Determinants of survival in primary cutaneous CD4+ small-to-medium-sized pleomorphic t-cell lymphoproliferative disorder (PC4SMPTCL): Analysis of a real-world pooled database

Abstract Background: PC4SMPTCL is a rare and distinct entity within the spectrum of cutaneous T-cell lymphomas, recognized for its predominantly indolent clinical course and favorable prognosis. Despite its generally benign behavior, a subset of patients can experience disease recurrence, progression, or, rarely, extracutaneous dissemination, underscoring the heterogeneity of clinical outcomes. Due to its rarity and diverse presentations, knowledge of prognostic determinants and optimal management is limited, and most current knowledge is derived from small case series. This study seeks to identify key prognostic factors impacting survival and event-free survival in patients with PC4SMPTCL through a comprehensive analysis of a real-world pooled database. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled and analyzed a pooled real-world database of cases that satisfy the diagnostic criteria for PC4SMPTCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 219 patients were included in the analysis. The median age was 53, with no sexual preponderance. Seventy-nine percent were solitary lesions. The most common sites were the head and neck (60%). While 85% were alive at 29 years, the median EFS was 27 years. Advanced stage, any recurrence, and response less-than CR were detrimental to OS and EFS. Multiple and multifocal lesions, and lower extremity lesions had worse EFS. Surgery, radiation, and their combination had superior EFS to steroids. OS and EFS were not impacted by sex, age, number of recurrences, Ki67%, CD30+, TCR clonality, or spontaneous regression. Conclusions: This large real-world analysis confirms that PC4SMPTCL is typically associated with excellent long-term outcomes. However, advanced stage at presentation, recurrent or multifocal disease, lower extremity involvement, and suboptimal treatment responses are associated with inferior survival and event-free survival. Surgery and radiation, alone or in combination, offer superior outcomes compared to steroid monotherapy. These findings provide valuable insights for risk stratification and emphasize the importance of individualized management strategies in optimizing patient outcomes in this rare cutaneous T-cell lymphoma.