title: CD5(-) diffuse large B-cell lymphoma with peculiar cyclin D1+ phenotype. Pathologic and molecular characterization of a single case.
abstract: Increased expression of cyclin D1 is notoriously associated with mantle cell lymphoma because of translocation t(11;14)(q13;q32) or variants involving the cyclin D1 gene. We present an unusual case of CD5-negative diffuse large B-cell lymphoma expressing cyclin D1 in the absence of translocation by fluorescence in situ hybridization analysis. Using array-comparative genomic hybridization, we found a complex karyotype without the characteristic chromosomal aberrations accompanying cyclin D1 translocation in mantle cell lymphoma; instead, there was monoallelic deletion of AKT interacting protein and glycogen synthase kinase-3 β genes, both involved in the AKT/glycogen synthase kinase-3 β cascade-controlling nuclear levels of cyclin D1. These findings suggest that posttranslational events regulating cyclin D1 activity may take place also in a subset of diffuse large B-cell lymphomas and contribute to lymphomagenesis. As a consequence, the sole cyclin D1 positivity by immunohistochemistry may not be enough to distinguish pleomorphic/blastoid mantle cell lymphoma from diffuse large B-cell lymphoma. Search for t(11;14) with fluorescence in situ hybridization probes should always be performed in doubtful cases.
authors.affiliation: Anatomic Pathology, Foundation IRCCS Policlinico San Matteo and University of Pavia, 27100 Pavia, Italy. m.lucioni@smatteo.pv.it
authors.forename: Marco
authors.initials: M
authors.lastname: Lucioni
authors.forename: Francesca
authors.initials: F
authors.lastname: Novara
authors.forename: Roberta
authors.initials: R
authors.lastname: Riboni
authors.forename: Giacomo
authors.initials: G
authors.lastname: Fiandrino
authors.forename: Marta
authors.initials: M
authors.lastname: Nicola
authors.forename: Sandra
authors.initials: S
authors.lastname: Kindl
authors.forename: Emanuela
authors.initials: E
authors.lastname: Boveri
authors.forename: Vassili
authors.initials: V
authors.lastname: Jemos
authors.forename: Luca
authors.initials: L
authors.lastname: Arcaini
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018956:CD5 Antigens / Q000378:metabolism*; D055028:Comparative Genomic Hybridization; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D046228:Microarray Analysis; D009367:Neoplasm Staging; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: C530104:CCND1 protein, human; D018956:CD5 Antigens; D019938:Cyclin D1