactive T-cells (2 cases) or as benign, reactive lymphoid infiltrates (3 cases), as confirmed by a polyclonal pattern in the @entity7513 analysis. Of the remaining 16 cases, a common clonal origin was confirmed in 8 cases by the presence of an identical clonal @entity7513 rearrangement or @entity588 rearrangement. In 4 cases, identification of distinct @entity7513 or @entity588 rearrangements gave evidence for the presence of two clonally unrelated @entity5 . The remaining 4 cases were not evaluable for technical reasons. Morphological, phenotypical, and molecular findings were compatible with a @entity706 of germinal center origin in the majority of cases. However, in 4 cases, flow cytometric analysis of the BM infiltrates revealed a @entity1072 phenotype. Two of these cases were clonally related to the @entity1892 and thus represented @entity6492 . In summary, discordant BM infiltrates in @entity1892 represent a heterogeneous group of disorders, encompassing cases with a clonally related, clinically occult small-cell component, as well as cases with two clonally distinct, unrelated @entity1892 presenting synchronously at different locations.
