Background and Objectives: Primary cutaneous anaplastic large cell lymphoma (pcALCL) has an overall favorable prognosis. However, we have previously suggested that patients with extensive limb involvement may have a worse outcome (J Am Acad Dermatol49:1049, 2003). The primary objective was to assess the potential prognostic factors in pcALCL, in particular the role of extensive regional single-limb disease (ERSL-D), defined as presentation with or progression to T2b or T2c involvement of a single limb, or T3b involvement of > 3 contiguous body regions. Our secondary objectives were to study the gene expression profiles and treatment responses of our patients with pcALCL that may correlate with clinical outcome. Patients and Methods: This was a retrospective study involving 48 patients with pcALCL diagnosed and managed at Stanford from 1990–2005. The potential prognostic factors for overall and disease-specific survivals (OS and DSS) were analyzed using the KM method and univariate and multivariate Cox regression. Cox regression was also used to identify risk factors for progresson to extracutaneous disease. Gene expression profiles were studied using cDNA microarrays. Results: The OS and DSS rates of the entire cohort were 76% and 85% at 5 yrs and 70% and 85% at 10 yrs, respectively. Our univariate analysis demonstrated age, ERSL-D, and progression to extracutaneous disease (as a time-dependent variable) as significant prognostic factors for OS, while ERSL-D and progression to extracutaneous disease were significant for DSS. Sex, presence of spontaneous regression, and lesion site were not significantly assoicated with OS or DSS. Patients with T1 (solitary skin lesion) disease had an overall more favorable OS and DSS compared to those with T2 (regional skin involvement) and T3 (generalized skin involvement) disease, although the differences were not statisticlly significant. In our multivariate analysis, age (HR 1.83, 95% CI 1.02–3.26) and progression to extracutaneous disease (HR 6.42, 95% CI 1.39–29.68) remained significant for OS, while ERSL-D (HR 29.31, 95% CI 1.72–500.82) and progression to extracutaneous disease (HR 13.12, 95% CI 1.03–167.96) remained independent prognostic factors for DSS. Presentation with T3 disease was a significant risk factor for progression to extracutaneous disease (HR 10.20, 95% CI 1.84–56.72). Microarray studies of 14 samples from 3 ERSL-D and 7 classic pcALCL patients were performed. The patients with ERSL-D and classic pcALCL formed distinct, separate clusters. Classic pcALCL showed concurrent upregulation of epidermal genes analogous to normal skin, while ERSL-D lacked this signature. Genes upregulated in ERSL-D (after subtraction of epidermal genes) included STAT5A, IL2Rα, HIPK2, WDR10 and those down-regulated included RXRA. These gene profiling data suggest that targeting IL2R (denileukin diftitox) or STAT5 (HDAC inhibitors) may be appropriate in ERSL-D while therapeutic resistance to bexarotene may be linked to lack of RXRA gene expression. Conclusion: Our data suggest that patients with ERSL-D have a worse clinical outcome associated with a distinct gene expression profile. More aggressive and targeted treatments may be indicated in this subgroup.
To identify prognostic factors in primary cutaneous anaplastic large cell lymphoma (pcALCL), focusing on extensive limb disease (ELD), defined as initial presentation or progression to multiple skin tumors in 1 limb or contiguous body regions, and to study gene expression profiles of patients with pcALCL.
ABSTRACT:Indoor tanning has become increasingly popular over the past decades, despite evidence of an increased risk of melanoma and, possibly, nonmelanoma skin cancer. Tanning bed proponents cite the health benefits of vitamin D to support indoor tanning, including concerns that reduced vitamin D levels or certain vitamin D receptor polymorphisms may be associated with increased incidence of various cancers, including cutaneous melanoma. However, most tanning devices primarily emit ultraviolet A, which is relatively ineffective in stimulating vitamin D synthesis. Health benefits can be fully dissociated from the ultraviolet exposure risks with vitamin D supplementation, although optimal levels remain to be established. Indoor tanning represents an avoidable risk factor for skin cancer, and education of the general public as well as the enactment and stricter enforcement of indoor tanning legislation are a public health imperative.
Although sutured epidermal closure and tissue adhesive are highly efficacious for upper eyelid blepharoplasty, physicians and participants felt that cosmesis with ECA was superior to that with fast-absorbing gut.
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