Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and ...the European Organization of Research and Treatment of Cancer collaborated to develop recommendations on diagnosis and treatment of BCC. A new classification into ‘easy-to-treat (common) BCC and ‘difficult-to-treat’ BCC is proposed. Diagnosis is based on clinicodermatoscopic features for ‘easy-to-treat’ BCCs. Histopathological confirmation is mandatory in ambiguous lesions and in BCCs located in high-risk areas. The first-line treatment of ‘easy-to-treat’ BCC is complete surgery. Microscopically controlled surgery shall be offered for high-risk BCC, recurrent BCC and BCC in critical anatomical sites. Topical therapies (5% imiquimod, 5% fluorouracil) and destructive approaches (curettage, electrocautery, cryotherapy, laser ablation) should be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial BCC and thin nodular BCC. The therapy for a ‘difficult-to-treat’ BCC should preferentially be discussed by a multidisciplinary tumour board. Hedgehog inhibitors, vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCCs. Immunotherapy with anti–programmed cell death 1 (PD-1) antibodies is a promising therapeutic option, currently being investigated in clinical trials. Radiotherapy represents a valid alternative to surgery for BCC on the face, especially in elderly patients. In patients with naevoid basal cell carcinoma syndrome (NBCCS), close surveillance and regular skin examinations are required to diagnose and treat BCCs at early stage. Long-term follow-up is recommended in patients with high-risk BCC subtypes, high-risk sites, multiple BCCs and NBCCS.
•Basal cell carcinoma (BCC) is the most common epithelial malignant tumour in white populations.•A new classification into “easy-to-treat” (common) BCC and “difficult-to-treat” BCC is proposed.•Surgery is the first-line therapy in all types of BCCs.•Treatment choice for advanced BCC should be discussed by a multidisciplinary tumour board.•Hedgehog inhibitors are used in "difficult-to-treat" BCC, and immunotherapy is a promising treatment under investigation.
Abstract Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European ...Dermatology Forum, the European Association of Dermato-Oncology and the European Organisation of Research and Treatment of Cancer was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. Diagnosis is made clinically using dermoscopy and staging is based upon the AJCC system. CMs are excised with 1–2 cm safety margins. Sentinel lymph node dissection is routinely offered as a staging procedure in patients with tumours >1 mm in thickness, although there is as yet no clear survival benefit for this approach. Interferon-α treatment may be offered to patients with stage II and III melanoma as an adjuvant therapy, as this treatment increases at least the disease-free survival and less clear the overall survival (OS) time. The treatment is however associated with significant toxicity. In distant metastasis, all options of surgical therapy have to be considered thoroughly. In the absence of surgical options, systemic treatment is indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies should be considered. BRAF inhibitors like dabrafenib and vemurafenib in combination with the MEK inhibitors trametinib and cobimetinib for BRAF mutated patients should be offered as first or second line treatment. Therapeutic decisions in stage IV patients should be primarily made by an interdisciplinary oncology team (‘Tumour Board’).
Abstract Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique collaboration of ...multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing guidelines and the expert’s experience. The diagnosis of cSCC is primarily based on clinical features. A biopsy or excision and histologic confirmation should be performed in all clinically suspicious lesions in order to facilitate the prognostic classification and correct management of cSCC. The first line treatment of cutaneous SCC is complete surgical excision with histopathological control of excision margins. The EDF–EADO–EORTC consensus group recommends a standardised minimal margin of 5 mm even for low-risk tumours. For tumours, with histological thickness of >6 mm or in tumours with high risk pathological features, e.g. high histological grade, subcutaneous invasion, perineural invasion, recurrent tumours and/or tumours at high risk locations an extended margin of 10 mm is recommended. As lymph node involvement by cSCC increases the risk of recurrence and mortality, a lymph node ultrasound is highly recommended, particularly in tumours with high-risk characteristics. In the case of clinical suspicion or positive findings upon imaging, a histologic confirmation should be sought either by fine needle aspiration or by open lymph node biopsy. In large infiltrating tumours with signs of involvement of underlying structures, additional imaging tests, such as CT or MRI imaging may be required to accurately assess the extent of the tumour and the presence of metastatic spread. Current staging systems for cSCC are not optimal, as they have been developed for head and neck tumours and lack extensive validation or adequate prognostic discrimination in certain stages with heterogeneous outcome measures. Sentinel lymph node biopsy has been used in patients with cSCC, but there is no conclusive evidence of its prognostic or therapeutic value. In the case of lymph node involvement by cSCC, the preferred treatment is a regional lymph node dissection. Radiation therapy represents a fair alternative to surgery in the non-surgical treatment of small cSCCs in low risk areas. It generally should be discussed either as a primary treatment for inoperable cSCC or in the adjuvant setting. Stage IV cSCC can be responsive to various chemotherapeutic agents; however, there is no standard regimen. EGFR inhibitors such as cetuximab or erlotinib, should be discussed as second line treatments after mono- or polychemotherapy failure and disease progression or within the framework of clinical trials. There is no standardised follow-up schedule for patients with cSCC. A close follow-up plan is recommended based on risk assessment of locoregional recurrences, metastatic spread or development of new lesions.
Summary
The interleukin (IL)‐1 family of cytokines is a central regulator of a myriad of immunological responses. It comprises several cytokines, including those belonging to the IL‐1, IL‐36 and ...IL‐18 subfamilies, as well as IL‐33. The IL‐1 family primarily plays a role in orchestrating innate immune responses, but is also involved in adaptive immunity. Increased interest in the IL‐1 family occurred following the discovery that dysregulation of IL‐1 signalling underlies the pathogenesis of several monogenic autoinflammatory diseases, characterized by sterile inflammation involving the skin and other organs. This also provided increased understanding of the role of innate immunity and the IL‐1 family in polygenic autoinflammatory skin conditions, such as neutrophilic dermatoses, as well as in some of the most common chronic inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa. Several therapeutic agents have been developed to inhibit the IL‐1 family members and their signalling pathways. These have shown therapeutic efficacy in several chronic inflammatory skin disorders. The aim of this review is to thoroughly describe the consequences of pathological dysregulation of the IL‐1, IL‐33, IL‐36 and IL‐18 pathways in dermatological conditions and to provide a forward‐looking update on therapeutic strategies targeting signalling by IL‐1 family cytokines.
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Nutrigenomic DNA reprogramming in different chronic diseases and cancer has been assessed through the stimulation of gene expression and mRNA synthesis versus DNA silencing by CpG DNA modification ...(methylation); histone modification (acetylation, methylation) and expression of small noncoding RNAs, known as microRNAs (miRNAs). With regard to the specific nutrigenomic effects in psoriasis, the influence of specific diets on inflammatory cell signaling transcriptional factors such as nuclear factor (NF)-κB and Wnt signaling pathways, on disease-related specific cytokine expression, pro/antioxidant balance, keratinocyte proliferation/apoptosis and on proliferation/differentiation ratio have been documented; however, the influence of dietary compounds on the balance between ‘good and bad’ miRNA expression has not been considered. This review aims to summarize knowledge about aberrant microRNAs expression in psoriasis and to emphasize the potential impact of some dietary compounds on endogenous miRNA synthesis in experimental conditions in vivo and in vitro. Among the aberrantly expressed miRNAs in psoriasis, one of the most prominently upregulated seems to be miR-21. The beneficial effects of phenolic compounds (curcumin and resveratrol), vitamin D, methyl donors, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) are discussed. Highly expressed miR-155 has been downregulated by flavonoids (through a quercetin-rich diet) and by vitamin D. Quercetin has been effective in modulating miR-146a. On the other hand, downregulated miR-125b expression was restored by vitamin D, Coenzyme Q10 and by microelement selenium. In conclusion, the miRNA profile, together with other ‘omics’, may constitute a multifaceted approach to explore the impact of diet on psoriasis prevention and treatment.
Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multidisciplinary experts from the European Dermatology ...Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed through dermatoscopy. If a melanoma is suspected, a histopathological examination is required. Sequential digital dermatoscopy and full-body photography can be used in risk persons to detect the development of melanomas at an earlier stage. Where available, confocal reflectance microscopy can improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the AJCC classification. Thin melanomas up to 0.8 mm tumor thickness does not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC whole-body examinations with CT or PET-CT in combination with brain MRI are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to support the frequency and extent of examinations. A stage-based follow-up scheme is proposed, which, according to the experience of the guideline group, covers the minimum requirements; further studies may be considered. This guideline is valid until the end of 2021.
Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients' quality of life and strongly interfere with sleep, ...social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.
Background Direct immunofluorescence (DIF), indirect immunofluorescence (IIF), and enzyme-linked immunosorbent assay (ELISA) are used for the laboratory diagnosis of bullous pemphigoid (BP). ...Objective The diagnostic value of DIF and IIF on rabbit and monkey esophagus or human salt-split skin and commercial ELISAs was assessed. Methods This was a single-center retrospective study where 313 patients with BP were compared with 488 control subjects. Results DIF was the most sensitive test (90.8%) whereas sensitivities for IIF on rabbit esophagus, IIF on monkey esophagus, IIF on salt-split skin, BP180 ELISA, and BP230 ELISA were 76.0%, 73.2%, 73.3%, 72.0%, and 59.0%, respectively. The sensitivity of the serologic tests was 88.8% altogether. The specificities for DIF, IIF on rabbit esophagus, IIF on monkey esophagus, IIF on salt-split skin, BP180 ELISA, and BP230 ELISA were 98%, 96.5%, 97.1%, 100%, 94.1%, and 99.2%, respectively. Limitations The retrospective nature of study was a limitation. Correlation of diagnostic data with clinical manifestations or disease course was not possible. Conclusions In suspected BP, both serologic tests and DIF have to be performed because of a sensitivity issue. Although the ELISAs had a relatively low sensitivity, the serologic tests altogether almost reached the level of sensitivity of DIF. The specificities of all assays were excellent.
Atopic dermatitis is a common inflammatory disease with a chronic and relapsing course. Although considered a childhood disease, it is now evident that atopic dermatitis is also common in adulthood ...and in the elderly population. Atopic dermatitis typically manifests with bilateral and symmetrical eczematous lesions on the face, trunk and skin folds. Itch is invariably present and may be very severe, markedly affecting daily life and sleep. In older adults, atopic dermatitis may have a high level of impact on quality of life, frequently burdening an already complex comorbid situation. The full assessment of disease burden (localizations, itch severity, sleep alterations, impact on quality of life, disease history, comorbidities) is crucial to identify the most appropriate treatment. In many cases, moderate-to-severe atopic dermatitis in the elderly population can be successfully and safely treated with biological agents inhibiting the interleukin-4/-13 pathway, whereas the use of Janus kinase inhibitors may pose concerns about the safety profile.
Background Early detection of basal cell carcinoma (BCC) is crucial to reduce the morbidity of this tumor. Objective We sought to investigate the variability and diagnostic significance of ...dermatoscopic features of BCCs. Methods We conducted retrospective dermatoscopic analysis of 609 BCCs and 200 melanocytic and nonmelanocytic lesions, and assessment of interrater reliability of dermatoscopic BCC criteria. Results Lesions included nonpigmented (15.1%), lightly pigmented (33.2%), pigmented (42.7%), and heavily pigmented (9%) BCCs. Classic BCC patterns including arborizing telangiectasia (57.1%), blue/gray ovoid nests (47.5%), ulceration (39.2%), multiple blue/gray globules (26.1%), leaflike areas (15.9%), and spoke-wheel areas (9%) were significantly increased in pigmented BCCs compared with nonpigmented and heavily pigmented BCCs ( P = .0001). Among nonclassic BCC patterns, we detected short fine superficial telangiectasia (10%) and multiple small erosions (8.5%), and described two new patterns named “concentric structures” (7.6%) and “multiple in-focus blue/gray dots” (5.1%). Dermatoscopic features suggestive of melanocytic lesions (eg, multiple brown to black dots/globules, blue/white veillike structures, and nonarborizing vessels) were observed in 40.6% BCCs and significantly increased in heavily pigmented BCCs ( P < .0001). Expert observers provided an accurate (sensitivity: 97%) and reliable (K: 87%) dermatoscopic diagnosis of BCC, although a significant difference in terms of specificity ( P = .0002) and positive predictive value ( P = .0004) was found. Arborizing telangiectasia, leaflike areas, and large blue/gray ovoid nests represented reliable and robust diagnostic parameters. Limitation The study was retrospective. Conclusion BCCs show a large spectrum of global and local dermatoscopic features; heavily pigmented BCCs show the most challenging combinations of dermatoscopic features.
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