Follicular lymphoma without t(14;18) and with BCL-6 rearrangement: a lymphoma subtype with distinct pathological, molecular and clinical characteristics.
Translocations involving the BCL-6 gene are frequently observed in diffuse large B cell lymphoma, but have rarely been reported in follicular lymphoma (FL). We studied a distinct cohort of FLs with a 3q27/BCL-6 gene rearrangement, but lacking the t(14;18) translocation. In 13/15 cases, translocations involved the 3q27 and the 14q32 regions. All cases displayed a marked follicular growth pattern and, in some instances, a monocytoid component. Tumor cells were CD5(-) CD20(+) CD23(-) CD43(-) BCL-6(+), and in the main CD10 negative (n = 10, 71%) and BCL-2 negative (n = 11, 78%). When compared to 20 typical t(14;18)(+) FLs, the presence of large follicles (P = 0.01) and a CD10(-)/BCL-2(-) phenotype were more frequently observed (P = 0.001) in our cohort. Clonal mutations arising in the BCL-6 first intron were observed in 5/7 cases with evidence of intraclonal heterogeneity, consistent with a germinal center origin. No significant difference was found in comparison to t(14;18)(+) FL regarding age, sex, performance status, bone marrow involvement or overall survival. However, in the 3q27(+) FL group, a stage III/IV disease and a bulky mass were less frequently observed. This study indicates that 3q27(+) FL without t(14;18) translocation have peculiar clinico-pathologic features and may correspond to a rare and distinct subtype of lymphoma originating from the germinal center.
Jardin
F
F
Department of Haematology and EMI 9906-IRFMP No. 23, Centre Henri Becquerel, Rouen, France.
Gaulard
P
P
Buchonnet
G
G
Contentin
N
N
Leprêtre
S
S
Lenain
P
P
Stamatoullas
A
A
Picquenot
J M
JM
Duval
C
C
Parmentier
F
F
Tilly
H
H
Bastard
C
C
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D007621:Karyotyping; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors