Histiocytic/dendritic cell transformation of indolent B-cell neoplasms: Clinical laboratory evidence of lineage conversion in hematolymphoid malignancies

It is well known that pluripotent progenitors of normal hematopoietic cells can differentiate into cell lineages that are distinct in morphology, immunophenotype and biological function . The conventional concept holds that once a hematopoietic progenitor is committed to a given lineage, its fate is sealed and irreversible. This phenomenon of lineage commitment has also been universally observed in hematolymphoid neoplasms in the past. For instance, follicular lymphoma (FL) [2] and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) [3] are fully differentiated indolent B-cell neoplasms and often transform during their prolonged disease course to malignancies with different morphology and more aggressive clinical behavior; however, the secondary neoplasms typically retain the original B-cell lineage immunophenotype. This perception of unidirectional evolution in mature hematolymphoid malignancies has been recently challenged by several clinical studies and in vitro experimental data. A few mature B-cell neoplasms, including FL and CLL/SLL, have been associated with subsequent or concurrent histiocytic/dendritic cell sarcoma (H/DS) . The latter neoplastic entity is distinct not only in morphology but also in immunophenotypic profile from the associated B-cell neoplasm. Given the conventional concept, these cases have been thought of as coincidental or two separate neoplasms in the same individual before laboratory diagnostic tests demonstrated genotypic features suggestive of a clonal origin between the primary B-cell neoplasm and secondary H/DS . Feldman et al. [7] in their recent article, investigated the clonal relationship between FL and concomitant or secondary H/DS in the same patients and provided for the first time convincing evidence that the two morphologically and immunophenotypically distinct neoplasms share B-cell genotypic identities, suggesting possible “trans-differentiation” of FL into H/DS. Subsequently, histiocytic/dendritic cell transformation has been reported in indolent B-cell neoplasms other than FL by other groups .