Dermoscopy of cutaneous adnexal tumours: a systematic review of the literature.

Cutaneous adnexal tumours (ATs) encompass a variegated group of hamartomas and benign or malignant tumours, originating from the hair follicle, sebaceous, eccrine or apocrine glands that may simulate other cutaneous neoplasms. This study aims to provide a comprehensive overview of the spectrum of clinical and dermoscopic features of ATs, to better define these lesions and assist in the differential diagnosis. We performed a two-step systematic search of the literature in PubMed, Embase and Cochrane Library databases from inception until 4 September 2020. In the first step, we aimed to define histological variants of ATs with descriptions of dermoscopic criteria. The second step included a search for the name of each previously identified AT variants in the same databases adding 'AND (epilum* or dermosc* or dermatosc*)'. All study types in English language reporting dermoscopic images of ATs were included. Collisions between ATs and other inflammatory or neoplastic skin lesions were excluded, with the exception of collisions with a sebaceous nevus. The protocol of this study was prospectively registered in PROSPERO (CRD42021244677). In total, 206 articles met our inclusion criteria, encompassing 372 ATs in 365 patients. Most ATs were apocrine-eccrine (n = 217, 58.3%, n = 173 benign) with a prevalence of poromas (n = 82), followed by follicular ATs (n = 88, 23.7%, n = 83 benign) and sebaceous ATs (n = 67, 18.0%, n = 49 benign). Most patients had a single AT lesion (320, 86.0%), while 42 (11.3%) had multiple ATs. A syndrome causing multiple ATs was identified in 15 patients. Histopathological analysis revealed 82% benign (n = 305) and 18.0% malignant (n = 67). ATs were classified according to their ability to mimic four groups of more common skin tumours: basal cell carcinoma, squamous cell carcinoma, melanocytic lesions and benign cutaneous lesions. Moreover, we have highlighted the ability of malignant variants of ATs to simulate benign skin lesions. This systematic review offers a comprehensive overview of the common clinical and dermoscopic features of follicular, sebaceous and apocrine-eccrine ATs and details possible differential dermoscopic features.

Flat scalp melanoma dermoscopic and reflectance confocal microscopy features correspond to histopathologic type and lesion location.

BACKGROUND: Dermoscopy and Reflectance Confocal Microscopy (RCM) features of scalp melanoma according to lesion location and histopathology have not been fully investigated. OBJECTIVES: To reveal dermoscopic and RCM features of scalp melanoma according to lesion location and histopathology. METHODS: We retrospectively retrieved images of suspicious, atypical excised, flat melanocytic lesions of the scalp, assessed on dermoscopy and RCM at five centres, from June 2007 to April 2020. Lesions were classified according to histopathological diagnoses of nevi, lentigo maligna melanoma (LM/LMM) or superficial spreading melanoma (SSM). Clinical, dermoscopic and RCM images were evaluated; LM/LMM and SSM subtypes were compared through multivariate analysis. RESULTS: Two hundred forty-seven lesions were included. In situ melanomas were mostly LM (81.3%), while invasive melanomas were mostly SSM (75.8%). Male sex, baldness and chronic sun-damaged skin were associated with all types of melanomas and in particular with LM/LMM. LMs were mostly located in the vertex area and SSM in the frontal (OR: 8.8; P < 0.05, CI 95%) and temporal (OR: 16.7; P < 0.005, CI 95%) areas. The dermoscopy presence of pseudo-network, pigmented rhomboidal structures, obliterated hair follicles and annular-granular pattern were associated with LM diagnoses, whereas bluish-white veil was more typical of SSM. Observations on RCM of atypical roundish and dendritic cells in the epidermis were associated with SSM (42.4%) and dendritic cells with LM (62.5%) diagnoses. Folliculotropism on RCM was confirmed as a typical sign of LM. CONCLUSIONS: Flat scalp melanomas reveal specific dermoscopic and RCM features according to histopathologic type and scalp location.

Vipera snakebite in Europe: a systematic review of a neglected disease.

In 2009, snakebites were included in the list of the World Health Organization (WHO) neglected diseases. Dermatological literature lacks current and up-to-date articles about snakebites and their management, despite the fact that dermatologists, especially from rural hospitals, can be called into the emergency room to consult the management of suspected snakebites. In this systematic review, we highlighted the main clinical and laboratory aspects of snakebites from Vipera spp. in Europe, by reviewing 3574 studies initially retrieved from PubMed, Embase and Cochrane CENTRAL databases. Of these, 78 were finally included in the systematic review. We found that the most involved taxon was V. berus in 63.3% and the most involved anatomic site of the bite was the upper limbs 53.1% with fang marks reported in 90.5%. The mean age of the patients was 32.9 years, and bites were slightly more common among males (58.2%). A wound washing was performed in 86.9% of cases before the hospitalization. The most frequently reported grade of envenomation was G2 (42.2%). In addition to local dermatological symptoms (extended erythema, oedema, cutaneous necrosis, hives, purpura, petechiae, acute compartment syndrome), numerous systemic symptoms have also been reported, including fatigue (14.4%), pain (75.3%), fever (49.2%), direct anaphylactoid reaction (5.3%), anxiety (60.8%), cranial nerve neurotoxicity (14.8%), dysesthesia/paraesthesia (7.9%), vomiting (33.7%), abdominal pain (23.3%), diarrhoea (15.4%), dyspnoea (6.3%), proteinuria (10.6%) and haematuria (9.3%). Secondary infections were present in 3.5% and disseminated intravascular coagulation in 3.1% of cases, and fasciotomy was performed in 4.2% cases, while an amputation in 6.9%. Only 0.9% of patients died. Antivenom was administered in 3053 cases. In conclusion, there is a pressing need for robust multi-centre randomized control trials, standardized protocol for snakebite management and antivenom administration across Europe and a National snakebite register for each European country.

The presence of eccentric hyperpigmentation should raise the suspicion of melanoma.

BACKGROUND: Melanocytic lesions with eccentric hyperpigmentation (EH), even though without other dermatoscopic features of melanoma, are often excised. OBJECTIVE: Aiming to understand whether the EH in a pigmented lesion is an accurate criterion of malignancy, we evaluated the capability of two evaluators, with different expertise, to correctly diagnose a melanoma when analysing a given lesion in toto versus a partial analysis, with only the EH or the non-hyperpigmented portion (non-EH) visible. METHODS: Dermatoscopic images of 240 lesions (107 melanomas and 133 nevi) typified by EH were selected. Facial, acral, mucosal lesions and lesions showing clear-cut features of melanoma (except for atypical network) were excluded. Clinical and dermoscopic features (main pattern and numbers of colours) were described for all cases. Each image was split in two through a software so that only the EH or the non-EH was visible. Two blinded evaluators examined three sets of images, two with customized images and one with the non-modified ones: they were asked to give a dichotomous diagnosis (melanoma or nevus) for each image. RESULTS: Melanomas were significantly more frequently typified by colour variegation (3 colours in 44.8% and 4 colours in 41.1% of cases) and atypical network (88.1% in the EH). No significant differences in diagnostic accuracy emerged between the two evaluators. Sensitivity improved in the evaluation of the whole lesions (mean sensitivity 89.7%) in comparison with the evaluation of EH or non-EH alone (72.7-62.6%). Specificity increased when evaluating the EH (54.1%). Positive predictive value (PPV) and likelihood ratio (LR+) of EH resulted 52.3% and 1.4, meaning that in one case out of two with EH is a melanoma. CONCLUSIONS: Lesions with EH are challenging, regardless of dermoscopic experience. The EH is a robust criterion for malignancy, since the evaluation of the whole lesion, through an intralesional comparative approach, increases sensitivity.

A meta-analysis on the influence of partial biopsy of primary melanoma on disease recurrence and patient survival.

BACKGROUND: Complete surgical excision is the preferred biopsy type for suspicious melanocytic lesions. However, partial biopsy is sometimes used in special situations. Previous studies have explored the effect of partial biopsy of a primary melanoma on patient outcome with controversial results. OBJECTIVE: We performed a meta-analysis on the influence of the type of biopsy of a primary melanoma on recurrence-free survival (RFS) and melanoma-related survival (MRS). METHODS: Clinical trials, observational cohort studies and case-control studies reporting absolute number of recurrences and/or melanoma-related deaths in patients undergoing a partial or excisional biopsy of melanoma were included in the meta-analysis. RESULTS: In all, the five included studies reported 3249 patients, 1121 (34.5%) of them in the partial biopsy group and 2128 (65.5%) in the excisional biopsy group. Despite a trend in favour of excisional biopsy in reducing the risk for recurrences, the forest plot related to RFS failed to demonstrate significant differences among groups (RR: 1.27; 95% CI 0.97-1.67; P: 0.09; random effects; I2 : 55%). The forest plot showed no difference in the risk of dying for melanoma-related causes for patients undergoing partial biopsy vs. excisions biopsy (RR: 1.50; 95% CI 0.98-2.30; P: 0.06; random effects; I2 : 60%). LIMITATIONS: The majority of the studies were retrospective, and follow-up time was not uniform among studies and not always reported. CONCLUSION: In conclusion, a partial biopsy can be performed in special situations, such as large primary tumours located in surgically sensitive areas, without altering MRS and RFS.

Adjuvant therapy for cutaneous melanoma: a systematic review and network meta-analysis of new therapies.

New drugs have been recently approved as adjuvant therapies for melanoma. In this Bayesian network meta-analysis, we aimed to assess the best therapeutic option in terms of recurrence-free survival (RFS), overall survival (OS) and adverse events (AEs). PubMed, Embase, Cochrane library and the American Society of Clinical Oncology databases were searched from inception until 20 August 2018. We estimated adjusted hazard ratios (HRs) for RFS and OS and relative odds ratios (ORs) for AEs and surface under the cumulative ranking (SUCRA) probabilities were calculated. A number of 872 records were identified, and six were finally included in the meta-analysis. A total of 4244 patients in six studies were randomized. The following therapies were considered in the selected studies: combined dabrafenib and trametinib, vemurafenib, nivolumab, ipilimumab and pembrolizumab. Nivolumab demonstrated the highest probability (75.1%) of being the best in term of RFS, followed by dabrafenib+trametinib, pembrolizumab, ipilimumab and vemurafenib; however, OS was not estimable. Concerning AEs, pembrolizumab and nivolumab showed the highest probability to be less associated with any and 3-4 grade AEs (83.1% and 64.4%, respectively). In conclusion, all new drugs are highly effective in adjuvant setting, and the best choice is dependent of patient's context.

Digital follow-up by means of dermatoscopy and reflectance confocal microscopy of actinic keratosis treated with Imiquimod 3.75% cream.

BACKGROUND: Imiquimod 3.75% cream (Zyclara® Meda, Stockholm, Sweden) is a new field-directed therapy for actinic keratosis (AK). OBJECTIVES: The aim is to evaluate efficacy and the morphologic dynamic changes induced by this treatment by means of dermatoscopy and reflectance confocal microscopy (RCM) of imiquimod 3.75% cream for the treatment of AKs of the face or scalp and to evaluate. METHODS: Thirty-two patients were treated with Imiquimod 3.75% cream. Demographic parameters, AK-FAS and AKASI scores and side-effects were collected. RCM and dermatoscopy on one target AKs were performed at each visit. We collected images at baseline (T0), after 1 week from the end of the first 2-week cycle (T1), after 1 week from the end of the entire treatment (T2) and 2 months after the end of treatment (T3). RESULTS: One target representative AK in the selected area of treatment of each patient was analysed. All dermoscopic and confocal parameters were reduced 2 months after the end of the therapy (T3) with a substantial reduction of AKASI and AK-FAS scores, and 17 cases (54.8%) were completely solved. Confocal microscopic analysis showed a reduction of keratinocytes disarray in 77.4% of cases; none showed crusts and parakeratosis. Inflammation was considerably decreased and was observed only in 12.9% of patients at the last visit. This improvement was not assessed on dermatoscopy because of inflammation and background erythema, which adversely influenced the assessments. LSRs were observed in almost all the patients during treatment being more severe after the first cycle of treatment (T1). CONCLUSIONS: Imiquimod 3.75% cream is effective in treating clinical and subclinical AKs with an easy management of side-effects. Dermatoscopy and mostly RCM allow non-invasive monitoring of treatment response in vivo.

The prevalent dermoscopic criterion to distinguish between benign and suspicious pink tumours.

BACKGROUND: Pink skin tumours are difficult to differentiate, clinically and dermoscopically. In previous studies, mainly focused on pigmented lesions, pattern analysis provided the best sensitivity and specificity values, as compared to other algorithms. These findings suggest that the global dermoscopic appearance, based on the evaluation of prevalent features, could represent a valuable and practical approach even when dealing with pink lesions. OBJECTIVE: In this study, we aimed to evaluate the diagnostic accuracy of a new dermoscopic approach for pink tumours based on the prevalent criterion, as compared to a standard diagnostic method (Menzies algorithm). METHODS: The databases of two referral centres were retrospectively evaluated to retrieve dermoscopic images of amelanotic/hypomelanotic skin lesions. Two experts in dermoscopy, blinded for the final diagnosis and for clinical and demographic information, evaluated separately dermoscopic pictures of 1000 lesions according to the Menzies score and to the prevalent criterion method. RESULTS: According to the high sensitivity model of the Menzies score, 129 (12.9%) lesions were considered as non-suspicious (of which 16 were false negative) and 871 (87.1%) as suspicious (of which 212 were false positive), with 97.6% sensitivity and 34.8% specificity. According to the high specificity model, 370 (37%) lesions were evaluated as non-suspicious (of which 105 were false negative) and 630 (63%) as suspicious (of which 60 were false positive), with 84.4% sensitivity and 81.5% specificity. Concerning the prevalent criterion method, 316 (31.6%) lesions were evaluated as non-suspicious (of which 46 were false negative) and 684 (68.4) as suspicious (of which 55 were false positive), with 93.2% sensitivity and 83.1% specificity. CONCLUSIONS: This study demonstrated that focusing on the prevalent dermoscopic features could allow to detect malignant pink tumours with similar sensitivity but higher specificity than using the conventional Menzies scoring system.

External validation and comparison of four confocal microscopic scores for melanoma diagnosis on a retrospective series of highly suspicious melanocytic lesions.

BACKGROUND: In vivo reflectance confocal microscopy significantly improves melanoma diagnosis as compared to clinical/dermoscopic examination alone. Several confocal criteria have been described allowing to differentiate melanoma from nevi; by combining different criteria, three pure confocal scores (Pellacani 2005, Segura 2009 and Pellacani 2012) and one mixed dermoscopic/confocal score (Borsari 2018) were constructed. OBJECTIVE: Our aim was to externally validate and compare the performance of these confocal scores. METHODS: We retrospectively enrolled excised melanocytic lesions which underwent confocal examination in a 2-year period. Lesions located on the face and acral sites were excluded. Both dermoscopic and confocal criteria considered in the four scores were evaluated by experts. Subsequently, specificity and sensitivity levels for each score were calculated, together with the positive and negative predictive values and likelihood ratios; also, receiver operating characteristic curves were constructed. RESULTS: A total of 389 patients with 422 lesions were retrospectively enrolled, of which 162 (38.4%) were melanomas and 260 (61.6%) were nevi (189 common and 71 Spitz/Reed nevi). The highest sensitivity levels were recorded for Segura 2009 with cut-off ≥-1 (92.0%), while Pellacani 2005 with cut-off ≥5 achieved the highest specificity (69.6%). The score by Borsari et al. showed the highest levels of positive and negative predictive values (59.8% and 91.5%) and likelihood ratios (2.4 and 0.1) as well as the highest area under the curve values (0.76; 95% CI 0.72-0.81; P < 0.001). CONCLUSIONS: High levels of accuracy were found for each of the four considered scores. No differences were found among scores in confirming melanoma diagnosis when positive; however, the score by Borsari 2018 was the best in excluding melanoma diagnosis when negative.

Alopecia neoplastica as a sign of visceral malignancies: a systematic review.

Alopecia neoplastica (AN) from visceral tumours is a rare form of cutaneous metastasis in which internal malignancies spread to the scalp. The diagnosis of AN may be very challenging, especially when its onset precedes the diagnosis of the primary tumour. We aimed to improve the knowledge on AN, highlighting that in case of scarring localized alopecia, a differential diagnosis with metastasis should always be considered. We performed a systematic review to describe the main demographic and clinical features associated with AN from visceral malignancies; a survival analysis was also performed. In 118 reports, accounting for 123 patients, we found that women were more affected by AN than men (53.7% vs. 46.3%). The most frequent site of the primary tumour was the gastrointestinal tract (24.4%), followed by breast (17.9%), kidney (8.1%), lung (7.3%), thyroid (7.3%), uterus (6.5%), central nervous system (6.5%), liver (3.3%) and other anatomic areas for 18.7% of cases. Furthermore, in more than half of the cases (66.1%), AN lesions were single and were mainly diagnosed after the primary visceral tumour (71.5%). Finally, survival analysis highlighted a lower progression-free survival in men; while, no significant differences in overall survival were reported among genders. In conclusion, metastatic skin disease should always be taken into consideration when dealing with patients with localized scarring alopecia.

Sclerosing nevus with pseudomelanomatous features: dermoscopic and confocal aspects.

BACKGROUND: Sclerosing nevus with pseudomelanomatous features (SNPFs) is a clinical and pathologic entity that mimics melanoma both clinically and histologically. The lesion is a melanocytic nevus, histologically characterized by fibrosis and a pseudomelanomatous proliferation. It is typically seen in young to middle-aged individuals, mainly on the back, where microtrauma or inflammatory changes are more frequent. Dermoscopic description of SNPF has been reported so far in one case series. OBJECTIVE: The aim of our study was to describe the dermoscopic and confocal features of SNPF. METHODS: Histopathologically confirmed cases of SNPF were retrospectively collected from three referral centres in Italy. Only lesions with available clinical, dermoscopic and histopathological data were included; confocal images were also retrieved, when available. Lesions were evaluated for the presence of 12 dermoscopic and five confocal criteria previously described. RESULTS: The study population included 93 lesions in as many patients (71 men and 22 women; median age: 38 years). Dermoscopically, we found a predominance of dark colours, in particular brown and blue, which were found in all lesions and the vast majority of the lesions (86/93; 92.5%) displayed at least one structureless area. By the combination of colours and structures, we observed that the majority of the lesions (67/92; 72%) were characterized by more than one structure and more than one colour. Confocal evaluation was performed on a subset of 24/93 lesions showing a regular architecture pattern (19/24 cases, 79%), with a predominance of the ringed pattern. The presence of focal cytologic atypia at the dermal-epidermal junction was present in 12/24 cases (50%) with a prevalent dendritic-shaped cell proliferation. CONCLUSIONS: The current study demonstrated that SNPF was frequently characterized, on dermoscopic examination, by more than one structure and more than one colour and on confocal microscopy by a regular ringed pattern with focal dendritic atypical cells.

Diagnostic accuracy of ex vivo fluorescence confocal microscopy in Mohs surgery of basal cell carcinomas: a prospective study on 753 margins.

BACKGROUND: Frozen histological sections are used for intraoperative margin assessment during Mohs surgery. Fluorescence confocal microscopy (FCM) is a new tool that offers a promising and faster alternative to frozen histology. OBJECTIVES: To evaluate prospectively in a clinical setting the accuracy of FCM vs. frozen sections in margin assessment of basal cell carcinoma (BCC). METHODS: Patients with BCC scheduled for Mohs surgery were prospectively enrolled. Freshly excised surgical specimens were examined by FCM and then frozen sections were evaluated. Permanent sections were obtained, in order to validate the sample technique. A blind re-evaluation was also performed for discordant cases. Sensitivity and specificity levels, as well as positive and negative predictive values (PPV and NPV, respectively), were calculated and receiver-operating characteristic curves generated. RESULTS: We enrolled 127 BCCs in as many patients (40·2% females). Seven hundred and fifty-three sections were examined. All BCCs were located in the head and neck area. In evaluating the performance of FCM vs. frozen sections, sensitivity was 79·8%, specificity was 95·8%, PPV was 80·5% and NPV was 95·7% [area under the curve 0·88, 95% confidence interval 0·84-0·92 (P < 0·001)]. Forty-nine discordant cases were re-evaluated; 24 were false positive and 25 false negative. The performance of FCM and frozen sections was also evaluated according to the final histopathological assessment. CONCLUSIONS: We found high levels of accuracy for FCM vs. frozen section evaluation in intraoperative BCC margin assessment during Mohs surgery. Some technical issues prevent the wide use of this technique, but new devices promise to overcome these limitations.

Dermoscopy and reflectance confocal microscopy for monitoring the treatment of actinic cheilitis with ingenol mebutate gel: Report of three cases.

Actinic cheilitis (AC) can precede the development of squamous cell carcinoma (SCC) of the lip, a location with higher risk of invasiveness and metastasis. Herein, we reported the use of ingenol mebutate (IngMeb) 0.015% gel on three consecutive days to treat three patients suffering from AC. All the three patients achieved complete clearance of AC with rapid clinical effect, favorable safety profile, good patient's compliance related to short time of applications, and few local skin reactions. So IngMeb is an attractive new therapy for AC. Moreover, the present case report adds further evidence to the usefulness of dermoscopy and Reflectance confocal microscopy (RCM) in the assessment and monitoring of treatment outcome.

Basal cell carcinoma: the utility of in vivo and ex vivo confocal microscopy.

The use of confocal microscopy is possible using two different modalities: first, at patient's bedside for a rapid in vivo diagnosis of basal cell carcinoma and second, in the operating room directly on freshly excised specimen for a fast ex vivo margin-controlled surgery. In the current review, we report the main application of confocal microscopy for basal cell carcinoma diagnosis and management in both modalities.

In vivo dermoscopic and confocal microscopy multistep algorithm to detect in situ melanomas.

BACKGROUND: Although several dermoscopic features of in situ melanoma have been identified, data on confocal features of in situ melanoma are still lacking. OBJECTIVES: To identify reflectance confocal microscopy (RCM) features of in situ melanoma and to develop a diagnostic score combining dermoscopy and RCM. METHODS: In total, 120 in situ melanoma and 213 nevi (test set) were retrospectively analysed to assess the presence of dermoscopic and RCM criteria. Facial and acral lesions were excluded. Spearman's correlation, univariate and multivariate regression models were used to identify features significantly correlated with in situ melanoma diagnosis. Multivariate results on the test set allowed the development of a multistep algorithm, that was tested on a validation set of 100 lesions. RESULTS: The dermoscopic findings of an atypical network and regression were independent predicting factors for in situ melanoma diagnosis [odds ratio (OR) 3·44, 95% CI (confidence interval) 1·70-6·97 and OR 4·17, 95% CI 1·93-9·00, respectively]. Significant confocal predictors for malignancy were epidermal pagetoid spread (OR 2·83, 95% CI 1·32-6·04) and junctional cytological atypia (OR 3·39, 95% CI 1·38-8·30 if focal, OR 8·44, 95% CI 3·21-22·16 if widespread). A multistep diagnostic algorithm able to predict in situ melanoma with a sensitivity of 92·5% and a specificity of 61% was developed. The validation set confirmed the high diagnostic value (sensitivity 92%, specificity 58%). CONCLUSIONS: An easy and reproducible multistep algorithm for in situ melanoma detection is suggested, that can be routinely used in tertiary centres.