title: Large-cell variants of mantle cell lymphoma: cytologic characteristics and p53 anomalies may predict poor outcome.
abstract: Large-cell variants are uncommon in mantle cell lymphoma (MCL). Here we describe the pathologic and clinical findings in five patients with large-cell lymphoma related to MCL (L-MCL), and compare them to a group of classic small-cell MCL (s-MCL) cases. Histologically, the MC origin of the large cells was evinced by their association with a small mantle cell component in the same tissue, or their distribution in a classic mantle zone pattern, or their development in a patient with previous s-MCL. The large cells were either pleomorphic mantle cells (case 1) or transformed blast-like cells (case 2-5). The median nuclear diameter, median nuclear area and proliferation index of L-MCLs and s-MCLs, were statistically different. Immunophenotypic characterization of four specimens of L-MCL and 10 of s-MCLs with a large panel of antibodies showed the classic findings of MCL, i.e. the IgM+ D+/-, CD5+, CD10-, CD23- phenotype in all cases except two (one CD5- and one CD23+), and the association with a loose follicular dendritic cell network. Two of four L-MCLs and 5/10 s-MCLs demonstrated rearrangements of the bcl-1 gene by Southern blot or by polymerase chain reaction (PCR); 2/4 L-MCLs and 1/9 s-MCLs had p53 mutations on single-strand conformation polymorphism analysis; none of the 14 specimens showed rearrangement of bcl-2 by PCR or bcl-6 and c-myc by Southern blot. All patients with 'transformed' histology (versus 37% of all others) died of lymphoma; their survival (15-18 months; median 17) was much shorter than that of all the others (28-117+ months; median 43) (P=0.0035). All three patients with p53 anomalies, two of whom had tumours with transformed histology, died of their disease in a short time (15, 18 and 28 months). In contrast, the presence of bcl-1 rearrangements did not have prognostic implications. This study documents the existence of large-cell variants of MCL and the poor prognosis associated with the 'transformed' cytologic type and/or p53 abnormalities.
authors.affiliation: Department of Pathology, Division of Hematopathology/Molecular Pathology, New York University Medical Center, NY, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Zoldan
authors.forename: G
authors.initials: G
authors.lastname: Inghirami
authors.forename: Y
authors.initials: Y
authors.lastname: Masuda
authors.forename: F
authors.initials: F
authors.lastname: Vandekerckhove
authors.forename: B
authors.initials: B
authors.lastname: Raphael
authors.forename: E
authors.initials: E
authors.lastname: Amorosi
authors.forename: K
authors.initials: K
authors.lastname: Hymes
authors.forename: G
authors.initials: G
authors.lastname: Frizzera
mesh_terms: D000368:Aged; D001483:Base Sequence; D015139:Blotting, Southern; D002471:Cell Transformation, Neoplastic; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D016159:Tumor Suppressor Protein p53