Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo–YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis.

BackgroundAn estimated 5%–10% of all cutaneous melanoma cases occur in families. This review describes susceptibility genes currently known to be involved in melanoma predisposition, genetic testing of familial melanoma patients, and management implications.ResultsCDKN2A is the major high-penetrance susceptibility gene with germline mutations identified in 20%–40% of melanoma families. A positive CDKN2A mutation status has been associated with a high number of affected family members, multiple primary melanomas, pancreatic cancer, and early age at melanoma onset. Mutations in the other melanoma predisposition genes—CDK4, BAP1, TERT, POT1, ACD, TERF2IP, and MITF—are rare, overall contributing to explain a further 10% of familial clustering of melanoma. The underlying genetic susceptibility remains indeed unexplained for half of melanoma families. Genetic testing for melanoma is currently recommended only for CDKN2A and CDK4, and, at this time, the role of multigene panel testing remains under debate. Individuals from melanoma families must receive genetic counseling to be informed about the inclusion criteria for genetic testing, the probability of an inconclusive result, the genetic risk for melanoma and other cancers, and the debatable role of medical management. They should be counseled focusing primarily on recommendations on appropriate lifestyle, encouraging skin self-examination, and regular dermatological screening.ConclusionsGenetic testing for high-penetrance melanoma susceptibility genes is recommended in melanoma families after selection of the appropriate candidates and adequate counseling of the patient. All patients and relatives from melanoma kindreds, irrespective of their mutation status, should be encouraged to adhere to a correct ultraviolet exposure, skin self-examination, and surveillance by physicians.

Background Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID‐19) pandemic. Methods A national registry, named DA‐COVID‐19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID‐19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID‐19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician‐ and patient‐reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS‐CoV‐2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS‐CoV‐2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID‐related death occurred. Conclusions Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab‐treated patients.