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.

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.

Dynamic dermoscopic and reflectance confocal microscopic changes of melanocytic lesions excised during follow up.

BACKGROUND: Digital dermoscopy follow up (DDF) is useful in improving the recognition of melanoma, catching early changes over time, although benign nevi can also show changes. Reflectance confocal microscopy (RCM) improves accuracy in diagnosing melanoma and decreases the number of unnecessary resections. OBJECTIVE: To evaluate dynamic dermoscopic and RCM changes during follow up of equivocal melanocytic lesions and assess the impact of adjunctive RCM to DDF for melanoma diagnosis. METHODS: A retrospective, multicenter study of extrafacial atypical melanocytic lesions excised during follow up was performed. Morphologic changes were evaluated, comparing dermoscopy and RCM baseline and follow-up images. RESULTS: One hundred thirty-seven atypical melanocytic lesions were studied, including 14 melanomas and 123 benign nevi. Significantly greater changes in DDF of atypical network, regression, atypical streaks, and asymmetrical growth as well as in dynamic RCM of atypical cells and dermal-epidermal junction disarray were noted in melanomas. With adjunctive dynamic RCM and major changes at DDF, sensitivity reached 100%, with 40.6% specificity. LIMITATIONS: Selected series of difficult to recognize lesions, with both DDF and dynamic RCM images. CONCLUSION: Adjunctive dynamic RCM improves early melanoma recognition sensitivity.

Self-reported measure of subjective distress in response to COVID-19 pandemic in patients referred to our skin cancer unit during the first wave.

During the Italian first wave of the COVID-19 pandemic, social restrictions and bad news spread daily by mass media inevitably had a huge influence on the mental state of the population. To assess how much the COVID-19 outbreak impacted the psychologic state of patients referring to our Skin Cancer Unit from March 9 to May 31, 2020, we administered to them a self-report questionnaire, the Impact of Event Scale-Revised (IES-R). To evaluate the trend of the IES-R score over time, we set a temporal cutoff of March 27 (the day with the highest number of deaths for COVID-19 in Italy during the first wave). Three hundred fifty-five patients completed the questionnaire, reporting an average IES-R score of 25.5 (±16.4); 32.4% of participants reached a total IES-R score >32. Patients who visited after March 27, 2020 reported a higher psychologic impact, since the IES-R score significantly increased from 23.6 (±15.6) to 28.3 (±17.2). A group reported higher scores (of participants reaching an IES-R score >32, 57.4% were women and 33.9% were men). We gathered that, at an early stage of events of this magnitude, it could be useful to submit the IES-R questionnaire in high-risk and oncologic patients: we could potentially identify individuals at risk of developing post-traumatic stress disorders, who might be tempted to postpone necessary medical consultations. This could be also the basis for increasing targeted psychologic support in selected patients.

The role of ultrasound examination for early identification of lymph-node metastasis of cutaneous squamous cell carcinoma: results from a single institutional center.

BACKGROUND: Metastasis from cutaneous squamous cell carcinoma (cSCC) mainly involve the regional nodal basin, with an incidence ranging from 2-4% until 15% in case of high-risk tumors. When dealing with high-risk cSCC, ultrasound examination is recommended every 3-4 months during follow-up. We aimed to determine the role of US examination in the early diagnosis of nodal metastasis from cSCC. METHODS: We conducted a retrospective cohort study enrolling consecutive cases of histopathologically verified cSCCs from January 2007 to March 2018. All the enrolled cases were followed for at least one year and all cases of histopathologically verified metastasis were registered. We also reported if ultrasound of the regional basin was performed between the primary diagnosis and metastasis and how the latter was identified, through ultrasounds or clinically. A Kaplan-Meier survival analysis was conducted on patients undergoing ultrasounds during follow-up. RESULTS: A total of 1881 cases, belonging to 1441 patients were included. Thirty-one cases of nodal metastasis diagnosed after the primary tumor, in as many patients, were identified. All of the selected metastasis derived from high-risk primary cSCCs. Only in 19 cases ultrasound examination was performed during follow-up; of these, 10 were diagnosed through ultrasounds and 9 clinically. Survival analysis demonstrated that the time interval between primary tumor and metastasis was significantly lower for patients with metastasis diagnosed by ultrasounds than clinically (P=0.036). CONCLUSIONS: Our study highlighted the need to optimize the use of nodal ultrasound examination for high-risk cSCCs in order to early detect metastasis.

Dark pigmented lesions: Diagnostic accuracy of dermoscopy and reflectance confocal microscopy in a tertiary referral center for skin cancer diagnosis.

BACKGROUND: There is lack of studies on the diagnostic accuracy of dermoscopy and reflectance confocal microscopy (RCM) for dark pigmented lesions. OBJECTIVE: To assess the diagnostic accuracy of dermoscopy plus confocal microscopy for melanoma diagnosis of dark pigmented lesions in real life. METHODS: Prospective analysis of difficult dark lesions with clinical/dermoscopic suspicion of melanoma referred for RCM for further analysis. The outcome could be excision or dermoscopic digital follow-up. RESULTS: We included 370 clinically dark lesions from 350 patients (median age, 45 y). Because of the clinical/dermoscopic/RCM approach, we saved 129 of 213 unnecessary biopsies (specificity of 60.6%), with a sensitivity of 98.1% (154/157). The number needed to excise with the addition of RCM was 1.5 for melanoma diagnosis. LIMITATIONS: Single institution based; Italian population only. CONCLUSIONS: This study showed that RCM coupled with dermoscopy increases the specificity for diagnosing melanoma, and it helps correctly identify benign lesions. Our findings provide the basis for subsequent prospective studies on melanocytic neoplasms belonging to patients in different countries.

Clinicopathological and dermoscopic features of amelanotic and hypomelanotic melanoma: a retrospective multicentric study.

BACKGROUND: Amelanotic and hypomelanotic melanoma (AHM) has a higher risk of delayed diagnosis and a significant lower 5-year melanoma-specific survival compared to pigmented melanoma. Our aim was the evaluation of the clinicopathological/dermoscopic features of amelanotic melanoma (AM) and hypomelanotic melanoma (HM). METHODS: All participants had a personal history of AHM. We defined HM as showing clinical/dermoscopic pigmentation in < 25% of the lesion's surface and histopathological focal pigmentation, while AM as melanomas with clinical/dermoscopic and histopathological absence of pigmentation. RESULTS: The most common phenotypic traits among the 145 AHM patients were as follows: phototype II, blue-grey eyes, and dark brown hair. Red hair was present in 23.8% AHM cases (AM = 22.60%; HM = 25.80%). The most affected area was the back (29.5%). A total of 67.1% were classified as AM and 32.9% as HM. The most represented hair colors in AM and HM were, respectively, blonde and dark brown hair. Median Breslow thickness was 1.7 mm, superficial spreading melanoma (SSM) and nodular melanoma (NM) were the most represented histotypes, and mitotic rate > 1 × mm2 was reported in 73.3% cases, and regression was significantly more present in HM. Dermoscopy showed high prevalence of white structureless zones (63.4%), linear looped vessels (58.8%), linear irregular vessels (50.0%), and arborizing vessels (47.2%). Multivariate logistic regression confirmed the association between the presence of pigmentation and the following: histological regression, dermoscopic globules, and arborizing vessels. CONCLUSIONS: Predominance of red hair in AHM patients was not confirmed. AHM affects mostly intermittent sun-exposed body areas. The deeper median Breslow thickness (versus pigmented melanoma), the association of AM with the nodular histotype, and the high mitotic rate highlight the AHM's aggressiveness. HM's higher levels of regression can be explained by the presence of pigmentation, driving the underlying immune response. AHM showed a polymorphous vascular pattern and significant presence of arborizing vessels (especially HM).

Treatment monitoring of 5-fluorouracil 0.5%/salicylic acid 10% lesion-directed therapy for actinic keratosis using dermoscopy and in-vivo reflectance confocal microscopy.

Recently, 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) topical solution has been included in the National Italian portfolio for lesion-directed treatment of grade I/II actinic keratosis (AKs) located on the face or scalp. To describe the utility of dermoscopy and RCM in treatment response monitoring of a series of AKs treated with 5-FU/SA as lesion-directed therapy. Consecutive patients were prospectively treated for a maximum of 12 weeks with 5-FU/SA for AKs located on the face or scalp. Clinical, dermoscopic, and confocal images of one index AK were acquired at each visit and pre-specified criteria were evaluated. Clinical, dermoscopic, and confocal responses were evaluated at last follow-up visit. Fourteen patients were enrolled, of which five were treated for 12 weeks, seven for 8, and two for 4 weeks. At a median follow up of 30 weeks, 64.3% (9/14) index AKs achieved complete clinical, 50% (7/14) complete dermoscopic and 42.9% (6/14) complete confocal clearance. Local skin reaction was mild and significantly decreased during therapy administration. Although the small number of cases, our study underlines the utility of both dermoscopy and in-vivo RCM in 5-FU/SA treatment response monitoring for AKs located on the face or scalp.

Clinical and Dermoscopic Features Associated With Difficult-to-Recognize Variants of Cutaneous Melanoma: A Systematic Review.

Importance: The clinical and dermoscopic features of the vast majority of uncommon variants of cutaneous melanoma have been rarely reported, leading to difficulty in making accurate diagnoses. Objective: To define the main clinical and dermoscopic features of the most frequently reported but uncommon histologic variants of cutaneous melanoma. Evidence Review: A 2-step systematic review of the literature was performed (from inception to November 2018) using PubMed, Embase, and Cochrane Central Register of Controlled Trials databases. The first step identified those uncommon variants of melanoma for which at least 1 case reporting dermoscopy was described in the literature. The keywords searched were melanoma, uncommon, rare, dermoscopy, and dermatoscopy. In the second step, each previously identified uncommon variant was searched for in the same databases by combining the following terms with melanoma, dermoscopy, and dermatoscopy: amelanotic, hypopigmented, animal, melanocytoma, balloon, desmoplastic, follicular, nested, nevoid, dermal, spitz*, spindle, and verrucous. The institution's database was also searched from January 2012 to September 2019 for histopathologically confirmed cases of the same melanoma variants. Each reviewer also assessed the quality of reporting in the included articles based on previously described guidelines. Findings: In total, 62 articles met the inclusion criteria, reporting 433 melanoma cases. An additional 56 cases of uncommon melanoma variants were retrieved from the institution's database for a total of 489 cases: 283 cases of amelanotic superficial spreading melanoma, 18 cases of animal-type and pigmented epithelioid melanocytoma, 7 cases of balloon cell melanoma, 71 cases of desmoplastic melanoma, 3 cases of follicular melanoma, 10 cases of nested melanoma, 33 cases of nevoid melanoma, 2 cases of primary dermal melanoma, 57 cases of spitzoid melanoma, and 5 cases of verrucous melanoma. These variants of melanoma occurred more frequently in women than men (147 cases vs 132 cases). Clinically, these tumors were mainly palpable (162 of 217 [74.7%]) or amelanotic (283 of 489 [57.9%]) lesions that could resemble other benign or malignant skin conditions; dermoscopy typically revealed a homogeneous pinkish background, white structures, and polymorphic vessels. The mean age of all included was 58 years (range, 1-89 years). Conclusions and Relevance: Uncommon melanoma variants may resemble both inflammatory disorders and other cutaneous neoplasms, representing a diagnostic pitfall even for the most experienced dermatologist. The purpose of this systematic review was to provide an extensive and detailed overview of specific clinical and dermoscopic features of each uncommon melanoma variant, highlighting the main criteria for differentiating these variants from other benign or malignant skin lesions.

Neck Melanoma: Clinical, Dermoscopic and Confocal Features.

BACKGROUND: The head and neck are considered one single anatomical unit. No data on clinical, dermoscopic and confocal aspects of neck melanoma are currently available. OBJECTIVES: To identify clinical, dermoscopic and confocal diagnostic features of neck melanomas. METHODS: Consecutive malignant (cases) and benign (controls) melanocytic skin lesions located on the neck, excised as suspected of being melanoma from March 2011 to February 2018, were retrospectively retrieved. Dermoscopic criteria of the 7-point checklist, integrated by other melanoma features (such as grey colour and irregular hyperpigmented areas) were assessed. Reflectance confocal microscopy (RCM) images were examined when available. RESULTS: 282 lesions located to the head and neck area were biopsied to rule out melanoma. Thirty-one out of 282 (11%) lesions were located on the neck: 21 melanomas and 10 naevi. Melanoma patients were older than patients with naevi (mean age: 60.4 vs. 37.9 years, p < 0.001). Neck melanomas were more frequently located on sun-damaged skin compared to naevi (76.2 vs. 30%, p = 0.02). Dermoscopically, neck melanomas were characterized by irregular dots/globules, grey colour and regression (76.2, 81 and 46.7% of cases) and showed criteria of lentigo maligna melanoma (LMM) in 52.4% of cases. Regression, grey colour, irregular hyperpigmented areas and criteria of LMM typified melanomas on sun-damaged skin, whereas tumours located on non-sun-damaged areas were often characterized by irregular pigmentation (blotches). RCM, implemented to dermoscopy, correctly diagnosed 10/12 melanomas and 3/5 naevi. CONCLUSION: Neck melanoma has peculiar clinical and dermoscopic aspects that could help clinicians to distinguish it from naevi and to diagnose melanoma earlier.

Merkel cell carcinoma arising on a pre-existing Bowen's disease: is it just by chance?

Merkel cell carcinoma (MCC) is a cutaneous carcinoma with neuroendocrine differentiation. It arises typically on sun-exposed areas of elderly men as an asymptomatic, rapidly growing, red nodule. Although it is usually found as a solitary nodule, in almost one third of cases MCC may be associated with other malignancies such as basal cell or squamous cell carcinomas. Merkel cell carcinoma should be considered as differential diagnosis every time we have a rapidly growing, red nodule, arising in an elderly patient with signs of sun-damage. We report a case of MCC developing in association with a pre-existing Bowen's disease. The association between MCC and Bowen's disease is quite common and their area of occurrence is usually a sun-exposed area. Ultraviolet radiation contributes to the etiology of both the malignancies.

Prevalence and risk factors of actinic keratosis in patients attending Italian dermatology clinics.

Actinic keratosis (AK) is a common keratinocyte intra-epidermal neoplasia. To assess AK prevalence and potential risk factors in patients attending Italian general dermatology clinics. This retrospective study was conducted on clinical data from consecutive white outpatients aged ≥30 years, attending 24 general dermatology clinics between December 2014 and February 2015. AK prevalence (entire population) and multivariate risk factor analysis (patients with current/previous AK and complete data) are presented. AK prevalence in 7,284 patients was 27.4% (95% CI: 26.4-28.4%); 34.3% in men and 20.0% in women (p<0.001). Independent AK risk factors in 4,604 patients were: age (OR: 4.8 [95% CI: 3.5-6.5] for 46-60 years, increasing with older age to OR: 41.5 [95% CI: 29.5-58.2] for >70 years), history of other non-melanoma skin cancers (OR: 2.7 [2.2-3.3]), residence in southern Italy/Sardinia (OR: 2.6 [2.1-3.0]), working outdoors >6 hours/day (OR: 1.9 [1.4-2.4]), male gender (OR: 1.7 [1.4-2.0]), facial solar lentigos (OR: 1.6 [1.4-1.9]), light hair colour (OR: 1.5 [1.2-1.8]), prolonged outdoor recreational activities (OR: 1.4 [1.2-1.7]), light eye colour (OR: 1.3 [1.1-1.6]), skin type I/II (OR: 1.3 [1.1-1.6]), and alcohol consumption (OR: 1.2 [1.0-3.3]). BMI ≥25.0 (OR: 0.6 [0.5-0.7]), regular sunscreen use (OR: 0.7 [0.6-0.8]), and a lower level of education (OR: 0.8 [0.7-1.0]) were independent protective factors. AK prevalence was high in Italian dermatology outpatients. We confirm several well-known AK risk factors and reveal possible novel risk and protective factors. Our results may inform on the design and implementation of AK screening and educational programmes.

Clinical Indications for Use of Reflectance Confocal Microscopy for Skin Cancer Diagnosis.

Importance: Reflectance confocal microscopy (RCM) improves diagnostic accuracy in skin cancer detection when combined with dermoscopy; however, little evidence has been gathered regarding its real impact on routine clinical workflow, and, to our knowledge, no studies have defined the terms for its optimal application. Objective: To identify lesions on which RCM performs better in terms of diagnostic accuracy and consequently to outline the best indications for use of RCM. Design, Setting, and Participants: Prospectively acquired and evaluated RCM images from consecutive patients with at least 1 clinically and/or dermoscopically equivocal skin lesion referred to RCM imaging, from January 2012 to October 2014, carried out in a tertiary referral academic center. Main Outcomes and Measures: A total of 1279 equivocal skin lesions were sent for RCM imaging. Spearman correlation, univariate, and multivariate regression models were performed to find features significantly correlated with RCM outcome. Results: In a total of 1279 lesions in 1147 patients, RCM sensitivity and specificity were 95.3% and 83.9%, respectively. The number of lesions needed to excise to rule out a melanoma was 2.4. After univariate and multivariate regression analysis, head and neck resulted as the most appropriate body location for confocal examination; RCM showed a high diagnostic accuracy for lesions located on sun-damaged skin (adjusted odds ratio [aOR], 2.13; 95% CI, 1.37-3.30; P=.001) and typified by dermoscopic regression (aOR, 2.13; 95% CI, 1.31-3.47; P=.002) or basal-cell carcinoma specific criteria (aOR, 9.35; 95% CI, 1.28-68.58; P=.03). Conclusions and Relevance: Lesions located on the head and neck, damaged by chronic sun-exposure, and dermoscopically typified by regression represent best indications for the use of RCM.

The extent of whole-genome copy number alterations predicts aggressive features in primary melanomas.

Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP-array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients.

Routine Clinical-Pathologic Correlation of Pigmented Skin Tumors Can Influence Patient Management.

BACKGROUND: Several studies have demonstrated the benefit of integrating clinical with pathologic information, to obtain a confident diagnosis for melanocytic tumors. However, all those studies were conducted retrospectively and no data are currently available about the role of a clinical-pathologic correlation approach on a daily basis in clinical practice. AIM OF THE STUDY: In our study, we evaluated the impact of a routine clinical-pathologic correlation approach for difficult skin tumors seen over 3 years in a tertiary referral center. RESULTS: Interestingly, a re-appraisal was requested for 158 out of 2015 (7.7%) excised lesions because clinical-pathologic correlation was missing. Of note, in 0.6% of them (13 out of 2045) the first histologic diagnosis was revised in the light of clinical information that assisted the Pathologist to re-evaluate the histopathologic findings that might be bland or inconspicuous per se. CONCLUSION: In conclusion, our study demonstrated that an integrated approach involving clinicians and pathologists allows improving management of selected patients by shifting from a simply disease-focused management (melanoma versus nevus) to a patient-centered approach.

Reasons for excision of skin tumors: a one-year prospective study in a tertiary skin cancer unit.

BACKGROUND: Biopsies and surgical excisions represent routine procedures in clinical settings dealing with skin cancer. OBJECTIVE: To evaluate the impact of clinical examination, dermoscopy, reflectance confocal microscopy and digital monitoring on the decision to excise or biopsy a lesion in routine practice. METHODS: Patients scheduled for biopsy or excision of a skin lesion were prospectively enrolled. The expert dermatologist was asked to select the main factor that prompted him/her to excise or biopsy the lesion. RESULTS: The most common reason for melanoma excision was clinical and dermoscopic morphology (70.3%), followed by dermoscopy (11.4%), monitoring (8.9%) and clinical context (8.2%). Most basal and squamous cell carcinomas were recognized both clinically and dermoscopically, while 18.6 and 15.0%, respectively, could only be detected with dermoscopic examination. CONCLUSION: Each part of the clinical examination has a contributory role in the diagnosis of melanoma and other skin cancers.