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. Keywords: mantle cell lymphoma; blastoid; histologic transformation Mantle cell lymphoma (MCL) is a distinct type of B-cell lymphoma characterized by the t(11;14)(q13; q32) and cyclin D1 overexpression. Histologically, MCL is typically composed of a monotonous population of small to medium-sized lymphoid cells with slightly irregular nuclear contours and a relatively low mitotic rate. Immunophenotypically, MCL expresses monotypic surface immunoglobulin, pan-B-cell antigens, and CD5, and is usually negative CD10 and CD23. 1,2 A histologically more aggressive form of MCL, blastoid variant, also occurs, either de novo or in patients with typical MCL. Two types of blastoid MCL are described, consisting of either lymphoblast-like (classic type) or large (pleomorphic type) cells with a high proliferative fraction. [3][4][5][6] In patients who have both typical and blastoid variant MCL, either simultaneously or sequentially, the relationship between these neoplasms is not well studied. One might assume that both the typical and blastoid variant MCL are clonally related, analogous to low-grade follicular lymphoma and diffuse large B-cell lymphoma. However, in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who develop diffuse large B-cell lymphoma, so-called Richter's syndrome, molecular genetic analysis indicates that the CLL/SLL and diffuse large B-cell lymphoma are clonally related in approximately 50% of cases. 7,8 In our review of the literature, we have identified only three patients in which the clonal...

CD5-positive follicular lymphoma: clinicopathologic correlations and outcome in 88 cases

“…12 All tissue sections underwent heat-induced antigen retrieval. The antibodies used were specific for CD3, CD20, CD43, BCL-6, MUM1, and Ki-67 (Dako, Carpinteria, CA, USA); CD5 and cyclin D1 (SP4; Labvision/Neomarkers, Fremont, CA, USA); CD10, CD23, and BCL2 (Novocastra/Vision Biosystem, Benton Lane, Newcastle-upon-Tyne, UK); CD21 (Leica Biosystems, Buffalo Grove, IL, USA); and PAX-5 (Transduction Labs, San Diego, CA, USA).…”

CD5-positive mucosa-associated lymphoid tissue (MALT) lymphoma: a clinicopathologic study of 14 cases

“…Immunohistochemical stains were performed using formalinfixed, paraffin-embedded sections of tissue or bone marrow core biopsy or clot using the avidin-biotin-peroxidase complex method and an automated immunostainer (Ventana-Biotech, Tucson, AZ) as described previously [16]. All tissue sections underwent heat-induced antigen retrieval.…”

Rearrangement and expression of the immunoglobulin μ-chain gene in human myeloid cells

“…Reverse transcription (RT) was performed using the Sensiscript RT Kit (Qiagen Inc.). The IgM V Hm DJ Hm transcripts were detected using nested PCR, 10,15,18 and the amplification products were gel-purified, cloned, and sequenced. 15 The rearranged IgM V Hm DJ Hm sequences were analyzed for the V, D and J region usage and evidence of somatic hypermutation, as described previously.…”