title: Hodgkin lymphoma variant of Richter transformation: morphology, Epstein-Barr virus status, clonality, and survival analysis-with comparison to Hodgkin-like lesion.
abstract: Hodgkin/Reed-Sternberg (HRS) cells in the setting of chronic lymphocytic leukemia (CLL) exist in 2 forms: type I with isolated HRS cells in a CLL background (Hodgkin-like lesion) and type II with typical classic Hodgkin lymphoma, a variant of Richter transformation (CHL-RT). The clinical significance of the 2 morphological patterns is unclear, and their biological features have not been compared. We retrospectively reviewed 77 cases: 26 of type I and 51 of type II CHL-RT; 3 cases progressed from type I to type II. We examined clinical features, Epstein-Barr virus (EBV) status, and clonal relatedness after microdissection. Median age for type I was 62 years versus 73 years for type II (P=.01); 27% (type I) versus 73% (type II) had a history of CLL. HRS cells were positive for EBV in 71% (55/77), similar in types I and II. Clonality analysis was performed in 33 cases (type I and type II combined): HRS cells were clonally related to the underlying CLL in 14 and unrelated in 19. ZAP-70 expression of the CLL cells but not EBV status or morphological pattern was correlated with clonal relatedness: all 14 clonally related cases were ZAP-70 negative, whereas 74% (14/19) of clonally unrelated cases were ZAP-70 positive. Overall median survival (types I and II) after diagnosis was 44 months. Advanced age was an adverse risk factor for survival, but not histologic pattern, type I versus type II. HRS-like cells in a background of CLL carries a similar clinical risk to that of CHL-RT and may progress to classic Hodgkin lymphoma in some cases.
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Chen
authors.affiliation: Molecular Diagnostic Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lynn
authors.initials: L
authors.lastname: Sorbara
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Theresa
authors.initials: T
authors.lastname: Davies-Hill
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: Molecular Diagnostic Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002472:Cell Transformation, Viral; D002999:Clone Cells / Q000473:pathology / Q000821:virology; D016208:Databases, Factual; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000821:virology; D005260:Female; D015321:Gene Rearrangement; D050438:Genes, Immunoglobulin Heavy Chain; D020022:Genetic Predisposition to Disease; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000473:pathology / Q000821:virology; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D012367:RNA, Viral
keywords: Chronic lymphocytic leukemia; Clonality; Epstein-Barr virus; Hodgkin lymphoma; Reed-Sternberg cell; Richter transformation; ZAP-70