Histiocytic sarcoma arising in indolent small B-cell lymphoma: report of two cases with molecular/genetic evidence suggestive of a ‘transdifferentiation’ during the clonal evolution

Abstract

The biologic relationship between small B-cell lymphoma and histiocytic sarcoma (HS) when occurring in the same patient remains unclear, though recent data suggest a possible 'transdifferentiation' from follicular lymphoma (FL) to HS. We investigated the clonal relationship in two cases of small B-cell lymphoma with subsequent HS. Case 1: A 62-year-old female with splenic marginal zone lymphoma (SMZL) developed HS in a groin lymph node 1 year after the primary diagnosis. PCR/sequence analysis of the IGH gene showed a monoclonal rearrangement carrying an identical nucleotide sequence of PCR products from the spleen with SMZL and the lymph node with HS. Case 2: A 61-year-old female with a remote history of FL developed supraclavicular lymphadenopathy, which was confirmed to be HS. PCR analysis of the HS detected a monoclonal rearrangement of the IGH gene and FISH analysis revealed IGH/BCL2 fusion, a genetic hallmark for FL. The transformed HSs showed partial retention of their prior B-cell lymphomas' signatures, including expression of OCT2 in both cases and expression of BCL6 and enhanced expression of BCL2 in case 2. Both HSs demonstrated hypermutated IGH variable regions, arguing against a common progenitor mechanism of the transformation process. The data suggest a common clonal origin of B-cell lymphoma and subsequent HS occurring in the same patient, indicating that 'transdifferentiation' occurs in other small B-cell lymphomas, in addition to the previously reported FL or B-cell lymphoma with IGH/BCL2.

Histiocytic Sarcoma : An Updated Literature Review Based on the 2008 WHO Classification

“…30,33,35 In addition, some cases showed nuclear positivity of OCT-2, a B-cellassociated transcription factor. Of interest, Chen et al recently reported that 4 of 7 sporadic HS cases with detectable clonal IG gene rearrangement expressed OCT-2.…”

“…Some cases of HS occur subsequent to or concurrent with B-or T-lymphoblastic lymphoma/leukemia or mature B-cell neoplasms such as follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, splenic marginal zone lymphoma and diffuse large B-cell lymphoma. 11,12,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Most associated mature B-cell lymphomas are low-grade B-cell lymphomas. The interval between the occurrence of lymphoma and that of HS is between 2 months and 17 years.…”

Immunohistochemical Detection of Possible Cellular Origin of Hepatic Histiocytic Sarcoma in Mice

“…12 In contrast, other studies have reported some human HS cases to be associated with follicular lymphoma, diffuse large Bcell lymphoma or mantle cell lymphoma. 4,[13][14][15] Similarly, previous reports described that several HS cases coexist with B-cell lymphoma, which might have a common clonal origin of the HS in mice, 16,17 thus indicating that HS may originate from clonal hematopoietic progenitor cells of lymphoma. Our study showed that germ cell tumors and lymphoma components do not coexist in murine hepatic HS cells using immunohistochemical analysis, thus suggesting that HS occurrence may stem from an independent origin in the liver rather than from the transformation of other tumors.…”

A rare case of follicular lymphoma with transformation to diffuse large B-cell lymphoma and transdifferentiation to histiocytic sarcoma

“…There have been isolated reports of H/DC tumors occurring in patients with FL, CLL/SLL, and splenic marginal zone lymphoma. [6,10,11,[13][14][15] Rarely, FL involving the lymph node with co-existing DLBCL and HS in a bone marrow biopsy has been identified. [16] Therefore, it is important to biopsy and evaluate lymph nodes and bone marrow lesions.…”

“…These studies have shown evidence of cross-lineage transdifferentiation of B-cells to histiocytic and dendritic cell sarcomas. [9][10][11] Interestingly, sporadic H/DC sarcomas have also shown evidence of clonal immunoglobulin receptor gene rearrangements. [3] 2.…”