Anorectal melanoma: systematic review of the current literature of an aggressive type of melanoma.

Anorectal melanoma (ARM) is a rare malignancy often associated with a poor prognosis due to its late diagnosis and aggressive biological behavior. This review aims to comprehensively investigate ARM's diagnosis, management, and treatment, emphasizing its clinical characteristics, laboratory findings, and implications for patient prognosis. A systematic literature search was conducted in PubMed, Embase, and Cochrane CENTRAL databases from inception to 1 July 2024. This review synthesizes existing literature to provide a comprehensive understanding of this rare primary malignancy. A total of 110 articles reporting on 166 patients were included. Gender data were available for 131 cases, comprising 67 females (51.1%) and 64 males (48.9%). The median age was 66 years. The overall median time to diagnosis was 4 months for anal melanoma, 3 months for rectal melanoma, and 4 months for anorectal junction melanoma. The clinical presentation was nodular in 98.2% of cases. Pre-diagnosis symptoms included bleeding in 84.9% of cases, mucous elimination (6%), pain (68.7%), tenesmus (16.9%), and changes in bowel movements (28.5%). Overall survival (OS) was reported in 82 cases, with a median OS of 11 months: 11 months for anal melanoma, 7 months for rectal melanoma, and 12 months for anorectal junction melanoma. ARM is a rare and aggressive melanoma subtype often diagnosed at an advanced stage, leading to a poor prognosis. A female predominance was observed, consistent with other mucosal melanomas. Anal melanoma exhibited better progression-free survival, and OS compared to rectal and anorectal junction melanoma.

The use of Reflectance Confocal Microscopy to diagnose Basal Cell Carcinoma in the United Kingdom: A Prospective Observational Trial at a Single Centre.

BACKGROUND: Previous work with Reflectance Confocal Microscopy (RCM) imaging has shown high sensitivity and specificity for Basal Cell Carcinoma (BCC), but to date there have been few studies on a UK cohort. OBJECTIVES: The study hypothesised that RCM could be used prospectively to accurately diagnose BCC in a private UK secondary care, single clinician setting. The study assessed the potential for RCM to be used as a routine diagnostic procedure. METHODS: 522 lesions were recruited prospectively where BCC featured in the differential diagnosis after clinical examination. 78 were subsequently excluded. Imaging used the arm-mounted confocal microscope unless access was restricted and required the handheld probe. The likelihood of BCC was scored for each modality, each diagnosis building on the last. Histology was assessed by a single blinded histopathologist [JJ]. RESULTS: 444 lesions from 326 patients were included in the analysis, including 327 BCCs. Median maximum diameter was 6 mm. The sensitivity and specificity for BCC was 69.42% (64.11% to 74.37%) and 52.99% (43.55% to 62.28%) for clinical examination alone; 91.77% (88.25% to 94.51%) and 41.03% (32.02% to 50.50%) plus dermoscopy; 98.78% (96.91% to 99.67%) and 85.47% (77.76% to 91.30%) plus RCM. For RCM PPV was 95.01% (92.14% to 97.07%) and NPV was 96.15% (90.44% to 98.94%). Area under the curve increased from 0.61 to 0.66 to 0.92 as modalities were added. CONCLUSION: This study demonstrates that RCM can, reliably and quickly, diagnose BCC, and that the addition of RCM to dermoscopy permits higher diagnostic accuracy for BCC in the UK. The specificity and sensitivity of the RCM diagnosis did not alter significantly with experience, reflecting the ease and speed of acquiring the skill. CLINICAL TRIAL REGISTRATION: NCT03509415.

Thin Amelanotic and Hypomelanotic Melanoma: Clinicopathological and Dermoscopic Features.

Background and Objectives: Amelanotic/hypomelanotic melanomas (AHMs) account for 2-8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical-pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods: We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the "pattern analysis" approach, which involves a simultaneous and subjective assessment of different criteria. Results: Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions: Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

A rapidly growing nodule on the face during pregnancy.

It is well known that adnexal skin tumors can simulate other cutaneous neoplasia and that various types of benign and malignant skin tumors can develop or modify during pregnancy. Here, we report a case of trichoblastoma mimicking a keratoacanthoma arising in a nevus sebaceous during pregnancy. Given its unique clinical and dermoscopic features, this case highlights the pivotal role of clinicopathological correlation in the diagnosis of adnexal tumors with an atypical clinical presentation.

Dermatoscopy and reflectance confocal microscopy for basal cell carcinoma diagnosis and diagnosis prediction score: A prospective and multicenter study on 1005 lesions.

BACKGROUND: Basal cell carcinoma (BCC) is usually diagnosed by clinical and dermatoscopy examination, but diagnostic accuracy may be suboptimal. Reflectance confocal microscopy (RCM) imaging increases skin cancer diagnostic accuracy. OBJECTIVE: To evaluate additional benefit in diagnostic accuracy of handheld RCM in a prospective controlled clinical setting. METHODS: A prospective, multicenter study in 3 skin cancer reference centers in Italy enrolling consecutive lesions with clinical-dermatoscopic suspicion of BCC (ClinicalTrials.gov: NCT04789421). RESULTS: A total of 1005 lesions were included, of which 474 histopathologically confirmed versus 531 diagnosed by clinical-dermatoscopic-RCM correlation, confirmed with 2 years of follow-up. Specifically, 740 were confirmed BCCs. Sensitivity and specificity for dermatoscopy alone was 93.2% (95% CI, 91.2-94.9) and 51.7% (95% CI, 45.5-57.9); positive predictive value was 84.4 (95% CI, 81.7-86.8) and negative predictive value 73.3 (95% CI, 66.3-79.5). Adjunctive RCM reported higher rates: 97.8 (95% CI, 96.5-98.8) sensitivity and 86.8 (95% CI, 82.1-90.6) specificity, with positive predictive value of 95.4 (95% CI, 93.6-96.8) and negative predictive value 93.5 (95% CI, 89.7-96.2). LIMITATIONS: Study conducted in a single country. CONCLUSIONS: Adjunctive handheld RCM assessment of lesions clinically suspicious for BCC permits higher diagnostic accuracy with minimal false negative lesions.

Dermoscopy of Lentiginous Melanomas and Equivocal Benign Pigmented Macules of the Scalp: A Case-Control Multicentric Study.

INTRODUCTION: Although the dermoscopic features of facial lentiginous melanomas (LM), including lentigo maligna and lentigo maligna melanoma, have been extensively studied, the literature about those located on the scalp is scarce. This study aims to describe the dermoscopic features of scalp LM and assess the diagnostic accuracy of dermoscopy to discriminate them from equivocal benign pigmented macules. METHODS: Consecutive cases of scalp LM and histopathology-proven benign but clinically equivocal pigmented macules (actinic keratoses, solar lentigos, seborrhoeic keratoses, and lichen planus-like keratoses) from four referral centres were included. Dermoscopic features were analysed by two blinded experts. The diagnostic performance of a predictive model was assessed. RESULTS: 56 LM and 44 controls were included. Multiple features previously described for facial and extrafacial LM were frequently identified in both groups. Expert's sensitivity to diagnose scalp LM was 76.8% (63.6-87.0) and 78.6% (65.6-88.4), with specificity of 54.5% (38.9-69.6) and 56.8% (41.0-71.7), and fair agreement (kappa coefficient 0.248). The strongest independent predictors of malignancy were (OR, 95% CI) chaos of colour (15.43, 1.48-160.3), pigmented reticular lines (14.96, 1.68-132.9), increased density of vascular network (3.45, 1.09-10.92), and perifollicular grey circles (2.89, 0.96-8.67). The predictive model achieved 85.7% (73.8-93.6) sensitivity, 61.4% (45.5-75.6) specificity, and 81.5 (73.0-90.0) area under curve to discriminate benign and malignant lesions. A diagnostic flowchart was proposed, which should improve the diagnostic performance of dermoscopy. CONCLUSION: Both facial and extrafacial dermoscopic patterns can be identified in scalp LM, with considerable overlap with benign pigmented macules, leading to low specificity and interobserver agreement on dermoscopy.

Dermoscopy of melanoma according to different body sites: Head and neck, trunk, limbs, nail, mucosal and acral.

Effective cancer screening detects early-stage tumours, leading to a lower incidence of late-stage disease over time. Dermoscopy is the gold standard for skin cancer diagnosis as diagnostic accuracy is improved compared to naked eye examinations. As melanoma dermoscopic features are often body site specific, awareness of common features according to their location is imperative for improved melanoma diagnostic accuracy. Several criteria have been identified according to the anatomical location of the melanoma. This review provides a comprehensive and contemporary review of dermoscopic melanoma criteria according to specific body sites, including frequently observed melanoma of the head/neck, trunk and limbs and special site melanomas, located on the nail, mucosal and acral region.

Melanoma in children: A systematic review and individual patient meta-analysis.

The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood.

Development and Implementation of a Web-Based International Registry Dedicated to Atypical Pigmented Skin Lesions of the Face: Teledermatologic Investigation on Epidemiology and Risk Factors.

Background: Atypical pigmented facial lesions (aPFLs) often display clinical and dermoscopic equivocal and/or overlapping features, thus causing a challenging and delayed diagnosis and/or inappropriate excisions. No specific registry dedicated to aPFL paired with clinical data is available to date. Methods: The dataset is hosted on a specifically designed web platform. Each complete case was composed of the following data: (1) one dermoscopic picture; (2) one clinical picture; (3) two lesion data, that is, maximum diameter and facial location (e.g., orbital area/forehead/nose/cheek/chin/mouth); (4) patient's demographics: family history of melanoma, history of sunburns in childhood, phototype, pheomelanine, eyes/hair color, multiple nevi/dysplastic nevi on the body; and (5) acquisition device (videodermatoscope/camera-based/smartphone-based system). Results: A total of 11 dermatologic centers contributed to a final teledermoscopy database of 1,197 aPFL with a distribution of 353 lentigo maligna (LM), 146 lentigo maligna melanoma (LMM), 231 pigmented actinic keratoses, 266 solar lentigo, 125 atypical nevi, 48 seborrheic keratosis, and 28 seborrheic-lichenoid keratoses. The cheek site was involved in half of aPFL cases (50%). Compared with those with the other aPFL cases, patients with LM/LMM were predominantly men, older (69.32 ± 12.9 years on average vs. 62.69 ± 14.51), exhibited larger lesions (11.88 ± 7.74 mm average maximum diameter vs. 9.33 ± 6.46 mm), and reported a positive history of sunburn in childhood. Conclusions: The iDScore facial dataset currently represents a precious source of data suitable for the design of diagnostic support tools based on risk scoring classifiers to help dermatologists in recognizing LM/LMM among challenging aPFL in clinical practice.

Case Report of Dermoscopic Aspects and Reflectance Confocal Microscopy Description of Segmental Leiomyoma and Relative Management.

Cutaneous leiomyoma is a benign tumor, mainly composed of smooth muscle cells and arising from the arrector pili muscle of hair follicles. The diagnosis of leiomyomas is of paramount importance, as they can often be associated with underlying malignancies (e.g., renal cell carcinoma, leiomyosarcoma) and specific genetic mutations. We report the case of a 27-year-old Caucasian male patient that presented to our attention with a rare segmental and Zoosteriform type II leiomyoma. We performed an analysis of the cutaneous lesions using dermoscopy, reflectance confocal microscopy (RCM) and histology. We found that, using dermoscopy, the leiomyomas showed a dermatofibroma-like appearance with a central hypopigmented area, peripheral delicate hyperpigmentation and also erythematous areas and ectatic vessels. RCM, although not specific, showed groups of hypo-reflective areas distributed in the most superficial papillary dermis, which in histology and immunohistochemistry corresponded to the most superficial protrusions in the papillary dermis of the tumoral bundles. Finally, we discuss the management of patients with multiple leiomyomas and stress the fact that, in the cases of multiple leiomyomas, an annual sonography of the kidneys associated with dermatological and (in women) gynecological consultations are needed to ensure the early identification of an underlying tumor. A genetic consultation to detect an eventual FH mutation is recommended, but since in some cases the FH result may be negative, the above recommended controls remain always of paramount importance.

Prevalence and clinical-pathological features of nevus-associated versus de novo melanoma: a retrospective cross-sectional study of 2806 cases.

Introduction: Nevus-associated melanoma (NAM) accounts for almost one third of all cutaneous melanomas; it is often associated with younger age, trunk location and lower Breslow's thickness compared to de novo melanoma (DNM). Objectives: To define the prevalence of NAM in a tertiary referral Center in Italy and to analyze its distribution according to demographics, clinical and histopathological variables. Methods: Data were retrospectively retrieved from the archive of the Pathology Unit from June 2011 to August 2020. NAMs were compared with DNMs according to demographic, clinical and histopathological variables. Results: A total of 2806 consecutive cases of melanoma were excised in 2537 patients. Of these, 431 (15.4%) were NAM. NAM patients were significantly younger than DNM patients (55.1±14.1 vs. 62.0±15.0 years, p<0.001); they were predominantly located on the trunk (64.0% vs. 47.9% of DNMs). Melanoma located on the head and neck, trunk and upper limbs respectively had 2.3 (95%CI:1.2-4.5, p:0.014), 3.2 (95%CI:2.1-5.1, p<0.001) and 3.5 (95%CI:2.0-6.1, p<0.001) more odds to be NAM than those on the lower limbs. Conclusions: Our results confirm the association of NAM with younger age and trunk location. We also demonstrated that body site differences of NAM distribution are enhanced before the sixth decade of life.

Effect of Reflectance Confocal Microscopy for Suspect Lesions on Diagnostic Accuracy in Melanoma: A Randomized Clinical Trial.

Importance: Previous systematic reviews and meta-analyses have concluded that given data paucity, a comparison of reflectance confocal microscopy (RCM) with dermoscopy is complex. They recommend comparative prospective studies in a real-world setting of suspect lesions. Objective: To test the hypothesis that RCM reduces unnecessary lesion excision by more than 30% and identifies all melanoma lesions thicker than 0.5 mm at baseline. Design, Setting, and Participants: This randomized clinical trial included 3165 patients enrolled from 3 dermatology referral centers in Italy between January 2017 and December 2019, with a mean (SD) follow-up of 9.6 (6.9) months (range, 1.9-37.0 months). The consecutive sample of 3165 suspect lesions determined through dermoscopy were eligible for inclusion (10 patients refused). Diagnostic analysis included 3078 patients (48 lost, 39 refused excision). Data were analyzed between April and September 2021. Interventions: Patients were randomly assigned 1:1 to standard therapeutic care (clinical and dermoscopy evaluation) with or without adjunctive RCM. Information available guided prospective clinical decision-making (excision or follow-up). Main Outcomes and Measures: Hypotheses were defined prior to study initiation. All lesions excised (baseline and follow-up) were registered, including histopathological diagnoses/no change at dermoscopy follow-up (with or without adjunctive RCM). Number needed to excise (total number of excised lesions/number of melanomas) and Breslow thickness of delayed diagnosed melanomas were calculated based on real-life, prospective, clinical decision-making. Results: Among the 3165 participants, 1608 (50.8%) were male, and mean (SD) age was 49.3 (14.9) years. When compared with standard therapeutic care only, adjunctive RCM was associated with a higher positive predictive value (18.9 vs 33.3), lower benign to malignant ratio (3.7:1.0 vs 1.8:1.0), and a number needed to excise reduction of 43.4% (5.3 vs 3.0). All lesions (n = 15) with delayed melanoma diagnoses were thinner than 0.5 mm. Conclusions and Relevance: This randomized clinical trial shows that adjunctive use of RCM for suspect lesions reduces unnecessary excisions and assures the removal of aggressive melanomas at baseline in a real-life, clinical decision-making application for referral centers with RCM. Trial Registration: ClinicalTrials.gov Identifier: NCT04789421.

Characteristics and management of skin cancers in very elderly patients: A real-world challenge for clinicians.

The increase life expectancy led to an expected increase in skin cancer incidence in older patients. Their treatment can require a complex decision-making process. Limited data are available on characteristics, management and outcome of skin tumours in nonagenarian and centenarian patients. The aim of our study was to describe epidemiology, clinical-pathological features and treatment strategies of skin cancers in a cohort of patients aged ≧95 years. A total of 116 patients ≧95 years of age presented for the evaluation of 225 skin lesions (mean of 1.94 lesions per patient). The mean age was 97.4 years, 57.8% were women. Most patients had an ECOG score of 3 (49.3%) or 4 (32%). Lesions were mainly located on the head and neck area (74.2%), upper (7.1%) and lower (6,2%) limbs. The majority of patients presented with non-melanoma skin cancers (183/225; 81.3%), 25/225 (11.1%) had actinic keratosis, 5 (2.2%) melanoma and 2 (0.9%) atypical fibroxanthoma. Forty-eight lesions (21.3%) were treated with surgery, 58 (25.8%) with radiotherapy. The management of 73 lesion (32.4%) was discussed at the multidisciplinary tumour board meeting. One patient died for the progression of a squamous cell carcinoma; 74 patients died for causes unrelated to skin tumours, 36 are still alive after a mean follow-up of 27.27 months. This cohort study confirms that age is not per se a contraindication for treatment of skin cancers in elderly patients. Our results support the importance of a patient-centred care approach that should take into consideration patient's preferences, comorbidities, compliance and possible adverse events.

Dermatological and Dermoscopic Baselines in BRCA Mutation Carriers.

Breast cancer-associated genes 1 and 2 (BRCA1 and BRCA2) are tumor suppressor genes encoding a large protein that is involved in many essential biological processes. BRCA mutated patients show an increased risk to develop several malignancies, including cutaneous malignancies, although inconsistently across multiple studies. We carried out an observational study on the main dermatological and dermoscopic aspects in a population of patients with BRCA 1/2 mutations, to identify the main clinical and dermoscopical features in this class of patients. A total of 52 patients with BRCA mutations were included in the current analysis. Clinical, dermoscopical, and pathological data were obtained during the dermatologic visits. Out of the entire cohort, 67.3% of patients showed brown hairs and 63.5% of patients showed brown eyes, with phototype III as the most frequent phototype (69.2%). A total of 2.017 melanocytic lesions in all patients were analyzed; specifically, 40 patients (76.9%) showed a total number of nevi > 10, while regarding the main observed dermoscopic features, a prevalence of reticular pattern in 63% of cases was observed, followed by a mixed pattern in 19.2% of cases. Regarding the cutaneous examination, eruptive angiomas (eCAs) were the main dermatologic manifestations in 46.2% of patients. Out of 52 patients and during a follow-up of 24 months one patient developed an in situ melanoma. Interestingly, none of the patients with eCAs showed a TN > 10, highlighting an inverse correlation. To date, there is insufficient evidence to warrant increased surveillance in patients with BRCA mutations or with a positive family history for BRCA mutations, in the absence of standard cutaneous risk factors. Further studies with larger samples of patients are needed to better investigate dermatological and dermatoscopic features in BRCA mutation carriers.

The role of stereotactic radiotherapy in addition to immunotherapy in the management of melanoma brain metastases: results of a systematic review.

Aim of this study was to systematically review the literature to assess efficacy and safety of stereotactic radiotherapy (SRT) in combination with immunotherapy for the treatment of melanoma brain metastases (MBM). The literature was searched using PubMed, Scopus, and Embase. Studies comparing SRT plus immunotherapy versus SRT or immunotherapy alone were deemed eligible for inclusion. Two studies showed improved overall survival after SRT plus immunotherapy in melanoma cancer patients with brain metastases. Three studies reported data on LC and DFS showing as SRT plus immunotherapy did not improve local control and DFS rates. G3-G4 toxicity was reported in only one study (20% in the SRT plus immunotherapy group versus 23% in the immunotherapy group). Despite SRT plus concurrent immunotherapy seems associated with possible survival advantage and low ≥ G3 late toxicity rates, the quality of evidence is very low. Therefore, in patients with brain metastases from melanoma, SRT plus immunotherapy should be evaluated on an individual basis after discussion by a multidisciplinary team.

Trends in cutaneous melanoma mortality in Italy from 1982 to 2016.

BACKGROUND: In Italy, comprehensive national studies, about mortality rates for cutaneous melanoma, are missing. The aim of this study was to analyze the trend of cutaneous melanoma mortality in Italy from 1982 to 2016. METHODS: Data on death certificates were obtained from Italian National Institute of Statistics (ISTAT: Istituto nazionale di STATistica, Indagine sulle cause di morte). Mortality rates were age-standardized on the European population 2013 and presented per 100,000 individuals. Age-adjusted mortality rates (AMRs) were calculated by sex, age group, and geographic areas. To identify changes in mortality rate trends, a joinpoint regression model was used, and the annual percent change (APC) was estimated. RESULTS: In Italy, a total number of 49,312 patients (44.0% women) died for cutaneous melanoma from 1982 to 2016. Melanoma mortality rates significantly increased in the study period in both sexes, with higher AMR values and a steeper increase in men (from 2.71 to 4.02; APC: 1.43; 95% CI 1.26-1.61) than women (from 1.94-2.10; APC: 0.23; 95% CI 0.00-0.46). The largest difference between men and women was observed in patients aged ≥65 years with APC of 2.17 in men (95% CI 1.97-2.37) and 0.37 in women (95% CI 0.08-0.66). CONCLUSION: In conclusion, the melanoma mortality rate in Italy progressively increased especially in elderly men. Several hypotheses might explain the observed age and geographic differences such as sun exposure habits or different strategies of prevention campaigns.

Comparative Analysis of PRAME Expression in 127 Acral and Nail Melanocytic Lesions.

PRAME (PReferentially expressed Antigen in MElanoma), a cancer testis antigen expressed in low levels in gonadal, endometrial, and adrenal gland tissues, has been recently considered a valuable tool in the differential diagnosis between benign and malignant melanocytic lesions. The aim of the current study is to perform PRAME immunostaining on a large series of benign and malignant acral lesions to evaluate the reproducibility of data reported in the literature and to validate PRAME as an affordable tool in the differential diagnosis between benign and malignant acral melanocytic tumors. Immunohistochemical analysis for PRAME was performed in 127 benign and malignant acral and nail melanocytic lesions. To better correlate PRAME expression with the nature (benign vs. malignant) of the lesions, we categorized PRAME tumor cells percentage positivity and intensity in a cumulative score obtained by adding the quartile of positive tumor cells (0, 1+, 2+, 3+, 4+) to PRAME expression intensity in tumor cells (0, 1+, 2+, 3+). Adopting an arbitrary PRAME expression score of < 5 versus ≥5 resulted in a correct identification of 82.5% of benign and 87.1% of malignant lesions. PRAME immunohistochemistry demonstrated good sensitivity and specificity in the diagnosis of acral melanocytic lesions, however, in line with the previous literature, we identified a subset of challenging cases such as acral Spitz nevi, in situ melanomas, and small, thin, invasive melanomas in which PRAME did not correlate with morphologic features. This suggests that PRAME can be a valid tool to be incorporated in a diagnostic clinicopathologic algorithm, subject to morphologic characteristics.

Unusual dermoscopic patterns of basal cell carcinoma mimicking melanoma.

BACKGROUND: Basal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort. OBJECTIVE: To identify dermoscopic "trump" characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings. METHODS: Retrospective, multicentric comparative study of atypical, non-facial basal cell carcinoma (≥1 seven-point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results. RESULTS: A total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001). CONCLUSIONS: These findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence.

Clinicopathological and Dermoscopic Baselines in Patients with Lynch Syndrome.

Despite the fact that Lynch Syndrome (LS) patients may also develop extra-colonic malignancies, research evaluating the association between LS and skin cancers is currently very limited. We performed a monocentric clinical and dermoscopic study involving 42 LS patients which referred to the Dermatology Unit for cutaneous screenings. In total, 22 patients showed a mutation in MLH1 and 17 patients a MSH2 mutation. Out of the entire cohort, 83% of LS patients showed brown hairs and 78% brown eyes, and the most frequent phototypes were III and II (respectively, 71.5% and 21%). A positive medical history for an internal malignancy was present in 36% of patients, with colon cancer as the most frequent malignancy in 60% of cases. A total of 853 cutaneous lesions have been analyzed: 47% of patients showed a total number of nevi > 10. The main observed dermoscopic features were a uniform reticular pattern (77% of patients), a mixed pattern (9% of patients) and a uniform dermal pattern (14% of patients). Eruptive cherry angiomas were present in 24% of cases, eruptive seborrheic keratosis in 26% and viral warts in 7% of cases; basal cell carcinoma was detected in 7% of cases. We have not found specific associations with specific skin manifestations, and the clinical and dermoscopic appearance of the pigmented lesions reflected the features present in the general population. To date, there are currently no guidelines for skin screening in LS patients. According to our study, there is insufficient evidence to ensure increased surveillance in LS patients; further studies with larger samples of patients are needed to better investigate dermatological and dermoscopic features in LS carriers.