Acral Melanocytic Nevi in a High-Risk Population: Prevalence, Clinical Characteristics and Dermatoscopic Patterns.

BACKGROUND: The prevalence of acral nevi and their dermatoscopic patterns have been mainly studied in Asian populations. Few data exist on the prevalence and clinico-dermatoscopic morphology of acral nevi in white populations. OBJECTIVES: The aim of this study was to assess the prevalence of acral nevi and evaluate their features in a cohort of Caucasian individuals at high risk for skin cancer. METHODS: We prospectively examined the palms and soles of 680 high-risk patients who underwent total body clinical and dermatoscopic documentation, as a part of their routine follow-up, between January 2016 and March 2020 at a skin cancer referral center in Greece. RESULTS: Overall, 334 acral lesions were detected in 217 (37.0%) of 585 patients in the study. The presence of acral nevi was associated with 2.6 higher odds of a total nevus count higher than 50 (OR: 2.6, p < 0.05, confidence intervals [CI]: 1.11-6.09). Of 334 acral nevi, 65.0% were clinically flat and 35.0% were clinically palpable. Palpable lesion had 19-fold higher probability of being located on the sole (OR: 19.44, p < 0.05, CI: 3.91-96.7). The parallel furrow pattern was present in 147 lesions (44.0%). In 76 lesions (22.8%), we observed a previously undefined pattern consisting of wavy lines, which was correlated with clinically palpable lesions (p < 0.001). The third most common pattern was homogeneous (10.5%), followed by the fibrillar (8.7%), the lattice-like (7.2%), the reticular (3.6%), and globular (3.3%). CONCLUSION: We observed a higher prevalence of benign acral melanocytic lesions than expected, probably related to our cohort selection of patients at high risk for developing skin cancer. Our study confirms the previously described dermatoscopic patterns and provides novel insights into the dermatoscopic morphology of acral palpable nevi, for which we described a new benign pattern consisting of wavy lines.

The Natural Evolution of Nevi with Peripheral Globules.

BACKGROUND: Peripheral globules (PG) in melanocytic lesions represent a concerning dermoscopic feature since they might be present in growing nevi and melanomas. Their natural evolution has not been fully elucidated, and an age-based management approach has been recommended. OBJECTIVES: The aim of this study was to calculate the growth rate of lesions with PG and investigate possible association with age, sex, location, and the global dermoscopic pattern. METHODS: We retrospectively selected the lesions of interest from a cohort of Caucasian patients who underwent sequential digital dermoscopy monitoring. Lesions with PG distributed at 75% or more of their circumference with available follow-up images or histopathologic report were included. The surface area was automatically calculated with the help of an incorporated tool used in the acquisition of the images. The images were also evaluated by independent investigators for the presence of pre-defined criteria. Growth-curve models were used to assess the growth rate. The outcome variable was the area of nevi in mm2, and scatterplots with Lowess curves were used to present the mean change of nevi during follow-up. RESULTS: A total of 208 lesions from 98 patients with a median age of 36 years (range 15-75) were included. The median follow-up time was 18 months (range 4-48). The mean growth rate for all nevi was 0.16 mm2/month (95% CI, 0.14-0.18, p < 0.001), ranging from -0.29 to 0.61 mm2/month. The growth rate was higher in nevi with a homogeneous dermoscopic pattern (p < 0.001). The number of peripheral globules during follow-up varied from increasing to complete disappearance. None of the lesions developed any melanoma-specific structure at follow-up. CONCLUSION: Nevi with PG grew at a mean rate of 0.16 mm2/month, and the growth rate was independent of age, gender, or anatomic location. Nevi with homogeneous pattern demonstrated the highest growth rate in our cohort. None of the monitored nevi with PG developed melanoma-specific criteria at follow-up.

A retrospective multicentric cohort study of checkpoint inhibitors-induced pruritus with focus on management.

BACKGROUND: Limited data on immune checkpoint inhibitor (ICI)-induced pruritus per se and efficacy of different therapeutic modalities in its management exist. OBJECTIVE: To study the quantitative and qualitative characteristics of ICI-induced pruritus per se and to assess the efficacy of the therapeutic modalities usually applied. METHODS: We retrospectively reviewed the records of 91 patients who were under treatment with ICIs for any kind of neoplasia and developed pruritus during treatment. RESULTS: Twenty out of 91 individuals (22.0%) with ICI-induced pruritus had pruritus as the only symptom, while 71/91 (78.0%) presented with pruritus coexisting with an additional cutaneous toxicity. Pruritus was treated with antihistamines (18/20, 90.0%) and/or topical regimens, as first-line choice. In resistant cases, as a second therapeutic intervention, narrow-band UVB (NBUVB), oral steroids and GABA analogs were added (70.0%). Statistical analysis revealed a significant difference in mean pruritus Numerical Rating Scale (NRS) scores between baseline and sequential visits. Moreover, subgroup analysis revealed a significant reduction in mean NRS scores in those treated with phototherapy. LIMITATIONS: Retrospective design, low number of patients and survivorship bias. CONCLUSION: Pruritus per se was present in a substantial portion of our cohort (22.0%). Our study confirms the efficacy of current treatment strategies and suggests NBUVB as a potential steroid-sparing therapeutic alternative.

Dermatoscopic shiny white structures in benign cutaneous tumours.

The dermatoscopic characteristics of shiny white structures (SWS) in malignant skin tumours are well described, but data on benign skin neoplasms are scarce. To evaluate dermatoscopic features of SWS in common benign tumours, we reviewed our database for histopathologically confirmed cases. The dermatoscopic images were evaluated for the presence of any type of SWS. Those images with SWS were further analyzed for their quantity, distribution and shape. Of 2420 evaluated benign tumours, 357 (14.8%) displayed SWS. The highest frequencies were observed in pyogenic granuloma (62/100, 62.0%), angioma (63/113, 55.8%) and adnexal tumours (42/84, 50.0%). The lowest frequency was found in common nevi (16/1032, 1.6%) and solar lentigo (0%). The presence of SWS was not associated with sex or anatomic location. SWS were usually diffuse and multiple. SWS may be present in a broad spectrum of benign tumours. Therefore, they should not be considered as de-facto indicators of malignancy.

Dermoscopic Clues of Histopathologically Aggressive Basal Cell Carcinoma Subtypes.

Background: The group of histopathologically aggressive BCC subtypes includes morpheaform, micronodular, infiltrative and metatypical BCC. Since these tumors are at increased risk of recurring, micrographically controlled surgery is considered the best therapeutic option. Although dermoscopy significantly improves the clinical recognition of BCC, scarce evidence exists on their dermoscopic criteria. Aim: To investigate the dermoscopic characteristics of histopathologically aggressive BCC subtypes. Materials and Methods: Dermoscopic images of morpheaform, micronodular, infiltrative and metatypical BCC were analyzed for the presence of predefined variables. Descriptive and analytical statistics were performed. Results: Most histopathologically aggressive BCCs were located on the head and neck. Infiltrative was the most common subtype. All subtypes, except micronodular BCC, rarely displayed dermoscopic pigmentation. The most frequent dermoscopic features of infiltrative BCC were arborizing vessels (67.1%), shiny white structures (48.6%) and ulceration (52.9%). The features prevailing in morpheaform BCC were arborizing vessels (68.4%), ulceration (n = 12, 63.2%) and white porcelain areas (47.4%). Micronodular BCC was typified by milky red structureless areas (53.8%), arborizing vessels (53.8%), short fine telangiectasias (50%), ulceration (46.2%) and blue structures (57.7%). The most common findings in metatypical BCC were arborizing vessels (77.8%), shiny white structures (66.7%), ulceration (62.9%) and keratin mass (29.6%). Limitations: Study population of only white skin and relatively small sample size in some groups. Conclusions: Our study provided data on the clinical, dermoscopic and epidemiological characteristics of histopathologically aggressive BCCs.

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.

Clinical associations and classification of immune checkpoint inhibitor-induced cutaneous toxicities: a multicentre study from the European Academy of Dermatology and Venereology Task Force of Dermatology for Cancer Patients.

BACKGROUND: Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). OBJECTIVES: To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. METHODS: This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. RESULTS: In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01-0·76] and vitiligo (OR 0·07, 95% CI 0·006-0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02-0·31), lichenoid reactions (OR 0·15, 95% CI 0·03-0·77) and eczematous reactions (OR 0·24, 95% CI 0·07-0·78), all compared with pruritic rash. CONCLUSIONS: Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy. Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer. The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus. Clinical awareness and specialized dermatological consultation should be advocated.

Evaluation of dermatoscopic criteria for early detection of squamous cell carcinoma arising on an actinic keratosis.

BACKGROUND: Advanced squamous cell carcinoma (SCC) can be discriminated easily from actinic keratosis (AK) based on clinical and dermatoscopic features. However, at the initial stage of dermal invasion, SCC might still be clinically flat and discrimination from AK remains challenging, even with the addition of dermatoscopy. OBJECTIVE: The aim of this study was to investigate the clinical and dermatoscopic criteria that could suggest early invasion and serve as potent predictors to discriminate early SCC from AK. METHODS: Clinical and dermatoscopic images of histopathologically diagnosed AKs and early SCCs were evaluated for the presence of predefined criteria by 3 independent investigators. RESULTS: A total of 50 early SCCs and 45 AKs were included. The main positive dermatoscopic predictors of early SCC were dotted/glomerular vessels (odds ratio [OR] 3.83), hairpin vessels (OR 12.12), and white structureless areas (OR 3.58), whereas background erythema represented a negative SCC predictor (OR 0.22). LIMITATIONS: The retrospective evaluation of images. Moreover, the differential diagnosis included in the study is restricted between AK and early SCC. CONCLUSIONS: We identified potent predictors for the discrimination of AK and early SCC that may better guide management decisions in everyday clinical practice.

Dermoscopic Predictors of Benignity and Malignancy in Equivocal Lesions Predominated by Blue Color.

BACKGROUND: Blue color in dermoscopy can be seen in a wide range of benign and malignant lesions, melanocytic or not. Some blue-colored dermoscopic criteria have been associated with specific tumors, such as blue-white veil with melanoma and homogeneous blue with blue nevi. However, when blue color occupies a large part of the lesion's surface, the dermoscopic assessment might be particularly challenging. OBJECTIVE: To identify dermoscopic predictors associated with benignity and malignancy in tumors characterized by a predominant dermoscopic presence of blue color. METHODS: We retrospectively screened our institutional database for tumors exhibiting blue color in at least 50% of their surface with available histopathologic diagnosis. Lesions with blue color covering less than 50% of their extent and lesions not histopathologically assessed were excluded. The dermoscopic images were evaluated for the presence of predefined criteria, including the characteristics of the blue color, coexisting colors, and the vascular structures. RESULTS: Of 91 included tumors, 53 were benign (35 blue nevi, 10 angiomas, and 8 seborrheic keratoses) and 38 malignant (12 melanomas and 26 basal cell carcinomas). Our analysis revealed 3 potent dermoscopic predictors of benignity: extension of blue color in more than 75% of the surface, diffuse distribution of blue color, and absence of vessels, posing a 2.3-fold, 5.6-fold, and 6.7-fold increased probability of benignity, respectively. In contrast, asymmetric distribution of blue color, blue clods, coexistence of gray color and linear vessels were significantly predictive of malignancy, posing a 8.9-fold, 2.8-fold, 13.5-fold, and 10.4-fold increased probability, respectively. CONCLUSION: In predominantly blue tumors, the probability of malignancy is high when blue color is seen in clods or is asymmetrically distributed and when gray color or linear vessels coexist. In contrast, a diffuse distribution of blue color, its expansion in more than 75% of the surface, and the absence of vessels are highly suggestive of a benign tumor.

Accuracy of dermoscopic criteria for the differential diagnosis between irritated seborrheic keratosis and squamous cell carcinoma.

BACKGROUND: Even with the addition of dermoscopy, a significant morphologic overlap exists between irritated seborrheic keratosis (ISK) and squamous cell carcinoma (SCC). OBJECTIVE: The aim of this study was to investigate the dermoscopic criteria that could serve as potent predictors for the differential diagnosis between ISK and SCC. METHODS: Dermoscopic images of histopathologically diagnosed ISKs and SCCs were evaluated by 3 independent investigators for the presence of predefined criteria. RESULTS: A total of 104 SCCs and 61 ISKs were included. The main dermoscopic predictors of SCC were dotted vessels (odds ratio [OR], 10.4), branched linear vessels (OR, 5.30), white structureless areas (OR, 6.78), white circles surrounding follicles (OR, 23.45), a diffuse irregular (OR, 2.55) or peripheral (OR, 2.8) vessel arrangement, and a central scale arrangement (OR, 3.35). Dermoscopic predictors of ISK were hairpin vessels (OR, 0.38), a diffuse regular vessel arrangement (OR, 0.39 and OR, 0.36), and white halos surrounding vessels covering more than 10% of the lesion (OR, 0.29 and OR, 0.12). LIMITATIONS: First, the retrospective design of the study; second, the differential diagnosis included in the study was restricted to ISK and SCC. CONCLUSIONS: We confirmed the significant morphologic overlap between ISK and SCC, but we also identified potent predictors for the differential diagnosis between these 2 entities.

Challenges in sarcoidosis and sarcoid-like reactions associated to immune checkpoint inhibitors: A narrative review apropos of a case.

Sarcoidosis and sarcoid-like reactions (SLRs) may develop in association with various malignancies, as well as in association to certain oncologic drugs, including immune checkpoint inhibitors (ICIs). We aimed to perform a narrative review with regard to the development of ICIs-associated sarcoidosis or SLRs, and to discuss the corresponding diagnostic and therapeutic challenges raised in this scenario. Apropos of a melanoma patient developing SLRs while treated with ipilimumab and nivolumab, we searched for clinically evident, ICIs-associated sarcoidosis or SLRs in the English literature. We recorded the oncologic characteristics, including type of malignancy and type of ICI, the phenotypic characteristics of sarcoidosis/SLRs, as well as the impact on immunotherapy. Including our patient, we identified 80 ICIs-associated sarcoidosis or SLRs cases. Both sexes were equally affected (40 F/40 M) and the most common malignancy was melanoma (65/80, 81.3%). Concerning the oncologic treatment, there was a predilection for pembrolizumab (23/80, 28.7%), followed by the ipilimumab/nivolumab combination (21/80, 26.3%), ipilimumab (18/80, 22.5%), nivolumab (16/80, 20.0%). Although in the majority of the cases (52/80, 65.0%) there was no need for systemic prednisolone for the management of sarcoidosis, a significant proportion of patients finally discontinued ICIs treatment (44/80, 55.0%). Phenotypically, sarcoidosis and SLRs highly imitate oncologic progression posing diagnostic difficulties. A therapeutic dilemma is also raised when there is a need for systemic prednisolone, since the latter may jeopardize the therapeutic efficacy of immunotherapy. Sarcoidosis and SLRs, though rare, can present in oncologic patients treated with ICIs. Clinicians should be aware of this possibility and the related diagnostic and therapeutic challenges they have to face in this scenario.

Dermoscopy of Juvenile Xanthogranuloma.

BACKGROUND: Dermoscopy is useful for the evaluation of juvenile xanthogranuloma (JXG). The classical "setting sun" pattern is characteristic of JXG, but its sensibility appears to be limited. An extensive description of other dermoscopic findings is not available in the literature. OBJECTIVES: The aim of this study was to valuate and describe the clinical and dermoscopic characteristics of a series of JXG cases. METHODS: This is a retrospective descriptive study, including cases with histopathologic diagnosis of JXG, and the availability of clinical and dermoscopic images, assessed for the presence of dermoscopic features based on the available literature. RESULTS: A total of 17 lesions were analyzed. 70.6% showed global symmetry, 35.3% presented the typical "setting sun" pattern. All lesions showed yellow-orange and/or pink-red structureless color. Other dermoscopic features were yellow globules (35.3%), shiny white streaks (23.5%), brown globules (17.6%), pale-brown network (11.8%), negative network (11.8%), erosion/ulceration (11.8%), rosettes (5.9%), and hemorrhage (5.9%). Scales were seen in 64.7% of patients. Vascular structures were observed in all the lesions, mostly in an irregular distribution (76.5%). The observed vessel types were dotted (52.9%), linear (52.9%), branching-arboriform (29.4%), comma-like (23.5%), hairpin-like (17.6%), globular (17.6%), coiled (11.8%), and milky-red globules (5.9%). CONCLUSIONS: Symmetry, yellow/orange-pink/red color, yellow globules, shiny white streaks, and irregularly distributed different types of vascular structures are the main dermoscopic features of JXG. This is the largest dermoscopic registry of JXG published to date.

Second primary melanomas in a cohort of 977 melanoma patients within the first 5 years of monitoring.

BACKGROUND: In retrospective studies, a second primary melanoma (SPM) develops in 2%-20% of melanoma patients. Scarce evidence exists on the usefulness of total-body photography (TBP) and digital dermatoscopic documentation (DDD) for detecting SPMs. OBJECTIVE: The primary aim was to quantify the risk and investigate the time of occurrence of SPMs. Secondary aims were to identify risk factors for SPM and to assess the usefulness of TBP and DDD for SPM detection. METHODS: This prospective cohort included patients with recently diagnosed melanoma that underwent sequential clinical and dermatoscopic examinations for up to 5 years. Life table analysis and Kaplan-Meier survival analysis were performed. Multivariate Cox models were constructed to identify factors affecting the outcome. RESULTS: An SPM developed in 46 of 977 (4.7%) patients. Life table analysis revealed a 5-year cumulative risk of 8.0% for SPM. High nevus count, fair phototype, and occupational sun exposure were potent predictors of SPM. Of all new melanomas, 17.3% were diagnosed by clinical and dermatoscopic examination, 48.1% by TBP, and 34.6% by DDD. LIMITATIONS: All patients followed the same protocol and diagnostic bias associated with sequential dermatoscopic imaging. CONCLUSION: In this cohort, melanoma patients were at 8% risk of an SPM developing within 5 years. TBP and DDD significantly contributed to the early detection of SPM.

Real-life data on basal cell carcinoma treatment: Insights on clinicians' therapeutic choices from an institutional hospital registry.

Basal cell carcinoma (BCC) is the most common skin cancer in white skin individuals. The treatment of choice is surgical excision, but several other therapeutic choices are available and might also be efficient and cost-effective in selected cases of low-risk BCC or when surgery is complicate or contraindicated. The aim of the current study was to analyze the applied treatments for BCC in the real-life practice of a tertiary hospital, and investigate factors associated to the tumor and the patients that might influence the treatment selection of clinicians. Data on all BCCs treated from 1st January 2018 to 31st December 2019 were extracted. A total of 751 BCCs from 585 patients were included. The baseline characteristics of patients and tumors, the type of applied treatment and the histopathologic report when available were analyzed. Most tumors were located on the head/neck (64.2%). The most frequently applied treatment was surgical excision (580/751, 77.2%). In 22.8% of tumors a nonsurgical treatment was selected. The most frequently selected alternative treatments were, imiquimod, cryosurgery, their combination (immunocryosurgery), and vismodegib. A pretreatment diagnosis of superficial BCC was associated with a 12-fold increased probability of selecting a nonsurgical treatment except of vismodegib. Every added year of age increased the probability of selecting a nonsurgical treatment by 3-fold. Every added mm of diameter increased the possibility of vismodegib use by 4%. Surgery is the most frequently applied BCC treatment, but nonsurgical modalities do also have an essential role in real settings.