72 results on '"Novoa RA"'
Search Results
2. Mola hidatidiforme completa con preeclampsia e hipertiroidismo: presentación clásica
- Author
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Rodrigo Arriagada D, Paulina Urrutia S, and Romina Novoa Ra
- Subjects
preeclampsia ,hipertiroidismo ,embarazo molar/complicaciones ,embarazo ,Obstetrics and Gynecology ,Mola hidatidiforme completa ,femenino - Abstract
Introducción: La enfermedad trofoblástica gestacional es un espectro de enfermedades de la placenta, existiendo entre ellas algunas con potencial de invasión y metástasis, dentro de las cuales se incluye la mola invasiva, coriocarcinoma, tumores del sitio de inserción de la placenta y mola hidatidiforme. Esta última a su vez se divide en mola completa y parcial, diferenciándose en histopatología, morfología, cariotipo, malignización y comportamiento clínico, que es el punto al cual nos referiremos en este caso. Caso clínico: mujer de 46 años ingresa por hemoptisis, metrorragia, disnea a pequeños esfuerzos, ortopnea y disnea paroxística nocturna, asociado a hipertensión, taquicardia, masa hipogástrica firme e inmóvil y edema de extremidades. Se realiza ecografía abdominal compatible con MH y bhCG elevada. Evoluciona con crisis hipertensivas, insuficiencia cardiaca congestiva y tirotoxicosis. Inicia trabajo de parto expulsando 665 grs de mola, presentando posteriormente a legrado uterino anemia severa y shock hipovolémico, requiriendo transfusiones y drogas vasoactivas. Se recupera progresivamente con posterior control al alta de bhCG indetectable a los 6 meses. Discusión: Es infrecuenta en la actualidad la presentación clínica clásica de la mola hidatidiforme completa debido al diagnóstico y control precoz del embarazo asociado al uso masivo de la ecografía. Sin embargo es relevante tener un alto grado de sospecha de esta patología debido a sus graves consecuencias, y así realizar una derivación y manejo precoz.
- Published
- 2017
3. Mola hidatidiforme completa con preeclampsia e hipertiroidismo: presentación clásica
- Author
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Arriagada D, Rodrigo, Novoa Ra, Romina, and Urrutia S, Paulina
- Subjects
preeclampsia ,hipertiroidismo ,embarazo molar/complicaciones ,embarazo ,molar pregnancy/complications ,Complete hydatidiform mole ,Mola hidatidiforme completa ,pregnancy ,hyperthyoidism ,femenino - Abstract
Introducción: La enfermedad trofoblástica gestacional es un espectro de enfermedades de la placenta, existiendo entre ellas algunas con potencial de invasión y metástasis, dentro de las cuales se incluye la mola invasiva, coriocarcinoma, tumores del sitio de inserción de la placenta y mola hidatidiforme. Esta última a su vez se divide en mola completa y parcial, diferenciándose en histopatología, morfología, cariotipo, malignización y comportamiento clínico, que es el punto al cual nos referiremos en este caso. Caso clínico: mujer de 46 años ingresa por hemoptisis, metrorragia, disnea a pequeños esfuerzos, ortopnea y disnea paroxística nocturna, asociado a hipertensión, taquicardia, masa hipogástrica firme e inmóvil y edema de extremidades. Se realiza ecografía abdominal compatible con MH y bhCG elevada. Evoluciona con crisis hipertensivas, insuficiencia cardiaca congestiva y tirotoxicosis. Inicia trabajo de parto expulsando 665 grs de mola, presentando posteriormente a legrado uterino anemia severa y shock hipovolémico, requiriendo transfusiones y drogas vasoactivas. Se recupera progresivamente con posterior control al alta de bhCG indetectable a los 6 meses. Discusión: Es infrecuenta en la actualidad la presentación clínica clásica de la mola hidatidiforme completa debido al diagnóstico y control precoz del embarazo asociado al uso masivo de la ecografía. Sin embargo es relevante tener un alto grado de sospecha de esta patología debido a sus graves consecuencias, y así realizar una derivación y manejo precoz. Background: Gestational trophoblastic disease is a spectrum of diseases of the placenta, existing some with potential for invasion and metastasis, among which include invasive mole, choriocarcinoma, tumors of the insertion site of the placenta and hydatidiform mole. The last one is divided into complete and partial mole, differing in histopathology, morphology, karyotype, and clinical malignant behavior, witch is the point we refer to in this case. Case report: 46 year old woman admitted for hemoptysis, metrorrhagia, dyspnea on slight exertion, orthopnea and paroxysmal nocturnal dyspnea associated with hypertension, tachycardia, firm and immovable hypogastric mass and limb edema. Abdominal ultrasound compatible with MH and high BhCG is performed. Evolve with hypertensive crisis, congestive heart failure and thyrotoxicosis. Labor starts driving out 665 grams of mole, after the curettage present hypovolemic shock and severe anemia requiring transfusions and vasoactive drugs. It gradually recovers further control the discharge of BhCG undetectable at 6 months. Discussion: It is currently infrequent classical clinical presentation of complete hydatidiform mole due to early diagnosis and management of pregnancy associated with the widespread use of ultrasound. However it is important to have a high degree of suspicion of this disease because of its serious consequences, and thus make a referral and early management.
- Published
- 2017
4. Mola hidatidiforme completa con preeclampsia e hipertiroidismo: presentación clásica
- Author
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Arriagada D, Rodrigo, primary, Novoa Ra, Romina, additional, and Urrutia S, Paulina, additional
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- 2017
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5. La madurez del fruto y el secado del cáliz influyen en el comportamiento poscosecha de la uchuva, almacenada a 12 °C (Physalis peruviana L.)
- Author
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Novoa Rafael H., Bojacá Mauricio, Galvis Jesús Antonio, and Fischer Gerhard
- Subjects
Plant ecology ,QK900-989 - Abstract
Se estudio el comportamiento fisicoquímico y fisiologico del fruto de uchuva durante la poscosecha. El fruto se cosecho en los grados de madurez 4 (color verde amarrillo) y 5 (amarillo), según norma 4850 de Icontec (Instituto de Normas Tecnicas y Certificacion), y se almaceno a 12 oC y 85% humedad relativa durante 30 d. Previamente, los calices se secaron a temperaturas de 18 oC y 24 oC durante 6 h. Se determino la intensidad respiratoria por cromatografia de gases y el contenido de acidos organicos y azucares por cromatografía liquida de alto desempeno. Los resultados mostraron que la uchuva es un fruto climaterico, que presenta el maximo de respiracion a los 12 d de almacenamien to. Los tratamientos con secado del caliz a 24 oC fueron mas eficientes, ya que el fruto respiro menos, comparado con las uchuvas cuyo caliz fue secado a 18 oC. Entre los acidos organicos evaluados, el acido citrico resulto predominante en el fruto, seguido por los acidos malico, ascorbico, tartarico y oxalico, respectivamente. La perdida de acido as corbico en el fruto fue total despues de12 d de almacenamiento. Los azucares predominantes en la uchuva fueron, en su orden, sacarosa, glucosa y fructosa. Frutos cosechados en grado de madurez (GM) 4 con secado del caliz a 24 oC y aquellos en GM 5 y secados a 18 °C conservaron mejor la concentración de sacarosa. Se presento Botrytis cinerea en frutos con secado del caliz a 18 oC.
- Published
- 2006
6. Site-discordant expression of myeloid cell nuclear differentiation antigen in blastic plasmacytoid dendritic cell neoplasm.
- Author
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Bulterys PL, Saleem A, Brown RA, Novoa RA, Rieger KE, Natkunam Y, and Fernandez-Pol S
- Abstract
Objectives: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic neoplasm that can show clinical, morphologic, and immunophenotypic overlap with acute myeloid leukemia. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed by myelomonocytic cells previously reported to be reliably absent in BPDCN and proposed as a useful adjunct for the distinction of BPDCN and acute myeloid leukemia. We encountered a case of BPDCN that showed strong nuclear expression of MNDA in bone marrow and breast samples and weak to absent expression in skin samples, prompting us to reevaluate the expression of MNDA in BPDCN., Methods: We collected all available BPDCN cases from the Stanford University archives collected in the past 10 years and subjected them to MNDA immunohistochemistry. In select cases, molecular profiling by next-generation sequencing was performed., Results: We found 4 cases (of 8 total examined [50%]) with convincing site-discordant MNDA expression. This expression was seen in 3 of 6 (50%) bone marrow samples, 1 of 2 (50%) breast soft tissue samples, and 3 of 14 (up to 21%) skin samples and was not obviously predicted by age, sex, history of myeloid neoplasm, or treatment history. In 2 cases, MNDA was strongly expressed in 2 distinct sites (breast/bone marrow, skin/bone marrow) and negative in subsequent samples., Conclusions: Our findings suggest that MNDA expression in BPDCN is anatomic site dependent and transient, with noncutaneous infiltrates showing more frequent expression than cutaneous infiltrates. These results caution against the use of MNDA to exclude BPDCN when considering the differential diagnosis of a blastic extramedullary infiltrate., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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7. Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis.
- Author
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Starrett GJ, Baikie BC, Stoff BK, Grossniklaus HE, Van Buren I, Berry EG, Novoa RA, Rieger KE, Sarin KY, Lynch CF, Royer MC, Piaskowski ML, Brownell I, Chu EY, Godse R, Chen SC, Yu KJ, Goldstein AM, Engels EA, and Sargen MR
- Abstract
Purpose: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment., Experimental Design: We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021., Results: We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions., Conclusions: The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies., (©2024 American Association for Cancer Research.)
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- 2024
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8. Histopathologic and Clinical Characterization of Brentuximab Vedotin-associated Rash.
- Author
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Narala S, Saleem A, Brown RA, Novoa RA, Kim YH, and Rieger KE
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- Humans, Female, Male, Middle Aged, Retrospective Studies, Aged, Adult, Immunoconjugates adverse effects, Skin Neoplasms pathology, Skin Neoplasms drug therapy, Antineoplastic Agents, Immunological adverse effects, Biopsy, High-Throughput Nucleotide Sequencing, Aged, 80 and over, Skin pathology, Skin drug effects, Skin immunology, Diagnosis, Differential, Brentuximab Vedotin adverse effects, Drug Eruptions pathology, Drug Eruptions etiology, Drug Eruptions diagnosis, Exanthema chemically induced, Exanthema pathology, Lymphoma, T-Cell, Cutaneous pathology, Lymphoma, T-Cell, Cutaneous drug therapy
- Abstract
Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient's underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug discontinuation. We performed a thorough clinical and histopathologic retrospective characterization of BVAR from a single institution. Utilizing polymerase chain reaction (PCR) and T-cell receptor high-throughput sequencing (TCR-HTS), we were able to isolate skin biopsy specimens from rash clinically suggestive of BVAR that also lacked a dominant TCR clone. A retrospective evaluation was performed of 26 biopsy specimens from 14 patients. Clinical features of BVAR included predominantly morbilliform or maculopapular morphology, delayed onset, and the trend toward moderate to severe classification, often requiring oral steroids. Most histopathologic specimens (25/26) showed spongiotic dermatitis as the primary reaction pattern. Many cases showed subtle findings to support a background interface or lichenoid eruption. Langerhans cell microabscesses were seen in one-fourth of specimens, and eosinophils were present in over one-half of the specimens. There were focal features mimicking CTCL, but these were not prominent. In 17 specimens with immunohistochemistry, the CD4:CD8 ratio in intraepidermal lymphocytes was relatively normal (1-6:1) in 65% (11/17) and 1:1 in 35% (6/17), demonstrating a trend toward increased CD8-positive cells compared with baseline CTCL. We have identified features that can help distinguish BVAR from a patient's CTCL, which can, in turn, help guide appropriate clinical management., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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9. Assessment of Correctness, Content Omission, and Risk of Harm in Large Language Model Responses to Dermatology Continuing Medical Education Questions.
- Author
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Cai ZR, Chen ML, Kim J, Novoa RA, Barnes LA, Beam A, and Linos E
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- Humans, Language, Dermatology education, Education, Medical, Continuing
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- 2024
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10. Cutaneous larva migrans in the northeastern US.
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Johanis M, Cheema KS, Young PA, Narala S, Saleem A, Novoa RA, and Bae GH
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- Humans, Female, Middle Aged, Ivermectin therapeutic use, Skin pathology, Epidermis, Larva Migrans diagnosis, Larva Migrans drug therapy, Larva Migrans epidemiology, Exanthema pathology
- Abstract
Cutaneous larva migrans (CLM) is a dermo-epidermal parasitic infection with a disproportionate incidence in developing countries, particularly in, and near tropical areas. It is characterized by erythematous, twisting, and linear plaques that can migrate to adjacent skin. Herein, we present an otherwise healthy 45-year-old woman who acquired a pruritic, erythematous, and serpiginous rash localized to her right medial ankle during a trip to New England. Oral ivermectin, the preferred first-line treatment for cutaneous larva migrans, was administered in combination with triamcinolone. This was followed by removal of the papular area via punch biopsy; treatment was successful with a one-week recovery. Although cutaneous larva migrans has traditionally been considered a tropical disease, clinicians should be cognizant of its expanding geographic spread.
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- 2023
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11. Best Practices for Clinical Skin Image Acquisition in Translational Artificial Intelligence Research.
- Author
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Phung M, Muralidharan V, Rotemberg V, Novoa RA, Chiou AS, Sadée CY, Rapaport B, Yekrang K, Bitz J, Gevaert O, Ko JM, and Daneshjou R
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- Humans, Artificial Intelligence, Dermatologists, Dermoscopy methods, Algorithms, Skin Neoplasms diagnostic imaging, Skin Neoplasms pathology, Melanoma pathology
- Abstract
Recent advances in artificial intelligence research have led to an increase in the development of algorithms for detecting malignancies from clinical and dermoscopic images of skin diseases. These methods are dependent on the collection of training and testing data. There are important considerations when acquiring skin images and data for translational artificial intelligence research. In this paper, we discuss the best practices and challenges for light photography image data collection, covering ethics, image acquisition, labeling, curation, and storage. The purpose of this work is to improve artificial intelligence for malignancy detection by supporting intentional data collection and collaboration between subject matter experts, such as dermatologists and data scientists., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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12. Erythema Gyratum Repens Secondary to Pulmonary Tuberculosis.
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Contag CA, Maloney N, Tayyar R, Aleshin MA, Novoa RA, and Ho DY
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- Humans, Erythema complications, Tuberculosis, Pulmonary complications
- Abstract
Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L22-0453.
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- 2023
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13. Evaluation of diagnosis diversity in artificial intelligence datasets: a scoping review.
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Chen ML, Rotemberg V, Lester JC, Novoa RA, Chiou AS, and Daneshjou R
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- Humans, Artificial Intelligence, Skin Diseases diagnosis
- Abstract
Competing Interests: Conflicts of interest: the authors declare they have no conflicts of interest.
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- 2023
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14. High prevalence of Leishmania spp. in dogs from Central West Colombia.
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Giraldo-Martínez LA, Petano-Duque JM, Uribe-García HF, Chacón-Novoa RA, Guzmán-Barragán BL, and Rondón-Barragán I
- Subjects
- Animals, Dogs, Prevalence, Colombia epidemiology, Cross-Sectional Studies, Zoonoses, Leishmania, Dog Diseases epidemiology
- Abstract
Leishmaniasis is a widespread disease caused by species of the genus Leishmania. In Colombia, this zoonosis is endemic in rural areas with a high prevalence in the departments of Antioquia, Santander, Meta, Tolima and Nariño. Dogs are the most important domestic reservoirs of the pathogen, given the epidemiological importance of dogs in the control of leishmaniasis is needed to determine the prevalence of Leishmania spp. in canine population of the rural area of Ibagué and to identify potential risk factors related to the presence of this parasite. A cross-sectional study was carried out in 173 dogs from the rural area of Ibagué. Leishmania spp. was detected by amplifying the Internal Transcribed Spacer (ITS-1) and two regions of the hsp70 gene through PCR. Factor associations were calculated through the Chisquare and odds ratio. Prevalence of Leishmania spp. infection in dogs was of 91.33% (158/173), where 36.71% (58/158) of the Leishmania spp. positive dogs showed one or more clinical signs of canine leishmaniasis and 63.29% (100/158) of the dogs were asymptomatic. Factors associated with the presence of the parasite did not show significance. In addition, hsp70D-PCR was proved to be highly efficient for the detection of Leishmania spp.
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- 2022
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15. Incidence Trends of Primary Cutaneous T-Cell Lymphoma in the US From 2000 to 2018: A SEER Population Data Analysis.
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Cai ZR, Chen ML, Weinstock MA, Kim YH, Novoa RA, and Linos E
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- Humans, United States epidemiology, Incidence, Data Analysis, SEER Program, Lymphoma, T-Cell, Cutaneous epidemiology, Lymphoma, T-Cell, Cutaneous pathology, Skin Neoplasms epidemiology
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- 2022
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16. Nutritional deficiency contributing to refractory erythroderma in hematopoietic cell transplant patients: Distinctive clinical and histopathologic findings.
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Winge MCG, Rieger KE, Kim J, Weng WK, Johnston LJ, Miklos DB, Win TS, Strelo J, Zaba LC, Pugliese SB, Novoa RA, and Kwong BY
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- Humans, Dermatitis, Exfoliative etiology, Hematopoietic Stem Cell Transplantation adverse effects, Malnutrition complications, Transplants pathology
- Abstract
Competing Interests: Conflicts of interest Dr Winge is a cofounder of PSOMRI Holding AB. Dr Kwong serves as a consultant for Oncoderm and Happy2ndBirthday. Authors Rieger, Kim, Weng, Johnston, Miklos, Strelo, Zaba, Pugliese, and Novoa have no conflicts of interest to disclose.
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- 2022
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17. Histologic subtype of cutaneous immune-related adverse events predicts overall survival in patients receiving immune checkpoint inhibitors.
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Hirotsu KE, Scott MKD, Marquez C, Tran AT, Rieger KE, Novoa RA, Robinson WH, Kwong BY, and Zaba LC
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- Administration, Cutaneous, Humans, Immunotherapy adverse effects, Retrospective Studies, Skin pathology, Immune Checkpoint Inhibitors adverse effects, Neoplasms drug therapy
- Abstract
Competing Interests: Conflicts of interest Dr Kwong is a consultant for Oncoderm and Happy 2nd Birthday. Dr Novoa is a consultant for Enspectra and Stemline therapeutics. Dr Rieger is a consultant for Pfizer and Kyowa Kirin. Drs Hirotsu, Marquez, Robinson, and Zaba and Authors Scott and Tran have no conflicts of interest to declare.
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- 2022
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18. Disparities in dermatology AI performance on a diverse, curated clinical image set.
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Daneshjou R, Vodrahalli K, Novoa RA, Jenkins M, Liang W, Rotemberg V, Ko J, Swetter SM, Bailey EE, Gevaert O, Mukherjee P, Phung M, Yekrang K, Fong B, Sahasrabudhe R, Allerup JAC, Okata-Karigane U, Zou J, and Chiou AS
- Abstract
An estimated 3 billion people lack access to dermatological care globally. Artificial intelligence (AI) may aid in triaging skin diseases and identifying malignancies. However, most AI models have not been assessed on images of diverse skin tones or uncommon diseases. Thus, we created the Diverse Dermatology Images (DDI) dataset-the first publicly available, expertly curated, and pathologically confirmed image dataset with diverse skin tones. We show that state-of-the-art dermatology AI models exhibit substantial limitations on the DDI dataset, particularly on dark skin tones and uncommon diseases. We find that dermatologists, who often label AI datasets, also perform worse on images of dark skin tones and uncommon diseases. Fine-tuning AI models on the DDI images closes the performance gap between light and dark skin tones. These findings identify important weaknesses and biases in dermatology AI that should be addressed for reliable application to diverse patients and diseases.
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- 2022
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19. Artificial intelligence for dermatopathology: Current trends and the road ahead.
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Chen SB and Novoa RA
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- Humans, Male, United States, Algorithms, Artificial Intelligence
- Abstract
Artificial intelligence (AI), including deep learning methods that leverage neural network-based algorithms, hold significant promise for dermatopathology and other areas of diagnostic pathology in research and clinical practice. There has been significant progress over past several years in applying AI to analyzing digital histopathology images for diagnosis. While much work in AI analysis of histopathology data remains investigational, recent regulatory agency approval in Europe and United States of AI-assisted tools for clinical use in histopathologic diagnosis of prostate and breast cancer herald broader movement of AI into the clinical diagnostic realm of anatomic pathology, including dermatopathology. However, significant challenges remain in translating AI from research into clinical practice, including algorithmic real-world performance, robustness to variation in data sets and practice settings, effective integration into clinical workflows, and cost effectiveness. This review introduces core concepts and terminology in AI, and assesses current progress and challenges in applying AI to dermatopathology., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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20. In Vivo reflectance confocal microscopy of cutaneous acute graft-versus-host disease: concordance with histopathology and interobserver reproducibility of a glossary with representative images.
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Saknite I, Gill M, Alessi-Fox C, Zwerner JP, Lehman JS, Shinohara MM, Novoa RA, Chen H, Byrne M, Gonzalez S, Ardigo M, and Tkaczyk ER
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- Humans, Microscopy, Confocal methods, Reproducibility of Results, Graft vs Host Disease diagnostic imaging, Skin Neoplasms pathology
- Abstract
Background: The reliability to non-invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature-level interpretation among RCM readers., Objectives: (1) Develop a glossary with representative images of RCM features of cutaneous acute graft-versus-host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features., Methods: Through an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement., Results: We present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71-79%) did not differ significantly from dermatopathologists (80%, 76-85%). The concordance between RCM and histopathology was 59%., Conclusions: By using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set., (© 2022 European Academy of Dermatology and Venereology.)
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- 2022
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21. Spitz nevus with EHBP1-ALK fusion and distinctive membranous localization of ALK.
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Bahrani E, Kunder CA, Teng JM, Brown RA, Rieger KE, Novoa RA, and Cloutier JM
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- Adolescent, Anaplastic Lymphoma Kinase genetics, Female, Gene Fusion, Humans, Anaplastic Lymphoma Kinase metabolism, Carrier Proteins metabolism, Nevus, Epithelioid and Spindle Cell genetics, Nevus, Pigmented, Skin Neoplasms genetics, Skin Neoplasms pathology
- Abstract
ALK rearrangements define a histopathologically distinctive yet diverse subset of Spitz tumors characterized by fusiform to epithelioid melanocytes with frequent fascicular growth and ALK overexpression. Molecularly, these tumors are characterized by fusions between ALK and a variety of gene partners, most commonly TPM3 and DCTN1. We describe an unusual case of a Spitz nevus occurring in a 13-year-old female that manifested ALK immunopositivity with cell membrane localization. The proliferation was polypoid and composed of elongated nests of epithelioid melanocytes with enlarged nuclei, prominent nucleoli, and abundant cytoplasm without significant atypia and lacking mitotic figures. The nevus exhibited strong and diffuse expression of p16. Targeted next-generation RNA sequencing revealed an in-frame EHBP1-ALK fusion, which has been reported only once in the literature. EHBP1 encodes an adaptor protein with plasma membrane targeting potential. Together, these findings suggest that the 5' ALK fusion partner in Spitz tumors may dictate the subcellular localization of the ALK chimeric oncoprotein. In summary, this case highlights a rare ALK fusion associated with a distinct immunohistochemical staining pattern and further expands the spectrum of ALK-rearranged melanocytic tumors., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2022
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22. Next-generation sequencing confirms T-cell clonality in a subset of pediatric pityriasis lichenoides.
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Raghavan SS, Wang JY, Gru AA, Marqueling AL, Teng JMC, Brown RA, Novoa RA, Kim Y, Zehnder J, Zhang BM, and Rieger KE
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- Adolescent, Child, Child, Preschool, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Cloning, Molecular, Genes, T-Cell Receptor beta genetics, Genes, T-Cell Receptor gamma genetics, Pityriasis Lichenoides genetics
- Abstract
Background: Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR-based assays. In this study, we sought to implement next-generation sequencing (NGS) as a more sensitive and specific test to examine for T-cell clonality within the pediatric population., Methods: We identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with NGS of T-cell receptor beta (TRB) and gamma (TRG) genes., Results: Of the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow-up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T-cell clonality. Two patients showed matching TRB clones from different anatomic sites., Conclusions: T-cell clonality is a common finding in PL, probably representing a "reactive clonality" rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2022
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23. Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.
- Author
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Fung MA, Vidal CI, Armbrecht EA, Andea AA, Cassarino DS, Comfere NI, Emanuel PO, Ferringer T, Hristov AC, Kim J, Lauer SR, Linos K, Missall TA, Motaparthi K, Novoa RA, Patel R, Shalin SC, Sundram U, Calame A, Bennett DD, Duncan LM, Elston DM, Hosler GA, Hurley YM, Lazar AJ, Lowe L, Messina J, Myles J, Plaza JA, Prieto VG, Reddy V, Schaffer A, and Subtil A
- Subjects
- Evidence-Based Medicine standards, Humans, Societies, Medical, United States, Dermatology standards, Pathology, Clinical standards, Skin Diseases pathology
- Abstract
Background: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests., Methods: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2., Results: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain.", Limitations: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded., Conclusions: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2022
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24. Clinicopathologic characterization of enfortumab vedotin-associated cutaneous toxicity in patients with urothelial carcinoma.
- Author
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Hirotsu KE, Rana J, Wang JY, Raghavan SS, Rieger KE, Srinivas S, Fan AC, Kwong BY, Novoa RA, and Zaba LC
- Subjects
- Antibodies, Monoclonal therapeutic use, Humans, Lymphatic Metastasis, Skin pathology, Urinary Bladder Neoplasms secondary, Antibodies, Monoclonal adverse effects, Antineoplastic Agents, Immunological adverse effects, Carcinoma, Transitional Cell drug therapy, Drug Eruptions etiology, Skin drug effects, Urinary Bladder Neoplasms drug therapy
- Abstract
Competing Interests: Conflicts of interest Dr Kwong is a consultant for Genentech, Oncoderm, Happy 2nd Birthday, and is on the advisory board of Kyowa Kirin. Drs Hirotsu, Rana, Wang, Raghavan, Rieger, Srinivas, Fan, Novoa, and Zaba have no conflicts of interest to disclose.
- Published
- 2021
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25. Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor.
- Author
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Brown RA, Cloutier JM, Bahrani E, Liman A, Tasso D, Palmer A, Manning MA, Galperin I, Rieger KE, Novoa RA, Lau H, and Louie CY
- Subjects
- Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase genetics, Gene Rearrangement, Granular Cell Tumor genetics, Granular Cell Tumor pathology, Head and Neck Neoplasms genetics, Head and Neck Neoplasms pathology, Humans, Immunohistochemistry, Male, Skin Neoplasms genetics, Skin Neoplasms pathology, Xanthomatosis pathology, Anaplastic Lymphoma Kinase metabolism, Granular Cell Tumor metabolism, Head and Neck Neoplasms metabolism, Scalp, Skin Neoplasms metabolism, Xanthomatosis metabolism
- Abstract
Abstract: Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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26. Cutaneous acral myofibroma with PDGFRB mutation in a patient with linear morphea en coup de sabre.
- Author
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Pepper MA, Theparee T, Messenger EA, Brown RA, and Novoa RA
- Subjects
- Administration, Oral, Adult, Biopsy methods, Connective Tissue Diseases pathology, Dermatologic Agents administration & dosage, Dermatologic Agents therapeutic use, Female, High-Throughput Nucleotide Sequencing methods, Humans, Methotrexate administration & dosage, Methotrexate therapeutic use, Mutation, Myofibroma complications, Myofibroma diagnosis, Myofibroma drug therapy, Scleroderma, Localized diagnosis, Scleroderma, Localized drug therapy, Skin Neoplasms pathology, Treatment Outcome, Myofibroma genetics, Receptor, Platelet-Derived Growth Factor beta genetics, Scleroderma, Localized complications
- Published
- 2021
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27. Telescope punch biopsy of normal-appearing skin to diagnose intravascular lymphoma.
- Author
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Winge MCG, Iberri DJ, Novoa RA, Kwong BY, and Zaba LC
- Subjects
- Biopsy, Humans, Skin, Lymphoma, Lymphoma, Large B-Cell, Diffuse, Telescopes
- Published
- 2021
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28. TrueImage: A Machine Learning Algorithm to Improve the Quality of Telehealth Photos.
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Vodrahalli K, Daneshjou R, Novoa RA, Chiou A, Ko JM, and Zou J
- Subjects
- Algorithms, Computational Biology, Ecosystem, Humans, Machine Learning, Pandemics, SARS-CoV-2, COVID-19, Telemedicine
- Abstract
Telehealth is an increasingly critical component of the health care ecosystem, especially due to the COVID-19 pandemic. Rapid adoption of telehealth has exposed limitations in the existing infrastructure. In this paper, we study and highlight photo quality as a major challenge in the telehealth workflow. We focus on teledermatology, where photo quality is particularly important; the framework proposed here can be generalized to other health domains. For telemedicine, dermatologists request that patients submit images of their lesions for assessment. However, these images are often of insufficient quality to make a clinical diagnosis since patients do not have experience taking clinical photos. A clinician has to manually triage poor quality images and request new images to be submitted, leading to wasted time for both the clinician and the patient. We propose an automated image assessment machine learning pipeline, TrueImage, to detect poor quality dermatology photos and to guide patients in taking better photos. Our experiments indicate that TrueImage can reject ~50% of the sub-par quality images, while retaining ~80% of good quality images patients send in, despite heterogeneity and limitations in the training data. These promising results suggest that our solution is feasible and can improve the quality of teledermatology care.
- Published
- 2021
29. ALK-positive compound Spitz nevus with extensive perineural and intraneural neurotropism.
- Author
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Brown RA, Wang JY, Raghavan SS, Zhang J, Wan DC, Born D, Koo M, Hazard FK, Novoa RA, and Rieger KE
- Subjects
- Child, Preschool, Female, Humans, Lip pathology, Mutation, Nevus, Epithelioid and Spindle Cell genetics, Peripheral Nerves pathology, Skin Neoplasms genetics, Anaplastic Lymphoma Kinase genetics, Nevus, Epithelioid and Spindle Cell pathology, Skin Neoplasms pathology
- Abstract
Historically recognized by their characteristic histopathologic features, Spitz neoplasms are now known to be molecularly defined by mutually exclusive recurrent abnormalities that cause activation of the MAPK pathway. Spitz neoplasms with ALK rearrangements frequently demonstrate polypoid growth with a plexiform arrangement of nested, fusiform melanocytes in intersecting fascicles. Although neurotropism has been described in indolent Spitz neoplasms, this feature is not frequently mentioned in publications on histopathologic assessment of this group of melanocytic tumors. Here, we present an unusual case of a 3-year-old female with an ALK-positive compound Spitz nevus with extensive perineural and intraneural neurotropism occurring on the vermilion border of the lower lip., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2021
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30. Histopathologic Characterization of Mogamulizumab-associated Rash.
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Wang JY, Hirotsu KE, Neal TM, Raghavan SS, Kwong BY, Khodadoust MS, Brown RA, Novoa RA, Kim YH, and Rieger KE
- Subjects
- CD4-CD8 Ratio, Drug Eruptions genetics, Drug Eruptions immunology, Drug Eruptions pathology, Exanthema genetics, Exanthema immunology, Exanthema pathology, Female, Genes, T-Cell Receptor, High-Throughput Nucleotide Sequencing, Humans, Male, Skin immunology, Skin pathology, T-Lymphocytes immunology, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Agents adverse effects, Drug Eruptions etiology, Exanthema chemically induced, Skin drug effects, T-Lymphocytes drug effects
- Abstract
Rash is one of the most common adverse events observed with mogamulizumab, an anti-C-C chemokine receptor 4 monoclonal antibody approved for previously treated mycosis fungoides (MF) and Sezary syndrome (SS). Given the nonspecific clinical presentations of this rash, histopathologic distinction from MF/SS is critical for informing clinical management. We performed a comprehensive characterization of the histopathologic findings in mogamulizumab-associated rash (MAR) with the integration of high-throughput sequencing of T-cell receptor (TCR) genes. Fifty-two biopsy specimens from 19 patients were evaluated retrospectively. Three major histologic reaction patterns were identified: spongiotic/psoriasiform dermatitis (33/52), interface dermatitis (11/52), and granulomatous dermatitis (8/52). Almost half of the specimens (21/52) showed at least 2 of these reaction patterns concurrently. Dermal eosinophils were not a consistent feature, being present in only half (27/52) of specimens and prominent in only 3. Features mimicking MF/SS, including lymphocyte exocytosis, lamellar fibroplasia, and adnexal involvement, were commonly seen but tended to be focal and mild. In 38/43 specimens with available immunohistochemistry, intraepidermal lymphocytes demonstrated a CD4:CD8 ratio ≤1 : 1. Low background levels of the patient's previously identified MF/SS-associated TCR sequence(s) were demonstrated in 20/46 specimens analyzed by high-throughput sequencing of TCR. We conclude that MAR may demonstrate diverse histologic features. Findings that may distinguish MAR from MF/SS include the inverted or normalized CD4:CD8 ratio within intraepidermal lymphocytes and demonstration of absent or nondominant levels of disease-associated TCR sequences. Correlation with the clinical findings and immunohistochemical and molecular characterization of the patient's MF/SS before mogamulizumab, when possible, may facilitate recognition of MAR.
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- 2020
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31. Diffuse PRAME expression is highly specific for malignant melanoma in the distinction from clear cell sarcoma.
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Raghavan SS, Wang JY, Toland A, Bangs CD, Rieger KE, Novoa RA, Charville GW, and Brown RA
- Subjects
- Antigens, Neoplasm analysis, Biomarkers, Tumor analysis, Biomarkers, Tumor metabolism, Diagnosis, Differential, Humans, Sensitivity and Specificity, Melanoma, Cutaneous Malignant, Antigens, Neoplasm biosynthesis, Melanoma diagnosis, Sarcoma, Clear Cell diagnosis, Skin Neoplasms diagnosis
- Published
- 2020
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32. Simultaneous coccidioidomycosis and phaeohyphomycosis in a kidney transplant recipient: A case report and literature review.
- Author
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Puing AG, Couture-Cossette A, Wang AX, Zygourakis CC, Cheng X, Stevens BA, Banaei N, Novoa RA, Ho DY, and Subramanian AK
- Subjects
- Antifungal Agents therapeutic use, Ascomycota isolation & purification, Biopsy methods, Coccidioides isolation & purification, Coccidioidomycosis drug therapy, Coccidioidomycosis microbiology, Coinfection drug therapy, Humans, Immunocompromised Host, Magnetic Resonance Imaging methods, Male, Middle Aged, Opportunistic Infections diagnosis, Opportunistic Infections drug therapy, Opportunistic Infections microbiology, Phaeohyphomycosis drug therapy, Phaeohyphomycosis microbiology, Polymerase Chain Reaction methods, Treatment Outcome, Coccidioidomycosis diagnosis, Coinfection diagnosis, Coinfection microbiology, Kidney Transplantation adverse effects, Phaeohyphomycosis diagnosis
- Abstract
Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here, we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted., (© 2020 Wiley Periodicals LLC.)
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- 2020
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33. PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features.
- Author
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Raghavan SS, Wang JY, Kwok S, Rieger KE, Novoa RA, and Brown RA
- Subjects
- Adult, Aged, Carrier Proteins genetics, Cohort Studies, Diagnosis, Differential, Dysplastic Nevus Syndrome genetics, Dysplastic Nevus Syndrome pathology, Female, Humans, Immunohistochemistry methods, Male, Melanoma pathology, Nevus, Epithelioid and Spindle Cell genetics, Nevus, Epithelioid and Spindle Cell pathology, Skin Neoplasms pathology, Tumor Suppressor Proteins genetics, Ubiquitin Thiolesterase genetics, Melanoma, Cutaneous Malignant, Antigens, Neoplasm genetics, Cell Proliferation genetics, Melanocytes pathology, Melanoma genetics, Skin Neoplasms genetics
- Abstract
Background: PRAME (PReferentially expressed Antigen in MElanoma) has shown utility in distinguishing melanoma from benign melanocytic lesions, but knowledge of its expression pattern in intermediate melanocytic and spitzoid proliferations is limited., Methods: Immunohistochemical expression of PRAME was examined in 112 melanocytic proliferations with intermediate histopathologic or spitzoid features., Results: Any intensity of nuclear PRAME staining in at least 60% of lesional melanocytes was determined as the best threshold for diffuse staining in this cohort. Nearly all non-spitzoid melanomas (23/24; 95.8%) demonstrated diffuse PRAME expression. PRAME was completely negative in 95.6% (43/45) of mitotically-active nevi, traumatized nevi, nevi with persistent/recurrent features, and dysplastic nevi. Most Spitz nevi (15/20) and atypical Spitz tumors (10/13) entirely lacked PRAME expression. One Spitz nevus, one atypical Spitz tumor, and one spitzoid melanoma (1/2) demonstrated diffuse PRAME expression., Conclusions: Although diffuse PRAME expression is generally limited to malignant melanoma, benign Spitz nevi and atypical Spitz tumors can infrequently express diffuse PRAME. PRAME immunohistochemistry can be useful in the evaluation of atypical melanocytic proliferations with intermediate histopathologic features but should be interpreted with caution in the setting of spitzoid neoplasms., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)
- Published
- 2020
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34. Concurrent Trypanosoma cruzi and Cytomegalovirus Reactivation in an Immunosuppressed Patient With Limited Cutaneous Systemic Sclerosis.
- Author
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Chang MS, Bae GH, Almazan T, Raghavan SS, Wang JY, Czech MM, Wang H, Banaei N, Blackburn BG, Novoa RA, and Rieger KE
- Abstract
Chagas disease, a multisystem infection caused by the protozoan Trypanosoma cruzi, is primarily found in Latin America. In recent years, prevalence has increased in the United States, where reactivation is the most common clinical scenario. Here, we describe cutaneous reactivation of T. cruzi in a patient with limited cutaneous systemic sclerosis on immunosuppression therapy who simultaneously presented with cytomegalovirus reactivation. Histopathology showed parasitized histiocytes in the superficial and deep dermis. Occasional epidermal keratinocytes were also parasitized, and rare organisms were also seen in the walls of blood vessels. Also noted were viral cytopathic changes within the vascular endothelium, and immunostaining confirmed cytomegalovirus. In this report, we describe the difference in cutaneous findings between reactivated and acute Chagas disease, and we also review the histopathologic features that help distinguish T.cruzi from other intracellular organisms.
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- 2020
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35. Differentiation syndrome during ivosidenib treatment with immunohistochemistry showing isocitrate dehydrogenase R132H mutation.
- Author
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Tabata MM, Chase M, Kwong BY, Novoa RA, and Fernandez-Pol S
- Subjects
- Aged, Diagnosis, Differential, Glycine therapeutic use, Humans, Immunohistochemistry, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Leukemic Infiltration diagnosis, Leukemic Infiltration genetics, Male, Mutation, Syndrome, Antineoplastic Agents therapeutic use, Glycine analogs & derivatives, Isocitrate Dehydrogenase genetics, Leukemic Infiltration pathology, Pyridines therapeutic use, Skin pathology
- Abstract
We report a case of differentiation syndrome in a patient receiving the IDH1 inhibitor ivosidenib, with skin biopsy showing isocitrate dehydrogenase (IDH) R132H-mutated leukemia cutis. A 72-year-old man with IDH1-mutated acute myeloid leukemia (AML), status-post allogeneic cell transplantation, on ivosidenib for 6 months, was admitted for culture-negative neutropenic fever, pink and purpuric plaques and patches on the legs, abdomen and back, edema, hypotension, and shortness of breath. Skin biopsy revealed an infiltrate of atypical, immature, myeloperoxidase-positive mononuclear cells compatible with leukemia cutis or Sweet syndrome. Although dermal edema and interstitial neutrophilic infiltrate with karyorrhexis characteristic of Sweet syndrome were not seen, the atypical cells lacked expression of CD117 and CD34, which were expressed in the original leukemia. Additional immunohistochemical staining of suspected blasts was strongly positive for IDH1 R132H, suggesting a diagnosis of leukemia cutis. As the immunophenotype of blasts in skin infiltrates can significantly differ from the immunophenotype seen in blood and bone marrow, this case shows that mutation-specific antibodies such as anti-IDH1 R132H may be useful to help distinguish malignant from non-malignant infiltrates in the skin. Furthermore, differentiation syndrome may show histopathologic features of leukemia cutis on skin biopsy., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2020
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36. Reticulohistiocytoma (solitary epithelioid histiocytoma) with mutations in RAF1 and TSC2.
- Author
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Bahrani E, Fernandez-Pol S, Wang JY, Aasi SZ, Brown RA, and Novoa RA
- Subjects
- Aged, Alleles, Biopsy, High-Throughput Nucleotide Sequencing methods, Histiocytosis, Non-Langerhans-Cell metabolism, Histiocytosis, Non-Langerhans-Cell surgery, Humans, Immunohistochemistry methods, Male, Mutation, Cheek pathology, Histiocytosis, Non-Langerhans-Cell diagnosis, Proto-Oncogene Proteins c-raf genetics, Tuberous Sclerosis Complex 2 Protein genetics
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- 2020
- Full Text
- View/download PDF
37. Diagnostic Utility of LEF1 Immunohistochemistry in Differentiating Deep Penetrating Nevi From Histologic Mimics.
- Author
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Raghavan SS, Saleem A, Wang JY, Rieger KE, Brown RA, and Novoa RA
- Subjects
- Adult, Diagnosis, Differential, Female, Humans, Immunohistochemistry, Lymphoid Enhancer-Binding Factor 1 analysis, Male, Middle Aged, Nevus, Blue diagnosis, beta Catenin analysis, beta Catenin biosynthesis, Biomarkers, Tumor analysis, Lymphoid Enhancer-Binding Factor 1 biosynthesis, Nevus, Pigmented diagnosis, Skin Neoplasms diagnosis
- Abstract
Deep penetrating nevi (DPNs) are intermediate grade lesions which have the capacity to recur, metastasize, or progress to melanoma. Differentiating DPN from other melanocytic lesions including blue and cellular blue nevi can be diagnostically challenging, and markers to distinguish these entities can be useful. Mutations of the β-catenin and mitogen-activated protein kinase pathways have recently been elucidated as distinctive of DPN. This pathway can subsequently activate lymphoid enhancer-binding factor 1 (LEF1), a transcription factor shown to facilitate the epithelial-mesenchymal transition to propagate tumorigenesis. Seventy-two cases in total were examined on hematoxylin and eosin sections and with β-catenin and LEF1 immunohistochemistry. This included: DPN (14), cellular blue nevi (19), blue nevi (15), congenital melanocytic nevi (12), and melanoma (12). Nuclear expression of LEF1, present throughout the entire depth of the lesion, was noted in 13/14 (93%) of DPN, 0/19 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 9/12 (75%) of melanoma cases. Nuclear expression of β-catenin, present throughout the entire depth of the lesion, was noted in 14/14 (100%) of DPN, 0/18 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 1/12 (8%) of melanoma cases. A majority of congenital melanocytic nevi demonstrated a gradient of LEF1 and β-catenin expression with more intense staining superficially and loss of staining with increasing depth. Deep, uniform nuclear LEF1 combined with β-catenin immunohistochemical staining can be useful in distinguishing DPN from histologic mimics.
- Published
- 2020
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38. Cutaneous T-cell lymphomas with pathogenic somatic mutations and absence of detectable clonal T-cell receptor gene rearrangement: two case reports.
- Author
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Rojansky R, Fernandez-Pol S, Wang E, Rieger KE, Novoa RA, Zehnder JL, Kunder CA, Kim YH, Khodadoust MS, and Brown RA
- Subjects
- Adult, Clone Cells pathology, Gene Rearrangement, Humans, Male, Middle Aged, Mutation, Lymphoma, T-Cell, Cutaneous diagnosis, Lymphoma, T-Cell, Cutaneous genetics, Receptors, Antigen, T-Cell genetics, Skin Neoplasms diagnosis, Skin Neoplasms genetics
- Abstract
Background: Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin lymphomas for which diagnosis can be challenging given the potential for overlap with inflammatory dermatoses. Current diagnostic criteria for CTCL incorporate clinical and histopathologic findings as well as results of T-cell receptor (TCR) gene sequencing. Molecular interrogation of TCR genes, TRG and TRB, has proven to be a critical tool for confirming diagnoses of CTCL and for disease tracking after initiation of therapy or after stem cell transplant. Methods for confirming a diagnosis of lymphoma in the absence of TCR gene clonality are lacking. We present two patients with CTCL with pathogenic somatic mutations in the absence of TRG and TRB clonality., Case Presentations: Case 1: A 38-year-old male had a 19-year history of a diffuse skin rash with papulosquamous, granulomatous, and verrucous features and progressive ulcerated plaques and tumors demonstrating an atypical CD4+ T-cell infiltrate with expression of cytotoxic markers CD56, TIA-1, granzyme, and perforin on histopathology. No definitive evidence for T-cell clonality was detected by conventional PCR of 6 biopsies or by next-generation sequencing (NGS) of 14 biopsies. Somatic mutational profiling of a skin biopsy revealed pathogenic mutations in PIKC3D and TERT promoter hotspots, confirming the presence of a clonal process. Case 2: A 69-year-old male with a 13-year history of progressive, diffuse hypertrophic and eroded plaques showed an atypical CD4+ T-cell infiltrate with subset expression of TIA-1 and granzyme on histopathology. No TCR clonality was detected by TCR-NGS of 6 biopsies. Somatic mutational profiling of a skin biopsy detected a pathogenic mutation in TP53, confirming the presence of a clonal process., Conclusions: These cases highlight how detection of pathogenic somatic mutations can confirm a diagnosis of lymphoma in a clinically and histopathologically suspicious cutaneous lymphoid proliferation without detectable TCR clonality.
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- 2020
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39. Disseminated tuberculosis presenting as medium-vessel vasculitis in an immunocompromised host.
- Author
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Wang JY, Brown RA, Pugliese S, Kwong BY, and Novoa RA
- Subjects
- Abscess diagnosis, Antitubercular Agents therapeutic use, Biopsy, Dermatomyositis drug therapy, Diagnosis, Differential, Follow-Up Studies, Humans, Immunocompromised Host, Immunosuppression Therapy adverse effects, Male, Middle Aged, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis isolation & purification, Skin pathology, Soft Tissue Infections diagnosis, Soft Tissue Infections microbiology, Treatment Outcome, Tuberculosis, Cutaneous drug therapy, Tuberculosis, Cutaneous pathology, Dermatomyositis complications, Skin microbiology, Soft Tissue Infections pathology, Tuberculosis, Cutaneous diagnosis, Vasculitis pathology
- Abstract
Cutaneous tuberculosis is an uncommon entity with several clinical forms recognized. Histopathologically, most cases are characterized by granulomatous inflammation and caseating necrosis, although less common findings, including vasculitis, have also been described. We report a 55-year-old male with a history of recently diagnosed dermatomyositis receiving immunosuppression with mycophenolate mofetil and prednisone, who developed multifocal soft tissue abscesses and an indurated erythematous plaque on the back. Skin biopsy of the back revealed a necrotizing medium-vessel vasculitis. Mycobacterium tuberculosis was detected in the skin via acid-fast bacilli stain and confirmed by tissue culture and polymerase chain reaction. Cutaneous findings improved rapidly with antituberculosis therapy. This case illustrates an uncommon clinical and histopathologic presentation of disseminated tuberculosis., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2020
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40. TERT and TERT promoter in melanocytic neoplasms: Current concepts in pathogenesis, diagnosis, and prognosis.
- Author
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Motaparthi K, Kim J, Andea AA, Missall TA, Novoa RA, Vidal CI, Fung MA, and Emanuel PO
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Carcinogenesis metabolism, Child, Humans, Melanocytes metabolism, Melanoma metabolism, Melanoma mortality, Melanoma pathology, Middle Aged, Mutation, Neoplasm Recurrence, Local metabolism, Nevus congenital, Nevus metabolism, Predictive Value of Tests, Prognosis, Promoter Regions, Genetic genetics, Skin Neoplasms diagnosis, Skin Neoplasms metabolism, Skin Neoplasms mortality, Telomerase metabolism, Young Adult, Melanoma, Cutaneous Malignant, Melanocytes pathology, Melanoma diagnosis, Skin Neoplasms pathology, Telomerase genetics
- Abstract
Background and Objective: Located on chromosome locus 5p15.33, telomerase reverse transcriptase (TERT or hTERT) encodes the catalytic subunit of telomerase which permits lengthening and preservation of telomeres following mitosis. Mutations in TERT promoter (TERT-p) upregulate expression of TERT, allowing survival of malignant cells and tumor progression in wide variety of malignancies including melanoma. The objective of this review is to examine the roles of TERT and TERT-p in the pathogenesis, diagnosis, and prognostication of cutaneous melanoma., Methods: All studies of TERT or TERT-p in cutaneous melanocytic neoplasms with the following inclusion criteria were reviewed: publication date between 2010 and 2019, English language, and series of ≥3 cases were reviewed for evidence supporting the role of TERT in pathogenesis, diagnosis, and prognosis. Studies with <3 cases or focused primarily on mucosal or uveal melanocytic tumors were excluded., Results and Conclusion: TERT-p mutations are frequent in chronic and non-chronic sun damage melanoma and correlate with adverse prognosis, inform pathogenesis, and may provide diagnostic support. While TERT-p mutations are uncommon in acral melanoma, TERT copy number gains and gene amplification predict reduced survival. Among atypical spitzoid neoplasms, TERT-p mutations identify biologically aggressive tumors and support the diagnosis of spitzoid melanoma. TERT-p methylation may have prognostic value in pediatric conventional melanoma and drive tumorigenesis in melanoma arising within congenital nevi. Finally, TERT-p mutations may aid in the differentiation of recurrent nevi from recurrent melanoma., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2020
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41. Successful treatment of HIV-negative Kaposi sarcoma with ipilimumab and nivolumab and concurrent management of baseline psoriasis and bullous pemphigoid.
- Author
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Tabata MM, Novoa RA, Bui NQ, and Zaba LC
- Published
- 2020
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42. Inflammatory alopecia in patients on dupilumab: a retrospective cohort study at an academic institution.
- Author
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Zhu GA, Kang KJW, Chen JK, Novoa RA, Brown RA, Chiou AS, Ko JM, and Honari G
- Subjects
- Adult, Humans, Inflammation chemically induced, Male, Retrospective Studies, Alopecia chemically induced, Antibodies, Monoclonal, Humanized adverse effects, Dermatitis, Atopic drug therapy
- Published
- 2020
- Full Text
- View/download PDF
43. Marking the Path Toward Artificial Intelligence-Based Image Classification in Dermatology.
- Author
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Novoa RA, Gevaert O, and Ko JM
- Published
- 2019
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44. Biomarker discovery analysis: Alterations in p14, p16, p53, and BAP1 expression in nevi, cutaneous melanoma, and metastatic melanoma.
- Author
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Sargen MR, Cloutier JM, Sarin KY, Rieger KE, Chu P, Swetter SM, and Novoa RA
- Subjects
- Aged, Biomarkers, Tumor metabolism, Case-Control Studies, Female, Follow-Up Studies, Genes, Tumor Suppressor, Humans, Lymphatic Metastasis, Male, Melanoma metabolism, Middle Aged, Nevus, Pigmented metabolism, Prognosis, Prospective Studies, Skin Neoplasms metabolism, Skin Neoplasms pathology, Melanoma, Cutaneous Malignant, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Melanoma pathology, Nevus, Pigmented pathology, Oncogene Proteins metabolism, Skin Neoplasms secondary, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Proteins metabolism, Ubiquitin Thiolesterase metabolism
- Published
- 2019
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- View/download PDF
45. Introduction, Dermatology, Data, and Informatics.
- Author
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Novoa RA
- Published
- 2019
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46. Artificial intelligence and dermatology: opportunities, challenges, and future directions.
- Author
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Schlessinger DI, Chhor G, Gevaert O, Swetter SM, Ko J, and Novoa RA
- Subjects
- Forecasting, Humans, Reproducibility of Results, Artificial Intelligence, Dermatology trends
- Abstract
The application of artificial intelligence (AI) to medicine has considerable potential within dermatology, where the majority of diagnoses are based on visual pattern recognition. Opportunities for AI in dermatology include the potential to automate repetitive tasks; optimize time-consuming tasks; extend limited medical resources; improve interobserver reliability issues; and expand the diagnostic toolbox of dermatologists. To achieve the full potential of AI, however, developers must aim to create algorithms representing diverse patient populations; ensure algorithm output is ultimately interpretable; validate algorithm performance prospectively; preserve human-patient interaction when necessary; and demonstrate validity in the eyes of regulatory bodies., (©2019 Frontline Medical Communications.)
- Published
- 2019
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47. Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology.
- Author
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Vidal CI, Armbrect EA, Andea AA, Bohlke AK, Comfere NI, Hughes SR, Kim J, Kozel JA, Lee JB, Linos K, Litzner BR, Missall TA, Novoa RA, Sundram U, Swick BL, Hurley MY, Alam M, Argenyi Z, Duncan LM, Elston DM, Emanuel PO, Ferringer T, Fung MA, Hosler GA, Lazar AJ, Lowe L, Plaza JA, Prieto VG, Robinson JK, Schaffer A, Subtil A, and Wang WL
- Subjects
- Dermatology standards, Humans, Pathology, Clinical standards, Medical Overuse prevention & control, Skin Diseases pathology
- Abstract
Background: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy, and physician decision-making., Objectives: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology., Methods: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience, and expert judgment, was used to develop AUC in dermatopathology., Results: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate" and 52 (25%) "rarely appropriate" and 43 (20%) having "uncertain appropriateness.", Limitations: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost., Conclusions: The ultimate decision to order specific tests rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-the AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
48. Evidence behind the use of molecular tests in melanocytic lesions and practice patterns of these tests by dermatopathologists.
- Author
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Emanuel PO, Andea AA, Vidal CI, Missall TA, Novoa RA, Bohlke AK, Hughes SR, Hurley MY, and Kim J
- Subjects
- Comparative Genomic Hybridization, Dermatology methods, Humans, In Situ Hybridization, Fluorescence, Melanoma genetics, Pathology methods, Reverse Transcriptase Polymerase Chain Reaction, Skin Neoplasms genetics, Melanoma diagnosis, Molecular Diagnostic Techniques methods, Practice Patterns, Physicians' statistics & numerical data, Skin Neoplasms diagnosis
- Abstract
Background: The gold standard for the diagnosis of melanocytic lesions is histologic examination. However, as histologic examination can have its limitations, there are many clinical scenarios in which additional testing may be appropriate in an attempt to render a definitive diagnosis., Methods: A literature review for three ancillary tests-comparative genomic hybridization (CGH)/single-nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and gene expression profiling by quantitative reverse transcription polymerase chain reaction (qRT-PCR)-was compiled and current use patterns were tabulated. Survey of the practice patterns of these tests by dermatopathologists was also accessed in the attendees of the American Society of Dermatopathology Annual Meeting (Chicago, 2016)., Results: Here we summarize the use of these molecular tests in melanocytic lesions. We found that 54.4% of the respondents surveyed utilize (or expect consultants to utilize) molecular testing of melanocytic lesions in their practice when appropriate., Conclusions: CGH/SNP arrays, FISH testing, and qRT-PCR applied to melanocytic lesions have allowed for more accurate classification. Just over half of those surveyed use molecular testing for melanocytic lesion with the majority sending their cases out for completion of the molecular test., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
49. Paraneoplastic granulomatous dermatitis in a patient with Hodgkin's disease: a diagnostic pitfall.
- Author
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Tabata MM, Novoa RA, and Martires KJ
- Subjects
- Aged, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents therapeutic use, Clobetasol administration & dosage, Clobetasol therapeutic use, Diagnosis, Differential, Drug Therapy, Combination, Fluorodeoxyglucose F18, Granuloma Annulare diagnostic imaging, Granuloma Annulare drug therapy, Granuloma Annulare pathology, Humans, Male, Paraneoplastic Syndromes diagnostic imaging, Paraneoplastic Syndromes drug therapy, Paraneoplastic Syndromes pathology, Positron-Emission Tomography, Triamcinolone administration & dosage, Triamcinolone therapeutic use, Back, Granuloma Annulare diagnosis, Hodgkin Disease, Paraneoplastic Syndromes diagnosis
- Abstract
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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2018
- Full Text
- View/download PDF
50. Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology.
- Author
-
Vidal CI, Armbrect EA, Andea AA, Bohlke AK, Comfere NI, Hughes SR, Kim J, Kozel JA, Lee JB, Linos K, Litzner BR, Missall TA, Novoa RA, Sundram U, Swick BL, Hurley MY, Alam M, Argenyi Z, Duncan LM, Elston DM, Emanuel PO, Ferringer T, Fung MA, Hosler GA, Lazar AJ, Lowe L, Plaza JA, Prieto VG, Robinson JK, Schaffer A, Subtil A, and Wang WL
- Subjects
- Diagnostic Tests, Routine, Humans, United States, Dermatology, Evidence-Based Medicine, Pathology
- Abstract
Background: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision-making., Objectives: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology., Methods: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience and expert judgment, was used to develop AUC in dermatopathology., Results: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate," 52 (25%) "rarely appropriate" and 43 (20%) "uncertain appropriateness.", Limitations: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost., Conclusions: The ultimate decision of when to order specific test rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
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