Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome.
To define reproducible criteria for subgroups of diffuse large B-cell lymphomas (DLBCL), including lymphomas with plasmablastic/plasmacytoid features (PB/PC-Fs), we investigated 66 DLBCL; the samples were categorized as either centroblastic (CB), immunoblastic (IB) or PB/PC-F applying standardized morphologic criteria. Blinded specimens were reviewed by three independent pathologists. The final consensus classification included 44 CB (67%), seven IB (10%) and 15 PB/PC-F (23%). The interobserver agreement between two centers (Vienna, Würzburg) was 93.5%. Most PB/PC-F were CD20+, cIgM+, MUM-1+, CD138+/-, bcl-6-, corresponding to an activated B-cell phenotype. Immunoglobulin-V(H) gene mutation analysis was consistent with a germinal or postgerminal center-cell origin. By fluorescence in situ hybridization analysis, 11/13 (85%) PB/PC-F had a monoallelic TP53 deletion. The pretreatment characteristics of patients with PB/PC-F included a tendency for more B symptoms, extranodal disease and a higher IPI. Importantly, PB/PC-F were resistant to standard chemotherapy (complete remission rate 47%, relapse rate 71%) and even autologous stem-cell transplantation. The median overall survival (OS) (14 months, P<0.002) and disease-free survival (6 months, P=0.02) were significantly shorter compared to patients with CB and IB. The OS difference was pronounced within the low and low-intermediate IPI risk group (P<0.001). Our data indicate a strong association of plasmablastic/plasmacytoid morphology with TP53 deletions, poor response to chemotherapy and short survival.
Simonitsch-Klupp
I
I
Department of Clinical Pathology, University of Vienna, Vienna, Austria.
Hauser
I
I
Ott
G
G
Drach
J
J
Ackermann
J
J
Kaufmann
J
J
Weltermann
A
A
Greinix
H T
HT
Skrabs
C
C
Dittrich
C
C
Lutz
D
D
Pötter
R
R
Mannhalter
C
C
Lechner
K
K
Chott
A
A
Jaeger
U
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D005803:Genes, Immunoglobulin; D016158:Genes, p53 / Q000235:genetics*; D018858:Germinal Center / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000145:classification / Q000401:mortality / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000401:mortality / Q000473:pathology*; D016400:Lymphoma, Large-Cell, Immunoblastic / Q000145:classification / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology*; D011379:Prognosis; D012367:RNA, Viral / Q000235:genetics; D017384:Sequence Deletion; D015996:Survival Rate; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D015415:Biomarkers; D012367:RNA, Viral