Erica Bo Kyung Wang, MD

All Publications

• Genetic alteration of class I HLA in cutaneous T-cell lymphoma. Blood Kwang, A. C., Duran, G. E., Fernandez-Pol, S., Najidh, S., Li, S., Bastidas Torres, A. N., Wang, E. B., Herrera, M., Bandali, T. I., Kurtz, D. M., Kim, Y. H., Khodadoust, M. S. 2024

  Abstract

  Abnormalities involving class I HLA are frequent in many lymphoma subtypes but have not yet been extensively studied in cutaneous T-cell lymphomas (CTCL). We characterized the occurrence of class I HLA abnormalities in 65 patients with advanced mycosis fungoides (MF) or Sézary syndrome (SS). Targeted DNA sequencing including coverage of HLA loci revealed at least one HLA abnormality in 26/65 patients (40%). Twelve unique somatic HLA mutations were identified across nine patients, and loss of heterozygosity or biallelic loss of HLA was found to affect 24 patients. Although specific HLA alleles were commonly disrupted, these events did not associate with decreased total class I HLA expression. Genetic events preferentially disrupted HLA alleles capable of presentation of greater numbers of putative neoantigens. HLA abnormalities co-occurred with other genetic immune evasion events and were associated with worse progression-free survival. Single-cell analyses demonstrated HLA abnormalities were frequently subclonal. Through analysis of serial samples, we observed disrupting class I HLA events change dynamically over the disease course. The dynamics of HLA disruption are highlighted in a patient receiving pembrolizumab, where resistance to pembrolizumab was associated with elimination of an HLA mutation. Overall, our findings show that genomic class I HLA abnormalities are common in advanced CTCL and may be an important consideration in understanding the effects of immunotherapy in CTCL.

  View details for DOI 10.1182/blood.2024024817

  View details for PubMedID 39388712

• What Is Melanoma? JAMA Wang, J. Y., Wang, E. B., Swetter, S. M. 2023

  Abstract

  This JAMA Patient Page describes melanoma, its risk factors, diagnosis, treatment, and prognosis.

  View details for DOI 10.1001/jama.2022.24888

  View details for PubMedID 36867424

• Clinical and Pathological Characteristics and Outcomes Among Patients With Subcutaneous Panniculitis-like T-Cell Lymphoma and Related Adipotropic Lymphoproliferative Disorders. JAMA dermatology Guitart, J., Mangold, A. R., Martinez-Escala, M. E., Walker, C. J., Comfere, N. I., Pulitzer, M., Rieger, K. E., Torres-Cabala, C. A., Pincus, L. B., Kumar, E. S., Wang, E. B., Park, K. E., Espinosa, M. L., Duvic, M., Kim, Y. H., Horwitz, S. 2022

  Abstract

  There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date.To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions.This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort was classified as (1) SPTCL or (2) adipotropic lymphoproliferative disorder (ALPD) for similar cases with incomplete histopathological criteria for SPTCL designation.Cases of SPTCL diagnosed between 1998 and 2018.The main outcome was disease presentation and evolution, including response to therapy, disease progression, and development of hemophagocytic lymphohistiocytosis.The cohort of 95 patients (median [range] age, 38 [2-81] years; female-to-male ratio, 2.7) included 75 cases of SPTCL and 20 cases of ALPD. The clinical presentation was similar for both groups with multiple (61 of 72 [85%]) or single (11 of 72 [15%]) tender nodules mostly involving extremities, occasionally resulting in lipoatrophy. Hemophagocytic lymphohistiocytosis (HLH) was only observed in SPTCL cases. With a mean follow-up of 56 months, 60 of 90 patients (67%) achieved complete remission with a median (range) of 3 (1-7) cumulative therapies. Relapse was common. None of the patients died of disease progression or HLH. Two patients with ALPD eventually progressed to SPTCL without associated systemic symptoms or HLH.In this case series of patients initially diagnosed as having SPTCL, results showed no evidence of systemic tumoral progression beyond the adipose tissue. The SPTCL experience in this study confirmed an indolent course and favorable response to a variety of treatments ranging from immune modulation to chemotherapy followed by hematopoietic stem cell transplantation. Morbidity was primarily associated with HLH.

  View details for DOI 10.1001/jamadermatol.2022.3347

  View details for PubMedID 36001337

• Mechanisms of resistance to anti-CCR4 antibody, mogamulizumab, in cutaneous T cell lymphoma Beygi, S., Fernandez-Pol, S., Duran, G., Wang, E. B., Kim, Y., Khodadoust, M. ELSEVIER SCI LTD. 2021: S8

  View details for Web of Science ID 000719152800016

• Pembrolizumab in mycosis fungoides with PD-L1 structural variants. Blood advances Beygi, S. n., Fernandez-Pol, S. n., Duran, G. n., Wang, E. B., Stehr, H. n., Zehnder, J. L., Ramchurren, N. n., Fling, S. P., Cheever, M. A., Weng, W. K., Kim, Y. H., Khodadoust, M. S. 2021; 5 (3): 771–74

  View details for DOI 10.1182/bloodadvances.2020002371

  View details for PubMedID 33560388

• Two Cases With Features of Lymphocyte Variant Hypereosinophilic Syndrome With STAT3 SH2 Domain Mutations. The American journal of surgical pathology Fernandez-Pol, S., Petersen, B., Murphy, J., Oak, J. S., Wang, E. B., Rieger, K. E., Kim, Y. H., Khodadoust, M. S., Suarez, C. J. 2020

  Abstract

  Lymphocyte variant hypereosinophilic syndrome (LV-HES) is a rare cause of eosinophilia that is due to eosinophilipoietic cytokine production by an immunophenotypically abnormal T-cell clone. The molecular pathogenesis of this disorder is largely unknown and only 1 case of LV-HES with a pathogenic STAT3 mutation has been described thus far. Here we report 2 cases of LV-HES with STAT3 SH2 domain mutations. These cases further support the model that activation of STAT3 signaling through STAT3 SH2 domain mutations is a recurrent event in LV-HES.

  View details for DOI 10.1097/PAS.0000000000001604

  View details for PubMedID 33060403

• Cutaneous T-cell lymphomas with pathogenic somatic mutations and absence of detectable clonal T-cell receptor gene rearrangement: two case reports. Diagnostic pathology Rojansky, R., Fernandez-Pol, S., Wang, E., Rieger, K. E., Novoa, R. A., Zehnder, J. L., Kunder, C. A., Kim, Y. H., Khodadoust, M. S., Brown, R. A. 2020; 15 (1): 122

  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 provento 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 confirma diagnosis of lymphoma in a clinically and histopathologically suspicious cutaneous lymphoid proliferation without detectable TCR clonality.

  View details for DOI 10.1186/s13000-020-01022-x

  View details for PubMedID 32988392

• Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma. Blood advances Weng, W. K., Arai, S. n., Rezvani, A. n., Johnston, L. n., Lowsky, R. n., Miklos, D. n., Shizuru, J. n., Muffly, L. n., Meyer, E. n., Negrin, R. S., Wang, E. n., Almazan, T. n., Million, L. n., Khodadoust, M. n., Li, S. n., Hoppe, R. T., Kim, Y. H. 2020; 4 (18): 4474–82

  Abstract

  The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned. The majority (80%) of the patients had stage IV disease and received multiple previous systemic therapies. All patients had active disease at the time of conditioning using total skin electron beam therapy, total lymphoid irradiation, and antithymocyte globulin, and received allograft infusion as outpatients. Cyclosporine or tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Patients tolerated the transplant well, with 1- and 2-year nonrelapse mortality of 3% and 14%, respectively. The day +180 cumulative incidence of grade 2 to 4 acute GVHD was 16%, and the 2-year incidence of moderate/severe chronic GVHD was 32%. With a median posttransplant follow-up of 5.4 years, the 2-, 3-, and 5-year overall survival rates were 68%, 62%, and 56%. Using high-throughput sequencing of the T-cell receptor for minimal residual disease monitoring, we observed that 43% achieved molecular remission, which was associated with a lower incidence of disease progression or relapse (9% vs 87%; P = .02). Our study also showed that patients who were aged ≥65 years at the time of allotransplant had similar clinical outcomes compared with younger patients. Thus, we have developed an alternative and potentially curative nonmyeloablative allogeneic transplant regimen for patients with advanced stage MF/SS. This trial was registered at www.clinicaltrials.gov as #NCT00896493.

  View details for DOI 10.1182/bloodadvances.2020001627

  View details for PubMedID 32941647

• Volumetric Modulated Arc Therapy and 3-Dimensional Printed Bolus in the Treatment of Refractory Primary Cutaneous Gamma Delta Lymphoma of the Bilateral Legs PRACTICAL RADIATION ONCOLOGY Obeid, J., Gutkin, P. M., Lewis, J., Skinner, L., Wang, E. B., Khodadoust, M. S., Kim, Y. H., Weng, W., Hoppe, R. T., Hiniker, S. M. 2019; 9 (4): 220–25

  View details for DOI 10.1016/j.prro.2019.02.016

  View details for Web of Science ID 000472574100020

• Low-dose Total Skin Electron Beam Therapy for Refractory Cutaneous CD30 Positive Lymphoproliferative Disorders. The Journal of dermatological treatment Panjwani, N., Yoo, C. H., Wang, E., Khodadoust, M. S., Kim, Y. H., Hoppe, R. T., Hiniker, S. M. 2019: 1–5

  Abstract

  We describe a case of a 48-year-old woman with a refractory cutaneous CD30 positive lymphoproliferative disorder treated successfully with total skin electron beam radiotherapy (TSEBT).

  View details for DOI 10.1080/09546634.2019.1628913

  View details for PubMedID 31179774

• The Combination of Duvelisib, a PI3K-delta,gamma Inhibitor, and Romidepsin Is Highly Active in Relapsed/Refractory Peripheral T-Cell Lymphoma with Low Rates of Transaminitis: Results of Parallel Multicenter, Phase 1 Combination Studies with Expansion Cohorts Horwitz, S. M., Moskowitz, A. J., Jacobsen, E. D., Mehta-Shah, N., Khodadoust, M. S., Fisher, D. C., Myskowski, P., Wang, E. K., Tawa, M., Davey, T., Blouin, W., Hancock, H., Ganesan, N., Galasso, N., Marzouk, E., Bahgat, A., Jester, H., Fong, S., Butt, A., Dogan, A., Kim, Y. H., Weinstock, D. M. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-115241

  View details for Web of Science ID 000454837602061

• Folliculocentric Mycosis Fungoides Masquerading as Angioedema and Allergic Contact Dermatitis. The journal of allergy and clinical immunology. In practice Jiang, S. Y., Yeh, J., Novoa, R., Wang, E., Chen, M. 2024

  View details for DOI 10.1016/j.jaip.2024.04.017

  View details for PubMedID 38727652

• Genomic abnormalities involving class I HLA are common in advanced cutaneous T-cell lymphoma Kwang, A., Duran, G., Fernandez-Pol, S., Li, S., Najidh, S., Torres, A., Herrera, M., Wang, E., Kurtz, D., Kim, Y. H., Khodadoust, M. ELSEVIER SCI LTD. 2023: S14

  View details for DOI 10.1016/j.ejca.2023.113019

  View details for Web of Science ID 001077487800032