Cutaneous lymphomas in adolescents and young adults: Clinical spectrum and physician-reported and patient-reported outcomes
Authors: Gregory R. Delost, Rachel L. Giesey, Luisa F. Christensen, Jeffrey Scott, Kevin D. Cooper
Journal: Journal of the American Academy of Dermatology (2019)

To the Editor: The increasing prevalence and distinguishing features of lymphomas in younger patients, along with their increased risk for secondary cancers and the unique epidemiologic pattern of cutaneous lymphomas, highlight the need to characterize the distribution and features of the disease in this subpopulation to better counsel patients and their families.1Ai W.Z. Keegan T.H. PDress D.J. et al.Outcomes after diagnosis of mycosis fungoides and Sézary syndrome before 30 years of age: a population-based study.JAMA Dermatol. 2014; 150: 709-715Crossref PubMed Scopus (25) Google Scholar, 2Rizzo F.A. Vilar E.G. Pantaleão L. et al.Mycosis fungoides in children and adolescents: a report of six cases with predominantly hypopigmentation, along with a literature review.Dermatol Online J. 2012; 18: 5PubMed Google Scholar We sought to investigate an adolescent and young adult (AYA) cohort in terms of cutaneous lymphoma distribution, itch, and objective clinical outcomes by retrospective chart review of a primary data set from the University Hospitals Cleveland Medical Center (UHCMC) Multidisciplinary Cutaneous Lymphoma Program during 1996-2017 at a level of specificity not recorded by the Surveillance, Epidemiology, and End Results 18 registry.3Surveillance, Epidemiology, and End Results Program. Research data (1973-2011), National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released 2014, based on the November 2013 submission.www.seer.cancer.govGoogle Scholar Cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL) patients were stratified into 3 groups: pediatrics (1-14 years), AYA (15-39 years), and adults (≥40 years). For AYA and adult patients with mycosis fungoides, physician-reported global assessment (PGA) best responses after therapy were classified as complete response or almost clear (CR/AC) or partial response. We measured the patient-reported outcome of change in itch (posttherapy minus baseline) using a 0 (no itch) to 10 (maximum itch) rating scale. High itch refers to an itch score of >5 of 10 and low itch a score of ≤5 of 10. Both Surveillance, Epidemiology, and End Results and UHCMC databases demonstrated a roughly 4:1 ratio of CTCL-to-CBCL cases. Most UHCMC CTCL pediatric (56.3%) and AYA (70.3%) cases were mycosis fungoides (Table I). Adult CTCL also was dominated by mycosis fungoides, but Sézary syndrome was underrepresented in the AYA population (0% AYA vs 6.9% adults). CD8+-associated mycosis fungoides variants were more common in the AYA population (18.8% AYA vs 4.9% adults) and were subcategorized as hypopigmented (6.3% AYA vs 0.2% adults), primary CD8+ aggressive (9.4% AYA vs 0.2% adults), and Woringer-Kolopp disease (3.1% AYA vs 0.5% adults). For CBCLs, most UHCMC AYA cases were either follicle-center or marginal-zone lymphomas, whereas diffuse B-cell lymphomas occurred only in the adults (0% AYA vs 18.8% adults).Table IUniversity Hospitals Cleveland Medical Center cohort patient distribution by CTCL and CBCL subtype and mycosis fungoides patient-reported and physician-reported treatment responses by ageCategoryPediatricAYAAdultCTCL subtype, n (%) Mycosis fungoides stage, n9 (56.3)45 (70.3)280 (69.3)IA731166IB61672II0227III0014IV0016 Sézary syndrome0 (0)0 (0)28 (6.9) Anaplastic large cell lymphoma CD30+2 (12.5)2 (3.1)38 (9.4) Primary CD4+ small-to-medium pleomorphic0 (0)3 (4.7)19 (4.7) Primary CD8+ aggressive0 (0)6 (9.4)17 (4.2) Null (CD4–/CD8–)1 (6.3)1 (1.6)5 (1.2) Granulomatous slack skin0 (0)0 (0)5 (1.2) Anaplastic large cell lymphoma CD30–0 (0)0 (0)4 (1.0) Adult T-cell leukemia or lymphoma0 (0)0 (0)3 (0.7) Woringer-Kolopp disease0 (0)2 (3.1)2 (0.5) Hypopigmented mycosis fungoides4 (25.0)4 (6.3)1 (0.2) Subcutaneous panniculitis-like T-cell lymphoma0 (0)0 (0)1 (0.2) Primary cutaneous γδ lymphoma0 (0)0 (0)1 (0.2) Extranodal NK/T-cell lymphoma0 (0)1 (1.6)0 (0) Total CTCL1664404CBCL subtype, n (%) Follicle center0 (0)5 (45.5)65 (55.6) Marginal zone0 (0)5 (45.5)26 (22.2) Diffuse large B-cell lymphoma leg type0 (0)0 (0)12 (10.3) Diffuse large B-cell lymphoma other0 (0)0 (0)10 (8.5) Blastic plasmacytoid dendritic cell0 (0)0 (0)1 (0.9) Other or not otherwise specified0 (0)1 (9.1)3 (2.6) Total CBCL011117Mycosis fungoides treatment responses Itch at diagnosis, high/low (% high)4/6 (40)∗Statistically significant between AYA and adults by χ2 analysis at P < .05.5/45 (10) Correlation with PGA, n/total (%)CR or AC in those with low baseline itch4/6 (67)33/45 (73)†Statistically significant between adults with high itch and low itch by χ2 analysis at P < .05. Not all patients reported baseline itch.CR or AC in those with high baseline itch2/4 (50)0/5 (0)CR and AC total18 (67)93 (79) Itch posttreatment, average change from baseline (n)–1 (7)–0.54 (28)AC, Almost clear; AYA, adolescent and young adult; CBCL, cutaneous B-cell lymphoma; CR, complete response; CTCL, cutaneous T-cell lymphoma; NK, natural killer; PGA, physician-reported global assessment.∗ Statistically significant between AYA and adults by χ2 analysis at P < .05.† Statistically significant between adults with high itch and low itch by χ2 analysis at P < .05. Not all patients reported baseline itch. Open table in a new tab AC, Almost clear; AYA, adolescent and young adult; CBCL, cutaneous B-cell lymphoma; CR, complete response; CTCL, cutaneous T-cell lymphoma; NK, natural killer; PGA, physician-reported global assessment. In terms of outcome in mycosis fungoides patients, 67% of AYA and 79% of adults achieved CR/AC best response PGA, and the mean time to achieve this response was similar between the groups (5.3 months AYA vs 5.5 months adults). The differences in PGAs between AYA and adults by treatment modality were not significant (Supplementary Table 1; available at https://data.mendeley.com/datasets/5p3drcd262/1). At baseline, a significantly greater proportion of AYA patients (4/10) than adults (5/50) had high itch (P = .015); adults with low itch at baseline had significantly better PGA outcomes after therapy (33 of 45 CR/AC) than those with high itch (0 of 5 CR/AC; P = .005). The AYA sample size was too limited to analyze outcome by itch subset. In conclusion, CD8+ T-cell–associated variants might be more likely to present in AYAs. In addition, a greater proportion of AYA than adult patients appear to exhibit higher itch; adults in the low-itch subset achieved better objective treatment outcomes than high-itch adults. Attention to such special clinical features, as well as the psychosocial aspects of cancer, in the AYA population when managing CTCL and CBCL and counseling patients can help provide more precision and patient-specific care to patients and their families.