title: IgV H mutations in blastoid mantle cell lymphoma characterize a subgroup with a tendency to more favourable clinical outcome.
abstract: Mantle cell lymphoma (MCL) is associated with a very unfavourable clinical course. This is particularly true for mantle cell lymphoma of the blastoid subtype (MCL-b). In order to define prognostic factors, we analysed the impact of immunoglobulin heavy chain variable (IgV H) gene somatic hypermutations on clinical outcome in a series of 21 cases of morphologically, phenotypically, and genotypically well-characterized MCL-b. Testing and estimation were performed using log-rank statistics and displayed on Kaplan-Meier graphs. Thirteen of 21 cases of MCL-b revealed a homology rate of > or = 99% compared to IgV H germ-line sequences in the databases and were scored as non-mutated. Eight of 21 cases (38%) of MCL-b were mutated. In MCL-b the mutation frequency was usually low and the mutation pattern was only rarely antigen-selected, in contrast to a control group of 11 cases with morphologically almost identical, but phenotypically and genotypically clearly distinguishable, diffuse large B cell lymphoma, derived, most likely, from germinal centre B cells. In our series of 21 MCL-b, positive IgV H mutational status, irrespective of varying homology thresholds, had no statistically significant prognostic impact on event-free or overall survival. However, mutated MCL-b tended to present more frequently at an earlier stage and without bone marrow involvement and to show lower rates of relapse and death, resulting in a more favourable clinical outcome.
authors.affiliation: Department of Pathology, State Hospital, St Gallen, Switzerland. sergio.cogliatti@kssg.ch
authors.forename: Sergio B
authors.initials: SB
authors.lastname: Cogliatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Dieter R
authors.initials: DR
authors.lastname: Zimmermann
authors.forename: Samuel
authors.initials: S
authors.lastname: Henz
authors.forename: Tim C
authors.initials: TC
authors.lastname: Diss
authors.forename: Michele
authors.initials: M
authors.lastname: Ghielmini
authors.forename: Ulrico
authors.initials: U
authors.lastname: Schmid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005803:Genes, Immunoglobulin / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods; D016019:Survival Analysis