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 3960 Poster Board III-896 Introduction Rare 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 Methods We 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. Results Case 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. Conclusion The 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. | | Case 1 | Case 2 | |:------------------------------------------- | ------ | ------ | | Primary neoplasm | SMZL | FL | | Interval between 1st and 2nd neoplasm (yrs) | 1 | 17 | | - | - | | | Immunohistochemical and other studies | | | | Leukocyte common antigen | | | | CD45 | W+ | W+ | | B-cell antigens | | | | CD20 | - | - | | CD79a | - | - | | Pax-5 | - | - | | OCT-2 | W/M+ | W+ | | BOB-1 | - | - | | T-cell antigens | | | | CD2 | - | - | | CD3 | - | - | | CD5 | - | - | | CD4 | W+ | W+ | | CD8 | - | - | | Follicle center antigens | | | | CD10 | - | - | | Bcl-6 | - | W/M+ | | Histiocytic/dendritic cell antigens | | | | CD68 | + | + | | CD163 | + | + | | CD1a | - | - | | CD21 | - | - | | CD23 | - | - | | CD35 | - | nd | | S100 | F+ | F+ | | Lysozyme | F+ | F+ | | Others | | | | MPO | - | - | | Bcl-2 | -/W+ | Br+ | | Ki-67 | 20-30% | 15-25% | | EBER ISH | - | - | | Genetic studies | | | | IGH gene rearrangement | Clonal | Clonal | | FISH 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 Table Analysis of Two Cases of Histiocytic Sarcoma Arising in Small B-cell Lymphoma Disclosures: No relevant conflicts of interest to declare.