Increased Incidence Of Melanoma and Non-Melanoma Skin Cancers In Patients With Hairy Cell Leukemia: A Single Institution Experience With 267 Patients From Memorial Sloan-Kettering Cancer Center
Authors: Watts Justin M , Kishtagari Ashwin , Devlin Sean , Stein Eytan M , Park Jae H , Lacouture Mario E , Tallman Martin 
Published: October 2019

Abstract
Chronic lymphocytic leukemia and other B-cell malignancies have been associated with melanoma and non-melanoma skin cancers (NMSC). However, an analysis of Surveillance, Epidemiology and End Results (SEER) data from 1973-2007 found that hairy cell leukemia (HCL), while associated with an increased second cancer risk overall, was not associated with melanoma. In addition, the incidence of NMSC in HCL patients has not been described to our knowledge. Per recent SEER data, the median age at melanoma diagnosis in the general population was 61 years with an age-adjusted incidence rate of 0.02%/year.

Methods
We identified 372 patients seen at Memorial Sloan-Kettering Cancer Center (MSKCC) over the past 30 years (1983-2013) with a morphologic diagnosis of HCL. Of these, we found 267 patients with ≥2 months of follow-up. We examined the medical records of these 267 patients for demographic data, treatment with purine analogs (PA), and co-occurring skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). Skin cancers were considered to be “co-occurring” if they were diagnosed up to 1 year before or any time after the diagnosis of HCL.

Results
In this 267 patient cohort, the median age at HCL diagnosis was 52.1 years (range 19.6-86.1), and the vast majority of patients were white, non-Hispanic males [Table 1]. 225 patients (84%) were treated with a PA, either cladribine or pentostatin.
Of 267 patients, 34 (12.7%) developed skin cancer: 11 (4.1%) melanoma and 25 (9.4%) NMSC [Table 2]. Twelve patients had SCC and 22 BCC. Eleven of 34 patients (32%) had >1 type of skin cancer: 9 BCC and SCC, 1 BCC and melanoma, and 1 SCC and melanoma.For the 34 patients with skin cancer, median follow-up from HCL diagnosis was 10 years (0.7-33.6), median age at HCL diagnosis was 57.5 years, and almost all patients were white, non-Hispanic males. Twenty-nine of the 34 patients (85%) received a PA. Nine patients (27%) either did not receive or were diagnosed with skin cancer before PA therapy. Eighteen patients (53%) were diagnosed with skin cancer between 1 year before and 5 years after HCL; 16 patients (47%) were diagnosed >5 years after HCL.

Conclusions
In 267 HCL patients with very long follow-up, we found a high incidence of all skin cancers (12.7%), melanoma (4.1%), and NMSC (9.4%). Furthermore, the risk of melanoma appears to be considerably higher in the HCL cohort than the general population (0.02%/year). Although these groups were not age, sex, or race-matched, both HCL and melanoma typically occur in white individuals, and one might expect the risk of melanoma to be lower in HCL patients if there was no association given that HCL usually presents at a younger age. Although a previous analysis of SEER data did not show an association between HCL and melanoma, many of these data were collected before PA therapy was introduced. Moreover, almost all melanoma patients in our cohort were previously treated with a PA, possibly explaining the increased risk. The pathogenesis of this apparent association is elusive, but immunosuppression induced by PA therapy in addition to inherent immunosuppression from HCL itself may be responsible. There also appears to be an increased risk of NMSC in our cohort; however, the precise incidence of NMSC in the general population is not available for comparison to our knowledge. Our findings reinforce that HCL patients should be screened aggressively for skin cancer, particularly given the risk of synchronous melanoma.

Disclosures:
No relevant conflicts of interest to declare.