Bio

Clinical Focus


  • Skin Cancer
  • Cancer > Cutaneous (Dermatologic) Oncology
  • Dermatology
  • Mycosis Fungoides - Dermatology
  • Mycosis Fungoides
  • Cutaneous Lymphoma
  • Cutaneous Lymphoma - Dermatology

Academic Appointments


Administrative Appointments


  • Director, Multi-disciplinary Cutaneous Lymphoma Program, Stanford University Medical Center (2004 - Present)
  • Director, Residency Program, Department of Dermatology, Stanford University Medical Center (2004 - Present)
  • Medical Director, Photopheresis Unit, Stanford University Medical Center (2004 - Present)

Honors & Awards


  • Alwin C. Rambar-James B.D. Mark Award for Excellence in Patient Care, Stanford University School of Medicine (2001)
  • Distinguished Service Award, Department of Dermatology, Stanford University School of Medicine (1995)
  • The Best Doctors in America: Pacific Region, Woodward/White, Inc (1996-)

Professional Education


  • Residency:Stanford University School of Medicine (1989) CA
  • Board Certification: Dermatology, American Board of Dermatology (1989)
  • Internship:Kaiser - San Francisco (1985)
  • Medical Education:Stanford University School of Medicine (1984) CA
  • Doctor of Medicine, Stanford University, Medicine (1984)
  • Bachelor of Arts, Wellesley College, Chemistry (1980)

Research & Scholarship

Current Research and Scholarly Interests


Clinical research in cutaneous lymphomas, especially, mycosis fungoides; studies of prognostic factors, long-term survival results, and effects of therapies. Collaborative research with Departments of Pathology and Oncology in basic mechanisms of cutaneous lymphomas. Clinical trials of new investigative therapies for various dermatologic conditions or clinical trials of known therapies for new indications.

Clinical Trials


  • Pilot Study of Brentuximab Vedotin (SGN-35) in Patients With MF With Variable CD30 Expression Level Recruiting

    The purpose of this study is to learn the effects of an investigational medication, SGN 35, on patients with cutaneous T cell lymphoma (CTCL), specifically mycosis fungoides (MF) and Sezary syndrome (SS). Despite a wide range of therapeutic options, the treatments are associated with short response duration, thus this condition is largely incurable. This investigational drug may offer less toxicity than standard treatments and have better tumor specific targeting. The primary objective is to explore the biologic activity of brentuximab vedotin (SGN-35) in patients with mycosis fungoides (MF) and Sézary syndrome (SS), the most common types of cutaneous T-cell lymphoma (CTCL), where expression of CD30 is variable. SGN-35 has significant biologic activity in Hodgkin's disease (HD) where only a small numbers of CD30 positive tumor cells are present, as well as in lymphomas with large numbers of CD30-expressing tumor cells such as systemic anaplastic large cell lymphoma (sALCL). This phase II exploratory study will evaluate the clinical response of brentuximab vedotin (SGN-35) in MF and SS where tumor cells express variable levels of CD30 target molecule. The grouping by CD30 expression levels (low, intermediate, high) is for accrual purposes only to ensure a wide range of CD30 expression. Given the exploratory nature of this study, it will be open-label, single-arm, and non-randomized trial. One centers will be involved to complete the accrual, a total of 24 patients with MF and SS. Enrollment will be based on CD30 expression levels by tissue immunohistochemistry (IHC), defined as low, intermediate or high expressers. The investigators will target 8 patients in each group for total of 24 patients. Of these 8 patients per group, up to 3 may be patients with SS. Each patient regardless of CD30 expression level will receive 1.8 mg/kg of SGN-35 IV every 21 days, up to 8 cycles of therapy. Patients with CR may receive 2 additional cycles. Patients who have PR may receive up to a maximum of 16 doses IF they are continuing to improve after 8 cycles. Patients who relapse within 6 months after CR maybe eligible for retreatment.

    View full details

  • Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma Recruiting

    Non-myeloablative approach for allogeneic transplant is a reasonable option, especially given that the median age at diagnosis is 55-60 years and frequently present compromised skin in these patients, which increases the risk of infection. Therefore, we propose a clinical study with allogeneic HSCT using a unique non-myeloablative preparative regimen, TLI/ATG, to treat advanced MF/SS.

    View full details

  • Study of Oral LBH589 in Adult Patients With Refractory/Resistant Cutaneous T-Cell Lymphoma Not Recruiting

    This study will evaluate the safety and efficacy of LBH589B in adult patients with refractory/resistant Cutaneous T-Cell Lymphoma and prior HDAC inhibitor therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

    View full details

  • Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome Not Recruiting

    RATIONALE: Lenalidomide may stop the growth of mycosis fungoides/Sezary syndrome by blocking blood flow to the cancer. PURPOSE: This phase II trial is studying how well lenalidomide works in treating patients with relapsed mycosis fungoides/Sezary syndrome.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

    View full details

  • Photopheresis as an Interventional Therapy for the Treatment of CTCL (Cutaneous T-Cell Lymphoma, Mycosis Fungoides) Stage 1A, 1B, 2A Not Recruiting

    The study objective is to demonstrate that the UVADEX® Sterile Solution formulation of methoxsalen used in conjunction with the UVAR XTS Photopheresis System can have a clinical effect on the skin manifestations of CTCL (mycosis fungoides) in early stage disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

    View full details

  • A Phase 3 Trial of Brentuximab Vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T-Cell Lymphoma Recruiting

    This is a Randomized, Open-Label, Phase 3 trial of brentuximab vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T-Cell Lymphoma

    View full details

  • Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma Not Recruiting

    This study will determine the maximum dose of KW-0761 administered intravenously that can be given safely in subjects with previously treated peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma(CTCL)and will see if it is effective in treating the disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Katie Turner, (650) 725 - 1202.

    View full details

  • A Trial of E7777 in Persistent and Recurrent Cutaneous T-Cell Lymphoma Recruiting

    The purpose of this trial is to assess the efficacy and safety of E7777 (improved purity ONTAK [denileukin diftitox]) in patients with persistent and recurrent cutaneous T-cell lymphoma. A Lead-in dose-finding part will be used to determine the dose of E7777 that should be used to test efficacy and safety.

    View full details

  • Low-dose (12 Gy) TSEBT+Vorinostat Versus Low-dose TSEBT Monotherapy in Mycosis Fungoides Not Recruiting

    The purpose of this study is to determine if vorinostat combined with low-dose total skin electron beam therapy (TSEBT) offers superior clinical benefit (efficacy & safety) over low-dose TSEBT alone.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, 650-421-6370.

    View full details

  • Phase I/II CPG 7909 + Local XRT in Recurrent Low-Grade Lymphomas Not Recruiting

    This is a single institution phase I / II trial to evaluate the safety, feasibility and efficacy of CpG injections (4 intratumoral injections followed by 6 peri-tumoral injections) combined with local irradiation in patients with recurrent low-grade lymphomas. Patients will receive low-dose radiotherapy to a single tumor site on days 1 and 2 (2 Gy each day). CpG injections will be administered into the same tumor site within the 24 hours before and the 24 hours after the radiation, and on days 8 and 15. Weekly doses of CpG will be then administered subcutaneously in the region of previous injections for 6 additional doses.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cameron Harrison, (650) 721 - 7186.

    View full details

  • A Single Agent Phase II Study of Romidepsin (Depsipeptide, FK228) in the Treatment of Cutaneous T-cell Lymphoma (CTCL) Not Recruiting

    GPI-04-0001 was a Phase II, non-randomized, open label, single arm study that was conducted at approximately 30 sites, primarily in the United States, Europe and Russia. It assessed the efficacy, safety, and tolerability of romidepsin as a treatment for cutaneous T-cell lymphoma (CTCL). Study patients (pts) received romidepsin in a dose of 14 mg/m^2 intravenously over 4 hours on Days 1, 8 and 15 of each 28-day cycle. The duration of study treatment was 6 cycles although pts who showed an objective response or stable disease could continue to receive therapy, at the discretion of the investigator, until disease progression or another withdrawal criterion was met.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sunil Arani Reddy, (650) 736 - 1234.

    View full details

  • Study to Evaluate the Safety and Efficacy of Adeno-IFN Gamma in Cutaneous B-cell Lymphoma Not Recruiting

    The primary objective of this study is to evaluate the efficacy of a four-month dosing period of intra-lesional injection of TG1042 in patients with relapsing CBCL. Patients will receive intra-tumoral injections of an adenoviral vector construct containing the human interferon gamma gene (TG1042), in an attempt to enhance immune responses with anti-tumor activity. This local administration induces tumour cell killing at the injected tumour sites.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

    View full details

  • Phase I/II Study of Intratumoral Injection of CPG 7909, a TLR9 Agonist, Combined With Local Radiation for Patients With Recurrent Mycosis Fungoides. Not Recruiting

    This is a single institution phase I / II trial to evaluate the safety and efficacy of intratumoral CpG injections combined with local radiation in patients with mycosis fungoides. Patients will receive low-dose radiotherapy to a single tumor site on days 1 and 2 (2 Gy each day). CpG injections will be administered into the same tumor site within 24 hours before or 24 hours after each radiation treatment. Weekly doses of (intratumoral or peritumoral injections) CpG will be then administered subcutaneously in the region of previous injections for 23 additional doses. The total treatment duration is 24 weeks.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mayita Romero, (650) 725 - 6452.

    View full details

  • A Phase II Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease Not Recruiting

    We hypothesize the addition of rituximab to prednisone for the initial treatment of chronic GVHD will increase the overall response rate, and enable a more rapid and effective steroid taper.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

    View full details

  • Safety and Efficacy of Nitrogen Mustard in Treatment of Mycosis Fungoides Not Recruiting

    This study will evaluate the efficacy, tolerability and safety of the topical application of mechlorethamine (MCH) formulations in patients with stage I or IIA mycosis fungoides (MF).

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

    View full details

  • Study of Human Monoclonal Antibody to Treat Mycosis Fungoides and Sezary Syndrome Not Recruiting

    The purpose of this study is to determine the efficacy of the drug, HuMax-CD4, in patients with mycosis fungoides(MF) and sezary syndrome who are intolerant to or do not respond to treatment with Targretin® and one other standard therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Daniel Navi, (650) 736 - 2300.

    View full details

  • Clinical Trial of PXD101 in Patients With T-Cell Lymphomas Not Recruiting

    This is an open-label, non-randomized trial to assess the effectiveness of PXD101 in patients with recurrent or refractory cutaneous or peripheral and other types of T-cell lymphomas. PXD101 is a new, potent histone deacetylase (HDAC) inhibitor. Patients are treated with belinostat(PXD101) 1000 mg/m2 on days 1-5 of a 21 day cycle.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

    View full details

  • A Randomized Phase II Study of Oral Sapacitabine in Patients With Advanced Cutaneous T-cell Lymphoma Not Recruiting

    This is an open label, randomized phase II study designed to evaluate the tolerability and response rate of high-dose and low-dose regimens in patients with advanced cutaneous T-cell lymphoma (CTCL) who have had progressive, recurrent, or persistent disease on or following 2 systemic therapies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Daniel Navi, (650) 736 - 2300.

    View full details

  • Safety, Pharmacodynamics (PD), Pharmacokinetics (PK) Study of SHP141 in 1A, 1B, or 2A Cutaneous T-Cell Lymphoma (CTCL) Recruiting

    The purpose of this study is to investigate the safety and tolerability of topical SHP141 applied directly to skin lesions in patients with Stage IA, IB, or IIA Cutaneous T-cell Lymphoma. This study will also investigate the effect of SHP141 on skin lesions in patients with Stage IA, IB, or IIA CTCL.

    View full details

  • Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma Recruiting

    The purpose of this trial is to develop an alternative treatment for patients with poor risk non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem cell transplant using the patient's own cells. This is followed with non-myeloablative transplant using stem cells from a related or unrelated donor to try and generate an anti-lymphoma response from the new immune system.

    View full details

  • A Phase 1 Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in Patients With Locally Advanced or Metastatic Solid Tumors Not Recruiting

    This Phase I, multicenter, first in human, open-label, dose escalation study will evaluate the safety, tolerability, and pharmacokinetics of MPDL3280A administered as single agent by intravenous (IV) infusion to patients with locally advanced or metastatic solid malignancies or hematologic malignancies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Rajapaksa Amanda, 650-725-6301.

    View full details

  • Study of Pralatrexate in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma Not Recruiting

    This study is being conducted to identify how much and how often pralatrexate, given with vitamin B12 and folic acid, can be given safely to patients with cutaneous T-cell lymphoma (CTCL) that has relapsed (returned after responding to previous treatment) or is refractory (has not responded to previous treatment). It is also being conducted to get information on whether or not pralatrexate is effective in treating relapsed or refractory CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cameron Harrison, (650) 721 - 7186.

    View full details

  • Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL Recruiting

    The purpose of this study is to compare the progression free survival of KW-0761 versus vorinostat for subjects with relapsed or refractory CTCL.

    View full details

  • Analysis of Cutaneous and Hematologic Disorders by High-Throughput Nucleic Acid Sequencing Recruiting

    The goal of this study is to identify genetic changes associated with the initiation, progression, and treatment response of response of cutaneous and hematologic disorders using recently developed high-throughput sequencing technologies. The improved understanding of the genetic changes associated with cutaneous and hematologic disorders may lead to improved diagnostic, prognostic and therapeutic options for these disorders.

    View full details

  • Phase II Total Skin Electron Beam Therapy (TSEBT 12 Gy) in Stage IB-IIIA Mycosis Fungoides Not Recruiting

    To examine the efficacy and safety of total skin electron beam therapy to a dose of 12 Gray (TSEBT 12 Gy) in patients who have mycosis fungoides (MF) staged as IB to IIIA.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cameron Harrison, (650) 721 - 7186.

    View full details

  • Forodesine in the Treatment of Cutaneous T-Cell Lymphoma Not Recruiting

    This is a Phase II, non-randomized, open-label, single-arm trial that will be conducted at up to 50 sites in North America, Europe and Australia. This study is designed to assess objective response (OR) [complete response (CR) or partial response (PR)] in subjects with cutaneous manifestations of CTCL with a requirement for maintenance of such objective response for at least 28 days in subjects with stage IIB, III, and IVA CTCL. Additionally, this study will evaluate the safety and tolerability of CTCL subjects Stages IB, IIA, IIB, III, or IVA treated with oral forodesine.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

    View full details

  • Extension Study in Subjects Who Relapsed After Complete Response on Study KW-0761-001 Not Recruiting

    This study will enroll subjects with either Peripheral T-Cell Lymphoma (PTCL) or Cutaneous T-Cell Lymphoma(CTCL),including mycosis fungoides (MF) and Sezary Syndrome (SS), who have relapsed after achieving a complete response in study, KW-0761-001.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, (650) 421 - 6370.

    View full details

  • An Open Label Study to Evaluate the Safety and Efficacy of Mechlorethamine(MCH) 0.04% Formulation in Mycosis Fungoides Not Recruiting

    To evaluate the efficacy and safety of topical application of MCH 0.04% in a propylene glycol ointment (PG)in patients with stage I or IIA MF previously treated with MCH 0.02% in a PG or AP ointment who did not achieve a complete response.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kokil Bakshi, (650) 421 - 6370.

    View full details

  • Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma Not Recruiting

    This study is designed to determine the recommended dose, safety, pharmacokinetics, and early efficacy of the combination of pralatrexate plus oral bexarotene in patients with relapsed or refractory CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, (650) 421 - 6370.

    View full details

  • A Study for Patients With Relapsed Cutaneous T-Cell Lymphoma Not Recruiting

    The purpose of the study is to determine the efficacy and safety of enzastaurin in patients with CTCL who failed prior therapies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

    View full details

Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • Transcriptome sequencing in Sezary syndrome identifies Sezary cell and mycosis fungoides-associated lncRNAs and novel transcripts BLOOD Lee, C. S., Ungewickell, A., Bhaduri, A., Qu, K., Webster, D. E., Armstrong, R., Weng, W., Aros, C. J., Mah, A., Chen, R. O., Lin, M., Sundram, U., Chang, H. Y., Kretz, M., Kim, Y. H., Khavari, P. A. 2012; 120 (16): 3288-3297

    Abstract

    Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma (CTCL) of unknown etiology in which malignant cells circulate in the peripheral blood. To identify viral elements, gene fusions, and gene expression patterns associated with this lymphoma, flow cytometry was used to obtain matched pure populations of malignant Sézary cells (SCs) versus nonmalignant CD4(+) T cells from 3 patients for whole transcriptome, paired-end sequencing with an average depth of 112 million reads per sample. Pathway analysis of differentially expressed genes identified mis-regulation of PI3K/Akt, TGF?, and NF-?B pathways as well as T-cell receptor signaling. Bioinformatic analysis did not detect either nonhuman transcripts to support a viral etiology of SS or recurrently expressed gene fusions, but it did identify 21 SC-associated annotated long noncoding RNAs (lncRNAs). Transcriptome assembly by multiple algorithms identified 13 differentially expressed unannotated transcripts termed Sézary cell-associated transcripts (SeCATs) that include 12 predicted lncRNAs and a novel transcript with coding potential. High-throughput sequencing targeting the 3' end of polyadenylated transcripts in archived tumors from 24 additional patients with tumor-stage CTCL confirmed the differential expression of SC-associated lncRNAs and SeCATs in CTCL. Our findings characterize the SS transcriptome and support recent reports that implicate lncRNA dysregulation in human malignancies.

    View details for DOI 10.1182/blood-2012-04-423061

    View details for Web of Science ID 000311619200020

    View details for PubMedID 22936659

  • Romidepsin Is Effective in Subcutaneous Panniculitis-Like T-Cell Lymphoma JOURNAL OF CLINICAL ONCOLOGY Bashey, S., Krathen, M., Abdulla, F., Sundram, U., Kim, Y. H. 2012; 30 (24): E221-E225

    View details for DOI 10.1200/JCO.2012.41.5976

    View details for Web of Science ID 000308082300002

    View details for PubMedID 22753921

  • In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study BLOOD Kim, Y. H., Gratzinger, D., Harrison, C., Brody, J. D., Czerwinski, D. K., Ai, W. Z., Morales, A., Abdulla, F., Xing, L., Navi, D., Tibshirani, R. J., Advani, R. H., Lingala, B., Shah, S., Hoppe, R. T., Levy, R. 2012; 119 (2): 355-363

    Abstract

    We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8(+) T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25(+), Foxp3(+) T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100(+), CD1a(+) dendritic cells. There was a trend toward greater reduction of CD25(+) T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993.

    View details for DOI 10.1182/blood-2011-05-355222

    View details for Web of Science ID 000299268900012

    View details for PubMedID 22045986

  • REVISITING LOW-DOSE TOTAL SKIN ELECTRON BEAM THERAPY IN MYCOSIS FUNGOIDES INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Harrison, C., Young, J., Navi, D., Riaz, N., Lingala, B., Kim, Y., Hoppe, R. 2011; 81 (4): E651-E657

    Abstract

    Total skin electron beam therapy (TSEBT) is a highly effective treatment for mycosis fungoides (MF). The standard course consists of 30 to 36 Gy delivered over an 8- to 10-week period. This regimen is time intensive and associated with significant treatment-related toxicities including erythema, desquamation, anhydrosis, alopecia, and xerosis. The aim of this study was to identify a lower dose alternative while retaining a favorable efficacy profile.One hundred two MF patients were identified who had been treated with an initial course of low-dose TSEBT (5-<30 Gy) between 1958 and 1995. Patients had a T stage classification of T2 (generalized patch/plaque, n = 51), T3 (tumor, n = 29), and T4 (erythrodermic, n = 22). Those with extracutaneous disease were excluded.Overall response (OR) rates (>50% improvement) were 90% among patients with T2 to T4 disease receiving 5 to <10 Gy (n = 19). In comparison, OR rates between the 10 to <20 Gy and 20 to <30 Gy subgroups were 98% and 97%, respectively. There was no significant difference in median progression free survival (PFS) in T2 and T3 patients when stratified by dose group, and PFS in each was comparable to that of the standard dose.OR rates associated with low-dose TSEBT in the ranges of 10 to <20 Gy and 20 to <30 Gy are comparable to that of the standard dose (? 30 Gy). Efficacy measures including OS, PFS, and RFS are also favorable. Given that the efficacy profile is similar between 10 and <20 Gy and 20 and <30 Gy, the utility of TSEBT within the lower dose range of 10 to <20 Gy merits further investigation, especially in the context of combined modality treatment.

    View details for DOI 10.1016/j.ijrobp.2011.01.023

    View details for Web of Science ID 000309412300060

    View details for PubMedID 21489711

  • Final Results From a Multicenter, International, Pivotal Study of Romidepsin in Refractory Cutaneous T-Cell Lymphoma JOURNAL OF CLINICAL ONCOLOGY Whittaker, S. J., Demierre, M., Kim, E. J., Rook, A. H., Lerner, A., Duvic, M., Scarisbrick, J., Reddy, S., Robak, T., Becker, J. C., Samtsov, A., McCulloch, W., Kim, Y. H. 2010; 28 (29): 4485-4491

    Abstract

    The primary objective of this study was to confirm the efficacy of romidepsin in patients with treatment refractory cutaneous T-cell lymphoma (CTCL).This international, pivotal, single-arm, open-label, phase II study was conducted in patients with stage IB to IVA CTCL who had received one or more prior systemic therapies. Patients received romidepsin as an intravenous infusion at a dose of 14 mg/m(2) on days 1, 8, and 15 every 28 days. Response was determined by a composite assessment of total tumor burden including cutaneous disease, lymph node involvement, and blood (Sézary cells).Ninety-six patients were enrolled and received one or more doses of romidepsin. Most patients (71%) had advanced stage disease (? IIB). The response rate was 34% (primary end point), including six patients with complete response (CR). Twenty-six of 68 patients (38%) with advanced disease achieved a response, including five CRs. The median time to response was 2 months, and the median duration of response was 15 months. A clinically meaningful improvement in pruritus was observed in 28 (43%) of 65 patients, including patients who did not achieve an objective response. Median duration of reduction in pruritus was 6 months. Drug-related adverse events were generally mild and consisted mainly of GI disturbances and asthenic conditions. Nonspecific, reversible ECG changes were noted in some patients.Romidepsin has significant and sustainable single-agent activity (including improvement in pruritus) and an acceptable safety profile, making it an important therapeutic option for treatment refractory CTCL.

    View details for DOI 10.1200/JCO.2010.28.9066

    View details for Web of Science ID 000282643600038

    View details for PubMedID 20697094

  • In Situ Vaccination With a TLR9 Agonist Induces Systemic Lymphoma Regression: A Phase I/II Study JOURNAL OF CLINICAL ONCOLOGY Brody, J. D., Ai, W. Z., Czerwinski, D. K., Torchia, J. A., Levy, M., Advani, R. H., Kim, Y. H., Hoppe, R. T., Knox, S. J., Shin, L. K., Wapnir, I., Tibshirani, R. J., Levy, R. 2010; 28 (28): 4324-4332

    Abstract

    Combining tumor antigens with an immunostimulant can induce the immune system to specifically eliminate cancer cells. Generally, this combination is accomplished in an ex vivo, customized manner. In a preclinical lymphoma model, intratumoral injection of a Toll-like receptor 9 (TLR9) agonist induced systemic antitumor immunity and cured large, disseminated tumors.We treated 15 patients with low-grade B-cell lymphoma using low-dose radiotherapy to a single tumor site and-at that same site-injected the C-G enriched, synthetic oligodeoxynucleotide (also referred to as CpG) TLR9 agonist PF-3512676. Clinical responses were assessed at distant, untreated tumor sites. Immune responses were evaluated by measuring T-cell activation after in vitro restimulation with autologous tumor cells.This in situ vaccination maneuver was well-tolerated with only grade 1 to 2 local or systemic reactions and no treatment-limiting adverse events. One patient had a complete clinical response, three others had partial responses, and two patients had stable but continually regressing disease for periods significantly longer than that achieved with prior therapies. Vaccination induced tumor-reactive memory CD8 T cells. Some patients' tumors were able to induce a suppressive, regulatory phenotype in autologous T cells in vitro; these patients tended to have a shorter time to disease progression. One clinically responding patient received a second course of vaccination after relapse resulting in a second, more rapid clinical response.In situ tumor vaccination with a TLR9 agonist induces systemic antilymphoma clinical responses. This maneuver is clinically feasible and does not require the production of a customized vaccine product.

    View details for DOI 10.1200/JCO.2010.28.9793

    View details for Web of Science ID 000282272700032

    View details for PubMedID 20697067

  • Prognostic Factors in Primary Cutaneous Anaplastic Large Cell Lymphoma Characterization of Clinical Subset With Worse Outcome ARCHIVES OF DERMATOLOGY Woo, D. K., Jones, C. R., Vanoli-Storz, M. N., Kohler, S., Reddy, S., Advani, R., Hoppe, R. T., Kim, Y. H. 2009; 145 (6): 667-674

    Abstract

    To identify prognostic factors in primary cutaneous anaplastic large cell lymphoma (pcALCL), focusing on extensive limb disease (ELD), defined as initial presentation or progression to multiple skin tumors in 1 limb or contiguous body regions, and to study gene expression profiles of patients with pcALCL.Retrospective cohort study.The Stanford Comprehensive Cancer Center and dermatology ambulatory clinics.A total of 48 patients with pcALCL evaluated from 1990 through 2005.Hazard ratios (HRs) for prognostic factors for overall survival (OS) and disease-specific survival (DSS) and risk factors for progression to extracutaneous disease were identified using Cox regression. Gene expression profiles of 9 typical pcALCL and 3 ELD samples were investigated using complementary DNA microarrays.Univariate analysis demonstrated age, ELD, and progression to extracutaneous disease as significant prognostic factors for OS, whereas ELD and progression to extracutaneous disease were significant for DSS. In multivariate analysis, age (HR, 1.83; 95% confidence interval [CI], 1.02-3.26) and progression to extracutaneous disease (HR, 6.42; 95% CI, 1.39-29.68) remained significant for OS, whereas ELD (HR, 29.31; 95% CI, 1.72-500.82) and progression to extracutaneous disease (HR, 13.12; 95% CI, 1.03-167.96) remained independent prognostic factors for DSS. Presentation with T3 disease was a risk factor for progression to extracutaneous disease (HR, 10.20; 95% CI, 1.84-56.72). Microarray data revealed that patients with ELD and typical pcALCL formed distinct clusters.Patients with ELD have a more aggressive course associated with a differential gene expression profile. More aggressive treatments may be indicated for patients with ELD and those whose disease progresses to extracutaneous disease because they have poorer outcomes.

    View details for Web of Science ID 000267010900006

    View details for PubMedID 19528422

  • TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC) BLOOD Kim, Y. H., Willemze, R., Pimpinelli, N., Whittaker, S., Olsens, E. A., Ranki, A., Dummer, R., Hoppe, R. T. 2007; 110 (2): 479-484

    Abstract

    Currently availabel staging systems for non-Hodgkin lymphomas are not useful for clinical staging classification of most primary cutaneous lymphomas. The tumor, node, metastases (TNM) system used for mycosis fungoides (MF) and Sézary syndrome (SS) is not appropriate for other primary cutaneous lymphomas. A usable, unified staging system would improve the communication about the state of disease, selection of appropriate management, standardization of enrollment/response criteria in clinical trials, and collection/analysis of prospective survival data. Toward this goal, during the recent meetings of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC), the representatives have established a consensus proposal of a TNM classification system applicable for all primary cutaneous lymphomas other than MF and SS. Due to the clinical and pathologic heterogeneity of the cutaneous lymphomas, the currently proposed TNM system is meant to be primarily an anatomic documentation of disease extent and not to be used as a prognostic guide.

    View details for DOI 10.1182/blood-2006-10-054601

    View details for Web of Science ID 000248112400008

    View details for PubMedID 17339420

  • Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma BLOOD Kim, Y. H., Duvic, M., Obitz, E., Gniadecki, R., Iversen, L., Osterborg, A., Whittaker, S., Illidge, T. M., Schwarz, T., Kaufmann, R., Cooper, K., Knudsen, K. M., Lisby, S., Baadsgaard, O., Knox, S. J. 2007; 109 (11): 4655-4662

    Abstract

    The efficacy and safety of zanolimumab in patients with refractory cutaneous T-cell lymphoma (CTCL) have been assessed in two phase 2, multicenter, prospective, open-label, uncontrolled clinical studies. Patients with treatment refractory CD4(+) CTCL (mycosis fungoides [MF], n = 38; Sézary syndrome [SS], n = 9) received 17 weekly infusions of zanolimumab (early-stage patients, 280 and 560 mg; advanced-stage patients, 280 and 980 mg). The primary end point was objective response (OR) as assessed by composite assessment of index lesion disease activity score. Secondary end points included physician's global assessment (PGA), time to response, response duration, and time to progression. ORs were recorded for patients in both CTCL types (MF, 13 ORs; SS, 2 ORs). In the high-dose groups (560 and 980 mg dose groups), a response rate of 56% was obtained with a median response of 81 weeks. Adverse events reported most frequently included low-grade infections and eczematous dermatitis. Zanolimumab showed marked clinical efficacy in the treatment of patients with refractory MF, with early onset of response, high response rate, and durable responses. The treatment was well tolerated with no dose-related toxicity other than the targeted depletion of peripheral T cells. A pivotal study has been initiated based on these findings.

    View details for DOI 10.1182/blood-2006-12-062877

    View details for Web of Science ID 000246946100017

    View details for PubMedID 17311990

  • Intravascular ALK-negative Anaplastic Large Cell Lymphoma With Localized Cutaneous Involvement and an Indolent Clinical Course Toward Recognition of a Distinct Clinicopathologic Entity AMERICAN JOURNAL OF SURGICAL PATHOLOGY Metcalf, R. A., Bashey, S., Wysong, A., Kim, J., Kim, Y. H., Gratzinger, D. 2013; 37 (4): 617-623

    Abstract

    Intravascular large T-cell or NK-cell lymphomas rarely present with cutaneous involvement. Intravascular cytotoxic T or NK lymphomas presenting in the skin (cIT/NKL) are often EBV, and reported cases follow a highly aggressive clinical course. Intravascular anaplastic large cell lymphoma (ALCL) by contrast is extraordinarily rare and, when it presents in the skin, raises the question of aggressive clinical behavior in the manner of cIT/NKL versus indolent clinical behavior in the manner of primary cutaneous ALCL. Here we describe a case of localized cutaneous intravascular anaplastic lymphoma kinase-negative ALCL (cIALCL) with a very indolent clinical course. The patient experienced a single cutaneous relapse and remains alive without disease 4 years after diagnosis. Review of the literature reveals multiple clinicopathologic differences between cIALCL and cIT/NKL: distribution (cIALCL, single skin region, P=0.021, Fisher exact test); histology (cIALCL, cohesive with necrosis, P=0.005); immunophenotype (cIALCL, strongly CD30, P=0.021; cIT/NKL, CD56 and/or EBV, P=0.003); and indolent clinical behavior with a trend toward better overall survival (P=0.067, Kaplan-Meier survival analysis). Our index case of cIALCL and 1 other tested case were immunohistochemically confirmed to be intralymphatic (contained within D2-40+vessels) as compared with the blood vessel localization of cIT/NKL. Recognition of cIALCLs as a distinct clinicopathologic entity, and in particular their distinction from aggressive, usually EBV cIT/NKLs, may be possible on the basis of a combination of clinicopathologic criteria, allowing for localized therapy in a subset of patients.

    View details for DOI 10.1097/PAS.0b013e318280aa9c

    View details for Web of Science ID 000316184000019

    View details for PubMedID 23480896

  • Clonal Identity and Differences in Primary Cutaneous B-Cell Lymphoma Occurring at Different Sites or Time Points in the Same Patient AMERICAN JOURNAL OF DERMATOPATHOLOGY Fujiwara, M., Morales, A. V., Seo, K., Kim, Y. H., Arber, D. A., Sundram, U. N. 2013; 35 (1): 11-18

    Abstract

    Primary cutaneous B-cell lymphomas (PCBCL) are rare. Marginal zone lymphomas and follicle center lymphomas (FCL) represent a majority of these cases, and a significant number of cases present with multiple lesions. It is unclear whether multiple lesions in PCBCL represent dissemination of a single clone or multiple new primary lymphomas. In the current study, we analyzed paired samples from 20 PCBCL patients at more than 1 site (16) or at the same site at different time points (4) and 12 patients with benign lymphoid infiltrates to investigate for the presence or absence of a clone, and if present, whether the clones were identical. Both IGH@ and IGK@ rearrangements were tested using the BIOMED-2 protocol. We identified a clone (IGH@ and/or IGK@) in 19 of 20 (95%) PCBCL patients and 2 of 12 (17%) benign lymphoid infiltrate patients. The B-cell clones were proven to be identical in 11 of 20 (55%) PCBCL patients, including 7 of 16(44%) biopsies from patients with 2 different sites and 4 of 4 biopsies (100%) from patients at the same site but different time points. In 4 cases (3 FCL and 1 marginal zone lymphoma), different clones were detected at different sites, suggesting the possibility of a second simultaneous primary lymphoma. Our results indicate that the presence of identical clones is highly suggestive of lymphoma. To our knowledge, this is the first report to investigate the detection of identical clones in 2 distinct biopsies in PCBCL patients. Although the study is small and the results need to be confirmed in a larger study, these findings suggest that a subset of PCBCL at different sites may represent different primary tumors rather than occurrence of a single disease.

    View details for DOI 10.1097/DAD.0b013e318255dbae

    View details for Web of Science ID 000314103600006

    View details for PubMedID 22588547

  • Clinically meaningful reduction in pruritus in patients with cutaneous T-cell lymphoma treated with romidepsin LEUKEMIA & LYMPHOMA Kim, Y. H., Demierre, M., Kim, E. J., Lerner, A., Rook, A. H., Duvic, M., Robak, T., Samtsov, A., McCulloch, W., Chen, S. C., Waksman, J., Nichols, J., Whittaker, S. 2013; 54 (2): 284-289

    Abstract

    Patients with cutaneous T-cell lymphoma (CTCL) frequently experience severe pruritus that can significantly impact their quality of life. Romidepsin is approved by the US Food and Drug Administration (FDA) for the treatment of patients with CTCL who have received at least one prior systemic therapy, with a reported objective response rate of 34%. In a phase 2 study of romidepsin in patients with CTCL (GPI-04-0001), clinically meaningful reduction in pruritus (CMRP) was evaluated as an indicator of clinical benefit by using a patient-assessed visual analog scale. To determine the effect of romidepsin alone, confounding pruritus treatments including steroids and antihistamines were prohibited. At baseline, 76% of patients reported moderate-to-severe pruritus; 43% of these patients experienced CMRP, including 11 who did not achieve an objective response. Median time to CMRP was 1.8 months, and median duration of CMRP was 5.6 months. Study results suggest that the clinical benefit of romidepsin may extend beyond objective responses.

    View details for DOI 10.3109/10428194.2012.711829

    View details for Web of Science ID 000313285400015

    View details for PubMedID 22839723

  • Cutaneous gamma delta T-cell Lymphomas A Spectrum of Presentations With Overlap With Other Cytotoxic Lymphomas AMERICAN JOURNAL OF SURGICAL PATHOLOGY Guitart, J., Weisenburger, D. D., Subtil, A., Kim, E., Wood, G., Duvic, M., Olsen, E., Junkins-Hopkins, J., Rosen, S., Sundram, U., Ivan, D., Selim, M. A., Pincus, L., Deonizio, J. M., Kwasny, M., Kim, Y. H. 2012; 36 (11): 1656-1665

    Abstract

    We reviewed our multicenter experience with gamma-delta (??) T-cell lymphomas first presenting in the skin. Fifty-three subjects with a median age of 61 years (range, 25 to 91 y) were diagnosed with this disorder. The median duration of the skin lesions at presentation was 1.25 years (range, 1 mo to 20 y). The most common presentation was deep plaques (38 cases) often resembling a panniculitis, followed by patches resembling psoriasis or mycosis fungoides (10 cases). These lesions tended to ulcerate overtime (27 cases). Single lesions or localized areas of involvement resembling cellulitis or pyoderma were reported in 8 cases. The most common anatomic site of involvement was the legs (40 cases), followed by the torso (30 cases) and arms (28 cases). Constitutional symptoms were reported in 54% (25/46) of the patients, including some with limited skin involvement. Significant comorbidities included autoimmunity (12 cases), other lymphoproliferative disorders (5 cases), internal carcinomas (4 cases), and viral hepatitis (2 cases). Lymphadenopathy (3/42 cases) and bone marrow involvement (5/28 cases) were uncommon, but serum lactose dehydrogenase (LDH) was elevated in 55% (22/39) of the patients. Abnormal positron emission tomography and/or computed tomography scans in 20/37 subjects mostly highlighted soft tissue or lymph nodes. Disease progression was associated with extensive ulcerated lesions resulting in 27 deaths including complications of hemophagocytic syndrome (4) and cerebral nervous system involvement (3). Median survival time from diagnosis was 31 months. Skin biopsies varied from a pagetoid pattern to purely dermal or panniculitic infiltrates composed of intermediate-sized lymphocytes with tissue evidence of cytotoxicity. The most common immunophenotype was CD3+/CD4+/CD5+/CD8+/BF1+/?-M1+/TIA-1+/granzyme-B+/CD45RA-/CD7-, and 4 cases were Epstein-Barr virus positive. This is the largest study to date of cutaneous ?? T-cell lymphomas and demonstrates a variety of clinical and pathologic presentations with a predictable poor outcome.

    View details for DOI 10.1097/PAS.0b013e31826a5038

    View details for Web of Science ID 000310059600008

    View details for PubMedID 23073324

  • A Comparative Analysis of Cutaneous Marginal Zone Lymphoma and Cutaneous Chronic Lymphocytic Leukemia AMERICAN JOURNAL OF DERMATOPATHOLOGY Levin, C., Mirzamani, N., Zwerner, J., Kim, Y., Schwartz, E. J., Sundram, U. 2012; 34 (1): 18-23

    Abstract

    The morphologic distinction between cutaneous marginal zone lymphoma (CMZL) and secondary cutaneous involvement by B-cell chronic lymphocytic leukemia (B-CLL) can be difficult. Both entities can show very similar architectural patterns of involvement in the skin and not uncommonly, the skin can be the first site of presentation of B-CLL in the elderly. We reviewed biopsies of 13 patients with cutaneous B-CLL and 14 patients with CMZL to compare their histologic and immunohistochemical features. CMZL and cutaneous B-CLL both predominantly exhibited a nodular pattern of skin involvement (9 of 13 B-CLL, 9 of 14 CMZL) with a minority of cases demonstrating a diffuse pattern (4 of 13 B-CLL, 4 of 14 CMZL). Although reactive germinal centers (12 of 14 cases) and plasma cells (10 of 14 cases) were seen more often in CMZL, plasma cells were also observed in cases of B-CLL (4 of 13). The lesional cells of B-CLL expressed CD79, CD5, CD23, and CD43, although CMZL did not express CD5 or CD43. Although we noted light chain restriction in 13 of 14 cases of CMZL cases, we also observed light chain restriction in 4 of 13 cases of B-CLL. Our results indicate that CMZL and B-CLL can be morphologically similar and both may show light chain restriction. Complete immunophenotyping is necessary to ensure that all cases are correctly classified.

    View details for DOI 10.1097/DAD.0b013e31821528bc

    View details for Web of Science ID 000299325900005

    View details for PubMedID 22257836

  • EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma BLOOD Kempf, W., Pfaltz, K., Vermeer, M. H., Cozzio, A., Ortiz-Romero, P. L., Bagot, M., Olsen, E., Kim, Y. H., Dummer, R., Pimpinelli, N., Whittaker, S., Hodak, E., Cerroni, L., Berti, E., Horwitz, S., Prince, H. M., Guitart, J., Estrach, T., Sanches, J. A., Duvic, M., Ranki, A., Dreno, B., Ostheeren-Michaelis, S., Knobler, R., Wood, G., Willemze, R. 2011; 118 (15): 4024-4035

    Abstract

    Primary cutaneous CD30(+) lymphoproliferative disorders (CD30(+) LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30(+) LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30(+) LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30(+) LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30(+) LPDs.

    View details for DOI 10.1182/blood-2011-05-351346

    View details for Web of Science ID 000296282200008

    View details for PubMedID 21841159

  • The frequency of dual TCR-PCR clonality in granulomatous disorders JOURNAL OF CUTANEOUS PATHOLOGY Dabiri, S., Morales, A., Ma, L., Sundram, U., Kim, Y. H., Arber, D. A., Kim, J. 2011; 38 (9): 704-709

    Abstract

    A granulomatous infiltrate in association with cutaneous T-cell lymphoma is uncommon. The diagnosis of mycosis fungoides can be difficult in the setting of an exuberant granulomatous infiltrate that obscures the neoplastic lymphoid infiltrate, thereby mimicking a granulomatous dermatitis. Therefore, the clinical context and supplemental molecular analysis, such as the demonstration of a monoclonal T-cell population, may assist in diagnosis. Monoclonal T-cell populations have been reported in association with inflammatory conditions and serve as a diagnostic pitfall. The frequency of T-cell clonality in association with granulomatous dermatitides has not yet been established.We identified 29 patients with granulomatous dermatitis who had biopsies at two distinct body sites. Results were correlated with clinical follow up and with clonal T-cell receptor-gamma chain rearrangement as detected by polymerase chain reaction-based analysis (dual TCR-PCR).Clinical follow up was obtained in 17 of 29 cases (58.6%). Twenty-five of 29 cases of granulomatous dermatitis lacked T-cell monoclonality. Three cases of granuloma annulare contained a T-cell clone in one of the two biopsies. One case of necrobiotic xanthogranuloma showed an identical T-cell clone in multiple biopsies.The use of dual TCR-PCR analysis, that is, T-cell clonality analysis in biopsy specimens from two different sites, serves as an adjunct to assist in distinguishing granulomatous inflammatory reactions from granulomatous T-cell lymphoma, including granulomatous mycosis fungoides. The occasional finding of a T-cell clone in a granulomatous dermatitis underscores the importance of clinicopathological correlation in daily diagnosis.

    View details for DOI 10.1111/j.1600-0560.2011.01727.x

    View details for Web of Science ID 000293177000005

    View details for PubMedID 21645036

  • Clinical End Points and Response Criteria in Mycosis Fungoides and Sezary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer JOURNAL OF CLINICAL ONCOLOGY Olsen, E. A., Whittaker, S., Kim, Y. H., Duvic, M., Prince, H. M., Lessin, S. R., Wood, G. S., Willemze, R., Demierre, M., Pimpinelli, N., Bernengo, M. G., Ortiz-Romero, P. L., Bagot, M., Estrach, T., Guitart, J., Knobler, R., Sanches, J. A., Iwatsuki, K., Sugaya, M., Dummer, R., Pittelkow, M., Hoppe, R., Parker, S., Geskin, L., Pinter-Brown, L., Girardi, M., Burg, G., Ranki, A., Vermeer, M., Horwitz, S., Heald, P., Rosen, S., Cerroni, L., Dreno, B., Vonderheid, E. C. 2011; 29 (18): 2598-2607

    Abstract

    Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.

    View details for DOI 10.1200/JCO.2010.32.0630

    View details for Web of Science ID 000291684600038

    View details for PubMedID 21576639

  • The Stanford University Experience With Conventional-Dose, Total Skin Electron-Beam Therapy in the Treatment of Generalized Patch or Plaque (T2) and Tumor (T3) Mycosis Fungoides ARCHIVES OF DERMATOLOGY Navi, D., Riaz, N., Levin, Y. S., Sullivan, N. C., Kim, Y. H., Hoppe, R. T. 2011; 147 (5): 561-567

    Abstract

    To review the Stanford University experience with total skin electron-beam therapy (TSEBT) of 30 Gy or greater as monotherapy in patients with mycosis fungoides (MF) and compare with subgroups receiving adjuvant nitrogen mustard (HN2), and further update our experience with repeated courses of TSEBT.Retrospective study.Academic referral center, multidisciplinary clinic.A total of 180 patients with MF treated from 1970 through 2007 with T2 MF (103 with generalized patch or plaque disease) or T3 MF (77 with tumor disease). Patients with extracutaneous disease were excluded.Total skin electron-beam therapy with or without adjuvant topical HN2.Clinical response rate, freedom from relapse (FFR), overall survival (OS), and progression-free survival (PFS) after TSEBT.The overall response rate (ORR) was 100%; 60% of patients achieved a complete clinical response (patients with T2 MF = 75%, those with T3 MF = 47%). The 5- and 10-year OS rates of the entire cohort were 59% and 40%, respectively. There were no significant differences in FFR (P = .30 for T2 disease; P = .50 for T3 disease), PFS (P = .10 for T2 disease; P = .40 for T3 disease), or OS (P = .30 for T2 disease; P = .50 for T3 disease) between adjuvant HN2 and TSEBT monotherapy cohorts. The ORR was 100% in patients receiving a second course of TSEBT with median FFR of 6 months.A TSEBT of 30 Gy or greater is highly effective in treating T2-T3 MF, with better outcomes in T2 disease. There was no clinical advantage to adjuvant HN2 as used in our cohort. Second courses of TSEBT are safe and efficacious and provide clinically meaningful palliation for select patients.

    View details for Web of Science ID 000290632100008

    View details for PubMedID 21576575

  • Sezary syndrome: Immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC) JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Olsen, E. A., Rook, A. H., Zic, J., Kim, Y., Porcu, P., Querfeld, C., Wood, G., Demierre, M., Pittelkow, M., Wilson, L. D., Pinter-Brown, L., Advani, R., Parker, S., Kim, E. J., Junkins-Hopkins, J. M., Foss, F., Cacchio, P., Duvic, M. 2011; 64 (2): 352-404

    Abstract

    Sézary syndrome (SS) has a poor prognosis and few guidelines for optimizing therapy. The US Cutaneous Lymphoma Consortium, to improve clinical care of patients with SS and encourage controlled clinical trials of promising treatments, undertook a review of the published literature on therapeutic options for SS. An overview of the immunopathogenesis and standardized review of potential current treatment options for SS including metabolism, mechanism of action, overall efficacy in mycosis fungoides and SS, and common or concerning adverse effects is first discussed. The specific efficacy of each treatment for SS, both as monotherapy and combination therapy, is then reported using standardized criteria for both SS and response to therapy with the type of study defined by a modification of the US Preventive Services guidelines for evidence-based medicine. Finally, guidelines for the treatment of SS and suggestions for adjuvant treatment are noted.

    View details for DOI 10.1016/j.jaad.2010.08.037

    View details for Web of Science ID 000286780400016

    View details for PubMedID 21145619

  • Phase I trial of a Toll-like receptor 9 agonist, PF-3512676 (CPG 7909), in patients with treatment-refractory, cutaneous T-cell lymphoma JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Kim, Y. H., Girardi, M., Duvic, M., Kuzel, T., Link, B. K., Brown, L. P., Rook, A. H. 2010; 63 (6): 975-983

    Abstract

    Mycosis fungoides and Sézary syndrome are a class of lymphomas of skin-trafficking T cells, and they are the most common forms of cutaneous T-cell lymphoma (CTCL). Mycosis fungoides and Sézary syndrome are chronic, frequently incurable diseases with limited therapeutic options. PF-3512676 (formerly CPG 7909) is a Toll-like receptor 9 agonist that is being investigated for treatment of patients with advanced cancer.This study was conducted to determine the safety and tolerability of single-agent PF-3512676 in patients with CTCL.In this phase I dose-escalation study, patients (N = 28) with treatment-refractory, stage IB to IVA CTCL were enrolled in 6 sequential cohorts and treated with PF-3512676 (0.08, 0.16, 0.24, 0.28, 0.32, or 0.36 mg/kg) administered as 24 weekly subcutaneous injections. Primary end points were safety and tolerability.Common adverse events (fatigue, rigors, injection-site reactions, myalgia, lymphopenia, leukopenia, neutropenia, and pyrexia) were mostly grade 1 or 2, and no patient developed specific symptoms associated with autoimmune disease. Clinical response rate to PF-3512676, as determined by both Composite Assessment of Index Lesion Severity and Physician Global Assessment, was 32% (3 complete clinical responses, 6 partial responses); the majority of responses (7/9; 78%) were ongoing at the end of study.This trial was not designed to rigorously assess efficacy.Single-agent PF-3512676 was well tolerated and demonstrated antitumor activity in patients with refractory CTCL.

    View details for DOI 10.1016/j.jaad.2009.12.052

    View details for Web of Science ID 000284968100003

    View details for PubMedID 20888065

  • Combined Use of PCR-Based TCRG and TCRB Clonality Tests on Paraffin-Embedded Skin Tissue in the Differential Diagnosis of Mycosis Fungoides and Inflammatory Dermatoses JOURNAL OF MOLECULAR DIAGNOSTICS Zhang, B., Beck, A. H., Taube, J. M., Kohler, S., Seo, K., Zwerner, J., Viakhereva, N., Sundram, U., Kim, Y. H., Schrijver, I., Arber, D. A., Zehnder, J. L. 2010; 12 (3): 320-327

    Abstract

    The distinction between mycosis fungoides (MF) and inflammatory dermatoses (ID) by clinicopathologic criteria can be challenging. There is limited information regarding the performance characteristics and utility of TCRG and TCRB clonality assays in diagnosis of MF and ID from paraffin-embedded tissue sections. In this study, PCR tests were performed with both TCRG and TCRB BIOMED-2 clonality methods followed by capillary electrophoresis and Genescan analysis using DNA samples from 35 MF and 96 ID patients with 69 and 133 paraffin-embedded specimens, respectively. Performance characteristics were determined for each test individually and in combination. TCRG and TCRB tests demonstrated identical sensitivity (64%) and specificity (84%) when analyzed as individual assays. The positive predictive value, negative predictive value, and change of posttest MF probability over a range of MF pretest probabilities were obtained. These data were used to construct an algorithm for sequential use of TCRG and TCRB. As single tests, commercially available BIOMED-2 PCR-based TCRG and TCRB clonality tests on paraffin-embedded tissue have no significant difference in terms of sensitivity and specificity. Combined use of the two tests in patients with intermediate pretest probabilities as proposed in the algorithm could improve test utility.

    View details for DOI 10.2353/jmoldx.2010.090123

    View details for Web of Science ID 000277531700009

    View details for PubMedID 20203005

  • A Phase II Study of SGN-30 in Cutaneous Anaplastic Large Cell Lymphoma and Related Lymphoproliferative Disorders CLINICAL CANCER RESEARCH Duvic, M., Reddy, S. A., Pinter-Brown, L., Korman, N. J., Zic, J., Kennedy, D. A., Lorenz, J., Sievers, E. L., Kim, Y. H. 2009; 15 (19): 6217-6224

    Abstract

    An open-label, multicenter, phase II study was conducted to define the safety and antitumor activity of the monoclonal antibody SGN-30 in patients with CD30(+) primary cutaneous anaplastic large cell lymphoma (pc-ALCL), lymphomatoid papulosis (LyP), or transformed mycosis fungoides (T-MF).In the initial course (six doses), patients received i.v. SGN-30 every 3 weeks; eligible patients could receive two additional courses. The initial dose level of 4 mg/kg was increased to 12 mg/kg by protocol amendment.The overall objective response rate [complete response (CR) + partial response (PR)] was 70% (16 of 23 patients): 10 patients achieved a CR and another 6 patients achieved a PR. Overall, clinical benefit of SGN-30, as assessed by achieving a response to therapy or stable disease (CR + PR + stable disease), was shown by 87% of patients during the study, including all patients with pc-ALCL or LyP and two thirds of patients with T-MF or with multiple clinical diagnoses. Nine of the 10 patients who achieved a CR and 5 of the 6 patients who achieved a PR were in remission at their follow-up evaluation (median duration, 84 days). Fifteen of 23 patients (65%) experienced at least one adverse event during the study, most of which were mild or moderate.SGN-30 was clinically active in 16 of 23 patients with heavily pretreated pc-ALCL, LyP, and T-MF and was well tolerated in this study.

    View details for DOI 10.1158/1078-0432.CCR-09-0162

    View details for Web of Science ID 000270498700034

    View details for PubMedID 19789316

  • Cutaneous Peripheral T-Cell Lymphoma Associated With a Proliferation of B Cells AMERICAN JOURNAL OF CLINICAL PATHOLOGY Mattoch, I. W., Fulton, R., Kim, Y., Hoppe, R., Warnke, R. A., Sundram, U. N. 2009; 131 (6): 810-819

    Abstract

    Although the new World Health Organization-European Organization for Research and Treatment of Cancer classification focuses on providing uniformity in the diagnosis of cutaneous lymphomas, cutaneous peripheral T-cell lymphoma (PTL) remains a poorly defined subgroup. As follow-up to a study of systemic PTL complicated by a proliferation of B cells, we studied 16 cases of cutaneous PTL that contained morphologically atypical T cells associated with a significant infiltrate of B cells (about 20%-50%). A clonal T-cell receptor gamma chain gene rearrangement was present in all cases. In contrast, a clonal immunoglobulin heavy chain gene rearrangement was present in only 1 case. Clinical staging in 14 cases identified systemic involvement in 2. At last follow-up, both patients with systemic involvement had died of disease, and the majority of patients with primary cutaneous disease were alive (11/12). The presence of numerous atypical B cells and T cells caused diagnostic confusion in these cases. Comprehensive pathologic studies, coupled with clinical staging, are necessary for the accurate diagnosis of this unusual manifestation of cutaneous PTL.

    View details for DOI 10.1309/AJCP5W0VOCSVOBRA

    View details for Web of Science ID 000266238600010

    View details for PubMedID 19461087

  • Low Stage Follicular Lymphoma: Biologic and Clinical Characterization According to Nodal or Extranodal Primary Origin AMERICAN JOURNAL OF SURGICAL PATHOLOGY Weinberg, O. K., Ma, L., Seo, K., Beck, A. H., Pai, R. K., Morales, A., Kim, Y., Sundram, U., Tan, D., Horning, S. J., Hoppe, R. T., Natkunam, Y., Arber, D. A. 2009; 33 (4): 591-598

    Abstract

    Studies suggest that primary extranodal follicular lymphoma (FL) is not infrequent but it remains poorly characterized with variable histologic, molecular, and clinical outcome findings. We compared 27 extranodal FL to 44 nodal FL using morphologic, immunohistochemical, and molecular genetic techniques and evaluated the clinical outcome of these 2 similarly staged groups. Eight cases of primary cutaneous follicle center lymphoma were also studied. In comparison to nodal FL, a greater number of extranodal FL contained a diffuse growth pattern (P=0.004) and lacked CD10 expression (P=0.014). Fifty-four percent of extranodal and 42% of nodal FL cases showed evidence of t(14;18), with minor breakpoints (icr, 3'BCL2, 5'mcr) more commonly found in extranodal cases (P=0.003). Outcome data showed no significant differences in overall survival (P=0.565) and progression-free survival (P=0.627) among extranodal, nodal, and primary cutaneous follicle center lymphoma cases. Analysis of all cases by t(14;18) status indicate that the translocation-negative group is characterized by a diffuse growth pattern (P=0.043) and lower BCL2 expression (P=0.018). The t(14;18)-positive group showed significantly better overall survival (P=0.019) and disease-specific survival (P=0.006) in comparison with the t(14;18)-negative group. In low stage FL, the status of t(14;18) seems to be more predictive of outcome than origin from an extranodal versus nodal site.

    View details for Web of Science ID 000264818800014

    View details for PubMedID 19065102

  • Indolent primary cutaneous B-cell lymphoma: Experience using systemic rituximab JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Morales, A. V., Advani, R., Horwitz, S. M., Riaz, N., Reddy, S., Hoppe, R. T., Kim, Y. H. 2008; 59 (6): 953-957

    Abstract

    Optimal treatment of indolent primary cutaneous B-cell lymphoma (CBCL), marginal zone lymphoma, and follicle center lymphoma, presenting as multiple lesions, has yet to be established. Rituximab is a chimeric monoclonal IgG1 antibody directed against the CD20 antigen of B cells. Clinical efficacy of systemic rituximab in CBCL has yet to be established.We sought to assess the efficacy of systemic rituximab in the treatment of CBCL.This was a retrospective study of 15 patients with indolent CBCL treated with intravenous rituximab (375 mg/m(2)) as a single agent. Variable maintenance regimen was used in a subset of patients. Responses were categorized as complete response, partial response, stable disease, or progressive disease. The efficacy end points included were objective response rate, time to response, time to progression, and duration of response.Ten patients with follicle center lymphoma and 5 with marginal zone lymphoma were included. The objective response rate was 87% (60% complete response, 27% partial response). All patients with follicle center lymphoma had a response with 80% achieving complete response. Of the patients with marginal zone lymphoma, 3 had a response, one stable disease, and one progressive disease. Median follow-up was 36 months. Median time to response, duration of response, and time to progression was 30 days, 24 months, and 24 months, respectively.The study was limited by the small sample size and retrospective design.This study, although small, suggests that rituximab is a reasonable first-line treatment option for indolent CBCL with multiple lesions where local treatment is not effective or desirable.

    View details for DOI 10.1016/j.jaad.2008.08.005

    View details for Web of Science ID 000261141600006

    View details for PubMedID 18817999

  • Cytologic Evaluation of Lymphadenopathy Associated With Mycosis Fungoides and Sezary Syndrome Role of Immunophenotypic and Molecular Ancillary Studies CANCER CYTOPATHOLOGY Pai, R. K., Mullins, F. M., Kim, Y. H., Kong, C. S. 2008; 114 (5): 323-332

    Abstract

    The most common presenting site of extracutaneous disease in mycosis fungoides and Sezary syndrome is the peripheral lymph node. Although fine-needle aspiration biopsy has been shown to be a valuable diagnostic technique in evaluating lymphadenopathy, its utility in patients with cutaneous T-cell lymphoma has not been extensively studied. With fine-needle aspiration biopsy, material can be collected for ancillary diagnostic studies and for morphologic evaluation.The authors report a series of 11 fine-needle aspiration biopsy specimens from 10 mycosis fungoides and Sezary syndrome patients. Flow cytometric immunophenotyping and T-cell receptor gamma chain polymerase chain reaction were performed on fine-needle aspiration biopsy material and correlated with cytologic findings.Seven of 10 patients had lymph node involvement by cutaneous T-cell lymphoma, with 3 cases exhibiting large-cell transformation and 4 cases exhibiting a small-cell pattern. Flow cytometric immunophenotyping identified an abnormal T-cell population in 6 cases. A clonal T-cell rearrangement by T-cell receptor gamma chain polymerase chain reaction (TCR-gamma PCR) was identified in 1 case in which insufficient events were present for evaluation by flow cytometry and in 1 case in which flow cytometry was not diagnostic of T-cell lymphoma. Two cases showed involvement by classic Hodgkin lymphoma diagnosed by immunohistochemistry on cell block material.Fine-needle aspiration biopsy in conjunction with immunophenotyping and T-cell receptor gamma chain polymerase chain reaction is significantly useful in evaluation of lymphadenopathy in patients with mycosis fungoides and Sezary syndrome, especially for triaging lymph nodes that would otherwise not be sampled or for evaluating multiple lymph nodes.

    View details for DOI 10.1002/cncr.23793

    View details for Web of Science ID 000260140500007

    View details for PubMedID 18798522

  • Clinicopathologic features and treatment outcomes in Woringer-Kolopp disease JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Lee, J., Viakhireva, N., Cesca, C., Lee, P., Kohler, S., Hoppe, R. I., Kim, Y. H. 2008; 59 (4): 706-712

    Abstract

    Woringer-Kolopp disease, also known as pagetoid reticulosis, is an exceedingly rare variant of mycosis fungoides. Accurate diagnosis and effective treatment is essential to prevent progression to debilitating disease. We identified 7 patients with Woringer-Kolopp disease treated at our institution. We review the major clinical and pathologic characteristics of this disease, focusing on treatment strategies and patient outcomes. All of our patients were successfully treated with skin-directed therapies including topical steroids, topical nitrogen mustard, psoralen plus ultraviolet A, narrow-band ultraviolet B, and radiation therapy. Our observations confirm that Woringer-Kolopp disease carries an excellent prognosis, and support that the most effective and appropriate treatment for recalcitrant or severe Woringer-Kolopp disease is localized radiation therapy.

    View details for DOI 10.1016/j.jaad.2008.04.018

    View details for Web of Science ID 000259550100018

    View details for PubMedID 18550209

  • Evaluation of B-cell clonality using the BIOMED-2 PCR method effectively distinguishes cutaneous B-cell lymphoma from benign lymphoid infiltrates AMERICAN JOURNAL OF DERMATOPATHOLOGY Morales, A. V., Arber, D. A., Seo, K., Kohler, S., Kim, Y. H., Sundram, U. N. 2008; 30 (5): 425-430

    Abstract

    Primary cutaneous B-cell lymphomas (CBCL) are a diverse group of lymphomas that are limited to the skin at the time of diagnosis. Recently, standardized polymerase chain reaction protocols for immunoglobulin (Ig) rearrangement in nodal malignancies using the BIOMED-2 method have been studied extensively. However, reports of investigations of Ig clonality in CBCL using the BIOMED-2 method have been scant. We hypothesized that clonality detection in CBCL with the BIOMED-2 method could effectively distinguish malignant from benign B-cell-rich infiltrates in the skin. Formalin-fixed tissue samples from 26 patients with CBCL and 23 with benign lymphoid infiltrates were analyzed for Ig clonality using standardized BIOMED-2 polymerase chain reaction protocols. The (14;18) translocation was also assessed. A clone was detected in 22 (85%) of the 26 patients with CBCL [12/15 (80%) marginal zone B-cell lymphoma; 10/11 (91%) follicle center lymphoma] and in 1 (4%) of the 23 patients with benign infiltrates. The (14;18) translocation was present in 3 (12%) of the 26 patients with CBCL [1/15 (7%) marginal zone B-cell lymphoma; 2/11 (18%) follicle center lymphoma]. Our preliminary data indicate that Ig clonality can be detected in formalin-fixed samples of CBCL with meaningful sensitivity (85%) and high specificity (96%) using the BIOMED-2 method. This study forms the basis for further investigating the role of Ig clonality in distinguishing CBCL from benign lymphoid infiltrates that may pose a challenge in morphologic diagnosis.

    View details for Web of Science ID 000259325000002

    View details for PubMedID 18806482

  • European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas BLOOD Senff, N. J., Noordijk, E. M., Kim, Y. H., Bagot, M., Berti, E., Cerroni, L., Dummer, R., Duvic, M., Hoppe, R. T., Pimpinelli, N., Rosen, S. T., Vermeer, M. H., Whittaker, S., Willemze, R. 2008; 112 (5): 1600-1609

    Abstract

    Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20% to 25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) Consensus Classification for Cutaneous Lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms were introduced. However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centers, which may be because consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the 3 main groups of CBCL. Because no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state-of-the-art management as currently practiced in major cutaneous lymphoma centers. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL.

    View details for DOI 10.1182/blood-2008-04-152850

    View details for Web of Science ID 000258956200013

    View details for PubMedID 18567836

  • T-cell clonality analysis in biopsy specimens from two different skin sites shows high specificity in the diagnosis of patients with suggested mycosis fungoides JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Thurber, S. E., Zhang, B., Kim, Y. H., Schrijver, I., Zehnder, J., Kohler, S. 2007; 57 (5): 782-790

    Abstract

    The diagnosis of mycosis fungoides (MF) is often difficult because of significant clinical and histopathologic overlap with inflammatory dermatoses. T-cell receptor (TCR)gamma chain rearrangement by polymerase chain reaction (PCR) (TCR-PCR) is a helpful adjuvant tool in this setting, but several of the inflammatory dermatoses in the differential diagnosis of MF may contain a clonal T-cell proliferation.We examined whether analysis for T-cell clonality and comparison of the clones with the standardized BIOMED-2 PCR multiplex primers for the TCRgamma chain from two anatomically distinct skin sites improves diagnostic accuracy.We examined two biopsy specimens each from 10 patients with unequivocal MF, from 18 patients with inflammatory dermatoses, and from 18 patients who could initially not be definitively given a diagnosis based on clinical and histopathologic criteria.Eight of 10 patients with unequivocal MF had an identical clone in both biopsy specimens. Two of 18 patients with inflammatory dermatoses were found to have a clone in one of the biopsy specimens. On further follow-up of the 18 patients with morphologically nondiagnostic biopsy specimens, 13 of 18 were later confirmed to have MF and 5 of 18 had inflammatory dermatoses. Eleven of 13 patients with MF had an identical clone in both biopsy specimens; two of 13 had a polyclonal amplification pattern in both biopsy specimens. Four of 5 patients with inflammatory dermatoses had no clone in either biopsy specimen. One patient with an inflammatory dermatosis had an identical clone in both specimens. The sensitivity of TCR-PCR analysis to evaluate for an identical clone at different anatomic skin sites (dual TCR-PCR) is 82.6% and the specificity is 95.7%.The number of patients in the study group was limited.These data suggest that dual TCR-PCR is a very promising technique with high specificity in distinguishing MF from inflammatory dermatoses.

    View details for DOI 10.1016/j.jaad.2007.06.004

    View details for Web of Science ID 000250387100004

    View details for PubMedID 17646032

  • Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC) BLOOD Olsen, E., Vonderheid, E., Pimpinelli, N., Willemze, R., Kim, Y., Knobler, R., Zackheim, H., Duvic, M., Estrach, T., Lamberg, S., Wood, G., Dummer, R., Ranki, A., Burg, G., Heald, P., Pittelkow, M., Bernengo, M., Sterry, W., Laroche, L., Trautinger, F., Whittaker, S. 2007; 110 (6): 1713-1722

    Abstract

    The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions.

    View details for DOI 10.1182/blood-2007-03-055749

    View details for Web of Science ID 000249671700010

    View details for PubMedID 17540844

  • Nephrogenic systemic fibrosis - Relationship to gadolinium and response to photopheresis ARCHIVES OF DERMATOLOGY Richmond, H., Zwerner, J., Kim, Y., Fiorentino, D. 2007; 143 (8): 1025-1030

    Abstract

    Nephrogenic systemic fibrosis (NSF), previously known as nephrogenic fibrosing dermopathy, is an idiopathic condition seen in patients with renal disease that is characterized by cutaneous sclerosis that can often result in contractures, pain, and functional disability as well as systemic complications. Recent reports have suggested a possible link with exposure to gadolinium, a commonly used radiocontrast agent. No current therapy has clearly demonstrated efficacy for NSF, although case reports suggest that extracorporeal photopheresis (ECP) may be of benefit. The purpose of this study was to explore the plausibility of a gadolinium linkage with NSF as well as to assess the efficacy of ECP in the treatment of a cohort of patients with NSF.We report our experience with 8 consecutive patients with NSF seen at the Stanford Medical Center, Palo Alta, California, from 2004 to 2006. Of the 8 patients, 6 had a history of arterial or venous thrombotic disease and 7 had a documented exposure to gadolinium within 1 week to several months prior to the onset of NSF. Specifically, all patients were exposed to gadodiamide. We treated 5 of the patients with ECP. After a mean number of 34 treatment sessions over a mean of 8.5 months, 3 patients experienced a mild improvement in skin tightening, range of motion, and/or functional capacity.Our data support the hypothesis that exposure to gadolinium, perhaps specifically gadodiamide, plays a role in the pathogenesis of NSF. Larger epidemiologic studies will be needed to confirm this association. In addition, our experience suggests that, if used for extended periods, ECP might have some mild benefit for patients with NSF. Larger, randomized, placebo-controlled trials of ECP should be performed to more specifically assess the benefit of ECP in the treatment of NSF.

    View details for Web of Science ID 000248723900008

    View details for PubMedID 17709661

  • Phase IIB multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma JOURNAL OF CLINICAL ONCOLOGY Olsen, E. A., Kim, Y. H., Kuzel, T. M., Pacheco, T. R., Foss, F. M., Parker, S., Frankel, S. R., Chen, C., Ricker, J. L., Arduino, J. M., Duvic, M. 2007; 25 (21): 3109-3115

    Abstract

    To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes.Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief ( > or = 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated.Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be >or = 185 days (34+ to 441+). Median TTP was 4.9 months overall, and 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE.Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.

    View details for DOI 10.1200/JCO.2006.10.2434

    View details for Web of Science ID 000248743800020

    View details for PubMedID 17577020

  • Second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary syndrome - Evidence from population-based and clinical cohorts ARCHIVES OF DERMATOLOGY Huang, K. P., Weinstock, M. A., Clarke, C. A., McMillan, A., Hoppe, R. T., Kim, Y. H. 2007; 143 (1): 45-50

    Abstract

    To assess risks for developing second malignancies in patients with mycosis fungoides or Sézary syndrome.Retrospective study of 2 cohorts.Nine population-based US cancer registries that constitute the Surveillance, Epidemiology, and End Results Program (SEER-9), and Stanford University referral center cohort of patients with cutaneous lymphoma. Patients with mycosis fungoides or Sézary syndrome from the SEER-9 registry diagnosed and followed up from 1984 through 2001 and from the Stanford University cohort diagnosed and followed up from 1973 through 2001.Relative risk was estimated using the standardized incidence ratio (SIR). The expected cancer incidence for both cohorts was calculated using age-, sex-, race-, and calendar year-specific SEER-9 incidence rates for the general population. Nonmelanoma skin cancers were excluded because these cancers are not routinely reported by the SEER database.In the SEER-9 cohort (n = 1798), there were 197 second instances of cancer (SIR = 1.32; 95% confidence interval [CI], 1.15-1.52) at all sites. Significantly elevated risk (P<.01) was observed for Hodgkin disease (6 cases; SIR = 17.14; 95% CI, 6.25-37.26) and non-Hodgkin lymphoma (27 cases; SIR = 5.08; 95% CI, 3.34-7.38). Elevated risk (P<.05) was also observed for melanoma (10 cases; SIR = 2.60; 95% CI, 1.25-4.79), and urinary cancer (21 cases; SIR = 1.74; 95% CI, 1.08-2.66). In the Stanford University cohort (n = 429), there were 37 second instances of cancer (SIR = 1.04; 95% CI, 0.76-1.44). Elevated risk (P<.01) was observed for Hodgkin disease (3 cases; SIR = 27.27; 95% CI, 5.35-77.54). Elevated risk (P<.05) was also observed for biliary cancer (2 cases; SIR = 11.76; 95% CI, 1.51-42.02).Updated SEER (population based) and Stanford (clinic based) data confirm the generalizability of earlier findings of increased risk of lymphoma in patients with mycosis fungoides or Sézary syndrome.

    View details for Web of Science ID 000243509100006

    View details for PubMedID 17224541

  • Cutaneous involvement by angioimmunoblastic T-cell lymphoma: a unique histologic presentation, mimicking an infectious etiology JOURNAL OF CUTANEOUS PATHOLOGY Jayaraman, A. G., Cassarino, D., Advani, R., Kim, Y. H., Tsai, E., Kohler, S. 2006; 33: 6-11

    Abstract

    Angioimmunoblastic T-cell lymphoma (AILT) is an aggressive peripheral T-cell lymphoma that is frequently accompanied by a cutaneous eruption. The cutaneous findings most commonly consist of a maculopapular eruption on the trunk. However, purpura, infiltrated or urticarial plaques, papulovesicular lesions, nodules, and erythroderma have also been reported. Histologic findings in the lymph node are characteristic, while those in the skin may show one of four patterns. Here, we review the previously reported histologic patterns and present a case of AILT involving the skin with a unique histologic appearance of necrotizing granulomas with abundant histiocytes and eosinophils, mimicking an infectious etiology.

    View details for Web of Science ID 000240405000002

    View details for PubMedID 16972945

  • Staging accuracy in mycosis fungoides and Sezary syndrome using integrated positron emission tomography and computed tomography ARCHIVES OF DERMATOLOGY Tsai, E. Y., Taur, A., Espinosa, L., Quon, A., Johnson, D., Dick, S., Chow, S., Advani, R., Warnke, R., Kohler, S., Hoppe, R. T., Kim, Y. H. 2006; 142 (5): 577-584

    Abstract

    To evaluate the usefulness of integrated positron emission tomography and computed tomography (PET/CT) in staging mycosis fungoides (MF) and Sézary syndrome and to correlate PET/CT data with histopathologic diagnosis of lymph nodes (LNs).A single-center, prospective cohort analysis.Academic referral center for cutaneous lymphoma.Thirteen patients with MF and SS at risk for secondary LN involvement. Interventions Patients were clinically evaluated based on general physical examination, total body skin examination, and laboratory screening. They underwent integrated PET/CT followed by excisional biopsy of LNs.We used PET/CT to assess LN size and metabolic activity. Enlarged LNs were defined as axillary or inguinal LNs with a short axis 1.5 cm or larger; or cervical LN, with a short axis 1.0 cm or larger. We classified LN pathologic results according to National Cancer Institute (LN1-4) and World Health Organization (WHO 1-3) criteria. We quantified PET activity using standardized uptake value (SUV) and correlated with LN grade.Based on CT size criteria alone, only 5 patients had enlarged LNs, whereas PET revealed hypermetabolic LNs in all 13 patients. Six patients had LN1-3, and 7 had effacement of LN architecture by lymphoma cells (LN4). Of the 7 patients with LN4 nodes, 4 had SS, and 3 had tumorous MF. Two patients with LN4 nodes had inguinal LNs smaller than 1.5 cm and would have been assigned an N0 classification without the use of integrated PET/CT. Correlation of SUV with LN grade revealed that LN1-3 nodes were associated with a mean SUV of 2.7 (median SUV, 2.2; range, 2.0-4.7) and LN4 nodes were associated with a mean SUV of 5.4 (median SUV, 3.9; range, 2.1-11.8). Patients with large cell transformation had the highest SUVs.For staging MF and SS, PET/CT was more sensitive in detecting LN involved by lymphoma compared with CT data alone and thus may provide more accurate staging and prognostic information. The intensity of PET activity correlated with histologic LN grade.

    View details for Web of Science ID 000237543100006

    View details for PubMedID 16702495

  • Expression of the bcl-6 and MUM1/IRF4 proteins correlate with overall and disease-specific survival in patients with primary cutaneous large B-cell lymphoma: a tissue microarray study JOURNAL OF CUTANEOUS PATHOLOGY Sundram, U., Kim, Y., Mraz-Gernhard, S., Hoppe, R., Natkunam, Y., Kohler, S. 2005; 32 (3): 227-234

    Abstract

    Systemic B-cell lymphomas have been studied using microarrays, which has led to a better understanding of their molecular characteristics. Initial microarray studies of these lymphomas have implicated several genes as important predictors of outcome. In this study, we used a tissue microarray (TMA) to characterize primary cutaneous large B-cell lymphomas (PCLBCL).We studied 14 patients for whom clinical follow up was available, including four patients whose lesions were limited to the leg on presentation. Immunohistochemical staining with CD20, CD44, CD21, CD5, CD10, bcl-2, bcl-6, Ki67, p53, and multiple myeloma 1 (MUM1) was examined.Our results identify two subgroups of lymphomas. The first group showed staining with bcl-6 and had an overall survival of 176 months (p = 0.003). The majority of this group was negative for MUM1. The second group lacked staining with bcl-6 and had an overall survival of 26 months, with a majority of these cases staining with MUM1. Three of four patients with PCLBCL of the leg showed no staining with bcl-6.Our study demonstrates the utility of TMAs in the analysis of PCLBCL and that expression of bcl-6 and MUM1 correlates with survival.

    View details for Web of Science ID 000226857100005

    View details for PubMedID 15701085

  • Clinical and pathological features of posttransplantation lymphoproliferative disorders presenting with skin involvement in 4 patients ARCHIVES OF DERMATOLOGY Beynet, D. P., Wee, S. A., Horwitz, S. S., Kohler, S., Horning, S., Hoppe, R., Kim, Y. H. 2004; 140 (9): 1140-1146

    Abstract

    Posttransplantation lymphoproliferative disorders (PTLDs) are lymphoid proliferations that can develop in recipients of solid organ or allogeneic bone marrow transplants. They are clinically and pathologically heterogeneous and range from polyclonal hyperplastic lesions to malignant lymphomas. Although extranodal involvement in PTLD is common, cutaneous presentation is rare, with only 19 cases reported previously.We describe 4 patients with cutaneous presentations of PTLD. All patients had relatively late-onset PTLD (>1 year after transplantation) with a median of 8 years from organ allograft to tumor diagnosis. The extent, number, and anatomic location of skin lesions varied from a localized patch to widespread nodules. None of the patients exhibited systemic symptoms at the time of PTLD diagnosis. Pathological findings ranged from plasmacytic hyperplasia to monomorphic PTLD. In situ hybridization detected Epstein-Barr virus messenger RNA in all 3 cases with evaluable tissue. All patients underwent reduction in immunosuppressive therapy and received other individualized treatments. Median follow-up was 2.5 years. At the most recent follow-up, 3 patients were in complete remission and 1 had residual disease.In this study, PTLD lesions presenting in the skin responded to therapy. Despite their relatively late occurrence after transplantation, most of these cases were positive for Epstein-Barr virus. As observed with other cutaneous lymphomas, the PTLDs with predominant skin involvement had a relatively favorable outcome.

    View details for Web of Science ID 000223835000014

    View details for PubMedID 15381556

  • CD30(+) cutaneous lymphoproliferative disorders: The Stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Liu, H. L., Hoppe, R. T., Kohler, S., Harvell, J. D., Reddy, S., Kim, Y. H. 2003; 49 (6): 1049-1058

    Abstract

    CD30+ cutaneous lymphoproliferative disorders (CLPDs) include lymphomatoid papulosis, borderline cases of CD30+CLPDs, and primary cutaneous anaplastic large cell lymphoma (PCALCL). Prior studies have shown CD30+CLPDs have an excellent prognosis.We sought to present the single-center experience of Stanford University, Stanford, Calif, in the management of CD30+CLPDs.A retrospective cohort analysis of 56 patients with CD30+CLPDs treated at our institution was performed.No patients with lymphomatoid papulosis died of disease, and overall survival was 92% at 5 and 10 years. Disease-specific survivals at 5 and 10 years for PCALCL were 85%. Disease-specific survival at 5 years for localized versus generalized PCALCL was 91% versus 50% (P =.31). PCALCL was highly responsive to treatment, but the relapse rate was 42%. In all, 3 patients progressed to extracutaneous stage of disease. No clinical or histologic factors analyzed were predictive of worse outcome in lymphomatoid papulosis and PCALCL.Similar to prior reports from multicenter European groups, the single-center experience at our institution demonstrates CD30+CLPDs have an overall excellent prognosis; however, cases of PCALCL with poor outcome do exist.

    View details for DOI 10.1016/S0190-9622(03)02484-8

    View details for Web of Science ID 000186784800009

    View details for PubMedID 14639383

  • Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome - Clinical prognostic factors and risk for disease progression ARCHIVES OF DERMATOLOGY Kim, Y. H., Liu, H. L., Mraz-Gernhard, S., Varghese, A., Hoppe, R. T. 2003; 139 (7): 857-866

    Abstract

    To study and update the clinical characteristics and long-term outcome of our patients with mycosis fungoides (MF) and Sézary syndrome (SS), and to identify important clinical factors predictive of survival and disease progression.A single-center, retrospective cohort analysis.Academic referral center for cutaneous lymphoma.Five hundred twenty-five patients with MF and SS evaluated and managed at Stanford University Cutaneous Lymphoma Clinic, Stanford, Calif, from 1958 through 1999.We calculated long-term actuarial overall and disease-specific survivals and disease progression by the Kaplan-Meier method, and relative risk (RR) for survival calculated from expected survivals in control populations.The majority of our patients presented with T1 (30%) or T2 (37%) disease; 18% presented with T3 and 15% with T4 skin involvement. Forty-three percent of deaths were attributable to MF, primarily in patients with T3 or T4 disease. The patients with a more advanced T classification and clinical stage had a worse survival outcome. Except for patients with T1 or stage IA disease, the RR for death is greater in patients with MF than in a control population (RR, 2.2 in stage IB/IIA disease, 3.9 in stage IIB/III disease, and 12.8 in stage IV disease). Despite similar overall survival in patients with stage IB or IIA disease, their disease-specific survivals were significantly different (P =.006). The most significant clinical prognostic factors in the univariate analysis were patient age, TNM and B classifications, overall clinical stage groupings, and the presence or absence of extracutaneous disease. In the multivariate analysis, patient age, T classification, and the presence of extracutaneous disease were the most important independent factors. The risk for disease progression to a more advanced TNM or B classification, worse clinical stage, or death due to MF correlated with the severity of the initial T classification. The risk for development of extracutaneous disease also correlated with T classification; none of these patients had T1 disease when their extracutaneous disease was detected.Patients with MF and SS have varying risks for disease progression or death. The most important clinical predictive factors for survival include patient age, T classification, and the presence of extracutaneous disease. The significant disease-specific survival differences between different clinical stages validate the usefulness of the present MF clinical staging system of the National Cancer Institute.

    View details for Web of Science ID 000184104500003

    View details for PubMedID 12873880

  • Gene expression profiles of cutaneous B cell lymphoma JOURNAL OF INVESTIGATIVE DERMATOLOGY Storz, M. N., van de Rijn, M., Kim, Y. H., Mraz-Gernhard, S., Hoppe, R. T., Kohler, S. 2003; 120 (5): 865-870

    Abstract

    We studied gene expression profiles of 17 cutaneous B cell lymphomas that were collected with 4-6 mm skin punch biopsies. We also included tissue from two cases of mycosis fungoides, three normal skin biopsies, and three tonsils to create a framework for further interpretation. A hierarchical cluster algorithm was applied for data analysis. Our results indicate that small amounts of skin tissue can be used successfully to perform microarray analysis and result in distinct gene expression patterns. Duplicate specimens clustered together demonstrating a reproducible technique. Within the cutaneous B cell lymphoma specimens two specific B cell differentiation stage signatures of germinal center B cells and plasma cells could be identified. Primary cutaneous follicular and primary cutaneous diffuse large B cell lymphomas had a germinal center B cell signature, whereas a subset of marginal zone lymphomas demonstrated a plasma cell signature. Primary and secondary follicular B cell lymphoma of the skin were closely related, despite previously reported genetic and phenotypic differences. In contrast primary and secondary cutaneous diffuse large B cell lymphoma were less related to each other. This pilot study allows a first glance into the complex and unique microenvironment of B cell lymphomas of the skin and provides a basis for future studies, which may lead to the identification of potential histologic and prognostic markers as well as therapeutic targets.

    View details for Web of Science ID 000182456200027

    View details for PubMedID 12713594

  • Topical nitrogen mustard in the management of mycosis fungoides - Update of the Stanford experience ARCHIVES OF DERMATOLOGY Kim, Y. H., Martinez, G., Varghese, A., Hoppe, R. T. 2003; 139 (2): 165-173

    Abstract

    To evaluate and update the response and survival outcomes and toxic effects in patients treated with topical nitrogen mustard (mechlorethamine hydrochloride) as primary therapy.A single-center, retrospective cohort analysis.Academic referral center for cutaneous lymphoma.A total of 203 patients with mycosis fungoides (clinical stages I-III) treated with topical nitrogen mustard as initial therapy.Long-term actuarial survival, freedom-from-relapse, and freedom-from-progression results as calculated by the Kaplan-Meier method.The overall response rate for the 203 patients was 83%, with a complete response rate of 50%. The median time to achieve complete response was 12 months (T1, 10 months; T2, 19 months), and the median time to relapse was 12 months. The duration of complete response increased with longer maintenance therapy; however, after completion of therapy, the response duration or relapse rate was similar regardless of maintenance regimen. Patients with T1 disease had better response and survival outcomes than those with T2 disease, with overall and complete response rates in T1 of 93% and 65%, respectively, and in T2, 72% and 34%, respectively. A similar clinical response was seen for patients with stage IIA vs IB. Sixty-eight percent of 203 patients received only topical nitrogen mustard therapy throughout their follow-up course, including most of the patients who achieved an initial complete response. The clinical response to topical nitrogen mustard as salvage therapy was similar to initial response rates. The efficacy results were similar in patients treated with aqueous vs ointment preparations. Freedom-from-progression rates in T1 disease (no progression to higher T classification or worse clinical stage) at 5 and 10 years were 92% and 85%, respectively, and in T2, 83% at 5 and 10 years. Fewer than 10% of patients experienced contact hypersensitivity reactions when topical nitrogen mustard was used as an ointment preparation. Only 8 patients (4%) developed secondary cutaneous malignancy, none attributable to topical nitrogen mustard monotherapy. Pediatric patients experienced no significant toxic effects with topical nitrogen mustard therapy.Topical nitrogen mustard remains an effective primary initial or salvage therapy in mycosis fungoides for patients with T1 and T2 disease. Long-term follow-up results confirm its safety.

    View details for Web of Science ID 000180971400006

    View details for PubMedID 12588222

  • Management with topical nitrogen mustard in mycosis fungoides. Dermatologic therapy Kim, Y. H. 2003; 16 (4): 288-298

    Abstract

    Topical nitrogen mustard (mechlorethamine, NM) has been used as primary therapy for management of patients with mycosis fungoides (MF) since the 1950s. Many investigators have demonstrated the efficacy of topical NM in patch and/or plaque disease of MF. Updated results from Stanford also confirm the clinical efficacy. The complete response (CR) rates reported are 76-80% for patients with limited patch/plaque (stage IA), and 35-68% for those with generalized patch/plaque (stage IB) disease. Topical NM can be used as an aqueous (water) or ointment-based preparation. The efficacy results are similar in patients who were treated with aqueous versus ointment preparations. Maintenance regimens used are variable, but there is no data to suggest that a longer maintenance duration results in greater potential for long-term remission. Most patients who achieve initial CR with topical NM tend to require NM-only for disease management. Topical NM is equally effective when used as salvage therapy with disease relapse. The most common toxicity of topical NM therapy is contact irritant or allergic reaction. The potential for allergic reaction is significantly reduced (< 10%) when NM is used as an ointment preparation. The potential for secondary skin cancer development is increased in patients who have used multiple sequential topical skin-damaging therapies or NM in the genital skin, but not in patients who have used NM as monotherapy (avoiding genital skin application). Topical NM is used safely in pediatric patients and there is no evidence of any clinically significant systemic absorption of topically applied NM.

    View details for PubMedID 14686971

  • Large atypical cells of lymphomatoid papulosis are CD56-negative: a study of 18 cases JOURNAL OF CUTANEOUS PATHOLOGY Harvell, J. D., Vaseghi, M., Natkunam, Y., Kohler, S., Kim, Y. 2002; 29 (2): 88-92

    Abstract

    Histologically, diffuse dermal infiltrates of large atypical lymphocytes can be seen in lesions as indolent as type C lymphomatoid papulosis (LyP) to ones as aggressive as NK/T-cell lymphoma. While lesions of lymphomatoid papulosis are definitionally positive for CD30, their ability to express CD56 has not been formally studied. The objective of the current study was to determine whether or not the large atypical cells of LyP express the natural killer cell marker, CD56.Biopsies from 18 patients with LyP were studied with monoclonal antibodies to CD30, CD56, CD8, and TIA-1. These included four type C LyP lesions. Clinical information was obtained by chart review and included extent of LyP lesions, presence/absence of disease at follow-up, and any associated hematologic malignancies,.None of the biopsies exhibited CD56 positivity within the large atypical cells of LyP. While some biopsies demonstrated CD56-positive, small, presumably reactive, lymphocytes within the infiltrate, their presence did not correlate with extent of disease, persistence of disease, or propensity for an associated non-LyP hematologic malignancy.The large atypical cells of types A and C LyP do not exhibit positivity for CD56, and thus a panel of antibodies that includes CD30 and CD56 can readily distinguish between the benign end of the spectrum of CD30-positive lymphoproliferations and aggressive NK/T-cell lymphoma.

    View details for Web of Science ID 000174804900004

    View details for PubMedID 12150138

  • Natural killer/natural killer-like T-Cell lymphoma, CD56+, presenting in the skin: An increasingly recognized entity with an aggressive course JOURNAL OF CLINICAL ONCOLOGY Mraz-Gernhard, S., Natkunam, Y., Hoppe, R. T., Leboit, P., Kohler, S., Kim, Y. H. 2001; 19 (8): 2179-2188

    Abstract

    To describe and identify the clinical and pathologic features of prognostic significance for natural killer (NK) and NK-like T-cell (NK/T-cell) lymphoma presenting in the skin.This study was a retrospective review of 30 patients with CD56+ lymphomas initially presenting with cutaneous lesions, with analysis of clinical and histopathologic parameters.The median survival for all patients was 15 months. Those with extracutaneous manifestations at presentation (11 patients) had a shorter median survival of 7.6 months as compared with those without extracutaneous involvement (17 patients), who had a more favorable median survival of 44.9 months (P =.0001). Age, gender, extent of cutaneous involvement, and initial response to therapy had no statistically significant effect on survival. Seven patients (24%) had detectable Epstein-Barr virus (EBV) within neoplastic cells. The patients with tumor cells that coexpress CD30 (seven patients) have not yet reached a median survival after 35 months of follow-up as compared with those with CD30- tumor cells (20 patients), who had a median survival of 9.6 months (P <.02). Routine histopathologic characteristics had no prognostic significance nor did the presence of CD3epsilon, EBV, or multidrug resistance.NK/T-cell lymphoma is an aggressive neoplasm; however, a subset with a more favorable outcome is identified in this study. The presence of extracutaneous disease at presentation is the most important clinical variable and portends a poor prognosis. The extent of initial skin involvement does not reliably predict outcome. Patients from the United States with NK/T-cell lymphoma presenting in the skin have a low incidence of demonstrable EBV in their tumor cells. Patients with coexpression of CD30 in CD56 lymphomas tend to have a more favorable outcome.

    View details for Web of Science ID 000168178300009

    View details for PubMedID 11304770

  • Clinical characteristics and outcome of patients with extracutaneous mycosis fungoides JOURNAL OF CLINICAL ONCOLOGY de Coninck, E. C., Kim, Y. H., Varghese, A., Hoppe, R. T. 2001; 19 (3): 779-784

    Abstract

    To identify prognostic factors predictive of outcome in patients with extracutaneous (stage IV) mycosis fungoides (MF) and to evaluate the risk of progression to extracutaneous disease by initial extent of skin involvement.One hundred twelve patients with extracutaneous disease at presentation or with progression and 434 patients with initial cutaneous-only disease were identified. Actuarial survival curves were plotted according to the Kaplan-Meier technique.The median survival of all stage IV patients was 13 months from the date of first treatment for stage IV disease. Sex, race, age, extent of skin involvement, and peripheral blood Sezary cell involvement were not significant to survival outcome. Eleven patients (10%) had a complete response to therapy resulting in a significantly improved median survival compared with patients with a partial or no response (1.70 v 0.91 years, P =.047 and 1.70 v 0.57 years, P =.011, respectively). At 20 years from diagnosis, the risk for progression to extracutaneous disease by initial extent of skin involvement was 0% for limited patch/plaque, 10% for generalized patch/plaque, 35.5% for tumorous disease, and 41% for erythrodermic involvement.This was a larger scale study over a longer time period than had been completed previously on extracutaneous MF. Prognostic factors important in the cutaneous stages of disease are no longer significant once extracutaneous disease develops. Patients who had a more favorable response to therapy may have had a biologically less aggressive disease than their less fortunate counterparts. The risk of developing stage IV MF is highest in patients presenting with tumorous or erythrodermic skin disease and is lowest in patients with limited skin involvement.

    View details for Web of Science ID 000166803100024

    View details for PubMedID 11157031

  • Co-expression of CD56 and CD30 in lymphomas with primary presentation in the skin: clinicopathologic, immunohistochemical and molecular analyses of seven cases JOURNAL OF CUTANEOUS PATHOLOGY Natkunam, Y., Warnke, R. A., Haghighi, B., Su, L. D., Le Boit, P. E., Kim, Y. H., Kohler, S. 2000; 27 (8): 392-399

    Abstract

    Natural killer and natural killer-like T-cell lymphomas presenting in the skin usually demonstrate aggressive behavior, an angiocentric distribution and a characteristic immunophenotype. In contrast, primary cutaneous CD30+ lymphoproliferative disorders form a heterogeneous spectrum including anaplastic large cell lymphomas, the majority of which display a good prognosis. Lymphomas with co-expression of CD56 and CD30 are extremely rare and the significance of this co-expression is unknown.Seven retrospectively identified cases of lymphomas with co-expression of CD56 and CD30 presenting in the skin comprise this study. Immunohistochemistry, in situ hybridization for Epstein-Barr virus and T-cell receptor gene rearrangement studies were performed on paraffin sections.This subset of cutaneous lymphomas showed a variable clinical course that ranged from resolution without treatment, treatment-failure and recurrence, to death from disease. Histologic, immunophenotypic and molecular studies were of limited utility in predicting prognosis.Cutaneous lymphomas co-expressing CD56 and CD30 share many clinicopathologic features with natural killer and natural killer-like T-cell lymphomas or anaplastic large cell lymphomas, two entities with widely disparate clinical behavior. It is important to recognize that these lymphomas may behave more aggressively than primary cutaneous anaplastic large cell lymphomas do. Longer follow-up and further investigations on larger numbers of cases are necessary to fully characterize this rare subset of cutaneous lymphomas.

    View details for Web of Science ID 000088444100003

    View details for PubMedID 10955685

  • Epidermotropic cutaneous B-cell lymphoma mimicking mycosis fungoides JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Chui, C. T., Hoppe, R. T., Kohler, S., Kim, Y. H. 1999; 41 (2): 271-274

    Abstract

    Cutaneous involvement by B-cell lymphoma is often secondary to systemic disease. Primary cutaneous B-cell lymphomas are less common, and patients generally have an excellent prognosis. We present a patient with cutaneous B-cell lymphoma with clinical and histologic features mimicking mycosis fungoides. Although the patient was initially misdiagnosed as having a T-cell lymphoma, immunophenotypic studies demonstrated that this was a B-cell lymphoma.

    View details for Web of Science ID 000081921900023

    View details for PubMedID 10426903

  • Mycosis fungoides and the Sezary syndrome SEMINARS IN ONCOLOGY Kim, Y. H., Hoppe, R. T. 1999; 26 (3): 276-289

    Abstract

    Mycosis fungoides (MF) and the Sézary syndrome are a group of extranodal non-Hodgkin's lymphomas of T-cell origin with primary cutaneous involvement. The group distinguishes itself from other primary cutaneous T-cell lymphomas (CTCLs) by its unique clinical features and histopathology. In its early stages, it often resembles common benign dermatoses, and therefore, a definitive diagnosis can be delayed. The affected T cells are characterized by a predominant CD4+ phenotype with frequent loss of CD7 (pan-T-cell antigen) and often demonstrate T-cell receptor (TCR) rearrangement. The prognosis of patients with MF is highly dependent on the extent and type of skin involvement. The initial cutaneous presentation of MF can be patches, plaques, tumors, or erythroderma. Patients who present with limited patch/plaque disease have an outstanding prognosis with an overall long-term survival that is similar to the expected survival of a matched control population. It is exceedingly rare for patients who present with limited or generalized patch/plaque disease without peripheral lymphadenopathy to have extracutaneous involvement. Therefore, the staging evaluation differs for patients with MF versus patients with other non-Hodgkin's lymphomas and should be tailored to the clinical presentation. Patients who have tumorous or erythrodermic skin involvement have a less favorable prognosis, and patients who present with extracutaneous disease have a poor prognosis. There are multiple therapeutic options for patients with MF and the Sézary syndrome. Selection of a specific treatment plan is based primarily on the clinical stage of the disease. The primary therapy for patients with patch/plaque disease without extracutaneous involvement is a topical regimen, whereas chemotherapy or other aggressive systemic regimens are reserved for those with recalcitrant disease or extracutaneous involvement. There is no evidence that early aggressive systemic therapy is preferable to conservative therapy in the management of limited disease. There are newer combination topical and/or systemic regimens that result in an improved clinical response and possibly a prolonged response duration. For advanced disease, standard therapies are often palliative and successful clinical response is often very short-lived. Therefore, all patients with recalcitrant or extracutaneous disease should be considered for newer investigative therapies.

    View details for Web of Science ID 000080809400005

    View details for PubMedID 10375085

  • Clinical characteristics and long-term outcome of patients with generalized patch and/or plaque (T2) mycosis fungoides ARCHIVES OF DERMATOLOGY Kim, Y. H., Chow, S., Varghese, A., Hoppe, R. T. 1999; 135 (1): 26-32

    Abstract

    To study the long-term results of treatment of patients with generalized patch and/or plaque mycosis fungoides and to identify clinical characteristics predictive of survival and response to treatment.A single-center, 35.5-year retrospective cohort analysis.Private referral medical center.One hundred seventy-six patients with generalized patch and/or plaque (T2) mycosis fungoides.Long-term actuarial survival and freedom-from-relapse results as calculated by the Kaplan-Meier method.The long-term (35.5-year) survival of patients with T2 mycosis fungoides is worse than the expected survival of a race-, age-, and sex-matched control population (P<.001). The median survival of the T2 group is 11.7 years. Patients younger than 58 years (median age) at presentation have a more favorable overall and disease-specific survival than the patients who are 58 years or older (P<.001 vs P<.025). Patient sex or race had no significant effect on overall survival. Patients who presented with palpable clinically significant lymph nodes (stage IIA) had long-term survival results similar to those without lymphadenopathy (stage IB), despite improved freedom-from-relapse outcome for patients with stage IB. Twenty-four percent of patients who progressed to more advanced disease had a lower complete response rate to initial therapy than did other patients (21% vs 65%) (P<.001). Patients who received total skin electron beam therapy had a better complete response rate than patients treated with topical mechlorethamine hydrochloride alone; the relapse-free results were superior in patients with a total dose of 30 Gy or higher and in patients who received topical mechlorethamine as adjuvant therapy following total skin electron beam therapy. Despite differences in freedom-from-relapse results among different treatment groups, long-term overall or disease-specific survivals were not significantly different.A significant proportion (24%) of patients with generalized patch and/or plaque (T2) mycosis fungoides experience disease progression to a more advanced clinical stage, and nearly 20% eventually die of the disease. Younger patients have a more favorable disease-specific long-term outcome than patients who are older. Presence of lymphadenopathy (stage IIA) at diagnosis does not predict worse long-term survival outcome. Clinical features predictive of disease progression include initial lymphadenopathy (stage IIA) and lack of complete response to initial treatment. Despite superior complete response rate to a 30-Gy or higher dose of total skin electron beam therapy, topical mechlorethamine proves to be a cost-effective initial treatment for patients with T2 disease. The concept of an adjuvant therapy after irradiation is appealing, although it may not lead to improved long-term survival.

    View details for Web of Science ID 000078112200004

    View details for PubMedID 9923777

  • Role of histology in providing prognostic information in mycosis fungoides JOURNAL OF CUTANEOUS PATHOLOGY SMOLLER, B. R., Detwiler, S. P., Kohler, S., Hoppe, R. T., Kim, Y. H. 1998; 25 (6): 311-315

    Abstract

    Many patients who present with patch and early plaque stage mycosis fungoides follow an indolent course and survive for many years following diagnosis. A certain subset of patients, however, have rapidly progressive disease leading to accelerated demise. We examined 21 histologic sections from initial biopsies taken from patients with stable disease and 26 from patients with rapidly progressive disease in order to evaluate the role of histology in predicting the disease course. Two or three authors examined each case and scored each of 24 histologic parameters using a previously described four-point scale with no knowledge of the patients' clinical courses. Interobserver agreement was quite high. The only histologic parameter that demonstrated statistical differences between the two groups of patients was degree of acanthosis. The degree of spongiosis, number of eosinophils, amount of hyperconvolution of dermal lymphocytes and density of the dermal infiltrate approached statistical significance but did not attain this level. All of these differences were quite small. No differences were seen for the other 19 parameters. Patients with rapidly progressive disease tended to have more acanthosis, a few more hyperconvoluted dermal lymphocytes, a slightly greater number of eosinophils and perhaps a slightly more dense dermal infiltrate than patients who had stable disease. However, as all of these changes were very slight, it appears unlikely that evaluation of any single biopsy specimen for the histologic parameters we studied is helpful in predicting the prognosis for a specific patient.

    View details for Web of Science ID 000074683500005

    View details for PubMedID 9694620

  • Mycosis fungoides in young patients: Clinical characteristics and outcome JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Crowley, J. J., Nikko, A., Varghese, A., Hoppe, R. T., Kim, Y. H. 1998; 38 (5): 696-701

    Abstract

    Mycosis fungoides (MF) can begin as early as the first decade of life. Few studies have reviewed MF in younger patients and none has been large enough to assess prognosis and outcome.We reviewed the clinical characteristics, prognosis, factors related to disease progression, and therapy in patients with MF younger than 35 years of age.Fifty-eight patients were entered into this retrospective cohort analysis. Results: Significantly fewer patients with MF who are younger than 35 years presented with erythroderma (T4) and more with limited patch/plaque (T1) disease than older patients. Duration of skin disease before diagnosis of MF did not vary between the two groups. The long-term survival of younger patients with MF is significantly decreased when compared with a race-, age-, and sex-matched control population (p < 0.001). Disease-specific survivals (DSS) of younger and older patients are similar, but young patients show a slight but significantly better overall DSS (p < 0.02). However, DSS comparison of generalized patch/plaque (T2) and tumor stage (T3) patients with MF showed no significant difference between young and old patients (p=0.47, p=0.59). Patient age was not a significant predictor of survival when controlled for T-stage. Sixteen of 58 young patients with MF have died, 13 because of MF (22%), compared with 138 of 500 older patients (28%) who died as a result of MF. All younger patients with MF who progressed had at least T2 disease at presentation. Fifty of 56 young patients with MF and T1-T3 disease were treated initially with total skin electron beam or topical nitrogen mustard. The response to therapy was similar in younger and older patients with MF.T1 disease is more common and T4 disease is unusual in young patients with MF compared with an older population of patients with MF. Young patients with T1 disease, all of whom were treated with either topical nitrogen mustard or total skin electron beam therapy, or both therapies, showed no disease progression. Overall, young patients with MF showed slightly better DSS, but this was because of differences in stage distribution.

    View details for Web of Science ID 000073485800006

    View details for PubMedID 9591813

  • Blastomycosis-like pyoderma in a man with AIDS JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Crowley, J. J., Kim, Y. H. 1997; 36 (4): 633-634

    View details for Web of Science ID A1997WR63000022

    View details for PubMedID 9092755

  • Clinical stage IA (limited patch and plaque) mycosis fungoides - A long-term outcome analysis ARCHIVES OF DERMATOLOGY Kim, Y. H., Jensen, R. A., WATANABE, G. L., Varghese, A., Hoppe, R. T. 1996; 132 (11): 1309-1313

    Abstract

    To study the long-term results of treatment of patients with stage IA mycosis fungoides and analyze the factors related to disease progression and the effect of initial therapy on survival and freedom from relapse.A single-center, 32(1/2)-year, retrospective cohort analysis.Private referral medical center.One hundred twenty-two patients with clinical stage IA (T1, N0, M0) mycosis fungoides.Long-term actuarial survival and freedom-from-relapse results as calculated by the technique of Kaplan-Meier.The long-term (30-year) survival of patients with stage IA mycosis fungoides is similar to the expected survival of a race-, age-, and sex-matched control population. The median survival of this group has not been reached at 32(1/2)-years. Eleven patients (9%) who progressed to more advanced disease had a lower complete response rate to initial therapy than did other patients (36% vs 82%) and an older mean age than did other patients with T1 disease (61 vs 48 years, P < .05). Only 3 (2%) of 122 patients died of disease. Among stage IA patients who achieved a complete response, 25% are relapse free at 10 years. Patients who received total skin electron beam therapy (n = 34) had a more favorable freedom-from-relapse outcome than those treated with topical mechlorethamine hydrochloride (nitrogen mustard) (n = 73, P < .05). No significant difference was seen in the long-term survival between the 2 treatment groups.Patients with clinical stage IA mycosis fungoides treated at Stanford University do not have an altered life expectancy. Fewer than 10% progressed to more advanced stages and few died of disease. Although the response rate to total skin electron beam therapy was superior to that of topical mechlorethamine, the longterm survival results were similar. Topical mechlorethamine is a cost-effective and convenient therapy for patients with limited patch and plaque mycosis fungoides.

    View details for Web of Science ID A1996VT34900008

    View details for PubMedID 8915308

  • REASSESSMENT OF HISTOLOGIC PARAMETERS IN THE DIAGNOSIS OF MYCOSIS-FUNGOIDES AMERICAN JOURNAL OF SURGICAL PATHOLOGY SMOLLER, B. R., Bishop, K., Glusac, E., Kim, Y. H., Hendrickson, M. 1995; 19 (12): 1423-1430

    Abstract

    The histologic diagnosis of mycosis fungoides (MF) can be difficult to establish and is based on interpretation of numerous subtle changes, most of which may be present to some degree in many inflammatory and neoplastic cutaneous conditions. To reassess the diagnostic criteria for making a histologic diagnosis of MF, we retrospectively reviewed histologic sections from 64 patients with mycosis fungoides (MF+) and compared the findings with sections from 47 patients who were biopsied to exclude MF and were shown not to have the disease (MF-). Patients were selected as MF+ or MF- independent of histologic findings based on the clinical course with at least 3 years of follow-up and immunophenotyping results. Following patient selection, at least two observers reviewed each slide without knowledge of final diagnosis and graded the intensity of approximately 25 histologic parameters. On univariate analysis, the following parameters were significant at beyond the p = 0.01 level: Pautrier's abscesses, haloed lymphocytes, exocytosis, disproportionate epidermotropism, epidermal lymphocytes larger than dermal lymphocytes, hyperconvoluted intraepidermal lymphocytes, and lymphocytes aligned within the basal layer. Haloed lymphocytes proved to be the most robust discriminator of MF from non-MF on multivariate analysis. These findings show that whereas many previously described features do discriminate between MF and inflammatory mimics, others are much less specific. Furthermore, few cases demonstrate all histologic features; for example, Pautrier's microabscesses were seen in only 37.5% of our cases. We conclude that a combination of specific histologic parameters can be used to establish a microscopic diagnosis of MF without the necessity of confirmatory immunophenotyping in the vast majority of cases.

    View details for Web of Science ID A1995TG92600009

    View details for PubMedID 7503364

  • CUTANEOUS GNATHOSTOMIASIS JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Crowley, J. J., Kim, Y. H. 1995; 33 (5): 825-828

    View details for Web of Science ID A1995TD25300021

    View details for PubMedID 7593786

  • PROGNOSTIC FACTORS IN ERYTHRODERMIC MYCOSIS-FUNGOIDES AND THE SEZARY-SYNDROME ARCHIVES OF DERMATOLOGY Kim, Y. H., Bishop, K., Varghese, A., Hoppe, R. T. 1995; 131 (9): 1003-1008

    Abstract

    There are no large studies evaluating patients with erythrodermic mycosis fungoides and Sézary syndrome to determine the important prognostic factors that may influence survival. This is important since new treatment modalities have been proposed as superior to existing primary therapies. We performed a retrospective cohort study of 106 patients with erythrodermic mycosis fungoides and Sézary syndrome, followed up in the Stanford (Calif) Mycosis Fungoides Clinic, to define the important prognostic factors in this group.Patients younger than 65 years have a more favorable survival profile than those 65 years or older (P < .005). Longer duration of symptoms before diagnosis ( > or = 10 years) tends to be associated with more favorable prognosis (p = .055). Lymph node stage is significantly correlated with survival; patients with overall stage III disease have more favorable prognosis than those with stage IV disease (P < .001). Patients with circulating Sézary cells in their blood have a significantly worse prognosis than those without (P < .005). Patient sex or race had no significant effect on overall survival outcome. Three distinct prognostic groups were identified, "favorable," "intermediate," and "unfavorable," according to the number of unfavorable prognostic factors (P < .005). The median survival in each group is 10.2, 3.7, and 1.5 years, respectively.In patients with erythrodermic mycosis fungoides and Sézary syndrome, the important prognostic factors are patient age at presentation, the overall stage, and peripheral blood involvement. Survival varies widely, depending on these variables. These prognostic factors should be evaluated when analyzing survival and/or treatment efficacy data of these patients.

    View details for Web of Science ID A1995RU13500004

    View details for PubMedID 7661601

  • LYMPHOCYTE ANTIGEN ABNORMALITIES IN INFLAMMATORY DERMATOSES APPLIED IMMUNOHISTOCHEMISTRY SMOLLER, B. R., Bishop, K., Glusac, E. J., Bhargava, V., Kim, Y. H., Warnke, R. A. 1995; 3 (2): 127-131
  • REASSESSMENT OF LYMPHOCYTE IMMUNOPHENOTYPING IN THE DIAGNOSIS OF PATCH AND PLAQUE STAGE LESIONS OF MYCOSIS-FUNGOIDES APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY SMOLLER, B. R., Bishop, K., Glusac, E. J., Kim, Y. H., Bhargava, V., Warnke, R. A. 1995; 3 (1): 32-36
  • CONSTITUTIVE ACTIVATION OF THE COLLAGENASE PROMOTER IN RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA FIBROBLASTS - ROLE OF ENDOGENOUSLY ACTIVATED AP-1 EXPERIMENTAL CELL RESEARCH Unemori, E. N., Mauch, C., Hoeffler, W., Kim, Y., Amento, E. P., BAUER, E. A. 1994; 211 (2): 212-218

    Abstract

    Recessive dystrophic epidermolysis bullosa (RDEB) is a mutilating disease of the skin characterized by recurrent blistering and erosions that result from compromised integrity of the basement membrane zone. In this study, fibroblasts derived from the skin of RDEB patients were characterized for expression of the major metalloproteinases, particularly interstitial collagenase. Consistent with previous reports on increased collagenase protein levels in fibroblasts from some RDEB patients, we found that steady-state levels of collagenase mRNA were significantly increased in fibroblast strains derived from three of five RDEB patients compared to fibroblasts obtained from normal donors. Stromelysin mRNA was elevated in the same three fibroblast strains, whereas expression of neither the 72- nor the 92-kDa type IV collagenases was different from that of controls. Tissue inhibitor of metalloproteinases was expressed in RDEB fibroblasts at levels similar to those observed in normal fibroblasts. To investigate the mechanism behind the steady-state elevation in collagenase and stromelysin expression, AP-1 expression and activation were studied. Although levels of Jun expression were not different from those seen in normal fibroblasts, AP-1 activity, as assessed by ability to bind to a TPA response element-containing oligonucleotide, was endogenously elevated in RDEB fibroblasts compared to normal fibroblasts. Transfection studies using a plasmid construct containing the collagenase promoter linked to a CAT reporter gene demonstrated that RDEB fibroblasts were able to support active transcription of the promoter compared to normal fibroblasts. These studies support the hypothesis that RDEB fibroblasts contain chronically activated AP-1, and perhaps other transactivating factors, that contribute to the cellular phenotype of collagenase and stromelysin overexpression.

    View details for Web of Science ID A1994NE89700006

    View details for PubMedID 8143767

  • Autoimmunity to anchoring fibrils. Advances in dermatology Kim, Y. H., Woodley, D. T. 1994; 9: 61-77

    View details for PubMedID 8060743

  • A DOUBLE-BLIND COMPARISON OF ADHESIVE BANDAGES WITH THE USE OF UNIFORM SUCTION BLISTER WOUNDS ARCHIVES OF DERMATOLOGY Woodley, D. T., Kim, Y. H. 1992; 128 (10): 1354-1357

    Abstract

    The assessment of cutaneous wound healing in humans has been hampered by the inability to evaluate multiple wounds with identical origins, treatment histories, and sizes. There have been no double-blind wound healing studies in humans that compared one wound dressing with another. The purpose of this study was to determine if identical suction blister wounds could serve as a model to evaluate and compare wound healing and overall cosmetic appearance of wounds treated with commercially available adhesive bandages. In a double-blind study, we compared superficial skin wounds of identical depth and diameter, created on the forearms of five human subjects by means of a suction blister device. The wounds were covered by two common, commercially available adhesive bandages or a copolymer of polyurethane membrane type of wound dressing. We compared the degree of reepithelialization, erythema, skin depression, and overall cosmetic appearance of wounds with respect to the specific adhesive bandages used.The wounds covered with the copolymer of polyurethane membrane were judged to have better overall appearance and advanced reepithelialization compared with identical wounds covered by the other wound dressings. With the use of x5 magnification for viewing the wounds on the final day of evaluation (between days 18 and 22), the wounds treated with the copolymer of polyurethane membrane were judged to be the least depressed wounds in fields of identical wounds in the three subjects studied. Concordance between the evaluators' "blinded" assessments was uniform, and no discrepancy between the evaluators' assessments occurred at any of the time points.Identical wounds created with a suction blistering device can be used reliably to detect differences between the performances of wound dressings in healing superficial wounds. Superficial cutaneous wounds covered with a copolymer of polyurethane dressing demonstrated a superior rate of reepithelialization, less depression, and a better overall cosmetic appearance than wounds covered with two commercially available adhesive bandages.

    View details for Web of Science ID A1992JT34300007

    View details for PubMedID 1417023

  • RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA PHENOTYPE IS PRESERVED IN XENOGRAFTS USING SCID MICE - DEVELOPMENT OF AN EXPERIMENTAL INVIVO MODEL JOURNAL OF INVESTIGATIVE DERMATOLOGY Kim, Y. H., Woodley, D. T., WYNN, K. C., GIOMI, W., BAUER, E. A. 1992; 98 (2): 191-197

    Abstract

    Recessive dystrophic epidermolysis bullosa (RDEB) is a subgroup of hereditary blistering diseases characterized by repetitive wounding and healing with subsequent extensive scarring. The purpose of this study was to establish a xenograft model that retains the RDEB phenotype and thus might be used as an experimental in vivo model to explore the molecular and biochemical mechanisms of the chronically wounded phenotype of RDEB. Full-thickness, tumor-free RDEB skin tissues were grafted onto the dorsum of severe combined immunodeficiency (SCID) mice. At 4, 8, 12, and 24 weeks after grafting, the xenografts were removed for examination. Immunofluorescence studies were performed using species-specific antibodies to human class I antigen, mouse class I antigen, human type IV and VII collagens and with cross-reacting antibody against bullous pemphigoid antigen (BPA). Staining with the antibody to human class I antigen, W6/32, and with the antibody to mouse class I antigen, 20.8.4s, confirmed the species-specific results obtained with the type IV and type VII collagen and laminin antibodies. The RDEB grafts showed essentially no staining with the type VII collagen antibody. Antibodies against laminin and BPA showed normal staining patterns in RDEB grafts. There was an overall paucity of anchoring fibrils in the grafts when examined with electron microscopy. Blisters could be induced in these grafts with minor trauma and showed a sublamina densa separation by immunomapping and electron microscopy. As late as 24 weeks post-transplantation, the RDEB grafts remain human, are not significantly replaced by mouse cells, and retain the RDEB disease phenotype.

    View details for Web of Science ID A1992HB07100012

    View details for PubMedID 1370678

  • H-1-NMR SPECTROSCOPY - AN APPROACH TO EVALUATION OF DISEASED SKIN INVIVO JOURNAL OF INVESTIGATIVE DERMATOLOGY Kim, Y. H., Orenberg, E. K., Faull, K. F., WADEJARDETZKY, N. G., Jardetzky, O. 1989; 92 (2): 210-216

    Abstract

    1H nuclear magnetic resonance (NMR) spectroscopy was tested for its applicability in evaluating diseased skin. In order to explore potential spectral markers characteristic of diseased tissue, perchloric acid (PCA) extracts of psoriasis and malignant melanoma tissues were compared with normal skin, and changes in melanoma after heat treatment were monitored. In psoriatic plaque extract, the spectral peak intensity ratios of Glu: Ser, creatine: Gly, and taurine: Ala were approximately three-fold compared with symptom-free or normal skin, whereas Val: Leu/Ile was one-half the normal skin ratio. In melanoma extracts, the phosphorylcholine (PC)/glycerophosphorylcholine (GPC): Ala, Glu: Ser, and lactate: Ala ratios were five-, three-, and two-fold higher, respectively, than normal skin and the Val: Leu/Ile ratio was two-thirds of normal skin. With heat treatment, PC/GPC: Ala and Glu: Ser ratios decreased, whereas lactate: Ala and Val: Leu/Ile ratios increased three-fold and one-third, respectively. Results indicate that 1H NMR spectroscopy is a sufficiently sensitive technique to distinguish normal from diseased skin. The main attraction of this technique lies in the possibility of non-invasive study of various skin diseases, malignant transformation of benign tumors, and responses to treatment. Several methodologic problems remain to be resolved before a meaningful interpretation of in vivo observations becomes feasible. Correlation of in vivo and in vitro findings is an essential step toward this goal.

    View details for Web of Science ID A1989T322300012

    View details for PubMedID 2537364

Conference Proceedings


  • Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides Chinn, D. M., Chow, S., Kim, Y. H., Hoppe, R. T. ELSEVIER SCIENCE INC. 1999: 951-958

    Abstract

    To compare the efficacy of total skin electron beam therapy (TSEBT) with or without adjuvant topical nitrogen mustard (+/- HN2) with topical nitrogen mustard (HN2) alone as initial management of T2 and T3 mycosis fungoides (MF).A retrospective analysis of 148 patients presenting to Stanford from January, 1970 through January, 1995 within 4 months of pathologic diagnosis of MF. Fifty-five patients with T2 and 27 with T3 disease received TSEBT +/- HN2. Fifty-four patients with T2 and 12 with T3 disease received HN2 alone. Boosts with radiotherapy were usually administered to cutaneous tumors of patients with T3 disease.TSEBT +/- HN2 yielded significantly higher complete response (CR) rates than did HN2 alone in patients with T2 and T3 disease (76% vs 39%, p = 0.03 for T2, and 44% vs 8%, p < 0.05 for T3, respectively). In T2 disease, treatment with adjuvant HN2 was associated with a longer freedom from relapse following TSEBT when compared to observation following a CR to TSEBT (p = 0.068). However, no significant differences in survival were observed for different management programs for T2 or T3 disease. In T2 disease, both TSEBT and HN2 were as effective as salvage therapy as when utilized as initial therapy. However, salvage therapy in T3 disease was rarely effective. Limited tumor involvement in T3 disease did not correlate with improved survival compared to more generalized tumorous disease. MF contributed to 27% and 68% of deaths in patients with T2 and T3 disease, respectively.Because of high response rates, management of significantly symptomatic or extensive T2 MF should include TSEBT, and adjuvant HN2 should be administered after a CR to TSEBT. Patients with T2 disease who fail TSEBT or HN2 can be salvaged with the other modality. TSEBT is also an effective treatment for T3 disease. The small subset of patients with limited T3 disease may also be treated with HN2 and local radiotherapy to the tumors. Further investigations are necessary to improve the overall outcome for T3 mycosis fungoides.

    View details for Web of Science ID 000079279100002

    View details for PubMedID 10192339

  • Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and Sezary syndrome: A critical reappraisal Kohler, S., Kim, Y. H., SMOLLER, B. R. MUNKSGAARD INT PUBL LTD. 1997: 292-297

    Abstract

    It is often difficult to make a clinical or histologic diagnosis of erythrodermic mycosis fungoides (MF) and Sezary syndrome (SS). Whereas the histologic parameters for making a diagnosis of MF with well-developed patch and plaque stage lesions are clearly defined, the same criteria appear to be less relevant for diagnosing MF in patients with erythroderma secondary to the disease. In order to better define the histologic features of erythrodermic MF and SS, we studied 28 routine histologic sections of 17 patients with known erythrodermic MF or SS. Sections were reviewed independently by 2 dermatopathologists. Each of 24 parameters was scored semi-quantitatively and the data were compared to data previously reported from a group of 64 patients with limited patch and plaque stage lesions of MF. When compared to biopsies from patients with limited patch/plaque lesions, biopsies taken from erythrodermic patients displayed more parakeratosis (p=0.0492) and acanthosis (p=0.0046), less disproportionate epidermotropism, fewer lymphocytes aligned within the basal layer (p=0.0045), fewer hyperconvoluted cells in the epidermis, more dermal hyperconvoluted cells (p=0.0191), more papillary dermal fibrosis (p=0.0002), more prominent teleangiectasias (p=0.0028) and more mitotic figures. The histologic features of erythrodermic MF and Sezary syndrome are even more subtle than the features of patch and plaque stage MF, thus rendering the histologic diagnosis more difficult.

    View details for Web of Science ID A1997XB68100005

    View details for PubMedID 9194582

Stanford Medicine Resources: