Dear Editor, Coronavirus disease 2019 (COVID-19) has become a pandemic condition, yet little is known about its dermatologic manifestations. 1,2 We report here on peculiar (perniosis-like) skin lesions, unreported in the previous years, observed in young outpatients visited in our dermatologic unit in the last 4 weeks of COVID-19 pandemic (March-April 2020). Similar cases were referred to us in the same period by paediatricians and dermatologists from Italy and European countries. We directly observed 14 cases including 11 children (average age 14.4 years, range 13-18) and three young adults (average age 29 years, range 23-39). In this series, three couples were siblings and the ratio female-male was 8 : 6. The cutaneous manifestations consisted of an acral eruption of erythemato-violaceous papules and macules, with possible bullous evolution, or digital swelling (Fig. 1a-c). Lesions were localized on the feet in eight cases, on the hands in four cases and on both sites in 2. Two

: Skin manifestations of COVID-19 infections are diverse and are new to the dermatology community. We had the opportunity to examine the clinical and histopathological features of several patients who were divided into 3 groups. The first group included 8 COVID-19–positive patients who were hospitalized and quarantined at home. The second group included children and young adults who presented with chilblain erythema, erythema multiforme, and urticaria-like lesions. This group of patients was negative for the COVID-19 gene sequences by polymerase chain reaction but had a high risk of COVID-19 infection. The third group included clinically heterogeneous and challenging lesions. These patients were not subject to either polymerase chain reaction tests or serological analyses because they sought dermatological attention only for a dermatosis. The histopathological analysis of these cases showed a wide spectrum of histopathological patterns. What appears to be constant in all skin biopsies was the presence of prominent dilated blood vessels with a swollen endothelial layer, vessels engulfed with red blood cells, and perivascular infiltrates, consisting mainly of cytotoxic CD8+ lymphocytes and eosinophils. In 2 cases, there was diffuse coagulopathy in the cutaneous vascular plexus. In the early phases of the disease, there were numerous collections of Langerhans cells in the epidermis after being activated by the virus. The presence of urticarial lesions, chilblains, targetoid lesions (erythema multiforme–like lesions), exanthema, maculohemorrhagic rash, or chickenpox-like lesions associated with the histopathological features mentioned previously should cause clinical dermatologists to suspect the possibility of COVID-19 infection, especially in patients with fever and cough.

Androgens and androgen receptors (AR) are involved in the pathogenesis of breast cancer. Epidemiological studies have shown a significant association between the risk of breast cancer and androgens. However, the functional role and clinical value of AR expression in breast carcinoma have still not been clearly defined. The present study was set up to investigate the prevalence of ARs in a series of consecutive invasive breast carcinomas (IBCs) and to evaluate the patterns of AR phenotypes in a series of selected invasive lobular carcinomas (ILCs). Among the 250 consecutive IBCs (consisting of 212 ductal and 38 lobular neoplasms), AR immunoreactivity was observed in 151/250 (60.4%) cases, being expressed in 118/212 (56%) ductal and 33/38 (87%) lobular carcinomas (a statistically significant difference, chi2=11.82). AR expression was frequently associated with ER (65.2%, chi2=14.33) and PR positivity (66.9%, chi2=7.36). Most AR positive cases showed a low proliferative index (63.7%) and a low or intermediate histological grade (G1-G2, 63.9%). Among the 80 selected ILCs, AR expression was observed in 64/80 (80%) cases. Our results confirm that ARs are expressed in most breast cancers. Moreover, we demonstrated that AR positivity is particularly marked in lobular neoplasms. In addition, AR positive carcinomas are frequently characterized by a low or intermediate grade, a low proliferative index and ER and/or PR co-expression.

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Immune checkpoint inhibitors for blocking the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are now available for squamous cell carcinoma of the head and neck (HNSCC) in relapsing and/or metastatic settings. In this work, we compared the resulting combined positive score (CPS) of PD-L1 using alternative methods adopted in routine clinical practice and determined the level of diagnostic agreement and inter-observer reliability in this setting. The study applied 5 different protocols on 40 tissue microarrays from HNSCC. The error rate of the individual protocols ranged from a minimum of 7% to a maximum of 21%, the sensitivity from 79% to 96%, and the specificity from 50% to 100%. In the intermediate group (1 ≤ CPS < 20), the majority of errors consisted of an underestimation of PD-L1 expression. In strong expressors, 5 out of 14 samples (36%) were correctly evaluated by all the protocols, but no protocol was able to correctly identify all the “strong expressors”. The overall inter-observer agreement in PD-L1 CPS reached 87%. The inter-observer reliability was moderate, with an ICC of 0.774 (95% CI (0.651; 0.871)). In conclusion, our study showed moderate interobserver reliability among different protocols. In order to improve the performances, adequate specific training to evaluate PD-L1 by CPS in the HNSCC setting should be coordinated.