Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen’s disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.

Background: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. Objective: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/ safety. Methods: Data of 389 HS patients treated with adalimumab in 21 Italian centres were reviewed. Sex, ages at onset/diagnosis/baseline, body mass index, smoking, phenotypes, previous treatments, concomitant antibiotics , and "therapeutic delay", defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using "Hidradenitis Suppurativa Clinical Response" (HiSCR) and "Dermatology Life Quality Index" (DLQI)/"Visual Analogue Scale for pain" (VAS pain), respectively. Logistic regression analysis was performed. Results: The "therapeutic delay" correlated to lack of response to adalimumab at week 16 (OR,1.92 for therapeutic delay  10 years; 95% CI,1.28-2.89; P=0.0016). HiSCR was achieved in 43.7% and 53.9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 versus baseline (p<0.0001 for both) and week 52 versus baseline (p<0.0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 [OR=1.74, 95% CI 1.04-2.91, p=0.0342]. Conclusion: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a "window of opportunity" in HS. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence response to adalimumab inducing a switch to non-TNFα-driven pathways.