Hypoxic transcriptomes predict survival and tumor-infiltrating immune cell composition in cutaneous melanoma.

Hypoxia has established associations with aggressive tumor phenotypes in many cancers. However, it is not currently understood whether tumor hypoxia levels map to distinct immune infiltrates in cutaneous melanoma, potentially unveiling novel therapeutic targets. To this end, we leveraged a previously identified seven-gene hypoxia signature to grade hypoxia levels of 460 cutaneous melanomas obtained from the Broad Institute GDAC Firehose portal. CIBERSORTx ( https://cibersortx.stanford.edu/ ) was employed to calculate the relative abundance of 22 mature human hematopoietic populations. Clinical outcomes and immune cell associations were assessed by computational means. Results indicated that patients with high-hypoxia tumors reported significantly worse overall survival and correlated with greater Breslow depth, validating the in-silico methodology. High-hypoxia tumors demonstrated increased infiltration of activated and resting dendritic cells, resting mast cells, neutrophils, and resting NK cells, but lower infiltration of gamma-delta T cells. These data suggest that high tumor hypoxia correlates with lower survival probability and distinct population differences of several tumor-infiltrating leukocytes in cutaneous melanomas.

Multiple Eruptive Keratoacanthomas Secondary to Nivolumab Immunotherapy.

Immune checkpoint inhibitors are increasingly being utilized for the treatment of advanced neoplastic disease and have been associated with wide-ranging cutaneous adverse effects. Though exceedingly rare, eruptive keratoacanthomas have been associated with the use of immune checkpoint inhibitors such as pembrolizumab and nivolumab, whose molecular target is the programmed cell death protein 1. Herein, we detail a case of numerous eruptive keratoacanthomas arising in a patient one month after initiation of nivolumab for recurrent metastatic oropharyngeal squamous cell carcinoma. Treatment with multiple rounds of intralesional corticosteroids and a several-month course of oral acitretin resulted in partial improvement. Subsequent treatment with intralesional 5-fluorouracil demonstrated near-complete resolution of the keratoacanthomas without discontinuation of nivolumab. Although eruptive keratoacanthomas secondary to immune checkpoint inhibitors are exceptionally rare, physicians should be aware of this cutaneous adverse effect as their use becomes more widespread.

Cutaneous Ovarian Carcinoma Metastases: Case Report and Literature Review.

Metastatic cutaneous ovarian carcinoma is a rare diagnosis with a poor prognosis. Cutaneous manifestations are variable in size and morphology. We report a woman presenting with cutaneous ovarian metastases mimicking reticulated dermatoses. Our patient presented with a four-month history of a mildly pruritic eruption in the setting of stage IV ovarian adenocarcinoma, for which she was undergoing carboplatin, doxorubicin, and bevacizumab chemotherapy. On exam, she had erythematous, indurated papules and plaques involving the right flank and breast, as well as a reticulated erythematous patch on the lower abdomen. Cutaneous ovarian metastases have varied presentations. Our case highlights an uncommon manifestation of ovarian metastases and reviews the prior literature.

Dupilumab-Associated Head and Neck Dermatitis With Ocular Involvement in a Ten-Year-Old With Atopic Dermatitis: A Case Report and Review of the Literature.

Facial and neck erythema secondary to dupilumab use is a side effect not reported in clinical trials; however, it has been reported aftermarket initially in adults and most recently in adolescents. We report the youngest known case of head and neck dermatitis (HND) secondary to Malassezia furfur accompanied by ocular involvement. Treatment with oral fluconazole 150 mg weekly was initiated with subsequent cutaneous improvement. Additionally, his conjunctivitis improved with fluorometholone 0.1% eye drops. As dupilumab becomes more accessible to children, understanding the pathophysiology of HND, characterizing the clinical course, and developing diagnostic and treatment guidelines for this age group will be imperative.

Tumor Necrosis Factor Inhibitor-Induced Eczematous Eruption: A Report of Two Cases and Review of the Literature.

Tumor necrosis factor-alpha (TNF-α) inhibitors are frequently used for the management of type 1 helper T-cell (Th1) immune-mediated chronic inflammatory conditions such as psoriasis and Crohn's disease. Although TNF-α inhibitors are usually well-tolerated, various cutaneous side effects are frequently observed, including eczematous or atopic dermatitis-like eruptions. It is postulated that the attenuation of the Th1 immune pathway with TNF-α inhibition causes a shift towards a type 2 helper T-cell (Th2) immune response, leading to the development of skin lesions grossly and histologically consistent with the Th2 mediated disease atopic dermatitis. Herein, we describe the development of an eczematous eruption in two patients with a history of Th1-mediated disease after months of therapy with a TNF-α inhibitor.

Dermatology leadership and a top-down approach to increasing diversity.

The reasons underlying the lack of diversity within dermatology can be broadly categorized into lack of mentorship, decreased awareness of the specialty during medical school, socioeconomic barriers associated with the application process, and implicit bias during resident selection. This contribution examines the need for diversity in medicine and provides insight into the reasons behind the low number of underrepresented minority residents in dermatology. Leadership strategies that may help increase diversity in the field are also reviewed.