Transformation of Indolent Small B-Cell Lymphoma to Histiocytic Sarcoma: Report of Two Cases with Molecular/Genetic Evidence of Clonal Relationship Between Two Morphologically and Immunophenotypically Distinctive Neoplasms.

Abstract

Abstract 3960Poster Board III-896 IntroductionRare cases of histiocytic sarcoma (HS) have been reported in association with indolent small B-cell neoplasms, either concurring with or following a small B-cell lymphoma. The biologic relationship between these two morphologically and immunophenotypically distinct neoplasms in same patients remains unclear, though recent data suggest a possible “transdifferentiation” from follicular lymphoma (FL) to HS. Patients and MethodsWe investigate the clonal relationship in two cases of B-cell lymphoma with subsequent HS, using immunohistochemical stains, PCR-based immunoglobulin heavy chain (IGH) gene rearrangement/sequencing analysis and interphase FISH study on formalin fixed, paraffin-imbedded tissue sections. ResultsCase 1 is a 62-year-old female with splenic marginal zone lymphoma (SMZL) who developed HS in a groin lymph node one year after the diagnosis of SMZL. PCR/sequence analysis of IGH gene showed a monoclonal rearrangement carrying identical DNA sequences of PCR products from the spleen with SMZL and the lymph node with HS. Case 2 is a 61-year-old female with a remote history of FL who developed supraclavicular lymphadenopathy and multiple other infiltrating foci. A supraclavicular lymph node biopsy demonstrated HS. PCR analysis detected a monoclonal rearrangement of the IGH gene and interphase FISH analysis revealed IGH/BCL-2 fusion, a genetic hallmark for FL. Although negative for other B-cell associated antigen markers, HSs show partial retention of primary neoplasms B-cell lymphomas' immunoprofiles, including expression of Oct-2 in both cases, and expression of bcl-6 and enhanced expression of bcl-2 in case 2. ConclusionThe data provide a genotypic evidence of common clonal origin between mature B-cell lymphoma and subsequent HS in the same patients, suggesting “transdifferentiation” to HS could occur in other small B-cell lymphoma, in addition to FL. The transformed HSs might have incompletely inherited primary neoplasms' expression signatures by retaining B-cell lymphomas' characteristic immunoprofile to certain extent. The exact mechanism governing the conversion of mature B-cell lymphoma to HS is largely a mystery and remains to be elucidated by more scientific studies, though a few pathways have been proposed for the process, including transdifferentiation, dedifferentiation and common progenitor models.TableAnalysis of Two Cases of Histiocytic Sarcoma Arising in Small B-cell LymphomaCase 1Case 2Primary neoplasmSMZLFLInterval between 1st and 2nd neoplasm (yrs)117--Immunohistochemical and other studiesLeukocyte common antigenCD45W+W+B-cell antigensCD20--CD79a--Pax-5--OCT-2W/M+W+BOB-1--T-cell antigensCD2--CD3--CD5--CD4W+W+CD8--Follicle center antigensCD10--Bcl-6-W/M+Histiocytic/dendritic cell antigensCD68++CD163++CD1a--CD21--CD23--CD35-ndS100F+F+LysozymeF+F+OthersMPO--Bcl-2-/W+Br+Ki-6720-30%15-25%EBER ISH--Genetic studiesIGH gene rearrangementClonalClonalFISH for IGH/BCL-2-+SMZL, splenic marginal zone lymphoma; FL, follicular lymphoma; +, positive; W+, weakly positive; W/M+, weakly to moderately positive; F+, focally positive; Br+, brightly positive; -, negative; nd, not done Disclosures:No relevant conflicts of interest to declare.