Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases

Abstract

The clinical, histological, phenotypic and genotypic features of 21 primary cutaneous B-cell lymphomas (CBCLs) have been investigated. The patients were 13 men and eight women aged 34-91 years (median 67) at diagnosis. Eighteen patients had localized disease, and three had multiple skin lesions at diagnosis. Twelve patients developed cutaneous or extracutaneous recurrences, and five died from malignant lymphoma 7-84 months (median 36) after diagnosis. Histological examination showed features of marginal zone/mucosa-associated lymphoid tissue (MALT)-type lymphoma in 12 cases. Three of these had transformed to diffuse large B-cell lymphoma (DLBCL) in relapse biopsies. The remaining cases were seven primary DLBCLs and two cases tentatively classified as follicle centre cell (FCC) lymphoma. The neoplastic B cells showed similar phenotypes and genotypes in most cases (CD20+, CD79+, CD5-, CD10-, cyclin D1-, bcl-2+, bcl-x-, bax-, t(14;18)-negative). p53 protein was expressed in five cases, and four harboured mis-sense or loss-of-function mutations in the p53 gene. Deletion or promoter region hypermethylation of the p16INK4a gene was detected in two patients with DLBCL. The level of retinoblastoma protein expression and the proliferative fraction were significantly higher in DLBCL (> 50%) than in MALT- or FCC-type lymphomas (< 10%). Features associated with an unfavourable prognosis were the presence of multiple skin lesions at diagnosis, transformation from MALT-type lymphoma to DLBCL, and possibly p16INK4a aberrations. It is concluded that most CBCLs are dissimilar from FCC lymphomas and seem to be more closely related to marginal zone/MALT-type lymphomas. It is also suggested that there are fundamental differences between DLBCL and other histological categories of CBCL, indicating that cutaneous DLBCL is a separate entity with an increased growth potential and genetic features similar to DLBCL originating in other anatomical sites.

Comparative expressed sequence hybridization studies of t(11;18)(q21;q21)-positive and -negative gastric MALT lymphomas reveal both unique and overlapping gene programs

“…34,36 Although the proteins that have a role in the pathogenesis of MALT lymphoma are still largely unknown (except for those involved in the NF-kB pathway), we compared the gastric MALT lymphoma expression patterns found in this study with the chromosomal locations of genes encoding proteins that are involved in the NF-kB pathway and/or proteins with previously reported altered expression in marginal zone lymphoma. [37][38][39][40][41][42][43][44][45][46] Of interest is that 18q21/MALT1 is overexpressed in all the three groups, consistent with reported MALT1 overexpression in MALT lymphomas regardless of the presence or absence of a t(11;18)(q21;q21). Overexpression of 11q21/ API2 did only occur in the two t(11;18)(q21;q21)-positive groups and not in the t(11;18)(q21;q21)-negative group and may be explained by API2-MALT-induced transcriptional activation of the API2 gene through NF-kB binding elements.…”

Genetic interactions between Pten and p53 in radiation-induced lymphoma development

“…This interval encodes only four transcripts as estimated from the Celera and Public databases, that is, Papss2, Pten, and two novel genes (Figure 1). We focused on the Pten gene initially because of its known activity as a tumor suppressor gene for a variety of tumor types including lymphomas (Gronbaek et al, 1998;Butler et al, 1999;Dahia et al, 1999;Herranz et al, 2000;Izumoto et al, 2001;Frisk et al, 2002;Kurose et al, 2002;Shin et al, 2002), and its possible role in radiation sensitivity (Wick et al, 1999).…”

IgV and bcl6 somatic mutation analysis reveals the heterogeneity of cutaneous B-cell lymphoma, and indicates the presence of undisclosed local antigens

“…[1][2][3][4][5][6] Although the clinical behavior of primary cutaneous BCL is dramatically different from those diagnosed in lymph nodes, 1,2,5,7-9 the morphology is strikingly similar. Until now no clear immunophenotypical or molecular differences have been known, [10][11][12] except that t(14;18) occurs rarely in skin follicular lymphomas (FLs), while it is characteristic of nodal FLs.…”