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Researchers better characterize associations between melanoma, lymphoid neoplasms
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Patients initially diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma and plasma cell neoplasm had mutually increased risks for second primary cutaneous melanoma, according to findings from a population-based study.
The reverse also appeared true: patients with a primary diagnosis of cutaneous melanoma had an increased risk for developing these lymphoid neoplasm subtypes as second cancers.
Contrastingly, patients with diffuse large B-cell lymphoma and Hodgkin lymphoma had elevated risk for melanoma after diagnosis, but patients with melanoma were not at increased risk for these subtypes as second cancers.
“We show for the first time that the association between cutaneous melanoma and lymphoid neoplasms varies substantially among the six most common lymphoid neoplasms subtypes,” Lindsay M. Morton, PhD, of the radiation epidemiology branch, division of cancer epidemiology and genetics at NCI, and colleagues wrote.
Previous studies indicated that survivors of lymphoid neoplasms are at increased risk for developing cutaneous melanoma, and that survivors of cutaneous melanoma are at increased risk for lymphoid neoplasms. Although disease subtypes are heterogeneous, whether this association varied among the neoplasms subtypes remained unclear.
“The aims of our study were to quantify risk [for] developing second primary cutaneous melanoma after subtype-specific first primary lymphoid neoplasms and assess clinical impact and, conversely, to quantify risk [for] developing subtype-specific second primary lymphoid neoplasms after first primary cutaneous melanoma and assess clinical impact,” researchers wrote.
Investigators used SEER data to identify all adult survivors of first lymphoid neoplasms or melanoma between 2000 and 2013.
They used standardized incidence ratios to evaluate risk for development of second primary melanoma and multivariable Poisson regression models to measure the impact of second cancer development on risk for all-cause mortality.
Analyses of first primary lymphoid neoplasm included 151,949 adults. Among these, 36,784 had CLL/small lymphocytic lymphoma (SLL), 33,443 had DLBCL, 26,212 had follicular lymphoma, 26,548 had plasma cell neoplasm, 11,406 had marginal zone lymphoma and 17,556 had Hodgkin lymphoma.
The mean age at diagnosis ranged from 60 to 66 years for all subtypes except Hodgkin lymphoma (mean age, 41.6 years).
Analyses of first primary cutaneous melanoma included 148,336 adults (55.6% men; mean age at diagnosis, 56.5 years). A majority of individuals (62.5%) had localized disease.
Analyses excluded individuals aged younger than 20 years at first primary diagnosis, non-Caucasians or those who had HIV.
Compared with the general population, risk for second primary cutaneous melanoma increased among patients diagnosed with CLL/SLL (SIR = 1.96; 95% CI, 1.74-2.21), DLBCL (SIR = 1.22; 95% CI, 1.02-1.45), follicular lymphoma (SIR = 1.32; 95% CI, 1.09-1.58), Hodgkin lymphoma (SIR = 1.75; 95% CI, 1.33-2.26) and plasma cell neoplasm (SIR = 1.33; 95% CI, 1.07-1.63).
Survivors of marginal zone lymphoma did not have significant increased risk (SIR = 1.27; 95% CI, 0.94-1.68).
The degree of risk appeared different across subtypes of lymphoid neoplasm (P for heterogeneity < .001).
Second primary cutaneous melanoma risk appeared higher in early follow-up for survivors of CLL/SLL (P for heterogeneity = .007) and marginal zone lymphoma (P for heterogeneity = .008).
Among survivors of plasma cell neoplasm, SIRs for melanoma risk decreased with increasing age (P = .02), appeared higher for women than men (P for heterogeneity = .008) and varied by treatment for plasma cell neoplasm (P for heterogeneity = .05).
Those with a primary diagnosis of melanoma appeared at increased risk for CLL/SLL (SIR = 1.44; 95% CI, 1.25-1.66), follicular lymphoma (SIR = 1.47; 95% CI, 1.21-1.77) and plasma cell neoplasm (SIR = 1.25; 95% CI, 1.06-1.47), but not for DLBCL, marginal zone lymphoma or Hodgkin lymphoma.
Researchers observed slight heterogeneity in risk for second cancer across the subgroups of survivors of first primary cutaneous melanoma.
SIRs for second primary DLBCL increased with increasing age at cutaneous melanoma diagnosis (P = .002). Risk for secondary disease increased among survivors of follicular lymphoma (P = .05) and Hodgkin lymphoma (P = .04) with early-stage disease.
Among survivors of most lymphoid neoplasms, development of melanoma increased risk for mortality (HR range = 1.52; 95% CI, 1.25-1.85 to HR = 2.46; 95% CI, 1.45-4.16).
Among survivors of cutaneous melanoma, lymphoid neoplasms also increased risk for mortality (HR range = 1.75; 95% CI, 1.15-2.65 to HR = 6.28; 95% CI, 5-7.88).
Researchers observed the highest risk for mortality among the most aggressive lymphoid neoplasm subtypes.
“Further research should seek to include treatment data for first and second neoplasms and characterize immune function [among] patients with subtype-specific lymphoid neoplasms and cutaneous melanoma to elucidate a potential role for specific immune perturbations in the etiology of these malignancies,” the researchers wrote. – by Melinda Stevens
Disclosures: The Intramural Research Program of the NCI funded the study. The authors report no relevant financial disclosures.
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