Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone.
Rare cases of histiocytic and dendritic cell (H/DC) neoplasms have been reported in patients with follicular lymphoma (FL), but the biologic relationship between the 2 neoplasms is unknown. We studied 8 patients with both FL and H/DC neoplasms using immunohistochemistry, fluorescence in situ hybridization (FISH) for t(14;18), and polymerase chain reaction (PCR)/sequencing of BCL2 and IGH rearrangements. There were 5 men and 3 women (median age, 59 years). All cases of FL were positive for t(14;18). The H/DC tumors included 7 histiocytic sarcomas, 5 of which showed evidence of dendritic differentiation, and 1 interdigitating cell sarcoma. Five H/DC tumors were metachronous, following FL by 2 months to 12 years; tumors were synchronous in 3. All 8 H/DC tumors showed presence of the t(14;18) either by FISH, or in 2 cases by PCR with the major breakpoint region (MBR) probe. PCR and sequencing identified identical IGH gene rearrangements or BCL2 gene breakpoints in all patients tested. All H/DC tumors lacked PAX5, and up-regulation of CEBPbeta and PU.1 was seen in all cases tested. These results provide evidence for a common clonal origin of FL and H/DC neoplasms when occurring in the same patient, and suggest that lineage plasticity may occur in mature lymphoid neoplasms.
Feldman
Andrew L
AL
Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892-1500, USA.
Arber
Daniel A
DA
Pittaluga
Stefania
S
Martinez
Antonio
A
Burke
Jerome S
JS
Raffeld
Mark
M
Camos
Mireia
M
Warnke
Roger
R
Jaffe
Elaine S
ES
D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D019070:Cell Lineage; D054338:Cell Transdifferentiation; D054740:Dendritic Cell Sarcoma, Follicular / Q000235:genetics* / Q000473:pathology*; D020566:Dendritic Cells, Follicular / Q000473:pathology / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D054747:Histiocytic Sarcoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction