title: 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: a divergent (bilineal) neoplastic transformation of an indolent B-cell lymphoma in a single individual.
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.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. endi.wang@duke.edu
authors.forename: Endi
authors.initials: E
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Papalas
authors.forename: Charles Blake
authors.initials: CB
authors.lastname: Hutchinson
authors.forename: Evan
authors.initials: E
authors.lastname: Kulbacki
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Siby
authors.initials: S
authors.lastname: Sebastian
authors.forename: Catherine
authors.initials: C
authors.lastname: Rehder
authors.forename: Damian
authors.initials: D
authors.lastname: Silbermins
authors.forename: Joseph
authors.initials: J
authors.lastname: Moore
authors.forename: Michael
authors.initials: M
authors.lastname: Datto
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D019254:Genes, bcl-2; D054747:Histiocytic Sarcoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction