Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

BACKGROUND: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. OBJECTIVES: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. METHODS: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. RESULTS: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. CONCLUSIONS: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

Artificial Intelligence in Dermatology: Challenges and Perspectives.

Artificial intelligence (AI) based on machine learning and convolutional neuron networks (CNN) is rapidly becoming a realistic prospect in dermatology. Non-melanoma skin cancer is the most common cancer worldwide and melanoma is one of the deadliest forms of cancer. Dermoscopy has improved physicians' diagnostic accuracy for skin cancer recognition but unfortunately it remains comparatively low. AI could provide invaluable aid in the early evaluation and diagnosis of skin cancer. In the last decade, there has been a breakthrough in new research and publications in the field of AI. Studies have shown that CNN algorithms can classify skin lesions from dermoscopic images with superior or at least equivalent performance compared to clinicians. Even though AI algorithms have shown very promising results for the diagnosis of skin cancer in reader studies, their generalizability and applicability in everyday clinical practice remain elusive. Herein we attempted to summarize the potential pitfalls and challenges of AI that were underlined in reader studies and pinpoint strategies to overcome limitations in future studies. Finally, we tried to analyze the advantages and opportunities that lay ahead for a better future for dermatology and patients, with the potential use of AI in our practices.

Artificial intelligence (AI) is the development of computer systems able to perform tasks that normally require human intelligence, such as visual perception, speech recognition, and translation between languages. The research on the use of AI in dermatology includes the ability of a machine to correctly classify a skin lesion. Skin cancer is the most common cancer worldwide and melanoma is the deadliest form of skin cancer. All skin cancers have a better prognosis when detected early in their development, hence their early detection is of paramount importance. Dermatologists use a dermatoscope­a specialized magnifying lens to improve their diagnostic capacity. However, even with the use of the dermatoscope, their ability to recognize skin cancer is far from perfect. AI has the ability to learn from dermoscopic images and subsequently provide an image-based diagnosis. Several studies compared the performance of machines and humans in classifying skin lesions from these images and showed that machines can classify skin lesions as good (and sometimes better) than humans. However, the application of AI in everyday clinical practice remains a challenge. In this article, we attempt to summarize the limitations and challenges that researchers found in their studies, and we provide strategies to improve the design of future studies. Finally, we describe the advantages and opportunities that could lay ahead for a better future for dermatology and patients.

Atypical presentation of cutaneous angiosarcoma: review of the literature.

Cutaneous angiosarcoma (CAS) is an aggressive tumour of vascular or lymphatic origin. Although relatively rare, it needs to be recognized and treated early. CAS typically arises on the head or neck as a bruise or raised purplish-red papule or plaque. However, it can sometimes resemble a benign skin lesion, leading to delay in diagnosis and consequent poor patient outcome. CAS may be mistaken for inflammatory, autoimmune or infectious disease, or for a benign skin tumour or post-traumatic lesion. We analyse the atypical clinical forms of this aggressive tumour and review the literature.

Vitiligo-like lesions in patients with advanced breast cancer treated with cycline-dependent kinases 4 and 6 inhibitors.

PURPOSE: Introduction of cyclin-dependent inhibitors was a milestone in therapeutics for patients with estrogen receptor+/HER2- metastatic breast cancer. Despite the wide use of such agents and remarkable improvement of survival rates, drug-related adverse events are not yet fully characterized. We describe vitiligo-like lesions as a new adverse event occurring in patients with advanced breast cancer treated with cyclin-dependent inhibitors. METHODS: We performed an international retrospective study including patients with advanced breast cancer who developed vitiligo-like lesions during treatment with cyclin-dependent kinases 4 and 6 inhibitors, in the period January 2018-December 2019. Patients > 18 years, both males and females, were recruited at six Dermatology Departments located in Italy (3), France (1) and Greece (2). We evaluated epidemiological and clinical characteristics, impact on quality of life and outcome of vitiligo-like lesions in patients treated with cyclin-dependent 4 and 6 inhibitors. The percentage of skin involved by vitiligo-like lesions was assessed using the Body Surface Area (BSA) score. Changes in patients' quality of life were investigated through the evaluation of the Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: Sixteen women (median age: 62.5 years; range 40-79 years) treated with cyclin-dependent kinases 4 and 6 inhibitors for advanced breast cancer presented with vitiligo-like lesions during follow-up visits. Cutaneous lesions consisted of white, irregular macules and patches located mainly on sun-exposed areas in 11/16 patients or diffuse to the entire body surface in 5/16. Cutaneous lesions clearly impaired the quality of life of patients tested (DLQI ≥ 10). CONCLUSIONS: We present for the first time, to our knowledge, a case series of vitiligo-like lesions developing in patients with advanced breast cancer treated with cyclin-dependent kinases 4 and 6 inhibitors. We showed that such lesions further impair the patients' quality of life and their treatment is challenging.

Serum Total 25-Hydroxyvitamin D Levels in Patients With Cutaneous Malignant Melanoma: A Case-Control Study in a Low-Risk Southern European Population.

BACKGROUND: Recent data have shown an inverse association between serum 25-hydroxyvitamin D concentration and incidence of several cancers, including cutaneous malignant melanoma (CMM). In addition, lower serum 25-hydroxyvitamin D levels have been associated with thicker or higher stage melanomas and worse survival in observational studies. MATERIALS AND METHODS: Ninety-nine patients diagnosed with primary CMM and 97 matched healthy controls entered the study. Demographic characteristics, risk factors for CMM, and clinical and histological characteristics were recorded for patients with primary CMM. Total serum 25-hydroxyvitamin D levels of melanoma patients measured by fully automated chemiluminescent vitamin D total immunoassay (Elecsys vitamin D total, Roche) at the time of diagnosis were compared with those of healthy controls. In addition, we tested the association of serum total 25-hydroxyvitamin D levels at melanoma diagnosis with known risk and prognostic factors for CMM. RESULTS: Of the melanoma patients, 49 (49.49%) had deficient serum total 25-hydroxyvitamin D levels (<20 ng/mL), 23 (23.23%) had insufficient levels (21-29 ng/mL), and 27 (27.27%) had adequate levels (>30 ng/mL). The median serum total 25-hydroxyvitamin D levels were significantly lower in melanoma patients (20.62 ng/mL) compared with healthy controls (24.71 ng/mL), but statistical significance was not reached (chi-square test, P = 0.051) No statistically significant association was found between serum total 25-hydroxyvitamin D levels and demographic characteristics; risk factors for CMM; prognostic factors, such as Breslow thickness and ulceration; as well as clinical characteristics, such as melanoma stage, clinical type, and location. CONCLUSIONS: Lower serum 25-hydroxyvitamin D levels were found in our Greek cohort of melanoma patients compared with healthy controls, without reaching, however, statistical significance; these levels were not statistically associated with established risk and prognostic factors for CMM.

René-Théophile-Hyacinthe Laennec (1781-1826) and the description of metastatic pulmonary melanoma.

In 19th century, the anatomo-clinical school of Paris linked clinical signs with anatomical lesions establishing clinical medicine. One of the most enlightened promoters of this method was the French physician René-Théophile-Hyacinthe Laennec, known as the inventor of stethoscope. In our article, we reveal his work on pulmonary melanoma.

High-frequency p16(INK) (4A) promoter methylation is associated with histone methyltransferase SETDB1 expression in sporadic cutaneous melanoma.

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16(INK) (4A) promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation-specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki-67 index), p16(INK) (4A) and SETDB1 expression were evaluated by immunohistochemistry. High-frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation (P = 0.0514). p16(INK) (4A) promoter methylation was higher in vertical growth-phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046). Importantly, p16(INK) (4A) methylation correlated with increased melanoma thickness according to Breslow index (P = 0.0495) and marginally with increased Clark level (I/II vs III/IV/V, P = 0.070). Low (1-30%) p16(INK) (4A) expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16(INK) (4A) methylation and p16(INK) (4A) expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0-5/mm(2) vs >5/mm(2) , P = 0.0869), advanced Clark level (III-V, P = 0.0380), epidermal involvement (P = 0.0331) and the non-chronic sun exposure-associated melanoma type (P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16(INK) (4A) promoter and several prognostic parameters in melanomas.

Methods of detection of circulating melanoma cells: a comparative overview.

Disease dissemination is the major cause of melanoma-related death. A crucial step in the metastatic process is the intravascular invasion and circulation of melanoma cells in the bloodstream with subsequent development of distant micrometastases that is initially clinically undetectable and will eventually progress into clinically apparent metastasis. Therefore, the use of molecular methods to detect circulating melanoma cells may be of value in risk stratification and clinical management of such patients. Herein, we review the currently applied techniques for the detection, isolation, enrichment and further characterization of circulating melanoma cells from peripheral blood samples in melanoma patients. Furthermore, we provide a brief overview of the various molecular markers currently being evaluated as prognostic indicators of melanoma progression.

Imiquimod: an immune response modifier in the treatment of precancerous skin lesions and skin cancer.

Actinic keratosis (AK) and basal cell carcinoma (BCC) are precancerous and cancerous skin lesions that should be treated especially when multiple or in cosmetically important areas. Apart from 5% 5-fluorouracil topical cream, which some feel is the gold standard topical treatment for AK, several invasive treatment modalities are available for AK and superficial BCC, such as cryotherapy, electrodessication, carbon dioxide laser and surgery causing patients discomfort and pain, pigmentary changes or necessitate multiple office visits. Additionally, there are precancerous lesions that necessitate non-invasive treatment with good esthetic results or skin cancer refractory to invasive techniques. Imiquimod is an immune response modifier approved by the FDA for the treatment of AK and superficial BCC lesions and its use is gradually expanded to various off-label precancerous and cancerous skin lesions.