Cutaneous Involvement By Peripheral T-Cell Lymphoma: Incidence, Characteristics, Treatment Trends, and Outcomes in the United States (2000-2021)

Background

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphomas, constituting less than 15% of all of them. Among its subtypes, cutaneous involvement presents a clinical challenge, often complicating diagnosis and treatment. Data on skin involvement in PTCL, which can be confused with primary cutaneous T-cell lymphomas, remains limited. Understanding the incidence, characteristics, treatment trends, and outcomes of cutaneous involvement in PTCL is crucial for improving patient care and prognosis.

Methods

This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, encompassing 22 registries from 2000 to 2021. Age, race, ethnicity, disease histology, primary disease site, stage, treatment, date of diagnosis, and date of last contact/death were collected. Statistical analyses were performed using R software. Kaplan-Meier methods were applied for survival analysis, and the Cox proportional hazards model assessed the impact of various covariates on overall survival. Only PTCLs with reported skin involvement were included; ALK-negative anaplastic large cell lymphoma (ALCL) was not included, given that only cases from 2021 were available.

Results

Cutaneous involvement by PTCLs was seen in 7.5% of cases (2243/29513); occurred more frequently in PTCL-Not otherwise specified (NOS) (69.0%), followed by ALK- positive ALCL (22.3%) and extra nodal natural killer/T-cell lymphoma (ENKTCL) (4.9%). Per summary stage, cases were commonly localized (41.9%) or distant (18.6%); the stage was unknown in 33.2% of cases. Male to female ratio was 1.4:1; 57.7% were older than 60 years (y). Most were Caucasians (79.3%), followed by African Americans (13.2%) and Asian/Pacific Islanders (5.1%). The locations involved included the head and neck (H/N) (21.3%), Trunk (17.8%), Lower Limb (16.9%), Upper Limb (14.9%), and overlapping sites (1.9%); NOS cases were 26.9%. Patients were treated with chemotherapy (40.1%), radiation only (27.9%) and chemotherapy with radiation (8%); 24% had unknown treatment.

Per Kaplan Meier, median overall survival (mOS) was significantly better in cases with skin involvement vs non-skin involvement (7 y vs 2 y, p<0.0001). Per subtype, ALK + ALCL pts had a higher mOS in comparison to other subtypes at 13 years vs PTCL, NOS (7 y), Adult T-cell leukemia/lymphoma (6 y), Angioimmunoblastic T-cell lymphoma (2 y) and ENKTCL (1 y) with p < 0.0001. Per location, higher mOS were seen in H/N (15 y), trunk (12 y), and upper limbs (11 y) in comparison to lower limbs (6 y), overlapping sites (3 y), and NOS (2 y); p<0.0001.

On Cox regression analysis, age >60y (HR = 3.63, 95% CI: 3.17-4.16), male sex (HR = 1.14, 95% CI: 1.01-1.28), African American race (HR = 1.53, 95% CI: 1.29-1.82), PTCL, NOS (HR = 1.33, 95% CI: 1.14-1.55), ENKTCL (HR = 2.70, 95% CI: 2.09-3.47), distant disease (HR = 1.29, 95% CI: 1.08-1.55), treatment with chemotherapy (HR = 1.40, 95% CI: 1.17-1.68)or in combination with radiation (HR = 1.49, 95% CI: 1.17-1.91) were poor prognostic factors.

Conclusion

Our analysis shows that more than 5% of cases of PTCL can have skin involvement, with PTCL NOS being the most prevalent. Patients over 60 years old and Caucasians are frequently affected. It tends to be localized on presentation. However, close to half of the patients are treated with chemotherapy-based regimens. Even though survival appears to be better overall when skin is involved with mOS over 5 years, older age, sex, race, disease subtype, stage, and treatment modality can impact outcomes. These findings highlight the complexity and variability of T-cell lymphomas with skin involvement, underscoring the need for precise diagnosis. Tailored treatments based on disease biology and characteristics such as stage and location are needed to improve patient outcomes.