The efficacy of long-term psoralen plus ultraviolet A and low-dose interferon-a combination therapy in mycosis fungoides: A literature review.

BACKGROUND/PURPOSE: Interferon (IFN)-a is often used in combination with psoralen plus ultraviolet A (PUVA) in patients with mycosis fungoides (MF) refractory to skin-targeted therapies in early or advanced stages. The main objective is to evaluate the effectiveness of combined PUVA and low-dose IFN-α-2a therapy in patients with early- and advanced-stage MF. METHODS: Sixty-eight patients who received a combination of PUVA twice or thrice a week and INF-a 3 MU thrice a week for at least 3 months were reviewed retrospectively. The treatment response was evaluated as complete remission (CR), partial remission, stable disease, or progression. RESULTS: At the initiation, the majority of patients (66.2%) had early-stage disease. In 27.9% of cases, this was the initial treatment administered following the diagnosis of MF. The median duration of combination therapy was 11 months. Complete remission was achieved in 45.6% of the patients with an overall response rate of 60.3%. The mean duration of response was 5 months. Complete remission was statistically significantly higher in early-stage patients (p < .05). No statistically significant correlation was observed between CR and gender, histopathological features, or laboratory parameters. In patients with CR, 80% experienced relapse, significantly higher in early-stage patients (p < .05). However, there was no significant difference in disease-free survival between early and advanced stages (p > .05). CONCLUSIONS: The study results indicated that PUVA + low-dose INF-a combination therapy was more effective in the early stage than in the advanced stage. Additionally, there was a high relapse rate after the cessation of treatment in patients who achieved CR.

Dermatoscopic profiling of inverted follicular keratosis in different skin phenotypes.

BACKGROUND: Inverted follicular keratosis (IFK) is a rare benign tumour of the follicular infundibulum. Owing to its similarity to other benign and malignant cutaneous lesions, it poses a diagnostic challenge. There is limited information on the dermatoscopic characteristics of IFK and the majority of cases have been reported in patients with lighter skin types. OBJECTIVES: To describe the prevalent dermatoscopic features of IFK, especially in patients with skin of colour. METHODS: We retrospectively analysed 35 histopathologically verified cases of IFK from a single university hospital in Turkey. RESULTS: With respect to the Fitzpatrick skin phototype, 2 (6%), 12 (34%), 16 (46%) and 5 (14%) patients had Fitzpatrick skin phototypes II, III, IV and V, respectively. Clinically, the majority of IFKs were hypopigmented or nonpigmented (83%). Pink-white structureless areas (54%), ulceration (54%), a central keratin mass (43%) and blood spots on keratin mass (43%) were the most frequent dermatoscopic findings. Pigmented structures were observed as blue-grey structureless areas in 12 lesions and as blue-grey clods in 5, primarily in Fitzpatrick phototype IV and V skin. The incidence of a pink, structureless area and blood spots on ulceration was found to be statistically significantly higher in individuals with fairer skin types, while a greater prevalence of blue-grey coloration was observed in those with skin of colour (P < 0.05). CONCLUSIONS: Although our study found some distinguishing dermatoscopic findings in IFK, diagnosis is generally confirmed by histopathology, as the clinical appearance and dermatoscopic findings may not be sufficient to differentiate it from other tumours, especially squamous cell carcinoma or keratoacanthoma. The dermatoscopic characteristics of dark skin are comparable to those of pale skin; however, hyperpigmentation can be more noticeable in skin of colour.

A Comprehensive Study on Aberrant CD20-Positive Mycosis Fungoides: Clinical and Prognostic Insights.

BACKGROUND: As the majority of T-cell lymphomas lack CD20 expression, cases of mycosis fungoides (MF) exhibiting aberrant CD20 expression are exceedingly uncommon. OBJECTIVES: We aim to comprehensively evaluate the clinical, histopathological, and prognostic features of 7 patients diagnosed with CD20-positive MF. METHODS: This retrospective study examines seven cases of MF with aberrant CD20 expression. The study provides details of demographics, clinical features, histopathology and treatment outcomes. Key time points include initial diagnosis of MF, detection of CD20 expression and follow-up, with a mean follow-up of 46 months. RESULTS: Aberrant CD20-positive MF was diagnosed at an average age of 58.6 years, approximately 5.6 years after first MF diagnosis. Following CD20 detection, patients presented with advanced disease stages, requiring treatments such as chemotherapy, brentuximab vedotin, and allogeneic hematopoietic stem cell transplantation. Four patients died from lymphoma, with an average survival time of 52 months. CONCLUSIONS: Aberrant CD20 expression in MF is rare but indicates a progressive course associated with poor prognosis. This often requires systemic chemotherapy and, in certain instances, allogeneic hematopoietic stem cell transplantation. This study provides important insights into the clinical attributes, disease progression, and treatment options for MF patients with aberrant CD20 expression. Further research is necessary to validate the effectiveness of emerging therapies and enhance our understanding of the underlying mechanisms and prognostic determinants specific to this unique MF subgroup.

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.

Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. OBJECTIVE: There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. METHODS: All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. RESULTS: A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). CONCLUSIONS: Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.

Integrated diagnosis of nevi with severely atypical features and impact of second opinions.

BACKGROUND: A subset of melanocytic proliferations is difficult to classify by dermatopathology alone and their management is challenging. OBJECTIVE: To explore the value of correlation with dermatoscopy and to evaluate the utility of second opinions by additional pathologists. METHODS: For this single center retrospective study we collected 122 lesions that were diagnosed as atypical melanocytic proliferations, we reviewed dermatoscopy and asked two experienced pathologists to reassess the slides independently. RESULTS: For the binary decision of nevus versus melanoma the diagnostic consensus among external pathologists was only moderate (kappa 0.43; 95% CI 0.25-0.61). If ground truth were defined such that both pathologists had to agree on the diagnosis of melanoma, 13.1% of cases would have been diagnosed as melanoma. If one pathologist were sufficient to call it melanoma 29.5% of cases would have been diagnosed as melanoma. In either case, the presence of dermatoscopic white lines was associated with the diagnosis of melanoma. In lesions with peripheral dots and clods, melanoma was not jointly diagnosed by the two pathologists if the patient was younger than 45 years. CONCLUSIONS: A considerable number of atypical melanocytic proliferations may be diagnosed as melanoma if revised by other pathologists. The presence of white lines on dermatoscopy increases the likelihood of revision towards melanoma. Peripheral clods indicate growth but are not a melanoma clue if patients are younger than 45 years.

Dermatoscopic finding of white circles in an invasive pigmented melanoma.

Dermatoscopic white circles, seen with both non-polarized and polarized dermatoscopy, are a known clue to actinic keratosis in a flat lesion and invasive squamous cell carcinoma in a raised lesion. We have not discovered a previous published example of this clue in a melanoma. We present a case report of a 70-year-old Australian male with a pigmented superficial spreading melanoma on the face, Breslow thickness 1 mm, with dermatoscopic white circles displayed with both polarized and non-polarized dermatoscopy, and with dermatopathological correlation.

Combined tumour of aberrant cytokeratin expressing acral lentiginous melanoma and poroma: Diagnostic challenge.

Combined tumours are uncommon and therefore these tumours may pose a diagnostic challenge. In the current case report, it is aimed to present the clinicopathological features of a combined tumour including melanoma with aberrant cytokeratin expression and poroma.

Postauricular linear basal cell carcinomas related to medical mask cords: a possible association.

Linear basal cell carcinoma (BCC) is a distinct clinical morphological variant of BCC. Although it has been speculated that trauma and the Koebner phenomenon may be linked to linear BCC, the pathophysiology has not yet been shown. Herein, 5 cases of BCC were presented that developed in the postauricular region as a result of trauma caused by the cords of the medical face masks worn during the COVID-19 pandemic.

Dermatoscopy of nodular/plaque-type primary cutaneous T- and B-cell lymphomas: A retrospective comparative study with pseudolymphomas and tumoral/inflammatory mimickers by the International Dermoscopy Society.

BACKGROUND: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available. OBJECTIVE: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes. METHODS: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed. RESULTS: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes. LIMITATIONS: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis. CONCLUSION: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses.

Allogeneic hematopoietic stem cell transplantation for heavily pretreated patients with mycosis fungoides and Sezary syndrome.

Allogeneic hematopoietic stem cell transplantation (AHSCT) is a promising strategy for treatment of heavily pretreated mycosis fungoides/Sezary syndrome (MF/SS). Herein, we aimed to evaluate the outcomes of AHSCT for heavily pretreated patients with MF/SS retrospectively. This analysis included consecutive 19 patients with MF/SS who received 20 AHSCT between 2012-2021 in our transplant center. Eight patients have been previously reported. Fifteen patients had diagnosis of MF and referred to SS in five patients. In our cohort, all cases had advanced disease (stages IIB: n = 1, IIIA: n = 7; IIIB: n = 4, IVA: n = 4, and IVB: n = 3). Nine patients (47.4%) had developed large cell transformation. Only two patients received AHSCT in complete response, one very good partial response and two partial response while the others had progressive disease (n = 15) before transplant. Seven (35%) patients were alive at the time of analysis, with a median follow up of 10.5 months (range, 0.3-113 months) after AHSCT. Nine patients (47.4%) died without disease relapse or progression. Non-relapse mortality was 35.9% at 1 year and 26.9% at 3 years and thereafter. For all patients the probability of overall survival was 48.5% and 32.3% at 1- and 5-year post-transplant, respectively. AHSCT for MF/SS resulted in an estimated progression free survival of 45.4% at 1 year. Given the poor prognosis of patients not receiving transplants and in the absence of curative non-transplantation therapies, our results support that AHSCT is able to effectively rescue 32.3% of the population of transplant eligible, heavily pretreated patients in 5 years.

Dermoscopic Features of Actinic Cheilitis and Other Common Inflammatory Cheilitis: A Multicentric Retrospective Observational Study by the International Dermoscopy Society.

BACKGROUND: Clinical differentiation between different cheilitis variants may be difficult. Application of mucoscopy, in addition to clinical background, could provide additional diagnostic clues facilitating initial patient management. OBJECTIVES: To determine mucoscopic clues differentiating actinic cheilitis from the main forms of inflammatory cheilitis, including eczematous cheilitis, discoid lupus erythematosus, and lichen planus of the lips. METHODS: This was a retrospective, multicenter study being a part of an ongoing project "Mucoscopy - an upcoming tool for oral mucosal disorders" under the aegis of the International Dermoscopy Society. Cases included in the current study were collected via an online call published on the IDS website (www.dermoscopy-ids.org) between January 2019 and December 2020. RESULTS: Whitish-red background was found in actinic cheilitis as well as in cheilitis due to discoid lupus erythematous and lichen planus. Polymorphous vessels were more likely to be seen in actinic cheilitis compared to other causes of cheilitis. White scales, ulceration, and blood spots predominated in actinic cheilitis and lichen planus, whereas yellowish scales typified eczematous and discoid lupus erythematous cheilitis. Radiating white lines although most common in lichen planus patients were also seen in actinic cheilitis. CONCLUSION: Despite differences in the frequency of mucoscopic structures, we have not found pathognomonic features allowing for differentiation between analyzed variants of cheilitis.

Dermatoscopic features of Spitz naevi on acral volar skin: Report of 11 cases.

Spitzoid melanocytic lesions characterized by spindle and/or epithelioid tumour cells can occur anywhere on the skin but the acral presentation of Spitz naevus is very rare and comprises about <4% of all Spitz naevi. However, data regarding their dermatoscopic features on the acral volar skin are scarce. Herein, 11 cases of acral Spitz naevus involving the glabrous skin with predominant dermatoscopic findings of atypical fibrillar pattern in non-pressure bearing areas, a structureless pigmentation involving both the furrows and the ridges are presented.

Dermatoscopic findings and dermatopathological correlates in clinical variants of actinic keratosis, Bowen's disease, keratoacanthoma, and squamous cell carcinoma.

Non-melanoma skin cancer (NMSC), predominantly squamous cell carcinoma (SCC) and basal cell carcinoma, is increasing worldwide. Dermatoscopy, which is one of the non-invasive diagnostic techniques, is important for early diagnosis of NMSC. In this study we aimed to determine dermatoscopic features of keratinocyte derived tumors including actinic keratosis (AK), Bowen's disease (BD), keratoacanthoma (KA), and SCC and correlate the dermatoscopic findings with pathology. A total of 242 lesions from 169 patients were included in the study and dermatoscopic and dermatopathological findings of the lesions were retrospectively studied. Revised pattern analysis was used for the dermatoscopic evaluation. Among 242 lesions, 145 were clinically flat (86 AK, 30 BD, and 29 SCC). Presence of vessels, ulceration, fiber sign, keratin mass, and blood spots decreased the probability of a lesion being AK. When the differential diagnosis was considered between KA and SCC vs AK and BD; vessel presence, ulceration, fiber sign, blood spots, white structureless, keratin, and centred vessels favored the diagnosis of KA and SCC. Our results may contribute to the determination of the lesions to be biopsied in patients with multiple AK on chronically sun damaged skin. In non-pigmented lesions when a final diagnosis cannot be established, knowledge of dermatopathologic and dermatoscopic correlation may significantly assist interpretation of dermatoscopic patterns and clues.

Congenital melanocytic naevi: An up-to-date overview.

Congenital melanocytic naevi are hamartomas of the neuroectoderm caused by genetic mosaicism. Congenital melanocytic naevi are seen in 1-6% of all live births and commonly classified based on the projected size in adults. Congenital melanocytic naevi appear in different colours, shapes, and sizes, and occasionally present with complications. In this review, we sought to evaluate congenital melanocytic naevi, their clinical, dermatoscopic, and reflectance confocal microscopic features, behavioural pattern over time, new trends in classification, underlying genetic factors and their influence on clinical manifestations and management, associated risks, complications, magnetic resonance imaging findings and their management in the light of recent literature.

Clinical and dermatoscopic characteristics of lichen planus-like keratosis in a West-Asian population.

BACKGROUND/OBJECTIVE: The clinical and dermatoscopic features of lichen planus-like keratosis have been described but the characteristics of this entity in a West-Asian population are not known. METHODS: We retrospectively analysed 82 histopathologically verified cases of lichen planus-like keratosis from 81 patients from Iran and Turkey. RESULTS: The majority of lichen planus-like keratoses were macules (61% n = 50), clinically pigmented (67.1% n = 55) and dermatoscopically multi-coloured (91.5% n = 75). The majority (63.4%) had a single dermatoscopic pattern, most frequently: structureless (35.4%), dots (14.6%) and angulated lines (8.5%). Of the lesions with more than one pattern (n = 30), the majority (n = 21) had asymmetry of pattern, the most common combinations being structureless plus dots (n = 8) and structureless plus angulated lines (n = 5). The most common structure was pigmented dots, most frequently grey and present in 70.7% of cases. Vessels were seen in 30.5% of lesions, being significantly more prevalent in non-pigmented, than pigmented, lichen planus-like keratoses (83.3% vs. 21.4% P < 0.001). When we compared lichen planus-like keratosis in the current study to that entity in a large North American study, the statistically significant differences in a West-Asian population included a greater frequency of pigmented variants, a lower incidence in females and a lower prevalence on the torso, in favour of the face. CONCLUSIONS: Lichen planus-like keratosis in a West-Asian population has clinical and dermatoscopic similarities to that entity in another studied population. The significant differences in gender association and anatomical site may be secondary to cultural factors.

Basosquamous carcinoma and melanoma collision tumor in a child with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis associated with hypersensitivity to ultraviolet radiation (UVR), being due to defects involving the nucleotide excision repair pathway. Patients with XP are prone to develop multiple cutaneous neoplasms including non-melanoma skin cancers and melanoma. Collision tumors in patients with XP have been reported in the literature including the following lesions, actinic keratosis, basal cell carcinoma, squamous cell carcinoma, and in situ melanoma. Herein, we present a rare collision tumor composed of melanoma and basosquamous carcinoma in a 13-year-old XP patient and describe the dermoscopic features.

Dermoscopic findings of Kaposi sarcoma and dermatopathological correlations.

BACKGROUND/OBJECTIVE: There are a limited number of studies regarding the dermoscopic features and dermatopathological correlations of Kaposi sarcoma. The primary objective of this study was to evaluate dermoscopic features of Kaposi sarcoma, and the secondary objective was to investigate their dermatopathological correlates. METHODS: Dermoscopic and clinical analysis of 222 lesions from 38 patients with histologically confirmed Kaposi darcoma were assessed by two investigators. A total of 83 biopsies were available from different clinical stages. Additionally, 3 mm punch biopsy was performed where newly defined dermoscopic findings were observed. Modified pattern analysis algorithm was used for the dermoscopic evaluation. RESULTS: The most common dermoscopic features of Kaposi sarcoma were white lines (55.9%) and white clods (37.8%) followed by surface scale (32.9%) and polychromatic colour change (22.1%). Four dot clods, white lines, white clods, collarette sign, serpentine vessels, dotted, curved and coiled vessels were the new dermoscopic findings of our study. Polychromatic colour change is correlated with the presence of hyaline globules probably with their birefringence properties, whereas we found no significant correlation between polychromatic colour change and honeycomb-like pattern of vascular spaces. CONCLUSIONS: White lines, white clods, four dot clods, collarette sign, serpentine vessels, dotted, curved and coiled vessels are the new dermoscopic features of Kaposi sarcoma, and polychromatic colour change is correlated with the presence of hyaline globules.

Dermatoscopic features of pigmented intraepidermal carcinoma on the head and neck.

BACKGROUND AND OBJECTIVE: Pigmented intraepidermal carcinoma is characterized by dermatoscopic dots and structureless areas, including dots in linear arrangement and by coiled vessels. There are no studies describing the dermatoscopic features of pigmented intraepidermal carcinoma on the head and neck. We aim to characterize the clinical and dermatoscopic appearance of this entity. PATIENTS AND METHODS: We retrospectively analyzed 79 cases of pigmented intraepidermal carcinoma on the head and neck. RESULTS: Pigmented intraepidermal carcinoma on the head and neck was characterized dermatoscopically by multiple colors (98.7 %, n = 78), pigmented circles (48.1 %, n = 38), white circles (17.7 %, n = 14), angulated lines (41.8 %, n = 33) and structureless areas (86.1 %, n = 68). Dots in linear arrangement were present in 13.9 % (n = 11). Coiled vessels were present in 7.6 % (n = 6), the dominant vessel type being prominent serpentine vessels (29.2 %, n = 23), thicker and/or redder in color than surrounding vessels, most being in the angular arrangement of the dermal plexus (24.1 %, n = 19). CONCLUSIONS: Pigmented intraepidermal carcinoma on the head and neck differs from current published descriptions of pigmented intraepidermal carcinoma, reaching statistical significance with a lower incidence of coiled vessels and a higher incidence of pigmented circles, with evident similarities to pigmented actinic keratosis at that location.

Comparison of the accuracy of human readers versus machine-learning algorithms for pigmented skin lesion classification: an open, web-based, international, diagnostic study.

BACKGROUND: Whether machine-learning algorithms can diagnose all pigmented skin lesions as accurately as human experts is unclear. The aim of this study was to compare the diagnostic accuracy of state-of-the-art machine-learning algorithms with human readers for all clinically relevant types of benign and malignant pigmented skin lesions. METHODS: For this open, web-based, international, diagnostic study, human readers were asked to diagnose dermatoscopic images selected randomly in 30-image batches from a test set of 1511 images. The diagnoses from human readers were compared with those of 139 algorithms created by 77 machine-learning labs, who participated in the International Skin Imaging Collaboration 2018 challenge and received a training set of 10 015 images in advance. The ground truth of each lesion fell into one of seven predefined disease categories: intraepithelial carcinoma including actinic keratoses and Bowen's disease; basal cell carcinoma; benign keratinocytic lesions including solar lentigo, seborrheic keratosis and lichen planus-like keratosis; dermatofibroma; melanoma; melanocytic nevus; and vascular lesions. The two main outcomes were the differences in the number of correct specific diagnoses per batch between all human readers and the top three algorithms, and between human experts and the top three algorithms. FINDINGS: Between Aug 4, 2018, and Sept 30, 2018, 511 human readers from 63 countries had at least one attempt in the reader study. 283 (55·4%) of 511 human readers were board-certified dermatologists, 118 (23·1%) were dermatology residents, and 83 (16·2%) were general practitioners. When comparing all human readers with all machine-learning algorithms, the algorithms achieved a mean of 2·01 (95% CI 1·97 to 2·04; p<0·0001) more correct diagnoses (17·91 [SD 3·42] vs 19·92 [4·27]). 27 human experts with more than 10 years of experience achieved a mean of 18·78 (SD 3·15) correct answers, compared with 25·43 (1·95) correct answers for the top three machine algorithms (mean difference 6·65, 95% CI 6·06-7·25; p<0·0001). The difference between human experts and the top three algorithms was significantly lower for images in the test set that were collected from sources not included in the training set (human underperformance of 11·4%, 95% CI 9·9-12·9 vs 3·6%, 0·8-6·3; p<0·0001). INTERPRETATION: State-of-the-art machine-learning classifiers outperformed human experts in the diagnosis of pigmented skin lesions and should have a more important role in clinical practice. However, a possible limitation of these algorithms is their decreased performance for out-of-distribution images, which should be addressed in future research. FUNDING: None.