Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma

• Published in: Virchows Archiv : an international journal of pathology Vol. 485; no. 2; pp. 323 - 334
• Main Authors: Chuang, Wen-Yu, Chang, Hung, Shih, Lee-Yung, Lin, Tsung-Chieh, Yeh, Chi-Ju, Ueng, Shir-Hwa, Kuo, Ming-Chung, Kao, Hsiao-Wen, Liu, Hsuan, Chang, Sheng-Tsung, Lee, Chih-Ling, Huang, Kuan-Po, Wang, Tong-Hong, Wan, Yung-Liang, Yu, Jau-Song, Hsueh, Chuen, Chuang, Shih-Sung
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2024; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; B-cell lymphoma; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; CD5 antigen; CD5 Antigens - metabolism; Copy number; Cyclin D1; Cyclin D1 - genetics; D1 protein; Female; Fluorescence in situ hybridization; Gene expression; Gene Rearrangement; Genomic analysis; Humans; Immunohistochemistry; Lymphoma; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Mantle-Cell - diagnosis; Lymphoma, Mantle-Cell - genetics; Lymphoma, Mantle-Cell - metabolism; Lymphoma, Mantle-Cell - pathology; Male; Mantle cell lymphoma; Medicine; Medicine & Public Health; Middle Aged; Original Article; Pathology; Proteins; SOXC Transcription Factors - genetics; Tumor cells; Tumors; Diffuse large B cell lymphoma; SOX11; Cyclin D1; CD5; Pleomorphic; Mantle cell lymphoma
• ISSN: 0945-6317; 1432-2307; 1432-2307
• DOI: 10.1007/s00428-024-03813-9

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(−) cyclin D1(+) SOX11(−), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1 -rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1 -rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1 -rearranged cases were similar to MCL, whereas CCND1 -non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1 -rearranged cases had a notable trend ( P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.