Risk Factors for Keratinocyte Carcinoma in Recipients of Allogeneic Hematopoietic Cell Transplants.

Importance: Allogeneic hematopoietic cell transplant (alloHCT) is known to increase the risk for keratinocyte carcinoma. The extent to which host characteristics, including pigmentary phenotype and UV radiation exposure, contribute is unknown. Objective: To identify and validate independent risk factors for keratinocyte carcinoma after alloHCT, including those associated with the transplant and the host. Design, Setting, and Participants: This retrospective cohort study analyzed a consecutive sample of alloHCT recipients from January 1, 2000, to December 31, 2014, at the Mayo Clinic, Rochester, Minnesota (n = 872) and University Hospitals Cleveland Medical Center, Cleveland, Ohio (n = 147). Participants from the Mayo Clinic were randomly allocated (2:1) into discovery (n = 581) and validation (n = 291) cohorts. Time to first keratinocyte carcinoma and information about transplant- and host-associated risk factors were extracted. A multivariate keratinocyte carcinoma risk model was created using a stepwise Cox proportional hazards regression model with P ≤ .05 for entry that incorporated all covariates that were individually statistically significant at α = 0.05 in the discovery cohort. The risk model was first internally validated using the Mayo Clinic validation cohort and then externally validated using the independent cohort of alloHCT recipients at University Hospitals Cleveland Medical Center. Data were analyzed from March 13, 2018, to June 12, 2019. Exposures: Allogeneic hematopoietic cell transplant. Main Outcomes and Measures: The primary outcome was time to development of the first cutaneous keratinocyte carcinoma after alloHCT; secondary outcome, time to development of the first individual basal and/or squamous cell carcinoma after alloHCT. Results: Of the 872 alloHCT recipients identified in the Mayo Clinic cohort (520 men [59.6%]; mean [SD] age, 48.3 [12.6] years), 95 (10.9%) developed keratinocyte carcinoma after alloHCT during 5349 person-years of follow-up. Of the 147 alloHCT recipients in the exernal validation cohort (86 men [58.5%]; mean [SD] age, 47.9 [17.5] years), 18 (12.2%) developed keratinocyte carcinoma after alloHCT in 880 person-years of follow up. Risk factors independently associated with keratinocyte carcinoma after alloHCT included age (hazard ratio [HR] per 10 years, 1.72; 95% CI, 1.21-2.42), chronic lymphocytic leukemia (HR, 2.47; 95% CI, 1.20-5.09), clinically photodamaged skin (HR, 3.47; 95% CI, 1.87-6.41), and history of cutaneous squamous cell carcinoma (HR, 2.60; 95% CI, 1.41-5.91). Harrell concordance statistics were 0.81 (95% CI, 0.72-0.90) and 0.86 (95% CI, 0.74-0.98) for internal and external validation of the keratinocyte carcinoma risk model, respectively. Conclusions and Relevance: This study found validated independent risk factors for keratinocyte carcinoma after alloHCT that are enriched with host- compared with transplant-associated risk factors. These findings highlight the importance of assessing host-associated risk factors for keratinocyte carcinoma in patients eligible for alloHCT. Future studies should examine whether keratinocyte carcinoma risk stratification before alloHCT may inform long-term surveillance strategies.

Incidence and Trends of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma: A Population-Based Study in Olmsted County, Minnesota, 2000 to 2010.

OBJECTIVE: To determine population-based incidence estimates of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: We reviewed the medical records of a population-based cohort diagnosed with nonmelanoma skin cancer between January 2, 2000, and December 31, 2010. The age- and sex-adjusted incidence rates were calculated and compared with estimates from previous periods. RESULTS: The age-adjusted BCC incidence (cases per 100,000 person-years) was 360.0 (95% CI, 342.5-377.4) in men and 292.9 (95% CI, 278.6-307.1) in women. The age-adjusted cSCC incidence (cases per 100,000 person-years) was 207.5 (95% CI, 193.9-221.1) in men and 128.8 (95% CI, 119.4-138.2) in women. From years 1976 to 1984 to years 2000 to 2010, the age- and sex-adjusted incidence (cases per 100,000 person-years) of BCC increased from 222.0 (95% CI, 204.5-239.5) to 321.2 (95% CI, 310.3-332.2) and that of cSCC from 61.8 (95% CI, 52.3-71.4) to 162.5 (95% CI, 154.6-170.3). Over time, the anatomical distribution of BCC shifted from the head and neck to the torso and that of cSCC shifted from the head and neck to the extremities. CONCLUSION: The incidences of BCC and cSCC are increasing, with a disproportionate increase in cSCC relative to BCC. There is also a disproportionate increase in the incidence of both tumors in women, as well as a shift of anatomical distributions.

Incidence and Clinical Features of Rare Cutaneous Malignancies in Olmsted County, Minnesota, 2000 to 2010.

BACKGROUND: The incidence of rare cutaneous malignancies is unknown. Current estimates of rare cutaneous malignancy incidences are based on broad epidemiologic data or single institution experiences, not population-based data. OBJECTIVE: To determine the incidence of several rare nonmelanoma skin cancers. MATERIALS AND METHODS: The authors conducted a retrospective chart review of a population-based cohort between the years 2000 and 2010. Residents of Olmsted County, Minnesota, who were diagnosed with a biopsy-proven nonmelanoma skin cancer-excluding basal cell carcinoma and squamous cell carcinoma-were included in this study. The primary outcome was tumor incidence. Additionally, the authors extracted patient demographics, tumor characteristics, treatment modalities, and outcomes. RESULTS: The age-adjusted and sex-adjusted incidences per 100,000 persons of multiple rare cutaneous malignancies were: atypical fibroxanthoma (1.8), sebaceous carcinoma (0.8), dermatofibrosarcoma protuberans (0.4), microcystic adnexal carcinoma (0.7), eccrine carcinoma (0.4), eccrine porocarcinoma (0.2), and leiomyosarcoma (0.2). CONCLUSION: The authors report population-based incidences and clinical characteristics for these rare cutaneous malignancies. The immune status and smoking status of patients and the treatment and outcomes of these tumors are reported. Additional studies in a broader population are needed to further define the epidemiology and outcomes of these malignancies.