The Risk of Developing Non-Melanoma Skin Cancers in Patients with Cutaneous T-Cell Lymphoma
Authors: Hafer Ramsay , Duong Teresa , Mandel Jenna , Yang Henry Y , Tolotta Julianna , Banner Lauren , Bhatti Safiyyah , Porcu Pierluigi , Nikbakht Neda 
Published: December 2024

Introduction
Cutaneous T-cell lymphomas (CTCL) are characterized by malignant proliferation of T-cells in the skin. While CTCL has been linked to increased risk of melanoma, the risks of the most common skin cancers, cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), remain unexplored in CTCL patients. Herein, we performed a large population-based, retrospective study to determine how the risks of developing cSCC and BCC in patients with CTCL compare to the general population or patients with psoriasis, an inflammatory skin disorder connected with an increased risk of non-melanoma skin cancers. Furthermore, we examined the risks of cSCC and BCC in these groups based on sex and across different anatomic locations.
Materials and Methods
This population-level retrospective cohort analysis utilized TriNetX, a global network of de-identified healthcare data containing the records of over 107 million patients from 62 healthcare organizations in the United States collaborative network, from 2008 to 2024. U.S. adults with CTCL (n=15,967), psoriasis (n=320,316), or healthy controls (n=5,855,402) were propensity matched for age, race, immunosuppressant use, and history of radiation and assessed for cSCC and BCC risks. Subgroup analysis was performed based on sex. Patients with a history of ultraviolet light therapy, photodynamic therapy, or photochemotherapy were excluded from all groups to further reduce the risk of confounding variables.
Results
Propensity score matching generated cohorts of CTCL, psoriasis, and healthy controls with similar baseline characteristics. The mean age was 59 in the CTCL cohort and 60 in the healthy control and psoriasis cohorts. All cohorts mostly comprised of white (66%) males (56%).
The risk of both keratinocyte malignancies (cSCC and BCC combined) was higher in the CTCL group compared to the healthy controls (RR, 1.78; 95% CI 1.62-1.95). This risk remained elevated, albeit at a lower level, when comparing CTCL group with the psoriasis cohort (RR, 1.44; 95% CI 1.32-1.59). Regarding malignancy subtypes, the risk of cSCC was the most highly elevated in the CTCL cohort compared to both the healthy (RR, 2.10; 95% CI 1.83-2.40) and psoriasis cohort (RR, 1.51; 95% CI 1.34-1.71). Similarly, BCC risk was increased in the CTCL cohort compared to the healthy (RR, 1.65; 95% CI 1.48-1.84) and psoriasis cohort (RR, 1.41; 95% CI 1.27-1.57).
Examining the anatomic locations of head, extremities, and trunk, the CTCL cohort exhibited a higher risk of keratinocyte malignancies regardless of the site of cSCC and BCC. For cSCC, the highest risk of development by anatomic location in CTCL patients was on trunk skin compared to both the healthy (RR, 3.23; 95% CI 2.08-5.01) and psoriasis cohort (RR, 1.91; 95% CI 1.33-2.75). The highest risk of BCC development in CTCL patients was on the extremities (RR, 2.09; 95% CI 1.65-2.66) compared to the healthy population.
When we analyzed males and females individually, the risks for cSCC and BCC remained elevated in the CTCL cohort compared to healthy controls for each sex, with males exhibiting the highest relative risks overall. We observed differences amongst sexes in respect to the order of risk for anatomic sites. In males with CTCL, the highest relative risk of cSCC was on the extremities (RR, 3.13; 95% CI 2.35-4.14). In contrast, females with CTCL had the highest relative risk of cSCC on the trunk (RR 3.00; 95% CI 1.48-6.13). In both sexes, there was a higher relative risk of BCC in the extremities and trunk in comparison to the face.
Discussion
Herein, we identify an increased risk of cSCC and BCC development for CTCL patients compared to both healthy and psoriasis patients. The risk of non-melanoma skin cancers remained high in CTCL patients in all anatomic locations (cSCC and BCC on head, extremities, and trunk) and in both males and females. Additionally, our analysis revealed that CTCL patients exhibited a greater risk for keratinocyte malignancies than psoriasis patients.
Non-melanoma skin cancer development in patients with CTCL has been associated with worse outcomes, including higher chances of local recurrences, metastasis, and mortality. Given this and our findings, CTCL patients may benefit from comprehensive skin cancer screening, particularly for cSCCs on the trunk and BCCs on extremities.