Roberto Novoa, MD

All Publications

• Dermatologist-level classification of skin cancer with deep neural networks. Nature Esteva, A., Kuprel, B., Novoa, R. A., Ko, J., Swetter, S. M., Blau, H. M., Thrun, S. 2017; 542 (7639): 115-118

  Abstract

  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.

  View details for DOI 10.1038/nature21056

  View details for PubMedID 28117445

• Gain of CD26 expression on the malignant T-cells in relapsed erythrodermic leukemic mycosis fungoides. Journal of cutaneous pathology Cedeno-Laurent, F., Wysocka, M., Obstfeld, A. E., Novoa, R. A., Vittorio, C. C., Kim, E. J., Weng, W., Rook, A. H. 2017

  Abstract

  Loss of CD26 surface expression on the circulating malignant T-cell is the most widely accepted diagnostic marker in patients with leukemic cutaneous T-cell lymphoma (CTCL). CTCL cases with reemergence of CD7 and/or CD26 surface expression are unusual and of uncertain prognosis. We report the case of an erythrodermic leukemic mycosis fungoides patient who had achieved temporary remission after a several months on multimodality immunotherapy and extracorporeal photopheresis, but who relapsed with aggressive disease phenotypically characterized by CD4+ T-cells with high CD26 expression. Polymerase chain reaction (PCR) studies and high throughput sequencing analyses from peripheral blood mononuclear cells at presentation and relapse consistently showed an identical clonal T-cell receptor (TCR) suggesting evolution of her original malignant clone which lacked CD26 expression. Interestingly, quantitative expression of the sialomucin, CD164, mirrored her clinical picture, thus favoring its reliability as a novel biomarker in CTCL.

  View details for DOI 10.1111/cup.12899

  View details for PubMedID 28083948

• Development of RET mutant cutaneous angiosarcoma during BRAF inhibitor therapy. Journal of cutaneous pathology Dai, J., Kunder, C. A., Chu, E. Y., Chan, E. F., Egan, C. L., Novoa, R. A. 2017

  Abstract

  Treatment with BRAF inhibitors may lead to paradoxical mitogen-activated protein kinase (MAPK) pathway activation and accelerated tumorigenesis in cells with preexisting oncogenic hits. This phenomenon manifests clinically in the development of squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) in patients treated with BRAF inhibitors. Cases of extracutaneous malignancies associated with BRAF inhibitors have also been reported. We present a case of a patient who developed a cutaneous angiosarcoma 6 months after initiation of vemurafenib therapy. Next-generation sequencing (NGS) revealed a mutation in RET, which lies upstream of the MAPK pathway. This case highlights that treatment with BRAF inhibitors may promote the accelerated growth of secondary malignancies. Physician awareness of the spectrum of secondary malignancies associated with BRAF inhibitor treatment will support their early detection and treatment.

  View details for DOI 10.1111/cup.13024

  View details for PubMedID 28796396

• Invasive Melanoma in a Patient with Congenital Ichthyosiform Erythroderma PEDIATRIC DERMATOLOGY Jaju, P., Novoa, R. A., Swetter, S. M., Sarin, K. Y. 2017; 34 (1): E35-E36

  View details for DOI 10.1111/pde.13012

  View details for Web of Science ID 000393955600008

• Invasive Melanoma in a Patient with Congenital Ichthyosiform Erythroderma. Pediatric dermatology Jaju, P., Novoa, R. A., Swetter, S. M., Sarin, K. Y. 2016

  Abstract

  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.

  View details for DOI 10.1111/pde.13012

  View details for PubMedID 27813222

• Low-Dose Radiotherapy for Primary Cutaneous Anaplastic Large-Cell Lymphoma While on Low-Dose Methotrexate CUTIS Cornejo, C. M., Novoa, R. A., Krisch, R. E., Kim, E. J. 2016; 98 (4): 253-256

  Abstract

  Primary cutaneous anaplastic large-cell lymphoma (pcALCL) is part of a spectrum of CD30+ primary cutaneous lymphoproliferative disorders (pcLPDs) that also includes lymphomatoid papulosis (LyP). Localized radiotherapy at doses of 34 to 44 Gy is first-line treatment of pcALCL, but the use of low-dose radiotherapy for pcALCL has not been reported. We present the case of a patient with a history of pcALCL/LyP who was treated with low-dose radiotherapy while on oral low-dose methotrexate (MTX) once weekly. This report suggests that low-dose radiotherapy can be an effective palliative treatment of pcALCL. Low-dose radiotherapy may offer certain advantages over traditional radiotherapy, such as a more economical and efficient treatment for patients, potentially fewer short-term and long-term side effects, and the potential for concomitant use with low-dose MTX.

  View details for Web of Science ID 000388917900015

  View details for PubMedID 27874877

• Epidermotropic metastasis of primary lung adenocarcinoma. Journal of cutaneous pathology Scott, G. D., Kwong, B. Y., Novoa, R. A. 2016; 43 (9): 798-801

  Abstract

  Cutaneous metastasis of lung cancer is a rare event and usually portends a grim prognosis. Several cases of lung cancer with cutaneous metastasis have been reported, but these have been largely limited to the dermis. Here we describe a unique case of cutaneous metastatic lung adenocarcinoma largely limited to the epidermis, mimicking Paget's disease or a cutaneous adnexal tumor.

  View details for DOI 10.1111/cup.12741

  View details for PubMedID 27234927

• Carpet beetle dermatitis: a possibly under-recognized entity INTERNATIONAL JOURNAL OF DERMATOLOGY MacArthur, K. M., Richardson, V., Novoa, R. A., Stewart, C. L., Rosenbach, M. 2016; 55 (5): 577-579

  View details for DOI 10.1111/ijd.12952

  View details for Web of Science ID 000374003900035

  View details for PubMedID 26475226

• Immunohistochemical analysis of lichenoid reactions in patients treated with anti-PD-L1 and anti-PD-1 therapy. Journal of cutaneous pathology Schaberg, K. B., Novoa, R. A., Wakelee, H. A., Kim, J., Cheung, C., Srinivas, S., Kwong, B. Y. 2016; 43 (4): 339-346

  Abstract

  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.Five cases of lichenoid dermatitis, including one case of lichenoid mucositis and one case of lichen sclerosus, associated with anti-PD-L1 and anti-PD1 therapy were compared with three biopsies of non-drug-related lichen planus (LP) and three lichen planus-like keratoses (LPLK) used as controls.Histopathologic and immunophenotypic analysis of these lichenoid lesions demonstrated significantly greater histiocytic infiltrates than observed in control lichenoid reactions (p = 0.0134). We also observed increased spongiosis and epidermal necrosis. No significant differences were seen in expression of CD3, CD4:CD8, CD20, PD-1, CD25, Foxp3, CXCL13 and PD-L1 expression.These findings expand the literature of immune-related toxicities of PD-L1 and PD-1 blockade to include lichenoid dermatitis and lichenoid mucositis. Of note, these cutaneous side effects were amenable to topical treatment, without the need for medication dose reduction or discontinuation.

  View details for DOI 10.1111/cup.12666

  View details for PubMedID 26762844

• Fistulizing Epstein-Barr virus-positive plasmablastic lymphoma in an HIV-positive man BRITISH JOURNAL OF DERMATOLOGY Rangel, J., Novoa, R., Morrison, C., Frank, D., Kovarik, C. 2016; 174 (2): 398-401

  Abstract

  Plasmablastic lymphoma (PBL) is an unusual subtype of non-Hodgkin lymphoma recently classified as a diffuse immunoblastic lymphoma with a plasma-cell immunophenotype. Originally described in the oral cavity of HIV-positive patients, it has also been recognized to occur rarely at other sites. We describe a previously unreported fistulizing presentation of Epstein-Barr virus (EBV)-positive PBL, reviewing its association with HIV-1 infection and its importance as an AIDS-defining malignancy.

  View details for DOI 10.1111/bjd.14089

  View details for Web of Science ID 000370014600029

  View details for PubMedID 26286218

• Erythematous Plaques on the Buttock JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Tan, C. Z., Novoa, R., Chen, J. K. 2016; 315 (1): 79-80

  View details for DOI 10.1001/jama.2015.13562

  View details for Web of Science ID 000367523000018

  View details for PubMedID 26746461

• Recurrent Subepidermal Blistering Dermatosis Heralding Disease Relapse in IgA Kappa Multiple Myeloma: Report of a Case and a Review of the Literature. Clinical lymphoma, myeloma & leukemia Leatham, H. W., Novoa, R., Liedtke, M., Kwong, B. Y. 2016; 16 (1): e1-5

  View details for DOI 10.1016/j.clml.2015.11.007

  View details for PubMedID 26708980

• Acquired port-wine stain with superimposed eczema following penetrating abdominal trauma. Cutis Langenhan, J., Novoa, R. A., Pappas-Taffer, L. 2015; 96 (6): 391-394

  Abstract

  Port-wine stains (PWSs), or capillary malformations, are common congenital lesions, but acquired lesions rarely present in the setting of trauma. We present the case of an 18-year-old man who developed a PWS and associated localized eczema following penetrating trauma to the left abdomen. The diagnoses were confirmed on biopsy. The patient's eczema improved with topical steroids. Magnetic resonance imaging of PWSs is recommended in order to rule out deeper arteriovenous malformations. More research is needed to elucidate the connection between PWS pathophysiology and the development of eczema.

  View details for PubMedID 26761933

• Presentation of Acute Megakaryoblastic Leukemia Associated with a GATA-1 Mutation Mimicking the Eruption of Transient Myeloproliferative Disorder PEDIATRIC DERMATOLOGY Boos, M. D., Lee, L. W., Freedman, J. L., Novoa, R. A., Chu, E. Y., Perman, M. J. 2015; 32 (5): E204-E207

  Abstract

  Children with trisomy 21 are prone to developing hematologic disorders, including transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL). The papulovesicular eruption of TMD provides an important clue to the diagnosis. In contrast, AMKL rarely has associated cutaneous findings. We report the case of a 22-month-old child with trisomy 21 who presented with the acute onset of diffusely scattered and crusted papules, plaques, and vesicles. A thorough infectious evaluation was negative and the patient was unresponsive to empiric antibiotic and antiinflammatory therapies. Complete blood count (CBC) was notable for mild pancytopenia, with a normal peripheral smear. Two weeks later he was reassessed and found to have a population of blasts on repeat CBC. Subsequent evaluation ultimately led to a diagnosis of AMKL. This is the first reported case of a cutaneous eruption in a young child with Down syndrome and transformed AMKL. When children with trisomy 21 present with the acute onset of crusted papules and vesicles that cannot be accounted for by an infectious etiology, a diagnosis of AMKL should be considered even in the absence of a history of TMD.

  View details for DOI 10.1111/pde.12643

  View details for Web of Science ID 000361184000003

  View details for PubMedID 26205501

• Erythrodermic Leukemia Cutis in a Patient With Pre-B-Cell Acute Lymphoblastic Leukemia. American Journal of dermatopathology Novoa, R. A., Wanat, K. A., Rosenbach, M., Frey, N., Frank, D. M., Elenitsas, R. 2015; 37 (8): 650-652

  Abstract

  The clinical differential diagnosis of erythroderma is extensive and includes both benign and malignant causes. The authors present an exceptional case of erythroderma secondary to pre-B-cell lymphoblastic leukemia cutis, with diagnostic findings on biopsy.

  View details for DOI 10.1097/DAD.0000000000000240

  View details for PubMedID 25436918

• Herlitz Junctional Epidermolysis Bullosa with a Novel Mutation in LAMB3 PEDIATRIC DERMATOLOGY Kittridge, A., Patel, R., Novoa, R., Tamburro, J. 2014; 31 (4): 530-532

  Abstract

  Herlitz junctional epidermolysis bullosa (H-JEB) is a rare, heritable mechanobullous disease that affects infants at birth and causes early death. This disease is primarily caused by compound heterozygous or homozygous mutations in one of three genes affecting the function of one of the three chains of the laminin-332 (formerly laminin-5) protein. Here we report a case of H-JEB with a novel heterozygous mutation in LAMB3,c.1597G>A (p.Ala533Thr). These findings attest to the molecular heterogeneity of JEB and emphasize the importance of genetic analysis to help make an accurate diagnosis, predict clinical prognosis, and identify phenotypic-genotypic relationships that may aid in prenatal diagnosis and genetic counseling for the future.

  View details for DOI 10.1111/pde.12018

  View details for Web of Science ID 000340598200037

  View details for PubMedID 23278291

• Hypertensive Emergency, Matlike Telangiectasias, and Calciphylaxis in POEMS Syndrome JAMA DERMATOLOGY Novoa, R. A., Honda, K. S., Campagnaro, E., Gerstenblith, M. R. 2014; 150 (6): 667-669

  View details for DOI 10.1001/jamadermatol.2013.7256

  View details for Web of Science ID 000337095800028

  View details for PubMedID 24718670

• Cutaneous epithelioid melanocytic neurofibroma arising in a patient with neurofibromatosis-1 JOURNAL OF CUTANEOUS PATHOLOGY Novoa, R. A., Kovarik, C. L., Low, D. W., Argenyi, Z. 2014; 41 (5): 457-461

  Abstract

  Tumors expressing both melanocytic and neural features can pose a diagnostic challenge to the dermatopathologist and provoke questions regarding their lineage. We report a case of a tumor arising on the right cheek of a 9-year-old boy with neurofibromatosis type 1 (NF-1). This neoplasm featured nests of non-pigmented epithelioid cells arising within a neurofibroma. The entire tumor stained strongly with S100, whereas the epithelioid population stained with MART-1, HMB-45 and MiTF. The neoplasm shows only scattered Ki-67 positivity. This tumor represents a neurofibroma with portions that have undergone melanocytic differentiation (melanocytic neurofibroma). This exceedingly rare tumor represents a distinct entity from neurotized melanocytic nevi, combined melanocytic nevi or pigmented neurofibromas and provides further evidence that melanocytes arise indirectly from ventromedial neural crest-derived Schwann cell precursors.

  View details for DOI 10.1111/cup.12297

  View details for Web of Science ID 000337515700008

  View details for PubMedID 24472086

• Cutaneous Complications in Hematopoietic Cell Transplant Recipients: Impact of Biopsy on Patient Management BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Paun, O., Phillips, T., Fu, P., Novoa, R. A., Honda, K. S., Lug, K. Q., Lazarus, H. M. 2013; 19 (8): 1204-1209

  Abstract

  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.

  View details for DOI 10.1016/j.bbmt.2013.05.006

  View details for Web of Science ID 000322607000013

  View details for PubMedID 23688396

• Acneiform eruptions associated with vemurafenib JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Petukhova, T. A., Novoa, R. A., Honda, K., Koon, H. B., Gerstenblith, M. R. 2013; 68 (3): E97-E99

  View details for DOI 10.1016/j.jaad.2012.09.015

  View details for Web of Science ID 000314823100006

  View details for PubMedID 23394928

• Vasculitis and panniculitis associated with vemurafenib JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Novoa, R. A., Honda, K., Koon, H. B., Gerstenblith, M. R. 2012; 67 (6): E271-E272

  View details for DOI 10.1016/j.jaad.2012.05.019

  View details for Web of Science ID 000312131200013

  View details for PubMedID 23158633

• IL-17 and Regulatory Cytokines (IL-10 and IL-27) in L-braziliensis Infection PARASITE IMMUNOLOGY NOVOA, R., Bacellar, O., Nascimento, M., Cardoso, T. M., Ramasawmy, R., OLIVEIRA, W. N., Schriefer, A., Carvalho, E. M. 2011; 33 (2): 132-136

  Abstract

  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.

  View details for DOI 10.1111/j.1365-3024.2010.01256.x

  View details for Web of Science ID 000286208100005

  View details for PubMedID 21226726

• Ecstasy use and its association with sexual behaviors among drug users in New York City JOURNAL OF COMMUNITY HEALTH Novoa, R. A., Ompad, D. C., Wu, Y. F., Vlahov, D., Galea, S. 2005; 30 (5): 331-343

  Abstract

  In the past two decades, recreational use of ecstasy has become a growing concern in the United States, although most studies assessing ecstasy use have focused on white, middle-class adolescents who use ecstasy during raves and in clubs. We assessed the prevalence of recent ecstasy use among predominantly minority heroin, cocaine, and crack users in New York City and the association between ecstasy and sexual risk above and beyond that of the other drugs. Between 2002 and 2004, injection and non-injection heroin, crack and cocaine users (N= 534) completed a risk behavior questionnaire that included items on ecstasy use. Logistic regression was used to investigate the relation between current ecstasy use and sexual behaviors. Of 534 illicit drug users, 69.7% were aged 25 years or older, 65.2% were Hispanic, 27.9% Black and 77.4% male; 36.7% were injectors. 17.2% of respondents reported recent (last six months) ecstasy use. In a multivariable logistic regression model, current ecstasy use was associated both with initiating sex before age 14 (adjusted odds ratio (AOR) = 1.51) and having two or more partners in the past two months (AOR = 1.86) after adjusting for age at study entry, current cocaine and marijuana use and being an injection drug user. This study suggests that ecstasy use may be more prevalent among urban drug users. Ecstasy use in urban settings, beyond clubs and raves, should continue to be monitored.

  View details for DOI 10.1007/s10900-005-5515-0

  View details for Web of Science ID 000231867700002

  View details for PubMedID 16175956