Skin cancer risk in CHEK2 mutation carriers.

CHEK2 mutations have been linked with an increased risk of breast cancer. A unique challenge for oncodermatologists and oncologists is in the monitoring and counselling of patients regarding skin cancer risk due to CHEK2 mutation carrier status. In this review, we highlight current information in the literature on the risk of melanoma and non-melanoma skin cancers in CHEK2 mutation carriers. On the molecular level, CHEK2 is a cell cycle regulator that has been linked to cancer pathogenesis, though evidence from clinical studies regarding skin cancer risk has been inconsistent and conflicting. For melanoma, one study has demonstrated a statistically significant twofold risk of melanoma in individuals with CHEK2 mutations, particularly the CHEK2*1100delC variant. Five other studies did not show an association. For non-melanoma skin cancer, fewer data exist, with one prevalence study of CHEK2 mutations in a cohort of patients with basal cell carcinomas. Although there are currently no known studies of CHEK2 and cutaneous squamous cell carcinoma (SCC), data from other disciplines associating CHEK2 with head and neck SCCs are emerging. Overall, while there is currently not enough evidence to make conclusive statements regarding increased risk of melanoma and non-melanoma skin cancers in CHEK2 carriers, a molecular mechanism associating the mutation with cutaneous malignancy pathogenesis is evident, and further work is needed. Patient with CHEK2 mutations may benefit from screening dermatologic examinations with particular attention to skin cancers.

De novo subacute cutaneous lupus erythematosus-like eruptions in the setting of programmed death-1 or programmed death ligand-1 inhibitor therapy: clinicopathological correlation.

Immune checkpoint inhibitors (ICI) may cause eruptions resembling cutaneous autoimmune diseases. There are six cases of immunotherapy-associated subacute cutaneous lupus erythematosus (SCLE) in the literature. We present details of five patients referred to the Skin Toxicity Program at the Dana-Farber Cancer Institute/Brigham and Women's Cancer Center who developed de novo immunotherapy-associated SCLE-like eruptions, along with clinicopathological correlation and highlight potential mechanistic features and important diagnostic points. Two patients were maintained on topical corticosteroids, antihistamines and photoprotection. One had complete clearance and two had improvement with addition of hydroxychloroquine. Four patients continued their immunotherapy uninterrupted, while one had immunotherapy suspended for a month before restarting at full dose. Histopathologically, this series illustrates the temporal evolution of ICI-induced immune cutaneous reactions with SCLE subtype. Looking beyond the universally present lichenoid infiltrate, features of evolving SCLE were evident. We hypothesize that programmed death-1 blockade may induce immunological recognition of previously immunologically tolerated drug antigens, leading to epitope spreading and the SCLE phenotype.