Roberto A. Novoa

Dermatologist-level classification of skin cancer with deep neural networks

Skin cancer, the most common human malignancy, is primarily diagnosed visually, beginning with an initial clinical screening and followed potentially by dermoscopic analysis, a biopsy and histopathological examination. Automated classification of skin lesions using images is a challenging task owing to the fine-grained variability in the appearance of skin lesions. Deep convolutional neural networks (CNNs) show potential for general and highly variable tasks across many fine-grained object categories. Here we demonstrate classification of skin lesions using a single CNN, trained end-to-end from images directly, using only pixels and disease labels as inputs. We train a CNN using a dataset of 129,450 clinical images—two orders of magnitude larger than previous datasets—consisting of 2,032 different diseases. We test its performance against 21 board-certified dermatologists on biopsy-proven clinical images with two critical binary classification use cases: keratinocyte carcinomas versus benign seborrheic keratoses; and malignant melanomas versus benign nevi. The first case represents the identification of the most common cancers, the second represents the identification of the deadliest skin cancer. The CNN achieves performance on par with all tested experts across both tasks, demonstrating an artificial intelligence capable of classifying skin cancer with a level of competence comparable to dermatologists. Outfitted with deep neural networks, mobile devices can potentially extend the reach of dermatologists outside of the clinic. It is projected that 6.3 billion smartphone subscriptions will exist by the year 2021 (ref. 13) and can therefore potentially provide low-cost universal access to vital diagnostic care.

IL-17 and Regulatory Cytokines (IL-10 and IL-27) in L. braziliensis Infection

Cutaneous leishmaniasis (CL) is characterized by high production of pro‐inflammatory cytokines and development of pathology. Individuals with subclinical L. braziliensis infection (SC) have a positive skin test to leishmania, but do not develop disease. We evaluated whether the downregulation of inflammatory response in SC is mediated by IL‐10 and IL‐27 and whether IL‐17 is associated with control of infection. Participants include SC individuals, patients with CL and healthy subjects. Cytokines protein and mRNA were detected by ELISA and real‐time PCR. IFN‐γ and TNF‐α levels were higher in CL than in SC group. The IL‐10 levels and mRNA for IL‐10 were similar in both SC and CL. mRNA for IL‐27 was increased in cells from SC after stimulation with L. braziliensis antigen. There was a tendency for increased levels of IL‐17 in SC compared to CL. The weak type 1 immune response observed in SC L. braziliensis infection is not because of the regulatory effects of IL‐10 and IL‐27. The control of Leishmania infection may be mediated by innate immune response with participation of IL‐17. The results from this pilot study warrant further larger studies to investigate the potential contributions of IL‐17 and IL‐27 to the control of L. braziliensis infection.

Immunohistochemical analysis of lichenoid reactions in patients treated with anti-PD-L1 and anti-PD-1 therapy.

Recent advances in the immunotherapeutic treatment of cancer have led to the development of multiple new directed therapies including monoclonal antibodies that block the immune checkpoint T‐cell receptor programmed death 1 (PD‐1) and the PD‐1 ligand, programmed death ligand 1 (PD‐L1). Various immune‐related toxicities have been associated with these drugs including, most commonly, skin rashes.

Corrigendum: Dermatologist-level classification of skin cancer with deep neural networks

This corrects the article DOI: 10.1038/nature21056

Acneiform eruptions associated with vemurafenib

To the Editor: Acneiform eruptions are follicular reactions composed of comedones and inflammatory papulopustules that simulate acne vulgaris but are most commonly induced by medications. Comedones secondary to ductal hypercornification and subsequent inflammation drive acne, whereas in acneiform reactions, inflammation triggers papule and pustule formation with comedones forming secondarily. Vemurafenib is a small-molecule BRAF kinase inhibitor with affinity for the BRAF mutation present in 40% to 60% of melanomas, recently approved to treat patients with unresectable or metastatic melanoma. Cutaneous side effects of vemurafenib are photosensitivity, alopecia, xerosis, papillomas, squamous cell carcinomas, panniculitis, keratosis pilariselike eruptions, facial erythema, and palmoplantar hyperkeratosis. Although acneiform eruptions occur in up to 80% of patients treated with sorafenib, a multikinase inhibitor targeting BRAF and CRAF kinases, only 1 prior case of facial cystic lesions was reported in a patient on vemurafenib. We report 3 patients with no history of acne or folliculitis who developed acneiform eruptions after treatment with vemurafenib. In the first case, a 46-year-old Caucasian man with metastatic melanoma and hypertension presented with multiple closed and open comedones and inflammatory papules and pustules on the face, scalp, chest, and back within 4 weeks of starting vemurafenib at the standard dose of 960 mg twice daily (Figs 1 and 2). Follow-up was not available as the patient died because of complications of melanoma. In the second case, a 51-year-old Caucasian woman with metastatic melanoma and migraines presented within 4 weeks of starting vemurafenib with comedones and inflammatory papules predominantly on her forehead (Fig 3). The comedones and inflammatory papules did not resolve with dose reduction for noncutaneous side effects to 720 mg twice daily; however, the patient did not pursue treatment for the acneiform eruption because it was not bothersome. In the third case, a 57-year-old Caucasian man with metastatic melanoma and hypertension presented within 5 weeks of starting vemurafenib with

Cutaneous Complications in Hematopoietic Cell Transplant Recipients: Impact of Biopsy on Patient Management

The utility of cutaneous biopsies in directing the management of post-hematopoietic cell transplantation (HCT) eruptions remains uncertain. We retrospectively analyzed 439 consecutive HCT procedures for malignant hematologic disorders performed at our institution between January 2005 and December 2012; 192 patients underwent 430 cutaneous biopsies. The clinical and dermatopathologic diagnosis differed in 240 cases (56%). Biopsy results led to a change in therapy in 69 (16%) episodes. Seventeen of 69 management changes occurred in response to a clinical diagnosis of graft-versus-host disease and resulted in augmentation of systemic immunosuppression. The management was modified with similar frequencies with respect to concordance or discordance between the clinical and histopathologic diagnosis (P = .51). We used classification and regression tree (CART) analysis, a decision-modeling technique, to predict the biopsy yield as expressed by impact on clinical management in the allogeneic and autologous setting. The models were cross-validated and then tested against a validation subset, and they maintained a high negative predictive value and high specificity. Although skin biopsies may not be mandatory for either diagnostic or therapeutic reasons, in carefully chosen circumstances, this procedure can yield extremely important data. We believe a prospective study should be undertaken to evaluate current practice data and to validate our decision tree models.

Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology

Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision‐making.

Invasive Melanoma in a Patient with Congenital Ichthyosiform Erythroderma.

We describe the case of a 26‐year‐old woman with a history of congenital ichthyosiform erythroderma (CIE) who initially presented with a stage IIA amelanotic melanoma on her forearm that was surgically excised. We also review the literature on CIE‐associated skin cancers and discuss the possible contribution of ichthyosis to the risk of cutaneous malignancies. Our findings emphasize the importance of close lifelong skin cancer screening in individuals with CIE and highlight the unique malignancy risk of these individuals.

Carpet beetle dermatitis: a possibly under-recognized entity

A 74-year-old man presented for evaluation of recalcitrant pruritic papules, pustules, and pinpoint vesicles of six months duration, initially involving his lower back and extending to the extremities by the time of presentation. He reported nocturnal worsening of pruritus and no known alleviating factors. His wife denied any similar symptoms but, notably, slept in a different room. The patient had a history of hypertension, hyperlipidemia, asthma, and prostate cancer. He had undergone definitive treatment for the cancer with brachytherapy eight years earlier. Additional daily medications included metoprolol, atorvastatin, fluticasone, albuterol, aspirin, cholecalciferol, and a multivitamin supplement. Physical examination revealed an erythematous papulopustular eruption with sparse rare vesicles (Fig. 1). Histopathology demonstrated a spongiotic dermatitis with superficial and deep eosinophilic infiltrates (Fig. 2a,b) suggestive of arthropod hypersensitivity reaction. Because of initial concerns for an infestation of Cimex lectularius, the patient’s home was evaluated by two different exterminators, each of whom independently diagnosed an infestation of carpet beetles. Final confirmation was obtained by the inspection of several collected samples of mature beetles and larvae (Fig. 2c–e) acquired

Paraneoplastic granulomatous dermatitis in a patient with Hodgkin’s disease: a diagnostic pitfall

The association of malignant lymphomas with non-necrotic epithelioid granulomas has been reported rarely since 1977. Hodgkin’s disease-associated widespread cutaneous granuloma annulare (GA) has been reported in only eight patients. We report the second case of subcutaneous GA associated with Hodgkin’s disease. A 73-year-old man with Epstein-Barr virus-associated Hodgkin’s lymphoma and paraneoplastic subcutaneous GA, presented 3 months after the diagnosis of malignancy. Examination revealed a large, broad erythematous, indurated, subcutaneous plaque spanning the majority of the left lower back and flank with no associated symptoms. Initial biopsy was suggestive of morphea. Prompted by positron emission tomography (PET) findings of increased fluorodeoxyglucose (FDG) uptake, a second, deeper biopsy was performed, revealing subcutaneous palisaded granulomatous dermatitis. After complete workup, the diagnosis most strongly suggested subcutaneous GA. This case highlights the importance of deep incisional biopsies, the fluorodeoxyglucose - positron emission tomography (FDG-PET) findings in GA and the rare association of GA with Hodgkin’s disease which may signal the presence of malignancy.