Epidemiological and clinical analysis of exposure-related factors in non-melanoma skin cancer: A retrospective cohort study.

BACKGROUND: The incidence of non-melanoma skin cancers (NMSCs) increased over last decades, probably due to environmental concerns or to the increase of frail patients with age related comorbidities. Currently, the relationship of increasing global skin cancer rates with increased ultraviolet radiations (UVRs) resulting from stratospheric ozone depletion, global warming, and air pollution from fossil-fuel combustion. AIMS: We conducted a retrospective epidemiological study including 546 NMSC patients managed at the Dermatology Unit of the Tor Vergata Hospital to highlight different trends of sun exposure or different comorbidities. METHODS: Descriptive and inferential statistical analyses were performed to evidence differences between continous variable and Spearman rank test for dicotomical variables. Charlson Comorbidity Index was calculated to obtain the 10-years survival rate in order to identify the mean comorbidity burden of our patients. RESULTS: Considering patients with comorbidities (73.81%), actinic keratoses (AKs) was the most frequent lesion. In patients with a history of previous melanoma, basal cell carcinoma (BCC) was predominant (ANOVA test, p < 0.05) with a statistically significant correlation (rho = 0.453; p < 0.01). Squamous cell carcinoma (SCC) showed a higher rate in arterial hypertension patients, followed by the chronic heart failure and hematologic neoplasms (60%, 29.7% and 32.1%, respectively) groups. Men were more affected than women, representing 61.54% of patients. Chronic sun exposure is directly correlated with SCC rho = 0.561; p < 0.01), whereas BCC correlated with a history of sunburns (rho = 0.312; p < 0.05). CONCLUSIONS: History of photo-exposition had an important role on NMSC development especially for work or recreational reasons. Sex, age, and presence of comorbidities influenced different NMSC types. BCC was more frequent in younger patients, associated with melanoma and sunburns. The presence of SCC is associated with older patients and the hypertension group. AKs were diagnosed predominantly in oldest men, with a chronic sun-exposure history, and hematologic neoplasms group.

Basosquamous carcinoma: Comprehensive epidemiological, clinical, dermoscopic, and confocal features from a single center institution.

BACKGROUND: Basosquamous carcinoma (BSC) is a rare and aggressive nonmelanoma skin cancer (NMSC) that exhibits features of both BCC and squamous cell carcinoma (SCC). The gold standard for diagnosis is histopathological examination. BSC is often challenging to diagnose and manage due to its mixed histological features and potential for aggressive behavior AIM: To identify specific features aiding clinicians in differentiating BSCs using non-invasive diagnostic techniques. METHODS: We conducted a retrospective descriptive, monocentric study of the epidemiological clinical, dermoscopic, and reflectance confocal microscopy (RCM) features of histopathologically proven BSCs diagnosed between 2010 and 2023. A total of 192 cases were selected. RESULTS: The study population consisted of 17 men (60.9%). Total 95.8% of patients at the time of diagnosis were ≥50 years. BSC occurred in the head and neck area in 124 cases (63.1%) of which 65 (33.9%) were in the H-zone. For 47.4% of patients, BSC presented as a macule with undefined clinical margins (43.3%). Dermoscopic images were available for 98 cases: the most common parameter was the presence of whitish structureless areas (59 [60.2%]), keratin masses (58 [59.2%]), superficial scales, and ulceration or blood crusts (49 [50%] both). Vessels pattern analysis revealed hairpin vessels (exclusively) and linear irregular vessels as the most frequent (55 [56.1%] both). RCM examination was performed in 21 cases which revealed specific SCC features such as solar elastosis (19 [90.5%]), atypical honeycomb pattern (17 [89%]), proliferation of atypical keratinocytes (16 [80%]) combined with BCC' ones as bright tumor islands (12 [57.8%]), and cleft-like dark spaces (11 [53.4%]). DISCUSSION: Our study reflects the largest cohort of BSCs from a single institution. We described an incidence rate of 4.7%, higher than reported in the Literature, with the involvement of patients ≥50years in almost 96% of cases and an overall male predominance. At clinical examination, BSC was described as a hyperkeratotic macule with undefined clinical margins with one or more dermoscopic SCC' features, whereas the presence of typical BCC aspects was observed in less than 10% of cases, differently from what was previously reported. At RCM analysis, BSCs presented with an atypical honeycomb pattern with proliferation of atypical keratinocytes, hyperkeratosis, and in nearly 55% of patients, bright tumor islands with cleft-like dark spaces. CONCLUSION: The distinctive dermoscopic patterns, along with the RCM features aid in the differentiation of BSCs from other NMSCs.

Dermoscopy of atypical pigmented lesions of the face: Variation according to facial areas.

Atypical pigmented facial lesions (aPFLs)-including lentigo maligna (LM) and lentigo maligna melanoma (LMM), solar lentigo (SL), pigmented actinic keratosis (PAK), atypical nevi (AN), seborrheic keratosis (SK) and lichen planus-like keratosis (LPLK)-can exhibit clinical and dermoscopic overlapping features. We aimed to investigate if and how 14 dermoscopic features suggestive for the aforementioned aPFLs vary according to six facial sites among 1197 aPFLs cases (excised to rule out malignancy) along with lesion and patients' metadata. According to distribution and association analysis, aPFLs on the forehead of a male patient aged > 69 years displaying the obliterated follicular openings pattern, appear to be more at risk of malignancy. Of converse, aPFLs of the orbital/cheek/nose area with evident and regular follicular openings with diameter < 10 mm in a female aged below 68 are probably benign. The obliterated follicular openings, keratin plugs, evident and regular follicular openings and target-like pattern features differed significantly among six facial areas in all aPFLs cases. Lesion of the nose may show both features suggestive of malignancy and benignity (e.g. many SL and PAK may display target-like pattern and some LM/LMM cases display keratin plugs and evident and follicular openings), making these features less specific.

Follicular colonization in melanocytic nevi and melanoma: A literature review.

The lentiginous spread of melanocytes into the hair follicle can be observed in a number of benign melanocytic neoplasms such as in nevi but also in sun-induced melanocytic hyperplasia and melanoma. The follicular colonization by melanocytes in melanoma is classified into three distinct patterns: primary follicular melanoma, melanoma with folliculotropism, and invasive melanoma arising from melanoma in situ with folliculotropism. The role of follicular colonization in melanoma pathologic staging is still a matter of debate though the description of the latter has been recommended by the International Collaboration on Cancer Reporting. In this review, we will discuss the role of follicular colonization in melanoma and melanocytic nevi as well as the facts and controversies regarding this topic.

Advanced Cutaneous Squamous Cell Carcinoma: Italian Multicentric Retrospective Analysis of Patient Profiles and Therapeutic Approaches.

BACKGROUND: Advanced cutaneous squamous cell carcinoma (aCSCC) represents an area of unmet clinical need, with no standardized treatments until the recent approval of immune checkpoint inhibitors (ICIs). OBJECTIVES: The aim of the study was to describe clinical characteristics and therapeutic strategies of a real-life Italian cohort of aCSCC patients managed at the beginning of cemiplimab approval as compassionate use in Italy. METHODS: A multicenter retrospective study was performed by 10 Italian centers in the period January 1, 2018-May 31, 2020. Patients aged ≥18 years and diagnosed with aCSCC (locally aCSCC and metastatic CSCC) were eligible for the study. Analysis of patients' characteristics and treatment strategies was performed. RESULTS: 239 patients were initially recruited in the study: 19 patients were excluded due to incomplete data collection, yielding a final cohort of 220 patients, of which 191 and 220 were included for patients' clinical characteristics and therapeutic intervention analysis, respectively. Median age at the time of diagnosis was 81 years (range: 72-86); nodal metastases were detected in 64/220 (29%) patients, and distant metastatic spread was reported in 33/220 (15%) patients. Most of our patients referred chronic occupational and/or recreational sun exposure, experienced ≥1 sunburn during their lifetime, never wore hats or used photoprotective filters, and presented with signs of cumulative sun damage (solar lentigines and/or actinic keratosis). Majority of our cohort received at least one intervention directed to the primary tumor (n = 212, 96.3%); surgery and radiotherapy were the most common therapeutic choices. Immunotherapy was administered to a small number of patients as compassionate use, especially in the metastatic setting. CONCLUSIONS: Our study outlines the complex and heterogeneous clinical and therapeutic landscape of aCSCC patients at the beginning of ICI era, highlighting the need of a standardized care for this fragile and high-need patient population.

Clinical Characteristics of an Italian Patient Population with Advanced BCC and Real-Life Evaluation of Hedgehog Pathway Inhibitor Safety and Effectiveness.

BACKGROUND: Advanced basal cell carcinoma (aBCC) represents a complex and clinically heterogeneous group of lesions for which curative surgery and/or radiotherapy is unlikely. Systemic therapy with hedgehog pathway inhibitors (HHIs) changed the treatment landscape for this complex patient population. OBJECTIVES: The aims of the present study are to describe the clinical characteristics of a real-life Italian cohort diagnosed with aBCC and to investigate effectiveness and safety of HHI. METHODS: A multicenter observational study was performed by twelve Italian centers in the period January 1, 2016 - October 15, 2022. Patients aged ≥18 years and diagnosed with aBCC (locally advanced [laBCC] and metastatic BCC [mBCC]) were eligible for the study. Methods for investigating tumor response to HHI included clinical and dermatoscopic evaluation, radiological imaging, and histopathology. For HHI safety assessment, therapy-related adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: We enrolled 178 patients under treatment with HHI: 126 (70.8%) and 52 patients (29.2%) received sonidegib and vismodegib, respectively. Comprehensive data on HHI effectiveness and disease outcome were available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of laBCC (n = 84, sonidegib; n = 45, vismodegib) and 3 patients of mBCC (n = 2, vismodegib; n = 1, sonidegib, off-label). Objective response rate was 76.7% (95% confidence interval [CI]: 82.3-68.7) and 33.3% (95% CI: 88.2-1.7) for laBCC (complete response [CR]: 43/129; PR: 56/129) and mBCC (CR: 0/3; PR: 1/3), respectively. High-risk aBCC histopathological subtypes and occurrence of >2 therapy-related AEs were significantly associated with nonresponse to HHI therapy ([OR: 2.61; 95% CI: 1.09-6.05; p: 0.03] and [OR: 2.74; 95% CI: 1.03-7.9; p: 0.04]), respectively. Majority of our cohort (54.5%) developed at least 1 therapy-related AE, most of which were mild-moderate in severity. CONCLUSIONS: Our results demonstrate the effectiveness and safety profile of HHI and confirm the reproducibility of pivotal trial results in real-life clinical setting.

Occupational exposure to arsenic, mercury and UV radiation and risk of melanoma: a case-control study from Italy.

BACKGROUND: Melanoma is mainly caused by sunlight radiation, but other environmental risk factors are not well known. We investigated the association between cutaneous melanoma and occupational exposure to arsenic, mercury and UV radiation. METHODS: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 frequency-matched controls. Detailed sociodemographic, clinical and host-related factors were collected, and all participants were physically examined using dermoscopy and following standard protocol for recording pigmented lesions. Four experts assessed exposure to arsenic, mercury and UV radiation based on occupational history. A multidimensional variable was created for each risk factor, by combining intensity and probability of exposure. Multivariable logistic regression models were run to calculate odds ratios (OR) and 95% confidence intervals (CI) of the association between exposure to these agents and melanoma. RESULTS: A total of 5.4% of the cases vs 2.4% of the controls were exposed to arsenic (OR = 3.12; 95% CI = 1.10-8.86 for high probability and high exposure to arsenic) after controlling for sex, age, smoking status, number of nevi, phototype and history of sunburns in childhood/adolescence. Occupational exposure to mercury and UV radiation was not associated with the risk of melanoma. CONCLUSIONS: Subjects exposed to arsenic at the workplace may be at increased risk of developing cutaneous melanoma in comparison to subjects not exposed to this agent. Further studies should be designed to investigate occupational exposure to arsenic and mercury and melanoma and confirm the findings are warranted.

A risk-scoring model for the differential diagnosis of lentigo maligna and other atypical pigmented facial lesions of the face: The facial iDScore.

BACKGROUND: Due to progressive ageing of the population, the incidence of facial lentigo maligna (LM) of the face is increasing. Many benign simulators of LM and LMM, known as atypical pigmented facial lesions (aPFLs-pigmented actinic keratosis, solar lentigo, seborrheic keratosis, seborrheic-lichenoid keratosis, atypical nevus) may be found on photodamaged skin. This generates many diagnostic issues and increases the number of biopsies, with a subsequent impact on aesthetic outcome and health insurance costs. OBJECTIVES: Our aim was to develop a risk-scoring classifier-based algorithm to estimate the probability of an aPFL being malignant. A second aim was to compare its diagnostic accuracy with that of dermoscopists so as to define the advantages of using the model in patient management. MATERIALS AND METHODS: A total of 154 dermatologists analysed 1111 aPFLs and their management in a teledermatology setting: They performed pattern analysis, gave an intuitive clinical diagnosis and proposed lesion management options (follow-up/reflectance confocal microscopy/biopsy). Each case was composed of a dermoscopic and/or clinical picture plus metadata (histology, age, sex, location, diameter). The risk-scoring classifier was developed and tested on this dataset and then validated on 86 additional aPFLs. RESULTS: The facial Integrated Dermoscopic Score (iDScore) model consisted of seven dermoscopic variables and three objective parameters (diameter ≥ 8 mm, age ≥ 70 years, male sex); the score ranged from 0 to 16. In the testing set, the facial iDScore-aided diagnosis was more accurate (AUC = 0.79 [IC 95% 0.757-0.843]) than the intuitive diagnosis proposed by dermatologists (average of 43.5%). In the management study, the score model reduced the number of benign lesions sent for biopsies by 41.5% and increased the number of LM/LMM cases sent for reflectance confocal microscopy or biopsy instead of follow-up by 66%. CONCLUSIONS: The facial iDScore can be proposed as a feasible tool for managing patients with aPFLs.

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.

Pyodermitis during Nivolumab Treatment for Non-Small Cell Lung Cancer: A Case Report and Review of the Literature.

Immunotherapy in oncology is replacing traditional therapies due to it specific action and limited side effects. Despite the high efficacy of immunotherapy, side effects such as bacterial infection have been reported. Bacterial skin and soft tissue infections represent one of the most important differential diagnoses in patients presenting with reddened and swollen skin and soft tissue. Among these infections, cellulitis (phlegmon) and abscesses are the most frequent. In most cases, these infections occur locally with possible contiguous spread, or as a multifocal manifestation, especially in immunocompromised patients. Herein, we report a case of pyodermitis in an immunocompromised district in a patient treated with nivolumab for non-small cell lung cancer. A 64-year-old, smoker male patient showed cutaneous lesions at a different evolution level in the left arm, all in a tattooed area, with one phlegmon and two ulcerated lesions. Microbiological cultures and gram staining revealed an infection caused by a methicillin-susceptible but erythromycin-resistant (ER-R), clindamycin-resistant (CL-R), and gentamicin-resistant (GE-R) Staphylococcus aureus strain. Despite immunotherapy becoming a milestone in oncologic treatment, more than the spectrum of immune-mediated toxicities of these agents needs to be investigated. This report highlights the importance of considering lifestyle and cutaneous background before starting immunotherapy for cancer treatment, with an emphasis on pharmacogenomics and the possibility of modified skin microbiota predisposing to cutaneous infections in patients treated with PD-1 inhibitors.

Mutational landscape in squamous cell carcinoma of the nail unit.

Squamous cell carcinoma (SCC) is the most common malignancy of the nail unit. Pathogenetic mechanisms are yet to be determined, and a deeper molecular characterization of this disease is still necessary. The aim was to obtain a molecular characterization of NU SCC samples using an NGS approach to identify the genetic drivers involved in this tumor. The presence of HPV infection was also assessed. Furthermore, the mutational status was correlated with specific clinical-pathological features for a better insight into the carcinogenesis of this uncommon tumor. We analysed twenty paraffin-embedded nail unit SCC samples from patients diagnosed with primary SCC of the nail unit by next genome sequencing. In the 20 tested samples, the neoplastic cells enrichment ranged from 10% to 50% (mean value: 25.7%). In 14/20 cases (70.0%), at least one mutation was detected; whereas in the other six cases (30.0%), no alterations were observed ('wild-type/WT cases'). Overall, a total of 23 mutations were identified in the 20 specimens. TP53 was the most mutated gene (6/20 cases, 30.0%), while cKit, GNAS, EGFR, DICER1 and CTNNB1 were observed in one sample each (5.0%). No clinical-pathological parameters (age, sex, depth of invasion-DOI, histological subtype, grading and HPV) were significantly associated with the mutational status. The nail unit SCC mutational landscape appeared to be heterogeneous, favouring the hypothesis of a complex pathogenesis and an interaction of multiple elements, including HPV infections. This wealth of information undoubtedly improves our understanding of SCC biology.

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.

Noninvasive diagnostic techniques in the preoperative setting of Mohs micrographic surgery: A review of the literature.

Mohs micrographic surgery (MMS) is considered the gold standard treatment for skin cancers. Though the high cure rates it offers, MMS presents some disadvantages, as it is a relatively time-consuming procedure involving several professionals (physicians and technicians). A better definition of tumor margins in the preoperative setting with any optical noninvasive diagnostic method may reduce the numbers of MMS steps and the overall duration of the procedure. The present review was conducted and reported using validated search strategies from the following databases: PUBMED and Ovid MEDLINE. Our review describes the use of procedures such as dermoscopy, optical coherence tomography, reflectance confocal microscopy and fluorescent confocal microscopy to determine tumor extension in the preoperative setting of Mohs surgery for the treatment of skin cancers. Presurgical margin assessment with noninvasive diagnostic techniques seem to provide a benefit in the patients' management, especially for tumors located in critical areas with a high risk of recurrence. The use is limited to the high costs and limited availability of new technologies.

Management of malignant cutaneous wounds in oncologic patients.

PURPOSE: Neoplastic wounds may develop as a result of primary tumor growth in the skin, due to metastasis, or due to skin invasion by tumors emerging from deeper levels. Malignant wounds may present as a crater-like ulcer, or as raised nodules with a cauliflower-like appearance. They are associated with malodor, necrosis, pain, bleeding, and secondary infection. The aim of our study is to better characterize fungating wounds and their management. METHODS: We retrospectively reviewed the database of the Wound Care Unit of the University of Bologna in order to identify individuals affected by neoplastic wound, between January 2019 and February 2021. RESULTS: We identified 9 females and 2 males with a mean age of 63 years; all were referred by the Oncology Unit. Management differed depending on the characteristics of the patients and the ulcers. Complete healing of the wound, following the parallel complete remission of the lymphoproliferative neoplasia, was observed in one individual. Among the others, one died because of breast cancer, while cutaneous lesions in 2 individuals deteriorated after 1 year of follow-up. Remission/relapse of the ulcer following the treatment course administered for the lymphoma were observed in one patient. CONCLUSIONS: Treatment of malignant fungating wounds is challenging. Considering the neoplastic nature of the wounds, complete healing or improvement cannot be expected with the application of classically prescribed dressing for wounds. A mostly palliative treatment, focusing on maintaining the patient's quality of life, is a reasonable choice.

BRAF V600K vs. BRAF V600E: a comparison of clinical and dermoscopic characteristics and response to immunotherapies and targeted therapies.

BACKGROUND: A number of mutations related to malignant melanoma (MM) have been identified, and of the mutated genes, BRAF has been found to be altered in > 50% of cases. Most of these have been BRAF V600E mutations, whereas the incidence of BRAF V600K may vary from 10% to 30%. Little is known about the clinical prognostic correlations of BRAF V600K MMs. We evaluated the clinical and dermoscopic features, incidence, therapy response and outcomes in the medium to long term. AIM: To compare the clinical and dermoscopic characteristics, the response to systemic therapies and the prognosis among MMs with BRAF V600E and BRAF V600K mutations. METHODS: We retrieved the data of patients tested in our centre for MM from 2012 to 2015, including clinical features, dermoscopic pictures, clinical history and tumour mutations. Only patients with BRAF V600E and BRAF V600K mutations were included. Any MMs positive for BRAF V600K mutation were collected, and the number of V600K cases and their features were used to extract the same number of patients with BRAF V600E from our database using a matching method. The clinical and dermoscopic presentation, therapy response and disease progression of the two groups were then evaluated. RESULTS: In total, 132 cases of BRAF V600E-mutated MMs were identified, and then randomized with a propensity-score method to match the 10 retrieved cases of BRAF V600K mutation. Both groups had a nodular appearance to the tumours and an advanced disease stage, and no significant differences in dermoscopic features were highlighted. During the follow-up period, four patients with BRAF V600K died of disease-specific causes. Moreover, we found a higher frequency of metastasis, a faster disease progression and more rapid mortality in patients with BRAF V600K. CONCLUSION: Despite the small size of this study, the results show similar clinical and dermoscopic characteristics between V600E and V600K mutations, but compared with BRAF V600E MMs, BRAF V600K MMs seem to be less responsive to therapy and have a worse prognosis.

Cutaneous Melanomas: A Single Center Experience on the Usage of Immunohistochemistry Applied for the Diagnosis.

Cutaneous melanoma (cM) is the deadliest of all primary skin cancers. Its prognosis is strongly influenced by the stage at diagnosis, with early stages having a good prognosis and being potentially treatable with surgery alone; advanced stages display a much worse prognosis, with a high rate of recurrence and metastasis. For this reason, the accurate and early diagnosis of cM is crucial-misdiagnosis may have extremely dangerous consequences for the patient and drastically reduce their chances of survival. Although the histological exam remains the "gold standard" for the diagnosis of cM, a continuously increasing number of immunohistochemical markers that could help in diagnosis, prognostic characterization, and appropriate therapeutical choices are identified every day, with some of them becoming part of routine practice. This review aims to discuss and summarize all the data related to the immunohistochemical analyses that are potentially useful for the diagnosis of cM, thus rendering it easier to appropriately applicate to routine practice. We will discuss these topics, as well as the role of these molecules in the biology of cM and potential impact on diagnosis and treatment, integrating the literature data with the experience of our surgical pathology department.

Topical Treatment of Actinic Keratosis and Metalloproteinase Expression: A Clinico-Pathological Retrospective Study.

Actinic keratosis is an intraepithelial proliferation of atypical keratinocytes that could progress into invasive squamous cell carcinoma. Most evidence suggests an important role of the dermal matrix metalloproteinases in the progression of atypical skin epithelial lesions. We evaluated the clinical efficacy of three different therapeutic modalities (a medical device containing 0.8% piroxicam cream and 50+ sunscreen, photodynamic therapy, and ingenol mebutate gel) to treat suspicious actinic keratoses, which were biopsied for histopathological examination and then analyzed for the expression of matrix metalloproteinases by immunohistochemistry. Clinical, dermoscopic, and reflectance confocal microscopy evaluations revealed a gradual decrease in all standard scores validated for actinic keratosis assessment at the end of the treatments. From a histopathological point of view, we documented the substantial restoration of normal skin architecture, while the immunohistochemical evaluation of matrix metalloproteinases showed a reduction in expression in the treated skin lesions compared to the baseline. As actinic keratoses are considered the precursors of squamous cell carcinoma, their treatment is crucial to prevent the development of a more aggressive disease. Our study monitored the evolution of actinic keratoses subjected to three different topical therapies, with the value of correlating clinical and histopathological findings. Moreover, as the matrix metalloproteinases are largely recognized factors involved in the pathogenesis and evolution of actinic keratosis to squamous cell carcinoma, the demonstration by immunohistochemistry of a reduction in their expression after the treatments adds new valuable concern to the field.

Eruptive Cherry Angiomas and Skin Melanoma: Further Insights into an Intriguing Association.

BACKGROUND: Some risk factors for malignant melanoma (MM) are recognized. OBJECTIVE: To compare the strength of association between MM and eruptive cherry angiomas (CAs) with that of other well-known associations. METHODS: This cross-sectional study included all subjects referred to the Outpatient Dermatology-Oncology and Dermoscopy Units of the Universities of Ferrara and Bologna, Italy, over a 5-month period and submitted to total body skin examination. We recorded: age, sex, cutaneous and non-cutaneous malignancies, presence of CAs, arbitrarily considered as "eruptive" when >10, >40 common melanocytic naevi or >2 clinically atypical naevi. The strength of association between the possible risk factors and MM was calculated by odds ratio in both the whole population and age quartiles. Variables associated with MM were included in multiple logistic regression analysis. RESULTS: 1,190 subjects were included; 615 had malignant skin tumours, 462 MM, 85 extracutaneous tumours. Five hundred and eighty-seven subjects had eruptive CAs, 485 subjects >40 melanocytic naevi and 368 more than 2 atypical melanocytic naevi. Eruptive CAs, especially in subjects younger than 70, and >2 atypical melanocytic naevi, mostly in subjects older than 50, were significantly associated with MM. The strength of these 2 associations was similar. The presence of >40 melanocytic naevi was not associated with MM. CONCLUSIONS: These findings confirmed an association between MM and eruptive CAs, which was as strong as the one between MM and >2 atypical melanocytic naevi. CAs seem an intriguing model of interaction between heterogeneous variables, like immunocompetence, stimuli inducing endothelial cell proliferation, and oncogenesis, which deserves further investigation.

Patidegib in Dermatology: A Current Review.

BACKGROUND: Basal cell carcinoma is one of the most common types of non-melanoma skin cancers, which can be locally destructive despite low-rate metastasis. Surgery is the treatment of choice, but it lacks of efficacy on advanced cases. Hedgehog pathway inhibitors are a class of drugs providing a new therapeutic option for patients affected by advanced disease. Besides systemic therapy, such as vismodegib and sonidegib, also topical inhibitors have been developed. Patidegib is able to decrease tumor burden, reducing the adverse effects induced by systemic targeted therapies. METHODS: We performed comprehensive research to summarize the use of patidegib in advanced and recurrent aggressive basal cell carcinomas. Only English language human studies were included in the search. RESULTS: Seven trials reported the application of patidegib. Both topical and systemic patidegib demonstrated safety, tolerability, and efficacy in naïve patients with stage II and III basal cell carcinomas, while stage IV disease and not-naïve patients did not show any benefit. CONCLUSION: Unlike systemic Hedgehog pathway inhibitors, patidegib 2% gel is not associated with systemic adverse effects and allows a better patient management. Considering the multidisciplinary management of neoplasia, in the era of precision medicine, it is mandatory to confide in pharmacogenomics to obtain personalized combined or sequential therapies.

Folliculotropism in head and neck lentigo maligna and lentigo maligna melanoma.

BACKGROUND: Lentigo maligna (LM) and lentigo maligna-melanoma (LMM) are histotypes of melanoma arising in skin with cumulative solar radiation damage. The extension of atypical melanocytes to the hair follicle (folliculotropism) is a histopathological feature of LM/LMM. Its role has not been totally clarified, but it may be correlated to treatment response in LM or to progression in LMM. OBJECTIVE: This retrospective, multicentric study aims to identify dermatoscopic features associated with folliculotropism in LMs/LMMs. PATIENTS AND METHODS: We analyzed cases of head and neck LMs/LMMs diagnosed between 2005-2014 at Melanoma Units, University of Bologna/Modena/Florence/Siena (Italy), Nice (France): 25 LMs and 73 LMMs were included. RESULTS: Grey circles (44 %) indicated an isthmic/bulb level of involvement, which were completely absent in the infundibular LM lesions (P = 0.041). In the group of LMMs, light/dark brown pseudonetwork and light brown structureless areas were an indicator of diffuse distribution of malignant melanocytes in the follicular units (P < 0.001 and P = 0.001, respectively), while grey circles indicated focal or diffuse distribution (P < 0.001). CONCLUSIONS: A better understanding of the extension of malignant melanocytes is helpful, aiding clinicians in their decision to perform a radical excision or obtaining a biopsy in the most invasive area of the lesion, which includes potential folliculotropism.