Clinical and biologic characteristics of MCL. (A) MCL diagnosis is based on morphology and immunophenotyping (CD20⁺, CD5⁺, CD23⁻, FMC7⁺). Pathologic subclassification recognizes 2 main subsets: classic and blastoid. (B) Fluorescence in situ hybridization (FISH) cytogenetics showing translocation t(11;14)(q13;q32) and immunohistochemistry for detection of cyclin D1 overexpression are helpful adjuncts in the diagnosis of MCL. Immunohistochemistry images provided by Stefania Pittaluga; images of FISH testing provided by Diane C. Arthur. (C) Tumor proliferation determines outcome. Figure adapted from original⁵  with permission. The expression levels of 20 genes related to cell proliferation were summarized in the proliferating signature average. Lowest (green) to highest (red) expression of the proliferation signature average in lymph node biopsies from 92 patients with MCL is shown with across a 16-fold range. Kaplan-Meier analysis for patients grouped into 4 quartiles on the basis of this score is shown. (D) CCND1 locus at 11q13 and cyclin D1 mRNA isoforms. Shaded boxes represent coding sequences, open boxes represent noncoding exon sequences. The 3′UTR of full-length 4.5-kb cyclin D1a contains binding sites for miRs (blue boxes) and AU-rich elements (red triangles); cyclin D1a isoforms with a truncated 3′UTR lack these elements. The alternatively spliced 1.7-kb cyclin D1b mRNA lacks exon 5 and retains part of intron 4. Illustration by Paulette Dennis.