Paraneoplastic dermatomyositis and Stevens-Johnson syndrome related to immunotherapy.

Paraneoplastic syndromes such as dermatomyositis, often emerge as the initial clinical manifestation across various cancer types and are characterized by the development of B-cell responses targeting cancer-cell antigens that cross-react with normal skin and muscle cells. While these syndromes may alleviate following antineoplastic intervention, their response to immunotherapy remains elusive due to the exclusion of patients with autoimmune phenomena from clinical trials. In this report, we present the case of a female patient with advanced urothelial cancer presenting with dermatomyositis, who subsequently underwent treatment with anti-PD1 immunotherapy and experienced the onset of Stevens-Johnson syndrome. We discuss these two autoimmune entities and provide a comprehensive review of the existing literature to elucidate similar associations.

Dermatomyositis, an inflammatory disorder that causes a skin rash, might be the first sign that someone has cancer. But when scientists test new cancer treatments, they often don't include people with this skin problem. So, we do not know much about how safe or effective these treatments are for them. Here's a story about someone who had bladder cancer and dermatomyositis. They received a treatment called immunotherapy, but it caused a serious problem called Stevens-Johnson syndrome. We also found similar cases in medical papers.

Use of Dermoscopy among Greek Dermatologists in Everyday Clinical Practice: A National Questionnaire-Based Study.

Background: Dermatoscopy has been established as an important diagnostic tool for a wide range of skin diseases. This study aims to evaluate the use of dermatoscopy in clinical practice among Greek dermatologists. Methods: A nationwide questionnaire-based survey was conducted collecting data on the frequency of dermatoscopic examinations, the types of lesions examined, training and educational resources, as well as factors influencing the choice to incorporate dermatoscopy into daily clinical routines. Results: A total of 366 Greek dermatologists participated in the survey. Most of the respondents reported the daily use of dermatoscopy in their practice. Pigmented and non-pigmented lesions, inflammatory diseases, cutaneous infectious, hair disorders, and nail lesions were the most common indications for dermatoscopy. Factors influencing the utilization of dermatoscopy included increased diagnostic accuracy, enhanced patient care, better patient communication and general compliance, and improved satisfaction among dermatologists. Conclusions: This national questionnaire-based study demonstrates that dermatoscopy has become an integral part of daily dermatological practice in Greece. The findings highlight the significance of structured training and education to promote dermoscopy's effective and routine use. Incorporating dermatoscopy into clinical practice not only improves diagnostic precision but also enhances patient care, contributing to the overall quality of dermatological services in Greece.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.

Seven Plus One Steps to Assess Pigmented Nail Bands (Melanonychia Striata Longitudinalis).

Melanonychia striata longitudinalis might involve one or more fingers and/or toes and might result from several different causes, including benign and malignant tumors, trauma, infections, and activation of melanocytes that might be reactive or related to the pigmentary trait, drugs and some rare syndromes. This broad differential diagnosis renders the clinical assessment of melanonychia striata particularly challenging. Nail matrix melanoma is relatively rare, occurs almost always in adults involves more frequently the first toe or thumb. The most common nail unit cancer, squamous cell carcinoma / Bowen disease (SCC) of the nail matrix is seldom pigmented. Histopathologic examination remains the gold standard for melanoma and SCC diagnosis, but excisional or partial biopsies from the nail matrix require training and is not routinely performed by the majority of clinicians. Furthermore, the histopathologic evaluation of melanocytic lesions of the nail matrix is particularly challenging, since early melanoma has only bland histopathologic alterations. Dermatoscopy of the nail plate and its free edge significantly improves the clinical diagnosis, since specific patterns have been associated to each one of the causes of melanonychia. Based on knowledge generated and published in the last decades, we propose herein a stepwise diagnostic approach for melanonychia striata longitudinalis: 1) Hemorrhage first 2) Age matters 3) Number of nails matters 4) Free edge matters 5) Brown or gray? 6) Size matters 7) Regular or irregular and, finally, "follow back".

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.

Clinical and Dermoscopic Characteristics of Cutaneous Sarcomas: A Literature Review.

Under the umbrella of cutaneous sarcomas (CS) we include a heterogeneous group of rare, malignant, mesenchymal neoplasia, such as dermatofibrosarcoma protuberans, atypical fibroxanthoma, cutaneous undifferentiated pleomorphic sarcoma, cutaneous angiosarcoma and leiomyosarcoma. Clinical presentation and histopathological examination are the cornerstone of CS diagnosis and classification. There are scarce data in the literature in regards to the clinical and dermatoscopic characteristics of CS and the role of dermatoscopy in their early identification. We performed a literature review, aiming to summarize current data on the clinical and dermatoscopic presentation of the most common types of cutaneous sarcomas that may facilitate early diagnosis and prompt management. Based on the available published data, CS are characterized by mostly unspecific dermatoscopic patterns. Dermatofibrosarcoma protuberans, Kaposi's sarcoma, and in a lesser degree, cutaneous angiosarcoma, may display distinct dermatoscopic features, facilitating their early clinical recognition. In conclusion, dermatoscopy, in conjunction with the overall clinical context, may aid towards suspicion of CS.

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.

Dermoscopy of Actinic Keratosis: Is There a True Differentiation between Non-Pigmented and Pigmented Lesions?

Dermoscopic features of actinic keratosis (AK) have been widely studied, but there is still little evidence for their diagnostic accuracy. Our study investigates whether established dermoscopic criteria are reliable predictors in differentiating non-pigmented actinic keratosis (NPAK) from pigmented actinic keratosis (PAK). For this purpose, dermoscopic images of 83 clinically diagnosed AK (45 NPAK, 38PAK) were examined, and the sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) were assessed. Features with statistical significance were the red pseudo-network (p = 0.02) for NPAK and the pigmented pseudo-network (p < 0.001) with a pigment intensity value even less than 10% for PAK (p = 0.001). Pigmented pseudo-network (Se: 89%, Sp: 77%, PPV: 77%, NPV: 89%) with a pigment intensity value of more than 10% (Se: 90%, Sp: 86%, PPV: 79%, NPV: 93%) had excellent diagnostic accuracy for PAK. Scale and widened follicular openings with yellowish dots surrounded by white circles were equally represented in both variants of AK. Linear wavy vessels and shiny streaks were more prominently observed in NPAK, as were rosettes in PAK, but these results failed to meet statistical significance. The red starburst pattern was near statistical significance for PAK. Therefore, pigmentation is the strongest dermoscopic predictor for the differentiation between NPAK and PAK.

Actinic Keratoses (AK): An Exploratory Questionnaire-Based Study of Patients' Illness Perceptions.

BACKGROUND: Decreased illness perception among actinic keratoses (AK) patients is a major barrier to the effective management of AK. OBJECTIVE: We aimed to investigate patients' illness and treatment perceptions, their correlation to demographics and AK/skin cancer history, and secondarily the influence of these perspectives on treatment and sunscreen use. MATERIALS AND METHODS: Participants completed questionnaires based on the Brief Illness Perception Questionnaire and statistical analysis was performed. RESULTS: In total, 208 AK patients were enrolled. A large proportion were poorly aware of the disease (41.4%), with less than half (43%) being familiar with AK. Patients were aware of the chronic nature of the disease and its correlation to sunlight regardless of demographic characteristics. The level of education played a role in disease awareness (p = 0.006), and treatment plan perception (p = 0.002). The increase in sunscreen protection after AK diagnosis was higher in women (p = 0.009) and younger patients (p = 0.044). Patients' concerns regarding treatment were mainly related to the duration (30%) and effectivity (25%). Dermatologists' statements highlighting that AK are precancerous lesions (86.2%) influenced patients' willingness for treatment. CONCLUSION: Improved awareness of AK is necessary to increase treatment seeking and compliance, regarding both treatment and sunscreen use. Dermatologists' statements may have critical influence on patients' decisions to receive treatment for AK.

How to spot a basosquamous carcinoma: a study on demographics, clinical-dermatoscopic features and histopathological correlations.

Basosquamous carcinoma (BSC) is a relatively rare type of neoplasm originating from basal cell carcinoma with features of squamous differentiation. BSC has an aggressive local behaviour with a tendency for recurrence and a less frequent metastatic potential The primary objective was to describe the dermatoscopic features of the tumour. Secondary goals were to detect the morphological features of the tumour along with patients' characteristics and to evaluate possible dermatoscopic and histopathological correlations Twenty-two patients with 25 BSCs were enrolled. All tumours were surgically excised and diagnosis was based on histopathology. Clinical and dermatoscopic images were evaluated by two investigators based on pre-defined criteria, and a statistical analysis was performed The median age of the patients was 78 years old (range: 52-88) and the male/female ratio was 2.14. All patients reported history of either occupational (50%) or recreational (50%) intensive sun exposure and 72.73% had signs of actinic keratosis. The most common anatomical site of the tumours was the head/neck area (72%). Clinically, nodular (64%), ulcerated (88%) and non-pigmented (76%) lesions prevailed. Dermatoscopically, 92% had prominent vasculature and monomorphous arborizing vessels with a diffuse arrangement, representing the most frequently observed type. Ulceration (88%), SCC dermatoscopic criteria (56%), white strands/blotches (56%) and features of pigmentation (40%) were also detected We suggest that the most common prototype of BSC is an ulcerated, facial nodule in elderly males with photo-damaged skin, dermatoscopically displaying combined features of mostly nodular BCC and, to a less extent, SCC.

Novel Insights for Patients with Multiple Basal Cell Carcinomas and Tumors at High-Risk for Recurrence: Risk Factors, Clinical Morphology, and Dermatoscopy.

INTRODUCTION: Basal cell carcinoma (BCC) quite frequently presents as multiple tumors in individual patients. Neoplasm's risk factors for local recurrence have a critical impact on therapeutic management. OBJECTIVE: To detect risk factors for multiple BCCs (mBCC) in individual patients and to describe clinical and dermatoscopic features of low- and high-risk tumors. MATERIALS & METHODS: Our study included 225 patients with 304 surgically excised primary BCCs. All patients' medical history and demographics were recorded. Clinical and dermatoscopic images of BCCs were evaluated for predefined criteria and statistical analyses were performed. RESULTS: Grade II-III sunburns before adulthood (OR 2.146, p = 0.031) and a personal history of BCC (OR 3.403, p < 0.001) were the major predisposing factors for mBCC. Clinically obvious white color (OR 3.168, p < 0.001) and dermatoscopic detection of white shiny lines (OR 2.085, p = 0.025) represented strongly prognostic variables of high-risk BCC. Similarly, extensive clinico-dermatoscopic ulceration (up to 9.2-fold) and nodular morphology (3.6-fold) raise the possibility for high-risk BCC. On the contrary, dermatoscopic evidence of blue-black coloration had a negative prognostic value for high-risk neoplasms (light OR 0.269, p < 0.001/partial OR 0.198, p = 0.001). CONCLUSIONS: Profiling of mBCC patients and a thorough knowledge of high-risk tumors' clinico-dermatoscopic morphology could provide physicians with important information towards prevention of this neoplasm.

Dermoscopy as a Tool in Differentiating Cutaneous Squamous Cell Carcinoma From Its Variants.

BACKGROUND: Dermoscopic features of cutaneous squamous cell carcinoma (cSCC) have been widely studied, but their accuracy should be further investigated. OBJECTIVES: This study assessed the diagnostic accuracy of a set of predetermined dermoscopic structures for 3 variants of cSCC, namely Bowen disease, keratoacanthoma and invasive cSCC. METHODS: Dermoscopic images of 56 histopathologically confirmed cSCC lesions (9 Bowen disease lesions, 7 keratoacanthomas, and 40 invasive cSCCs) were examined, and the diagnostic accuracy of dermoscopic structures was assessed. Discriminative ability of statistically significant positive predictors was determined using receiver operating characteristic (ROC) curves, and defined as an area under the ROC curve >0.700. RESULTS: Dermoscopic structures with statistical significance and discriminative ability were: for Bowen disease, clustered glomerular vessels and erosions; for keratoacanthoma, a central keratin plug; and for invasive cSCC, a mixed color of the background. Clustered and glomerular vessels had, for Bowen disease, perfect diagnostic accuracy, with: sensitivity of 88.9% for both features; specificity of 97.9% and 93.6%, respectively; positive predictive value (PPV) of 88.9% and 72.7%, respectively; and negative predictive value (NPV) of 97.8% for both. Erosions had, for BD, high specificity (87.2%) and NPV (91.1%), but low sensitivity (55.6%) and PPV (45.5%). A central keratin plug had, for keratoacanthoma, high specificity (87.8%) and NPV (93.5%), but low sensitivity (57.1%) and PPV (40%). A mixed background color had, for invasive cSCC, high specificity (81.3%) and PPV (89.7%), but low sensitivity (65%) and NPV (48.2%). CONCLUSION: Dermoscopy accurately differentiates BD, through clustered glomerular vessels, from keratoacanthoma and invasive cSCC. Dermoscopic structures of keratoacanthoma and invasive cSCC overlap, and only histopathologic analysis differentiates them precisely.

Female Patient with Two Simultaneous Giants Facial Basal Cell Carcinomas Demonstrates a Positive Response to Vismodegib as a Monotherapy.

Basal cell carcinoma (BCC) is the most frequent histological type of cancer in the world and accounts for approximately 80% of all skin cancers. In the majority of cases, they are slow-growing, low metastatic potential tumors, easy to cure by surgical or nonsurgical procedures. Giant BCC (GBCC) is a rare variant of BCC and according to the American Joint Committee on Cancer, this includes lesions with a diameter larger than 5 cm. GBCC's incidence has been reported to be less than 1%, and it displays a more aggressive behavior with both local invasion and higher metastatic potential. Archodaki et al. specifically reported that metastasis was present in 17.6% of GBCC patients during the primary examination. Patients with GBCC who are not suitable for either surgery or radiotherapy since 2012 seem to have another therapeutic option. Vismodegib is an oral small-molecule inhibitor of the Hedgehog pathway (HPI) that was approved for treating metastatic or locally advanced BCC in patients who are poor candidates for surgery or radiotherapy. In this case, we present a woman with two simultaneous facial GBCCs who was treated successfully using vismodegib as a monotherapy.

Cystic lung disease in Birt-Hogg-Dubé syndrome. A case series.

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant inherited disease caused by mutations in the folliculin (FLCN) gene. It is characterized by lung cysts, skin fibrofolliculomas and an increased risk for the development of renal cancer, especially chromophobe. Lung cysts in the context of BHDS are typically lower lobe predominant, paramediastinal, in relation to the fissures and often elliptical shaped. Skin manifestations can easily go unnoticed. Respiratory physicians need to have a high degree of vigilance as they can be the first to suspect the disease in the setting of diffuse cystic lung disease. Meticulous skin examination and referral to a dermatologist is of utmost importance as it can establish the diagnosis in the least invasive way. Correct diagnosis is crucial as it may allow for genetic counseling to the affected family and the implementation of a monitoring strategy for early detection of renal cancer.

Lichen Planopilaris Developing at the Margins of a Sebaceous Nevus of Jadassohn: Co-existence or Etiologic Association?

Sebaceous nevus (SN), is a skin hamartoma, combining a variety of epidermal, follicular, sebaceous, and apocrine abnormalities. Although usually present at birth, it may become apparent later in life appearing as a yellowish-brown, verrucous plaque with alopecia. SN is implicated with secondary tumors arising on the hairless plaque during the adulthood. Lichen planopilaris is a common, primary lymphocytic scarring alopecia of unknown etiology, characterized by lichenoid/interface perifollicular lymphocytic infiltrate occurring at the level of the infundibulum and the isthmus. Here, we present a case of a 48-year-old Caucasian male with lichen planopilaris lesions developing at the periphery of a preexisting SN. Our case raises the question, whether the development of lichen planopilaris was coincidental, or is it indicative of an etiologic association between the lichen planopilaris and SN.

BRAF Mutation Status in Primary, Recurrent, and Metastatic Malignant Melanoma and Its Relation to Histopathological Parameters.

BACKGROUND: BRAF mutations are a common finding in malignant melanoma (MM). Nevertheless, apart from their significance as a therapeutic target in advanced melanoma, their prognostic value is still debated. OBJECTIVE: To assess BRAF mutation status in primary, recurrent, or metastatic MM and its correlations with histopathological findings. METHODS: We analyzed 203 samples from 178 consecutive patients: 129 primary cutaneous MM, 49 metastatic and recurrent MM of unknown primary site, and 25 cases of recurrences or metastases of primary MM. BRAF mutations in exon 15 were identified with real-time polymerase chain reaction and/or direct sequencing or pyrosequencing. Histopathological examination was performed according to standard procedures. RESULTS: We observed a 42.1% prevalence of BRAF mutations at codon 600 among our patients, 84% of whom harbored the V600E mutation. Mutations showed a statistically significant increase in younger patients (P = 0.011), in ulcerated tumors (P = 0.020), and in tumors lacking solar elastosis in adjacent dermis (P = 0.008). Mutations were also more common in male patients, as well as in primary MMs of the torso, and in nonvisceral metastases, however without reaching statistical significance. Logistic regression analysis identified type and ulceration as the only significant predictors of BRAF mutation. The highest frequencies of mutated BRAF were identified in superficial spreading and nodular types, and the lowest in acral lentiginous and lentigo maligna types. In situ MM and primary dermal melanoma displayed intermediate frequencies. CONCLUSION: Frequency of mutated BRAF is type-related and correlated with ulceration, a known adverse prognostic factor.