title: Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network.
abstract: Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological characteristics. Cytomorphological subtypes, growth pattern and markers of proliferation (mitotic and Ki-67 indices) were analysed. In addition to the known cytological subtypes, classical (87.5%), small cell (3.6%), pleomorphic (5.9%) and blastic (2.6%), we identified new pleomorphic subgroups with mixtures of cells (classical + pleomorphic type; 1.6%) or transitions (classical/pleomorphic type; 1.6%), which, however, did not differ significantly in overall survival time. Exactly 80.5% of cases displayed a diffuse growth pattern, whereas 19.5% of cases had a nodular growth pattern, which was associated with a slightly more favourable prognosis. A high proliferation rate (mitotic or Ki-67 indices) was associated with shorter overall survival. Cut-off levels were defined that allowed three subgroups with different proliferation rates to be discriminated, which showed significantly different clinical outcomes (P < 0.0001). Based on this large clinicopathological study of prospective clinical trials, multivariate analysis confirmed the central prognostic role of cell proliferation and its superiority to all other histomorphological and clinical criteria.
authors.affiliation: Department of Haematopathology and Lymph Node Registry, University Hospitals of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Tiemann
authors.forename: Carsten
authors.initials: C
authors.lastname: Schrader
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Martin H
authors.initials: MH
authors.lastname: Dreyling
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Andrew
authors.initials: A
authors.lastname: Norton
authors.forename: Francoise
authors.initials: F
authors.lastname: Berger
authors.forename: Philip
authors.initials: P
authors.lastname: Kluin
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Stephano
authors.initials: S
authors.lastname: Pileri
authors.forename: Ennio
authors.initials: E
authors.lastname: Pedrinis
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Feller
authors.forename: Hartmut
authors.initials: H
authors.lastname: Merz
authors.forename: Dirk
authors.initials: D
authors.lastname: Janssen
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Han
authors.initials: H
authors.lastname: Krieken
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Michael
authors.initials: M
authors.lastname: Unterhalt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Reza
authors.initials: R
authors.lastname: Parwaresch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D020522:Lymphoma, Mantle-Cell / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen