Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

Background: Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, making it difficult to differentiate between these two neoplasms during the diagnostic process. This systematic review aims to summarize available evidence on cases of sarcoma that were initially diagnosed as melanoma. Methods: A comprehensive search of the MEDLINE/Pubmed, EMBASE, and SCOPUS databases was conducted through March 2023. We included case series and case reports of sarcoma patients that were initially diagnosed as malignant melanoma. PRISMA guidelines were followed. Results: Twenty-three case reports and four case series with a total of 34 patients were included. The clinical presentation was heterogeneous, and the most involved anatomical regions were lower limbs (24%), head/neck (24%), and upper limbs (21%). IHC positivity was reported for S100 (69%), HMB45 (63%), MelanA (31%), and MiTF (3%). The main reasons for a second assessment were unusual presentation (48%) and uncertain diagnosis (28%). EWSR1 translocation was investigated in 17/34 patients (50%) and found to be positive in 16/17 (94%). The final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%). Conclusions: Melanoma and some histotypes of sarcoma share many similarities. In cases of atypical lesions, a second diagnosis should be considered, and ESWR1 translocation should be investigated.

Laser-assisted exosome delivery (LAED) combines ablative fractional lasers with immediate topical application of exosomes. Here, we introduce the LAED concept and report two uncontrolled feasibility observations: a 62-year-old man with atrophic acne scars and a 68-year-old woman with diffuse dyschromia underwent fractional CO₂ laser treatment followed by topical exosomes. Both cases showed early, encouraging signals of clinical improvement and shorter downtime, with good tolerability. An exploratory day-7 patient self-evaluation using a 5-point Likert scale for speed/comfort of recovery yielded 5/5 in both cases. Given the two-case, non-comparative design, causality cannot be inferred, and efficacy remains hypothesis-generating. These preliminary findings motivate controlled trials with standardized objective and patient-reported measures and longer follow-up to determine whether LAED truly enhances the cosmetic benefits of fractional laser treatment.

Skin scars represent a complex therapeutic challenge, with significant functional, aesthetic, and psychological implications. Despite advances in laser therapy, monotherapy has significant limitations, particularly for patients with complex scars with atrophic, hypertrophic, vascular, and pigmentary components. The combined use of multiple laser sources, in sequential or simultaneous mode, allows for the selective targeting of specific tissue components and improves clinical efficacy while maintaining a good safety profile. This narrative review critically analyses the available evidence on combination therapies for atrophic, hypertrophic, keloid, and post-surgical and burn scars. Protocols combining ablative lasers (CO₂, Er:YAG), non-ablative lasers (1540–1550 nm), vascular lasers (PDL, Nd:YAG) and intense pulsed light (IPL) are reported. Possible integrations with adjuvant techniques, such as radiofrequency, platelet-rich plasma (PRP), and laser-assisted drug delivery, are also mentioned as areas for future development. The available data suggest a promising role for multimodal strategies, but the literature remains limited by small cohorts, heterogeneous protocols, and short follow-up periods. Although adverse events are generally mild and transient, typically involving erythema, oedema, or temporary dyschromia, an awareness of safety considerations remains essential, particularly in higher phototypes and when using ablative modalities. Further prospective and multicentre studies are needed to define standardised protocols and consolidate the role of combination therapies in the management of scars.

Clear Cell Sarcoma (CCS) of soft tissue is a rare and highly malignant neoplasm primarily affecting young adults, often presenting in the deep soft tissues of the extremities. Despite morphological and immunophenotypic similarities to melanoma, CCS arises from connective tissues and is characterized by a distinct genetic hallmark: the EWSR1-ATF1 fusion resulting from t(12;22)(q13;q12) translocation. This genetic signature is absent in melanoma, making molecular diagnosis essential for accurate differentiation. Additionally, recent evidence highlights the utility of PRAME as an immunohistochemical marker to distinguish CCS from melanoma and other neoplasms. Clinically, CCS commonly involves tendons and aponeuroses, with metastatic potential leading to poor prognoses despite optimal local disease management. Histologically, CCS features lobular growth, spindle-to-epithelioid cells with clear cytoplasm, and low mitotic activity, often necessitating a multimodal diagnostic approach incorporating histopathology, immunohistochemistry, and molecular testing. Therapeutically, wide surgical excision remains the cornerstone for localized disease, with sentinel lymph node biopsy aiding in staging. Adjuvant radiotherapy is considered in select cases, while chemotherapy has limited efficacy in metastatic settings. Emerging treatments, including targeted therapies focusing on EWSR1-ATF1-driven pathways and immune checkpoint inhibitors, offer hope for improved outcomes. This review synthesizes current knowledge on CCS, emphasizing diagnostic challenges, the role of PRAME, and advancements in therapeutic strategies to enhance patient care.