Elongated linear vessels simulating branching vessels and diffuse structureless orange areas as prominent dermoscopic features of diffuse flat facial and extrafacial granuloma faciale: A case series.

Dermoscopy can be an important help for the diagnosis of skin cancers and inflammatory cutaneous diseases. The list of the dermoscopic features reported in granuloma faciale is wide and includes vascular and non-vascular features. We report here three cases of diffuse flat facial and extrafacial granuloma faciale that exhibited elongated linear vessels simulating branching vessels and diffuse structureless orange areas. The differential diagnosis between flat-type granuloma faciale, basal cell carcinoma and cutaneous sarcoidosis can be extremely difficult, making histology mandatory before any treatment.

Amelanotic/hypomelanotic lentigo maligna: Dermoscopic and confocal features predicting diagnosis.

BACKGROUND: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage. OBJECTIVES: To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM. METHODS: Dermoscopic and RCM images of histopathologically diagnosed AHLM/LMM, amelanotic/hypomelanotic benign lesions (AHBL), and amelanotic/hypomelanotic basal and squamous cell carcinomas (AHBCC/AHSCC) of the head and neck from consecutive patients were retrospectively collected and blindly evaluated by three observers to assess presence or absence of dermoscopic and RCM criteria. RESULTS: Overall, 224 lesions in 216 patients including LM/LMM (n = 55, 24.6%), AHBL (n = 107, 47.8%) and AHBCC/AHSCC (n = 62, 27.7%) were analysed. Multivariable analysis showed that milky-red areas (OR = 5.46; 95% CI: 1.51-19.75), peripheral light brown structureless areas (OR = 19.10; 4.45-81.96), linear irregular vessels (OR = 5.44; 1.45-20.40), and asymmetric pigmented follicles (OR = 14.45; 2.77-75.44) at dermoscopy, and ≥3 atypical cells in five fields (OR = 10.12; 3.00-34.12) and focal follicular localization of atypical cells at dermo-epidermal junction (DEJ) (OR = 10.48; 1.10-99.81) at RCM were significantly independent diagnostic factors for AHLM/LMM vs. AHBL. In comparison with AHBCC/AHSCC, peripheral light brown structureless area (OR = 7.11; 1.53-32.96), pseudonetwork around hair follicles (OR = 16.69; 2.73-102.07), and annular granular structures (OR = 42.36; 3.51-511.16) at dermoscopy and large dendritic (OR = 6.86; 3.15-38.28) and round pagetoid cells (OR = 26.78; 3.15-227.98) at RCM led to a significantly increased risk of diagnosing AHLM/LMM. CONCLUSIONS: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma may have the same dermoscopic features of AHM on other body sites, such as milky red areas, peripheral light brown structureless areas and linear irregular vessels. These features, asymmetric pigmented follicles and at RCM ≥ 3 atypical cells in five fields and focal follicular extension of atypical cells at DEJ may help in recognizing AHLM/LMM even when LM conventional features (e.g., obliteration of hair follicles under dermoscopy and large pagetoid cells under RCM) are absent or present only in very small areas of the lesion.

Cutaneous side effects and types of dermatological reactions in metastatic melanoma patients treated by immunotherapies or targeted therapies: A retrospective single center study.

Immunotherapy and target therapy have revolutionized treatment of stage III/IV melanoma. Both treatments show a favorable toxicity profile even if cutaneous adverse events (AEs) are frequent (30%-40% of cases). This is a retrospective single center cohort study that included patients with stage IV or inoperable stage III metastatic melanoma (AJCC 8th) who received BRAFi + MEKi therapy or immunotherapy with Checkpoint inhibitors. All cutaneous AEs were ascertained by a dermatologist based on clinical and histological findings. The primary outcome was to provide a detailed clinical dermatological classification of cutaneous adverse events and an evaluation of the incidence of skin toxicity in the two arms of therapy (immunotherapy and target therapy). A total of 286 patients with stages III-IV metastatic melanoma were included: 146 received immunotherapy and 140 target therapy. In the immunotherapy cohort, 63 (43.1%) cutaneous reactions were observed while 33 skin reactions (23.6%) were identified in patients treated with target therapy. All the skin toxicities observed were grade I, excepted four cases: an erythema multiforme-like eruption, a grade III psoriasis and two grade III maculopapular rashes. Immunotherapy in older age resulted statistically related to skin toxicities (p = 0.011), meanly in metastatic setting (p = 0.011). Cumulative incidence of skin toxicities was 65.63% in immunotherapy cohort (p = 0.001). Also multivariate logistic regression shows a significant association between skin adverse events and immunotherapy (odds ratio [OR] = 0.50; 95% confidence interval [CI]: 0.29-0.85, p: 0.01) and between cutaneous AEs and metastatic setting (OR = 1.97; 95% CI: 1.04-3.74, p: 0.04). We have also shown that as the age of initiation of therapy increases the probability of developing skin toxicity grows. However, stratifying by type of therapies the effect of age persists only in immunotherapy (OD: 1.04; CI: 1.01-1.06; p: 0.04) while for target therapy age does not affect the onset of skin toxicity (OD 1.01; CI 0.98-1.04; p = 0.42). No differences were shown between patients on target therapy and immunotherapy regarding gender. Patients were also evaluated regarding concomitant therapies and seems that Levotyroxine may be involved in AEs during immunotherapy treatment. More studies are needed to deepen this aspect, also considering the medical history and diverse drug associations. Cutaneous adverse events are characterized by heterogeneous manifestations, are more often seen in patients on immunotherapy and dermatologists can play a crucial role in multidisciplinary care.

To what extent is quality of life impaired in vitiligo? A multicenter study on Italian patients using the dermatology life quality index.

BACKGROUND: It is believed that vitiligo has an impact on the overall patient quality of life (QoL). OBJECTIVE: To estimate QoL in a fairly large sample of Italian vitiligo patients by using the Dermatology Life Quality Index (DLQI) questionnaire. METHODS: One hundred and sixty-one vitiligo patients referred to 9 dermatological centers were offered to participate by filling in the Italian version of the DLQI questionnaire. RESULTS: The mean total DLQI score was 4.3 (SD ±4.9; range: 0-22). In multivariate analysis, DLQI >5 was associated with female gender, stability of the disease over time and involvement of the face at disease onset. CONCLUSIONS: The impairment of QoL is overall limited in Italian vitiligo patients, especially if it is compared with results from other available studies. This could be due to cultural and ethnic characteristics of the sample.

Subungual Metastasis from Ovarian Cancer: Case Report and Brief Review of the Literature.

Introduction: Visceral solid cancers can metastasize in almost any organ, including the skin and its appendages. Case Presentation: We report here the case of a 19-year-old Caucasian girl carrying a diagnosis of malignant germ cell tumor of the ovary, with pulmonary and brain metastases, that developed a painful red-violaceous subungual papule of the 4th finger of the left hand, associated with an over-curvature of the nail plate. Dermoscopy was characterized initially by different shades of pink and red, while after few weeks, it showed black pigmentation due to subcorneal hematomas, hemorrhagic crusts, and a rainbow pattern. Histology confirmed a diagnosis of a metastasis from a poorly differentiated carcinoma of ovarian origin. Discussion and Conclusion: A brief review on the diagnosis and treatment of subungual metastases is reported.

Is Pediatric Melanoma Really That Different from Adult Melanoma? A Multicenter Epidemiological, Clinical and Dermoscopic Study.

PURPOSE: To improve the diagnostic accuracy and optimal management of pediatric melanomas. METHODS: We conducted a retrospective descriptive, multicenter study of the epidemiological, clinical, and dermoscopic characteristics of histopathologically proven melanomas diagnosed in patients less than 18 years old. Data on sociodemographic variables, clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, and outcome were collected from the databases of three Italian dermatology units. We performed a clinical evaluation of the morphological characteristics of each assessed melanoma, using both classic ABCDE criteria and the modified ABCDE algorithm for pediatric melanoma to evaluate which of the two algorithms best suited our series. RESULTS: The study population consisted of 39 patients with a histologically confirmed diagnosis of pediatric melanoma. Comparing classic ABCDE criteria with the modified ABCDE algorithm for pediatric melanomas, the modified pediatric ABCDE algorithm was less sensitive than the conventional criteria. Dermoscopically, the most frequent finding was the presence of irregular streaks/pseudopods (74.4%). When evaluating the total number of different suspicious dermoscopy criteria per lesion, 64.1% of the lesion assessments recognized two dermoscopic characteristics, 20.5% identified three, and 15.4% documented four or more assessments. CONCLUSIONS: Contrary to what has always been described in the literature, from a clinical point of view, about 95% of our cases presented in a pigmented and non-amelanotic form, and these data must be underlined in the various prevention campaigns where pediatric melanoma is currently associated with a more frequently amelanotic form. All the pediatric melanomas analyzed presented at least two dermoscopic criteria of melanoma, suggesting that this could be a key for the dermoscopic diagnosis of suspected pediatric melanoma, making it possible to reach an early diagnosis even in this age group.

A retrospective observational study on cutaneous adverse events induced by immune checkpoint inhibitors.

BACKGROUND: Cutaneous adverse events (CAEs) related to oncological therapies are a common scenario in daily clinical practice. METHODS: This is a retrospective observational study collecting the data regarding CAEs of patients treated with immune checkpoints inhibitors (ICIs) in four different Italian centers. RESULTS: Of 323 patients included, 305 were evaluable for this analysis; 182 patients (59.7%) had metastatic cutaneous melanoma (CM), 99 (32.5%) non-small cell lung cancer (NSCLC) and 24 (7.8%) renal cell carcinoma (RCC). The most frequent CAEs that we found, considering all the 305 patients, were pruriginous maculopapular rash (10.2% of the patients), vitiligo-like areas (7.2% of the patients), psoriasiform rash (6.2% of the patients), asymptomatic maculopapular rash (4.6% of the patients), and lichenoid rash (4.3% of the patients). Vitiligo-like areas occurred more frequently in patients with CM, while a lichenoid rash was more frequently observed in patients with RCC. Treatment interruption was related to drug-induced CAEs in 15.4% of melanoma patients and 0.0% of lung and kidney patients. Patients developing a cutaneous adverse event had better overall response rate and higher progression free survival and overall survival than the patients without CAEs. CONCLUSIONS: Our study brings new information on the characteristics of CAEs related to ICIs treatment in three different types of cancers, CM, NSCLC and RCC.

Clinical characteristics of Becker's nevus in children: report of 118 cases from Italy.

We performed a retrospective study covering a 10-year period (January 1997-January 2007) on children referred to our unit or followed up for Becker's nevus (BN). The aim of this study was to better define the characteristics of BN in childhood, when this hypermelanosis is more frequent than the limited number of studies might suggest. Our data show that BN in children has predilection sites similar to those in adults, but hypertrichosis is rarer. Sun exposure does not appear to play an etiopathogenetic role. The higher incidence in men reported in adult case studies was not found in children. During and after puberty, androgenic stimulation is known to play a pathogenetic role in BN, especially in men, but our cases were mostly younger than 6 years old.

Long-term vemurafenib therapy in advanced melanoma patients: cutaneous toxicity and prognostic implications.

BACKGROUND: The introduction of targeted therapies for the treatment of BRAF-mutated metastatic melanoma was associated with different cutaneous adverse events (AEs). OBJECTIVES: To describe the type, frequency and severity of cutaneous AEs related to vemurafenib; to understand the association between AEs and vemurafenib efficacy in terms of median overall survival (OS) and median progression-free survival (PFS); to identify molecular characteristics of long-term responders. METHODS: This observational, retrospective, monocentric study included all consecutive patients with unresectable stage III or stage IV melanoma and BRAF V600E mutation that started treatment with vemurafenib between May 2012 and May 2014. RESULTS: 62 patients with a median age of 56 years (range 26-82) were enrolled and received vemurafenib for a median period of 7.9 months (range 0.8-63.7). Among them, 45 patients presented at least one skin AE, 12 reduced the dosage due to cutaneous toxicity, and only one firstly reduced and after stopped the therapy. No specific molecular biomarkers were detected in long-term survivors. CONCLUSIONS: Among long-term survivors, skin AEs seem to be less frequent and less severe. Results on multivariable analysis revealed that the presence of at least one G2 toxicity is a protective factor considering PFS, but not in terms of OS.

Vitiligo-like lesions in a patient treated with nivolumab for renal cell carcinoma.

RATIONALE: The introduction of immune check-point inhibitors (ICIs) in the treatment of solid neoplasms is associated with the need to know and manage a new type of side effects that are commonly defined immune-mediated adverse events. Dermatologic immune-mediated adverse events are relatively common. Vitiligo-like lesions, defined as hypopigmented skin lesions, have already been associated with the use of ICIs in particular in patients with malignant melanoma, probably due to a common autoimmune mechanism against both melanoma cells and normal melanocytes. The onset of vitiligo-like lesions is very rare in non-melanoma patients and nowadays only few cases are described in the literature. PATIENT CONCERNS: We described the case of a heavily pre-treated woman affected by renal cell carcinoma that has been treated with nivolumab for 2 years obtaining a stabilization of disease after an initial mild progression. After 9 months from the beginning of nivolumab, when the disease has reached its maximum stabilization, the patient developed vitiligo-like lesions of the back win halo nevi. DIAGNOSES: Vitiligo like lesion of the back not pre-existing before nivolumab treatment. The etiology was assumed to be nivolumab related as a result of an autoimmune activation against normal melanocytes. INTERVENTIONS: The patient was followed with dermatological evaluations without changes in nivolumab dose and schedule OUTCOMES:: No variations of the described lesions were recorded after the first description. The patients underwent a durable stabilization of her tumor. LESSONS: This case on the one hand is the first case of vitiligo-like lesions associated with ICIs in patients affected by renal cell carcinoma, and on the other hand it seems to confirm that the onset of immumomediate adverse reactions, but in particular vitiligo lesions, can probably be considered a sign of response to immunological treatments probably as a consequence of activation of the immune response.

Correlation of Stomatitis and Cutaneous Toxicity With Clinical Outcome in Patients With Metastatic Renal-Cell Carcinoma Treated With Everolimus.

BACKGROUND: In clinical practice, discontinuation or dose reduction of everolimus may be induced not only by grade 3 or 4 toxicities but also by prolonged grade 2 toxicities, such as stomatitis and/or cutaneous toxicity, which share some pathogenetic mechanisms. We assessed the correlation between either everolimus discontinuation or dose reduction induced by stomatitis-cutaneous toxicity events (SCTE) and clinical outcome of patients with metastatic renal-cell cancer (mRCC). PATIENTS AND METHODS: We retrospectively reviewed the clinical data of patients with mRCC treated with everolimus in 2 Italian centers. Clinical evidence of SCTE was evaluated, and corresponding clinical data were reviewed for response and clinical outcome. RESULTS: Seventy-nine mRCC patients treated with everolimus (57 male, 22 female; median age 66 years; range, 44-88 years) were evaluated. SCTE were observed in 20 (25%) of 79 patients at a median of 30.5 days of everolimus treatment (range, 10-270 days). Partial response or stable disease was achieved in 15 (79%) of 19 evaluable patients with SCTE compared to 28 (48%) of 58 with no SCTE (P = .03). At a median follow-up of 19 months, a significant difference was found in the median PFS equal to 7.8 months (95% confidence interval [CI], 2.8-24.4) in SCTE patients versus 4.3 months (95% CI, 2.7-7.5) in non-SCTE patients (P = .029), and in the median OS equal to 30.6 months (95% CI, 19.6-not reached) in SCTE patients versus 13.5 months (95% CI, 9.9-17.7) in non-SCTE patients (P = .0007). CONCLUSION: These data suggest that SCTE may be a predictive marker of favorable outcome in mRCC patients treated with everolimus.

Parental Use and Educational Campaigns on Sunbed Use Among Teenagers and Adolescents.

This study aimed to evaluate the prevalence of sunbed use among teenagers and the association between familial behavior and the adoption of UV-protective practices in this age group. We also assessed the impact of an educational program on students' knowledge about the potential risks of sunbed use. The educational intervention focused on: (i) skin effects of UV radiation, (ii) photoaging and photocarcinogenesis, (iii) risk factors for skin cancer, (iv) indoor sun tanning and misleading concepts such as possible protective effect of sunbed use on skin cancer risk, (v) sun protection and relation with skin phototype, and (vi) early diagnosis of melanoma using the ABCDE check list and the ugly duckling sign. We carried out a survey of 3098 students and found a strong association between parental sunbed use and students' use of the same (P < 0.0001). Students who attended the educational intervention were more aware that sunbed use cannot prevent sunburns (P = 0.03) than those who did not attend, making adjustments for confounding variables. However, sunbed use by parents influenced the desire to use a sunbed more than participation in the educational intervention (P < 0.0001). In conclusion, although our results indicate that educational interventions can improve knowledge of the risk of sunbed use. They also reveal a strong correlation between sunbed use by teenagers and parental behavior that highlights the importance of educational interventions involving families.

Melanoma attributable to sunbed use and tan seeking behaviours: an Italian survey.

Melanoma is the most deadly form of skin cancer and its incidence is increasing worldwide. In 2009, the International Agency for Research on Cancer classified the entire UV spectrum as carcinogenic. In many countries, including Italy, the use of tanning equipment by minors and individuals with high risk phenotypes has been banned. This study assessed tan-seeking behaviour in a Mediterranean population with a relatively high melanoma incidence, where a considerable time is spent tanning outdoors. Subjects spending the most time in the sun were typically young single men, who use significantly less sunscreen and sunglasses. The overall prevalence of sunbed use was 22% in youth (≤35 years old) and 18% of them used sunbeds throughout the year. Sunbed use in youth was greater for phenotypes at risk. In Italy, 3.8% of melanoma cases are attributable to sunbed use, more in women (4.2% vs 3.1%, for women and men respectively) and much more in the young (17%). Of 8013 new melanoma cases in 2008 in Italy, 293 were attributable to sunbed use, with a high proportion of these in women (168) and 1045 were attributable to sun exposure. Among youth, 172 cases were attributable to sunbed use and 140 exclusively to sunbed use. This analysis reveals that a large number of cancers each year in Italy could be avoided by changing cultural attitudes to tanning. Sun avoidance and protection is generally inadequate in adults, especially young men. These results have important implications for the primary prevention of melanoma.

Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis.

Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60-3.53) and 1.64 (95% CI 1.02-2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63-1.13) for CM and 1.03 (95% CI 0.95-1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.

Evaluation of the antibacterial activity of a special silk textile in the treatment of atopic dermatitis.

BACKGROUND: Increased skin Staphylococcus aureus colonization is frequently found in atopic patients. The reduction of local overinfection decreases skin inflammation and improves the flares. OBJECTIVE: To evaluate the effectiveness of the antimicrobial activity of a silk fabric (MICROAIR DermaSilk) coated with alkoxysilane quaternary ammonium with durable antimicrobial properties (AEGIS AEM 5572/5) in children affected by atopic dermatitis (AD). METHODS: Sixteen children, 12 affected by AD with symmetric eczematous lesions on the antecubital areas and 4 without any cutaneous disease, used, for 7 days, tubular arm covers made of this special silk fabric but only one of each pair was coated with AEGIS AEM 5572/5. Microbiological examinations were done with standard cultural swabs and by means of quantification of bacterial agents using agar plates at baseline, after 1 h and after 7 days. RESULTS: After 7 days a significant improvement in the mean value of the 'local SCORAD' index was observed in both the covered areas compared to the values obtained at baseline. The reduction in the mean number of colony forming units per square centimetre was similar in both areas. CONCLUSIONS: Although this special silk fabric seems to be able to improve skin lesions in AD, we were unable to demonstrate that such silk fabrics coated with AEGIS AEM 5572/5 have an antibacterial activity in vivo, as shown in vitro.

Purpura after application of EMLA cream in two children.

The eutectic mixture of local anesthetic cream, a 1 : 1 mixture of prilocaine and lidocaine, 2.5% each, is frequently used in pediatric and dermatologic practice to obtain local anesthesia. Side effects include transient skin blanching, erythema, urticaria, allergic contact dermatitis, irritant contact dermatitis, hyperpigmentation, and purpura. We report two children with a purpuric reaction after application of this mixture cream. Purpura after application of this anesthetic cream is a rare nonallergic reaction and only 17 occurrences have been reported, to our knowledge, in the literature. Patch tests could not be performed in our two patients because of lack of parental consent but we suggest that the purpuric reactions were most probably of toxic origin. The pathogenesis of purpura after application of eutectic mixture of local anesthetics cream, which resolves within 2 weeks without dermatologic sequelae and without any specific therapy, is complex. The lesions are probably caused by the direct effect of the cream components on the vessels but many other factors, such as atopic dermatitis, prematurity, subjective predisposition to purpura, trauma, and thrombocytopenia may play important pathogenetic roles.