Treatment of Cutaneous Squamous Cell Carcinoma with Immune Checkpoint Inhibitors in Special Populations

Cutaneous squamous cell carcinoma (cSCC) may develop in patients with dysregulated immune activation (pre-existing autoimmune diseases or immunosuppression due to hematopoietic/solid organ transplant recipients), patients with a compromised immune function (long-term immunosuppression), and patients carrying chronic viral infections, or those affected by lymphoproliferative diseases. It should be also considered that patients presenting with immunosuppression have a high incidence of cSCC (65–250-times higher than general population), highlighting the central role played by the immune system in the development of cSCC. All these cases must be considered as “special populations” for treatment with immune checkpoint inhibitors (ICIs), as the safety and activity of these drugs have not been studied on these specific cases, since these patients were excluded from clinical trials leading to approval of ICIs. It is therefore important to gain as much information as possible from the analysis of real-life data, to derive an indication to be adopted in everyday clinical setting. Moreover, therapeutic alternatives other than ICIs are scarce, mainly consisting in chemotherapy and anti-EGFR agents, whose activity is lower than immunotherapy and whose toxicity (particularly with chemotherapy) are not sustainable by this frail population. Here, we describe the current evidence of treatment with ICIs in special populations and conclude that it is necessary to find a balance between treatment risks (toxicities) and benefits (efficacy), as well as engaging a multidisciplinary team of experts to thoroughly manage and treat these patients.

The New Era of Biologics in Atopic Dermatitis: A Review

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder affecting all ages and ethnic groups. The age-dependent varying appearance and extent of pruritic lesions are accompanied by distinct individual suffering, highlighting the importance of effective treatment options. Over the past years, systemic drugs have considerably extended therapeutic approaches of patients with moderate to severe AD, in particular, new biologics, most notably dupilumab has appeared as major breakthrough. In addition to monoclonal blockade of IL-4 and IL-13 pathway, more cytokines have been found to play a substantial role in AD pathogenesis, presenting potential targets for new therapy options.

Variability in the Histopathological Diagnosis of Nonmelanocytic Lesions Excised to Exclude Melanoma

Introduction. The differential diagnosis of lesions excised to exclude melanoma include a variety of benign and malignant melanocytic and non-melanocytic lesions. Objectives. We examined the variability between pathologists in diagnosing non-melanocytic lesions. Methods. As part of a larger study prospectively examining the diagnosis of lesions excised to exclude melanoma in 198 patients at a primary care skin cancer clinic in Newcastle, Australia, we compared diagnosis made by 5 experienced dermatopathologists, of 44 non-melanocytic lesions in 44 patients aged 22-90. Results. Forty-four lesions (out of 217 in total) were non-melanocytic. Among the 5 pathologists who examined each case there was marked variability in the terminology used to diagnose each case. The most common variability was found between seborrheic keratosis, large cell acanthoma, solar lentigo, and lichenoid keratosis. The diagnosis made by the majority of the pathologists was deemed to be the reference diagnosis. Versus majority diagnosis, 4% of benign lesions were considered malignant, and 7% of malignant diagnoses were considered as benign. Conclusions. The different terminology adopted and lack of consensus in the diagnosis of these non-melanocytic lesions in this setting suggests that training AI systems using gold standards may be problematic. We propose a new management classification scheme called MOLEM (Management of Lesions Excised to exclude Melanoma) which expands the previously described MPATH-dx to include non-melanocytic lesions.