title: Sequence analysis proves clonal identity in five patients with typical and blastoid mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) is typically composed of small irregular lymphoid cells. Blastoid variants, composed of lymphoblast-like (classic type) or large (pleomorphic type) cells, arise de novo or in patients with typical MCL. Although it has been assumed that blastoid variant represents histologic transformation of typical MCL, the clonal relationship between the two tumors has rarely been assessed at the molecular level. We identified five patients with typical MCL who subsequently developed the blastoid variant. There were two men and three women with a median age of 65 years (range, 34-70) at diagnosis of typical MCL involving lymph nodes. The median interval between typical and blastoid MCL was 36 months (range, 11-103). Subsequent blastoid variant MCL involved soft tissue (two), lymph node (one), ileum (one), or rectum (one). All typical and blastoid neoplasms were positive for CD20, cyclin D1, and monotypic surface immunoglobulin light chain, and all typical cases were positive for CD5. Two blastoid neoplasms lost CD5 expression, one of which aberrantly expressed CD10. Immunostaining for Ki-67 showed a median proliferative fraction of 20% in typical and 70% in blastoid neoplasms. Sequence analysis of the VDJ regions of the rearranged IgH allele proved clonal identity in each set of paired samples in all five patients. These results support the concept that blastoid MCL arising in patients with typical MCL represents histologic transformation of the original neoplastic clone.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Candy C
authors.initials: CC
authors.lastname: Cromwell
authors.forename: Ashwini P
authors.initials: AP
authors.lastname: Mehta
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D056741:Cyclin D; D016213:Cyclins / Q000032:analysis; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D019394:Ki-67 Antigen / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013997:Time Factors; D050441:VDJ Exons
chemical_list: D015703:Antigens, CD; D056741:Cyclin D; D016213:Cyclins; D007143:Immunoglobulin Heavy Chains; D019394:Ki-67 Antigen