Abstract
BackgroundThe translocation t(14;18)(q32;q21) is the genetic hallmark of follicular lymphoma (FL) and can be observed in 85–90% of cases. Whether the translocation is restricted to cells with germinal center B-cell phenotype or can be observed in other cell types of the microenvironment remains debated. Of interest, cases of associated histiocytic and dendritic cell sarcomas arising in the background of FL have been shown to be clonally related and carry the t(14;18), suggesting a “transdifferentiation” of the malignant FL clone into a neoplasm of a different hematopoietic lineage.MethodsWe analyzed the presence of the t(14;18)(q32;q21) as a surrogate marker of the malignant clone in cells of the FL microenvironment using combined fluorescence immunophenotyping and interphase cytogenetics targeting the BCL2 gene locus. In addition to non-lymphoid cells in FL, we analysed FL with preserved IgD+ mantle zones and cases of in situ follicular neoplasia (ISFN) to investigate whether cells of non-germinal center B-cell phenotype are part of the malignant clone.ResultsSix (40%) of 15 manifest FL cases with preserved IgD+ mantle zones did not harbour the t(14;18)(q32;q21) translocation. In all t(14;18) + FL cases, follicular dendritic cells and endothelial cells lacked the t(14;18) translocation. 2/9 FL revealed t(14;18)- IgD+ mantle zone B-cells. In the seven ISFN cases, the t(14;18) translocation was strictly confined to germinal center cells.ConclusionsThe t(14;18) translocation in follicular lymphoma is limited to B-cells. The origin of IgD+ mantle cells is heterogeneous, in the majority of cases belonging to the neoplastic clone, whereas a minority of cases of manifest FL show nonneoplastic mantle zones, similar to ISFN.
Highlights
The translocation t(14;18)(q32;q21) is the genetic hallmark of follicular lymphoma (FL) and can be observed in 85–90% of cases
The observation of non-lymphoid neoplasms, e.g. tumors of dendritic cells occurring in patients with follicular lymphoma sharing the chromosomal translocation t(14;18)(q32;q21), the genetic hallmark of FL, suggested a “transdifferentiation” of the malignant FL clone into a neoplasm of a different lineage or origin of the two neoplasms from a single precursor cell [2]
Fifteen cases of FL grade 1/2 with a predominant follicular growth pattern and morphologically and phenotypically detectable IgD+ mantle zone structures without IgD expression in the neoplastic germinal centers were included in the analysis (Fig. 1a-c)
Summary
The translocation t(14;18)(q32;q21) is the genetic hallmark of follicular lymphoma (FL) and can be observed in 85–90% of cases. The observation of non-lymphoid neoplasms, e.g. tumors of dendritic cells occurring in patients with follicular lymphoma sharing the chromosomal translocation t(14;18)(q32;q21), the genetic hallmark of FL, suggested a “transdifferentiation” of the malignant FL clone into a neoplasm of a different lineage or origin of the two neoplasms from a single precursor cell [2] This and subsequent observations provided evidence for a common clonal origin of FL and dendritic cell neoplasms and it has been concluded that some sort of “lineage plasticity” may occur in mature lymphoid neoplasms. One of the 23 cases analyzed, harbored the t(14;18)
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