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.

Ablative fractional CO₂ laser is an established tool for dermatologic and aesthetic indications. Non-ablative wavelengths, such as 1540 and 1570 nm, are increasingly being combined with CO₂ laser to optimise the results while reducing the recovery time. A narrative review of the literature was conducted, including ex vivo, in vivo, and in vitro studies, as well as human clinical trials that evaluated the efficacy, safety, and histological impact of dual-laser systems. Preclinical studies have shown that sequential application of fractional CO₂ followed by 1540/1570 nm expands the thermal coagulation zone without increasing the ablation depth. At the histological level, the dual protocol promotes collagen remodelling with greater thermal precision. On a clinical level, a combined treatment has shown efficacy in improving scars, striae distensae, skin laxity, and wrinkles, with reduced recovery times compared to CO₂ monotherapy. Preliminary data also suggest potential benefits in inflammatory conditions such as hidradenitis suppurativa. The sequential CO₂ + 1540/1570 nm combination represents an effective and well-tolerated approach in regenerative dermatology. Current evidence supports its use as a versatile, safe, and reproducible technique for skin rejuvenation and scar modulation; however, further comparative studies are needed to standardise protocols.

Psoriasis is a chronic, immune-mediated skin disease significantly impacting women, with disease severity often modulated by hormonal fluctuations. This review examines the influence of hormonal changes on the course of psoriasis in women, focusing on key life stages—including the menstrual cycle, pregnancy, postpartum, and menopause—and their impact on disease progression and symptomatology. Estrogen, the principal female sex hormone, plays a critical role in immune modulation. Variations in estrogen levels, which occur naturally throughout a woman’s life, are associated with fluctuations in psoriasis severity. Low estrogen levels, as seen during menstruation or menopause, are linked to symptom exacerbation, while elevated levels during pregnancy may reduce symptoms in some women. However, responses are variable, with others experiencing no change or worsening during pregnancy. Postpartum, the rapid decline in estrogen often triggers severe flare-ups, while menopause, marked by a sustained estrogen reduction, frequently correlates with increased disease severity and flare frequency. The review also addresses the profound impact of psoriasis on women’s quality of life, including physical discomfort, psychological distress, and social stigma. Additionally, fertility concerns are discussed, as severe psoriasis and associated treatments may increase the risk of adverse pregnancy outcomes. Consideration is given to hormonal therapies, lifestyle modifications, and their effects on psoriasis, underscoring the need for personalized treatment approaches that account for hormonal influences. Understanding these hormonal dynamics is essential for developing targeted, effective management strategies that enhance quality of life for women affected by psoriasis.

Background: Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to their lack of typical pigmentation and often benign clinical appearance. Misdiagnosis is common, leading to delays in treatment and potentially worse outcomes. This systematic review aims to synthesise evidence on cases of AAM initially misdiagnosed as other conditions, to better understand their clinical and epidemiological characteristics, diagnostic pitfalls, and management strategies. Methods: A comprehensive search of the MEDLINE/PubMed, EMBASE, and SCOPUS databases was conducted up to March 2024. Case reports and small case series of AAMs initially misdiagnosed as other conditions were included. Data on patient demographics, clinical presentation, and diagnostic methods were collected and analyzed. Results: Of the 152 records identified, 26 cases from 23 articles met the inclusion criteria. A demographic analysis revealed that the gender distribution appears to be perfectly balanced, with an age range of 38 to 91 years. Misdiagnoses included non-healing ulcers or traumatic lesions (37.5%), benign proliferative lesions (29.2%) and infectious lesions (20.8%). The foot was the most affected site (53.8%). Notably, a histological evaluation was performed in 50% of cases involving the upper extremities, in contrast to only 7.1% of cases involving the foot and 0% of cases of the heel. This discrepancy suggests a reluctance to perform biopsies in the lower extremities, which may contribute to a higher misdiagnosis rate in these areas. Conclusions: The underutilization of biopsy in the diagnosis of lower extremity lesions contributes significantly to the misdiagnosis and delay in treatment of AAMs. Especially when the clinical assessment and dermoscopy are inconclusive, biopsies of suspicious lesions are essential. Immunohistochemistry and markers such as PRAME are critical in differentiating melanoma from other malignancies such as clear cell sarcoma. This review highlights the need for increased vigilance and a proactive diagnostic approach to increase early detection rates and improve prognostic outcomes.

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.

Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade sarcoma that presents diagnostic challenges due to its resemblance to benign lesions