Assessment of Liquid Biopsy in Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type.

Liquid biopsy assessment has first been established in solid tumors, allowing the detection of either circulating tumor cells, cell-free vesicles, and/or circulating cell-free tumor DNA (ctDNA) in the plasma or other biological fluids. In systemic diffuse large B-cell lymphomas (DLBCLs), ctDNA is detectable, reflecting tumor mutational status, and may predict clinical outcome ( Bohers et al., 2018 Bohers E. Viailly P.J. Becker S. Marchand V. Ruminy P. Maingonnat C. et al. Non-invasive monitoring of diffuse large B-cell lymphoma by cell-free DNA high-throughput targeted sequencing: analysis of a prospective cohort. Blood Cancer J. 2018; 8: 74 Crossref PubMed Scopus (57) Google Scholar ). In addition, the dynamics of ctDNA correlates with clinical response ( Deng et al., 2020 Deng Q. Han G. Puebla-Osorio N. Ma M.C.J. Strati P. Chasen B. et al. Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas. Nat Med. 2020; 26: 1878-1887 Crossref PubMed Scopus (180) Google Scholar ; Kurtz et al., 2019 Kurtz D.M. Esfahani M.S. Scherer F. Soo J. Jin M.C. Liu C.L. et al. Dynamic risk profiling using serial tumor biomarkers for personalized outcome prediction. Cell. 2019; 178: 699-713.e19 Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar , Kurtz et al., 2018 Kurtz D.M. Scherer F. Jin M.C. Soo J. Craig A.F.M. Esfahani M.S. et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma. J Clin Oncol. 2018; 36: 2845-2853 Crossref PubMed Scopus (233) Google Scholar ). Primary cutaneous DLBCL-leg type (PCDLBCL-LT) is an aggressive cutaneous lymphoma, which presents as a rapid progressive tumor(s) in older adults ( Willemze et al., 2019 Willemze R. Cerroni L. Kempf W. Berti E. Facchetti F. Swerdlow S.H. et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019; 133: 1703-1714 Crossref PubMed Scopus (611) Google Scholar ). The mutational landscape of PCDLBCL-LT showed activated B-cell–like DLBCL canonical mutations ( Mareschal et al., 2017 Mareschal S. Pham-Ledard A. Viailly P.J. Dubois S. Bertrand P. Maingonnat C. et al. Identification of somatic mutations in primary cutaneous diffuse large B-cell lymphoma, leg type by massive parallel sequencing. J Invest Dermatol. 2017; 137: 1984-1994 Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar ; Zhou et al., 2019 Zhou X.A. Louissaint Jr., A. Wenzel A. Yang J. Martinez-Escala M.E. Moy A.P. et al. Genomic analyses identify recurrent alterations in immune evasion genes in diffuse large B-cell lymphoma, leg type. J Invest Dermatol. 2019; 138: 2365-2376 Abstract Full Text Full Text PDF Scopus (45) Google Scholar ), especially with the high prevalence of MYD88L265P (70%) and CD79B (40%) mutations that allow its classification in the MCD or C5 subgroup among DLBCLs ( Chapuy et al., 2018 Chapuy B. Stewart C. Dunford A.J. Kim J. Kamburov A. Redd R.A. et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018; 24: 679-690 Crossref PubMed Scopus (902) Google Scholar ; Schmitz et al., 2018 Schmitz R. Wright G.W. Huang D.W. Johnson C.A. Phelan J.D. Wang J.Q. et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018; 378: 1396-1407 Crossref PubMed Scopus (1036) Google Scholar ). Genetic analysis on primary tumors may be limited not only by tumor site and sample size but also by spatial and temporal mutational heterogeneity ( Condoluci and Rossi, 2019 Condoluci A. Rossi D. The future of cell-free DNA testing to guide therapeutic decisions in B-cell lymphomas. Curr Opin Hematol. 2019; 26: 281-287 Crossref PubMed Scopus (11) Google Scholar ; Phallen et al., 2017 Phallen J. Sausen M. Adleff V. Leal A. Hruban C. White J. et al. Direct detection of early-stage cancers using circulating tumor DNA. Sci Transl Med. 2017; 9 (9)eaan2415 Crossref PubMed Google Scholar ). Droplet digital PCR (ddPCR) and its increased sensitivity of 0.01% ( Diaz and Bardelli, 2014 Diaz L.A. Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014; 32: 579-586 Crossref PubMed Scopus (1589) Google Scholar ) may detect infraclinical systemic involvement and seem appropriate for single hot-spot mutation detection such as MYD88L265P. Next-generation sequencing (NGS) may be more appropriate to capture the mutational landscape of ctDNA ( Galimberti et al., 2019 Galimberti S. Genuardi E. Mazziotta F. Iovino L. Morabito F. Grassi S. et al. The minimal residual disease in non-Hodgkin’s lymphomas: from the laboratory to the clinical practice. Front Oncol. 2019; 9: 528 Crossref PubMed Scopus (18) Google Scholar ).