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1.
Acad Med ; 2024 Mar 25.
Article En | MEDLINE | ID: mdl-38527013

PROBLEM: Holistic review is a multifaceted concept that aims to increase diversity and applicant fit with program needs by complementing traditional academic requirements with appraisal of a wider range of personal characteristics and experiences. Behavioral interviewing has been practiced and studied in human resources, business, and organizational psychology for over 50 years. Its premise is that future performance can be anticipated from past actions. However, many of the interview approaches within the holistic framework are resource intensive and logistically challenging. APPROACH: The Vanderbilt University School of Medicine instituted a competency-based behavioral interview (CBBI) to augment the selection process in 2012. Behavioral interviews are based on key competencies needed for entering students and require applicants to reflect on their actual experiences and what they learned from them. The authors reviewed 5 years of experience (2015-2019) to evaluate how CBBI scores contributed to the overall assessment of applicants for admission. OUTCOMES: The final admission committee decision for each applicant was determined by reviewing multiple factors, with no single assessment determining the final score. The CBBI and summary interview scores showed a strong association (P < .005), suggesting that the summary interviewer, who had access to the full applicant file, and the CBBI interviewer, who did not, assessed similar strengths despite the 2 different approaches, or that the strengths assessed tracked in the same direction. Students whose 2 interview scores were not aligned were less likely to be accepted to the school. NEXT STEPS: The review raised awareness about the cultural aspects of interpreting the competencies and the need to expand our cultural framework throughout interviewer training. Findings indicate that CBBIs have the potential to reduce bias related to over-reliance on standardized metrics; however, additional innovation and research are needed.

2.
Telemed J E Health ; 30(5): 1411-1417, 2024 May.
Article En | MEDLINE | ID: mdl-38150704

Introduction: Teledermatology adoption continues to increase, in part, spurred by the COVID-19 pandemic. This study analyzes the utility and cost savings of a store-and-forward teledermatology consultative system within the Veterans Health Administration (VA). Methods: Retrospective cohort of 4,493 patients across 14 remote sites in Tennessee and Kentucky from May 2017 through August 2019. The study measured the agreement between the teledermatology diagnoses and follow-up face-to-face clinic evaluations as well as the cost effectiveness of the teledermatology program over the study period. Results: Fifty-four percent of patients were recommended for face-to-face appointment for biopsy or further evaluation. Most patients, 80.5% received their face-to-face care by a VA dermatologist. There was a high level of concordance between teledermatologist and clinic dermatologist for pre-malignant and malignant cutaneous conditions. Veterans were seen faster at a VA clinic compared with a community dermatology site. Image quality improved as photographers incorporated teledermatologist feedback. From a cost perspective, teledermatology saved the VA system $1,076,000 in community care costs. Discussion: Teledermatology is a useful diagnostic tool within the VA system providing Veteran care at a cost savings.


COVID-19 , Cost Savings , Dermatology , Skin Diseases , Telemedicine , United States Department of Veterans Affairs , Humans , Dermatology/economics , Dermatology/standards , Dermatology/organization & administration , Retrospective Studies , Skin Diseases/diagnosis , Skin Diseases/economics , United States , Telemedicine/economics , United States Department of Veterans Affairs/organization & administration , Female , Kentucky , Male , Quality Control , Middle Aged , Tennessee , SARS-CoV-2 , Remote Consultation/economics , Aged , Cost-Benefit Analysis
3.
JAMA Netw Open ; 6(10): e2336483, 2023 10 02.
Article En | MEDLINE | ID: mdl-37782499

Importance: Natural language processing tools, such as ChatGPT (generative pretrained transformer, hereafter referred to as chatbot), have the potential to radically enhance the accessibility of medical information for health professionals and patients. Assessing the safety and efficacy of these tools in answering physician-generated questions is critical to determining their suitability in clinical settings, facilitating complex decision-making, and optimizing health care efficiency. Objective: To assess the accuracy and comprehensiveness of chatbot-generated responses to physician-developed medical queries, highlighting the reliability and limitations of artificial intelligence-generated medical information. Design, Setting, and Participants: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes or no) or descriptive answers. The physicians then graded the chatbot-generated answers to these questions for accuracy (6-point Likert scale with 1 being completely incorrect and 6 being completely correct) and completeness (3-point Likert scale, with 1 being incomplete and 3 being complete plus additional context). Scores were summarized with descriptive statistics and compared using the Mann-Whitney U test or the Kruskal-Wallis test. The study (including data analysis) was conducted from January to May 2023. Main Outcomes and Measures: Accuracy, completeness, and consistency over time and between 2 different versions (GPT-3.5 and GPT-4) of chatbot-generated medical responses. Results: Across all questions (n = 284) generated by 33 physicians (31 faculty members and 2 recent graduates from residency or fellowship programs) across 17 specialties, the median accuracy score was 5.5 (IQR, 4.0-6.0) (between almost completely and complete correct) with a mean (SD) score of 4.8 (1.6) (between mostly and almost completely correct). The median completeness score was 3.0 (IQR, 2.0-3.0) (complete and comprehensive) with a mean (SD) score of 2.5 (0.7). For questions rated easy, medium, and hard, the median accuracy scores were 6.0 (IQR, 5.0-6.0), 5.5 (IQR, 5.0-6.0), and 5.0 (IQR, 4.0-6.0), respectively (mean [SD] scores were 5.0 [1.5], 4.7 [1.7], and 4.6 [1.6], respectively; P = .05). Accuracy scores for binary and descriptive questions were similar (median score, 6.0 [IQR, 4.0-6.0] vs 5.0 [IQR, 3.4-6.0]; mean [SD] score, 4.9 [1.6] vs 4.7 [1.6]; P = .07). Of 36 questions with scores of 1.0 to 2.0, 34 were requeried or regraded 8 to 17 days later with substantial improvement (median score 2.0 [IQR, 1.0-3.0] vs 4.0 [IQR, 2.0-5.3]; P < .01). A subset of questions, regardless of initial scores (version 3.5), were regenerated and rescored using version 4 with improvement (mean accuracy [SD] score, 5.2 [1.5] vs 5.7 [0.8]; median score, 6.0 [IQR, 5.0-6.0] for original and 6.0 [IQR, 6.0-6.0] for rescored; P = .002). Conclusions and Relevance: In this cross-sectional study, chatbot generated largely accurate information to diverse medical queries as judged by academic physician specialists with improvement over time, although it had important limitations. Further research and model development are needed to correct inaccuracies and for validation.


Artificial Intelligence , Physicians , Humans , Cross-Sectional Studies , Reproducibility of Results , Software
4.
Res Sq ; 2023 Feb 28.
Article En | MEDLINE | ID: mdl-36909565

Background: Natural language processing models such as ChatGPT can generate text-based content and are poised to become a major information source in medicine and beyond. The accuracy and completeness of ChatGPT for medical queries is not known. Methods: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes/no) or descriptive answers. The physicians then graded ChatGPT-generated answers to these questions for accuracy (6-point Likert scale; range 1 - completely incorrect to 6 - completely correct) and completeness (3-point Likert scale; range 1 - incomplete to 3 - complete plus additional context). Scores were summarized with descriptive statistics and compared using Mann-Whitney U or Kruskal-Wallis testing. Results: Across all questions (n=284), median accuracy score was 5.5 (between almost completely and completely correct) with mean score of 4.8 (between mostly and almost completely correct). Median completeness score was 3 (complete and comprehensive) with mean score of 2.5. For questions rated easy, medium, and hard, median accuracy scores were 6, 5.5, and 5 (mean 5.0, 4.7, and 4.6; p=0.05). Accuracy scores for binary and descriptive questions were similar (median 6 vs. 5; mean 4.9 vs. 4.7; p=0.07). Of 36 questions with scores of 1-2, 34 were re-queried/re-graded 8-17 days later with substantial improvement (median 2 vs. 4; p<0.01). Conclusions: ChatGPT generated largely accurate information to diverse medical queries as judged by academic physician specialists although with important limitations. Further research and model development are needed to correct inaccuracies and for validation.

6.
Blood ; 140(5): 419-437, 2022 08 04.
Article En | MEDLINE | ID: mdl-34758074

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.


Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Sezary Syndrome , Skin Neoplasms , Clinical Trials as Topic , Humans , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/pathology , Lymphoma, T-Cell, Cutaneous/therapy , Mycosis Fungoides/diagnosis , Mycosis Fungoides/pathology , Mycosis Fungoides/therapy , Neoplasm Staging , Sezary Syndrome/diagnosis , Sezary Syndrome/pathology , Sezary Syndrome/therapy , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/therapy , United States
7.
Med Clin North Am ; 105(4): 737-755, 2021 Jul.
Article En | MEDLINE | ID: mdl-34059248

The cutaneous lymphomas are malignancies of T-cell and B-cell lymphocytes in which the skin is the primary organ of involvement. The cutaneous T-cell lymphomas include variants that can mimic the presentation of common skin diseases or arthropod bites. Mycosis fungoides, the most common cutaneous T-cell lymphoma, usually presents as fixed asymptomatic patches or plaques in sun-protected areas. The cutaneous B-cell lymphomas have fewer variants that often present as papules or nodules that can mimic nonmelanoma skin cancers. Some therapies for cutaneous lymphoma have unique side effects such as central hypothyroidism, hyperlipidemia, and peripheral neuropathy.


Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/therapy , Skin Diseases/diagnosis , Skin Neoplasms/pathology , Aged , Aged, 80 and over , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Arthropods , Bexarotene/adverse effects , Bites and Stings/diagnosis , Brentuximab Vedotin/adverse effects , Diagnosis, Differential , Humans , Hyperlipidemias/chemically induced , Hypothyroidism/chemically induced , Lymphoma, Primary Cutaneous Anaplastic Large Cell/diagnosis , Lymphoma, T-Cell, Cutaneous/classification , Lymphomatoid Papulosis/diagnosis , Mycosis Fungoides/diagnosis , Peripheral Nervous System Diseases/chemically induced , Prognosis , Sezary Syndrome/diagnosis , Skin Diseases/pathology
8.
J Am Acad Dermatol ; 85(1): 121-127, 2021 Jul.
Article En | MEDLINE | ID: mdl-33333150

INTRODUCTION: Low-dose total skin electron beam therapy provides a durable treatment response for skin lesions caused by cutaneous T-cell lymphoma. We prospectively assessed the durability of response and quality of life for patients receiving low-dose total skin electron beam therapy using a novel rotational technique and dosing regimen. METHODS: Patients completed baseline Skindex-29 quality-of-life surveys and had baseline Modified Severity-Weighted Assessment Tool score recorded. Patients received 12 Gy in 12 fractions with a dual-field rotational technique. The primary outcome was overall response rate, with the secondary outcomes being time to treatment response, duration of clinical benefit, and quality-of-life change. RESULTS: We enrolled 20 patients and recorded an overall response rate of 90%. The median time to treatment response was 6.5 weeks. The baseline Modified Severity-Weighted Assessment Tool score was 55.6 and it declined to a median of 2.2 at last follow-up (P < .001). The median duration of clinical benefit was 21 months. There was a decline in the Skindex-29 total score and every subdomain when each follow-up visit was compared (P = .004). CONCLUSIONS: This prospective study demonstrated a very high overall response rate and improvement in skin-related quality of life. Low-dose rotational total skin electron beam therapy can be implemented routinely in clinical practice.


Mycosis Fungoides/radiotherapy , Quality of Life , Skin Neoplasms/radiotherapy , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Radiotherapy/methods , Radiotherapy Dosage , Severity of Illness Index , Surveys and Questionnaires , Time-to-Treatment , Treatment Outcome
9.
J Am Acad Dermatol ; 83(2): 703-704, 2020 Aug.
Article En | MEDLINE | ID: mdl-32305443
10.
Biol Blood Marrow Transplant ; 25(2): 279-286, 2019 02.
Article En | MEDLINE | ID: mdl-30219700

Little is known about the anatomic distribution of cutaneous chronic graft-versus-host disease (cGVHD). Using data from the cGVHD Consortium Improving Outcomes Assessment Study, we describe the frequency and extent of erythema and superficial and deep sclerosis in 8 anatomic sites in patients with incident disease (ie, new cGVHD diagnosis within 3 months of study entry) receiving systemic therapy. Of 339 patients with incident disease, 182 (54%) had skin involvement. When an extremity was involved, the same type of disease was present contralaterally in 92% of cases, revealing a high level of symmetry. As anticipated, erythema was the most common incident feature; however, sclerotic skin involvement at the time of cGVHD diagnosis was more common than has been suggested by previous studies. Erythema occurred in 155 (85%) and sclerosis in 53 (29%) of the patients with skin involvement (46% and 16%, respectively, of the entire cohort of 339 incident cGVHD cases). Erythema was least common on the lower extremities (n = 71; 39% of patients with skin involvement). Moveable sclerosis was rare on the head, neck, and scalp (n = 4; 2%). Deep sclerosis did not occur in this region, and instead was most likely to occur on the upper extremities (n = 14; 8%) and lower extremities (n = 14; 8%). More than one-half of patients with erythema (n = 107; 58.7%) had diffuse involvement (4 or more of 8 sites involved), compared with less than one-third of those with sclerosis (n = 16; 30.2%).


Hematopoietic Stem Cell Transplantation , Neoplasms , Skin Diseases , Adult , Allografts , Chronic Disease , Female , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Graft vs Host Disease/pathology , Humans , Incidence , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/pathology , Neoplasms/therapy , Prospective Studies , Skin Diseases/epidemiology , Skin Diseases/etiology , Skin Diseases/pathology
12.
J Natl Compr Canc Netw ; 16(6): 742-774, 2018 06.
Article En | MEDLINE | ID: mdl-29891526

This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.


Carcinoma, Merkel Cell/therapy , Medical Oncology/standards , Merkel cell polyomavirus/isolation & purification , Skin Neoplasms/therapy , Aftercare/standards , Carcinoma, Merkel Cell/diagnosis , Carcinoma, Merkel Cell/epidemiology , Carcinoma, Merkel Cell/virology , Chemoradiotherapy/methods , Chemoradiotherapy/standards , Humans , Incidence , Skin Neoplasms/diagnosis , Skin Neoplasms/virology , Societies, Medical/standards , United States/epidemiology
13.
Cutis ; 101(4): 293-296, 2018 Apr.
Article En | MEDLINE | ID: mdl-29763476

Linear IgA bullous dermatosis (LABD) is an autoimmune blistering rash caused by IgA autoantibodies against the epidermal basement membrane zone. It commonly is drug induced, often in association with systemic vancomycin. We report a case of a previously healthy 77-year-old man who developed a diffuse macular rash and hemorrhagic bullae on the left leg 10 days after placement of a vancomycin-impregnated cement spacer (VICS) during a revision knee arthroplasty and initiation of postoperative treatment with intravenous (IV) vancomycin. The lesions initially were limited to the leg in which the hardware was placed, but the patient later developed painful palmoplantar and oropharyngeal blisters as well as edematous, erythematous plaques on the back and buttocks. A punch biopsy from a lesion on the left thigh revealed neutrophil-rich subepidermal bullae, and immunofluorescence revealed linear IgA and C3 deposition along the dermoepidermal junction, confirming a diagnosis of LABD. This report illustrates the importance of considering antibiotic-impregnated cement spacers, which frequently are used to manage prosthetic joint infections, as potential culprits in patients with cutaneous eruptions.


Anti-Bacterial Agents/adverse effects , Linear IgA Bullous Dermatosis/chemically induced , Vancomycin/adverse effects , Aged , Anti-Bacterial Agents/administration & dosage , Bone Cements , Humans , Knee Prosthesis/adverse effects , Male , Vancomycin/administration & dosage
15.
Dermatol Online J ; 22(5)2016 May 15.
Article En | MEDLINE | ID: mdl-27617516

BACKGROUND: Tumor stage mycosis fungoides (MF) is a subtype of cutaneous T-cell lymphoma (CTCL). Tumor stage MF is rarely curable. Treatment is aimed towards controlling the disease and minimizing side effects from therapy. OBJECTIVE: To characterize clinicopathologic features of tumor stage MF and the impact of clinical characteristics and treatment modalities on patient outcome. METHODS: A retrospective chart review was conducted on 39 patients with tumor stage MF followed at Vanderbilt University between July 1995 and July 2010. RESULTS: The median age of diagnosis was 61 years (IQR: 54-70). Sixty-nine percent of the patients were male (27/39). The median follow-up time was 13.6 months (IQR: 5.5-35.9). Among the patients younger than 60 years at the time of initial diagnosis (n = 19), median overall survival (OS) was 7.0 years (95% CI: 2.1-17.9), compared with 3.3 years (95% CI: 2.4-9.3) in patients who were 60 years or older at initial diagnosis. Ten patients with T1/T2 stage at diagnosis had median OS of 5.0 years (95% CI 3.2-7.0). Twenty-eight patients with T3 stage at diagnosis had median OS of 5.8 years (95% CI 2.4-14.2). Median OS for patients with large cell transformation (LCT) and without LCT was 3.3 and 7.7 years, respectively. LIMITATIONS: This is a retrospective study with the bias of a tertiary-care referral center. CONCLUSION: Although LCT and older age at diagnosis were not statistically significant negative prognostic indicators of OS, there was a trend towards statistical significance for LCT. Clinical stage at diagnosis may not affect OS in patients who develop tumor stage MF.


Mycosis Fungoides/mortality , Skin Neoplasms/mortality , Age Factors , Aged , Anticarcinogenic Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Bexarotene , Cell Transformation, Neoplastic , Disease Progression , Female , Furocoumarins/therapeutic use , Humans , Male , Middle Aged , Mycosis Fungoides/pathology , Mycosis Fungoides/therapy , Neoplasm Staging , Prognosis , Radiotherapy/methods , Retrospective Studies , Skin/pathology , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Tertiary Care Centers , Tetrahydronaphthalenes/therapeutic use , Ultraviolet Therapy/methods
16.
J Natl Compr Canc Netw ; 14(5): 574-97, 2016 05.
Article En | MEDLINE | ID: mdl-27160235

Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.


Carcinoma, Basal Cell , Skin Neoplasms , Humans , Carcinoma, Basal Cell/diagnosis , Carcinoma, Basal Cell/therapy , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , United States
17.
Semin Oncol ; 43(3): 370-83, 2016 06.
Article En | MEDLINE | ID: mdl-27178691

Many malignant hematologic neoplasms can directly and indirectly involve the skin with lesions that are disfiguring, painful, and compromise integumentary function. The majority of lymphomas that directly infiltrate the skin are of T-cell origin but B-cell lymphomas, and other hematologic neoplasms, including acute myeloid and lymphoblastic leukemias, can also have cutaneous involvement, whereas some have an indolent course, eg, mycosis fungoides and marginal zone lymphoma, and easily respond to localized therapy with overall survival (OS) measured in years to decades. Others have a more clinically aggressive course, eg, natural killer (NK)/T-cell lymphoma and diffuse large B-cell lymphoma, leg type, that require high-dose multimodality therapy, and have an OS measured in months to a few years. Lymphoma can also lead to secondary cutaneous alterations, including a variety of paraneoplastic phenomena. We present an overview of direct and indirect skin involvement by malignant lymphocytes and other hematologic neoplasms. We also describe molecular and immunophenotypic aspects of these diseases and how they are treated.


Hematologic Neoplasms/pathology , Hematologic Neoplasms/classification , Hematologic Neoplasms/immunology , Humans , Lymphoma, B-Cell/etiology , Lymphoma, B-Cell/pathology , Lymphoma, T-Cell/pathology , Mycosis Fungoides/pathology , Paraneoplastic Syndromes/etiology , Paraneoplastic Syndromes/pathology , Skin Neoplasms/pathology , Skin Neoplasms/secondary
18.
Dermatol Clin ; 33(4): 765-76, 2015 Oct.
Article En | MEDLINE | ID: mdl-26433848

Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to an expansion of peripheral blood dendritic cell populations and an enhanced TH1 immune response in cutaneous T-cell lymphoma (CTCL). Because of its excellent side effect profile and moderate efficacy, ECP is considered first-line therapy for erythrodermic mycosis fungoides (MF) and Sézary syndrome. Patients with a measurable but low blood tumor burden are most likely to respond to ECP, and the addition of adjunctive immunostimulatory agents may also increase response rates. There may be a role for ECP in the treatment of refractory early stage MF, but data are limited.


Mycosis Fungoides/drug therapy , Photopheresis/methods , Sezary Syndrome/drug therapy , Skin Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant/methods , Humans , Immunomodulation , Methoxsalen/pharmacokinetics , Methoxsalen/therapeutic use , Mycosis Fungoides/mortality , Photopheresis/adverse effects , Photosensitizing Agents/pharmacokinetics , Photosensitizing Agents/therapeutic use , Sezary Syndrome/mortality , Skin Neoplasms/mortality , Treatment Outcome
19.
Blood ; 126(4): 508-19, 2015 Jul 23.
Article En | MEDLINE | ID: mdl-26082451

The pathogenesis of mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is unknown. Although genetic alterations have been identified, none are considered consistently causative in MF. To identify potential drivers of MF, we performed whole-genome sequencing of MF tumors and matched normal skin. Targeted ultra-deep sequencing of MF samples and exome sequencing of CTCL cell lines were also performed. Multiple mutations were identified that affected the same pathways, including epigenetic, cell-fate regulation, and cytokine signaling, in MF tumors and CTCL cell lines. Specifically, interleukin-2 signaling pathway mutations, including activating Janus kinase 3 (JAK3) mutations, were detected. Treatment with a JAK3 inhibitor significantly reduced CTCL cell survival. Additionally, the mutation data identified 2 other potential contributing factors to MF, ultraviolet light, and a polymorphism in the tumor suppressor p53 (TP53). Therefore, genetic alterations in specific pathways in MF were identified that may be viable, effective new targets for treatment.


Exome/genetics , Genome, Human , High-Throughput Nucleotide Sequencing/methods , Mutation/genetics , Mycosis Fungoides/genetics , Oncogenes/genetics , Sequence Analysis, DNA/methods , Skin Neoplasms/genetics , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mycosis Fungoides/pathology , Mycosis Fungoides/therapy , Retrospective Studies , Skin Neoplasms/pathology , Skin Neoplasms/therapy , Ultraviolet Rays
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