Sequential Development of Histiocytic Sarcoma and Diffuse Large B-cell Lymphoma in a Patient With a Remote History of Follicular Lymphoma With Genotypic Evidence of a Clonal Relationship

Abstract

Follicular lymphoma (FL) often transforms to diffuse large B-cell lymphoma (DLBCL) during its protracted clinical course. Rarely, histiocytic sarcoma (HS) occurs secondary to or concurrent with FL, although the biological relationship between these 2 morphologically and immunophenotypically distinct entities in the same individual has not been well characterized. We report a unique case showing the sequential occurrence of first, HS and then DLBCL in a patient with a remote history of FL. In this case, HS developed 17 years after the diagnosis of FL and was shown to partly retain the immunophenotypic features characteristic of FL, while showing the morphologic and immunophenotypic profiles diagnostic of HS. DLBCL occurred 18.5 years after FL. Both HS and DLBCL harbored the IGH/BCL2 fusion gene, a hallmark of FL, per interphase fluorescence in situ hybridization analysis. Immunoglobulin gene rearrangement studies showed a clonal rearrangement of the IGH gene in both HS and DLBCL with identical amplicons, suggesting a shared origin of the neoplastic clones. These data support the hypothesis of transdifferentiation or transevolution in a mature B-cell neoplasm, and, in addition, suggest the possibility of a divergent (bilineal) neoplastic transformation of FL in a single individual.

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

“…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.…”

Histiocytic/Dendritic Cell Transformation of B-Cell Neoplasms: Pathologic Evidence of Lineage Conversion in Differentiated Hematolymphoid Malignancies

“…17,18 The types of primary B-cell malignancy include FL [8][9][10][11][12][13] in 12 cases, CLL/ SLL 14,15 in 8 cases, DLBCL 9 in 1 case, and splenic marginal zone lymphoma 12 in the remaining 1 case. Secondary neoplasms include histiocytic sarcoma (HS) [8][9][10][11][12][13]15 in 15 cases, interdigitating dendritic cell sarcoma (IDCS) 8,14,15 in 6 cases, and Langerhans cell sarcoma 15 in the remaining 1 case. Of note, 3 cases demonstrated a biphasic presentation of neoplasms secondary to FL, or a divergent clonal evolution, with concurrent HS and DLBCL in 2 cases (cases 9 and 11 in the Table) and sequential development of HS and DLBCL in 1 case (case 13).…”

“…3,4 While rare cases of small B-cell malignancies have been described either preceding or concurring with histiocytic/dendritic cell sarcoma (H/DS), [5][6][7] the clonal relationship between these 2 morphologically and immunophenotypically distinct neoplasms in the same individual has not been completely characterized until recently. [8][9][10][11][12][13][14][15] Here, we provide a brief review of this unusual clinicopathologic phenomenon with emphasis on clinical laboratory evaluation of the clonal relationship between primary B-cell neoplasms and secondary or concurrent H/DS.…”

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.…”