Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge.

The coronavirus disease 2019 (COVID‐19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 symptoms are not limited to the respiratory tract, but complications have been described involving other organs including brain. At present, data on SARS‐CoV‐2 neuropathological features are limited [4, 5, 8, 10] and most frequently focused on cases presenting neurological symptoms.

Italy was the first European nation to be massively infected by SARS-CoV-2. Up to the end of May 2020, more than 33,000 deaths had been recorded in Italy, with a large prevalence among males, those over 75 years of age, and in association with co-morbidities. We describe the lung pathological and immunohistochemical post-mortem findings at the autopsy of nine patients who died of SARS-CoV-2-associated disease. We found in the lung tissues of all patients histological changes consistent with diffuse alveolar damage in various evolution phases ranging from acute exudative to acute proliferative to fibrotic phase. Alveolar damage was associated with prominent involvement of the vascular component in both the interstitial capillaries and the mid-size vessels, with capillary fibrin micro-thrombi, as well as organized thrombi even in medium-sized arteries, in most cases not related to sources of embolism. Eosinophilic infiltrate was also seen, probably reactive to pharmacological treatment. Viral RNA of SARS-CoV-2 was detected from the lung tissues of all the nine patients. Immunohistochemistry for the receptor of the SARS-CoV-2, ACE2, and its priming activator TMPRSS2 revealed that both proteins co-localize in airway cells. In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD). Pneumocytes, but not endothelial cells, also expressed TMPRSS2. There are no distinctive histological features of SARS-CoV-2 infection with respect to SARS-CoV-1 and other DAD with different aetiology. The identification of the cause of death in the course of SARS-CoV-2 infection is more likely multifactorial.

This study examined the association between dynamic angiopoietin-2 assessment and COVID-19 short- and long-term clinical course. We included consecutive hospitalized patients from 1 February to 31 May 2020 with laboratory-confirmed COVID-19 from 2 Italian tertiary referral centers (derivation cohort, n = 187 patients; validation cohort, n = 62 patients). Serum biomarker levels were measured by sandwich enzyme-linked immunosorbent assay. Lung tissue from 9 patients was stained for angiopoietin-2, Tie2, CD68, and CD34. Cox model was used to identify risk factors for mortality and nonresolving pulmonary condition. Area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of 3- and 10-day angiopoietin-2 for in-hospital mortality and nonresolving pulmonary condition, respectively. Three-day angiopoietin-2 increase of at least twofold from baseline was significantly associated with in-hospital mortality by multivariate analysis (hazard ratio [HR], 6.69; 95% confidence interval [CI], 1.85-24.19; P = .004) with AUROC = 0.845 (95% CI, 0.725-0.940). Ten-day angiopoietin-2 of at least twofold from baseline was instead significantly associated with nonresolving pulmonary condition by multivariate analysis (HR, 5.33; 95% CI, 1.34-11.77; P ≤ .0001) with AUROC = 0.969 (95% CI, 0.919-1.000). Patients with persistent elevation of 10-day angiopoietin-2 levels showed severe reticular interstitial thickening and fibrous changes on follow-up computed tomography scans. Angiopoietin-2 and Tie2 were diffusely colocalized in small-vessel endothelia and alveolar new vessels and macrophages. Angiopoietin-2 course is strongly associated with COVID-19 in-hospital mortality and nonresolving pulmonary condition. Angiopoietin-2 may be an early and useful predictor of COVID-19 clinical course, and it could be a relevant part of disease pathogenesis. Angiopoietin-2 blockade may be a COVID-19 treatment option.

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