title: Primary Cutaneous Extranodal Natural Killer/T-Cell Lymphoma Misdiagnosed as Peripheral T-Cell Lymphoma: The Importance of Consultation/Referral and Inclusion of EBV In Situ Hybridization for Diagnosis.
abstract: BACKGROUND
  Primary cutaneous T-cell lymphomas (CTCL) are heterogenous extranodal non-Hodgkin lymphomas including a few distinct and provisional entities. Compared with the West, Asian populations have a relatively higher frequency of nonmycosis fungoides CTCL. Primary cutaneous extranodal natural killer/T-cell lymphoma (PC-ENKTL) is distinct from other CTCL by the presence of EBV association.
  
  
  METHODS
  In our recent retrospective Asian study of PC-ENKTL, we identified 5 cases initially misdiagnosed as various CTCL. We fully characterized these cases with immunohistochemistry, EBV in situ hybridization, and clonality study for T-cell receptor (TCR) γ-chain gene (TRG).
  
  
  RESULTS
  The 5 patients included 3 males and 2 females with a median age of 45. All tumors were positive for EBER. Two cases were clonal for TRG gene rearrangement but without expression of βF1 or TCR-γ (TCR-silent T-cell origin), 1 tumor expressed TCR-γ (γδ T-cell origin), and the remaining 2 were polyclonal for TRG and negative for TCR expression (NK-cell origin). On the basis of the initial diagnoses (2 as peripheral T-cell lymphoma, unspecified, 2 as primary cutaneous anaplastic large-cell lymphoma, and 1 as subcutaneous panniculitis-like T-cell lymphoma), all patients received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with additional radiotherapy in 3. All patients experienced persistent disease or relapse despite treatment in a mean duration of 8.8 months (range, 1 to 12 mo).
  
  
  CONCLUSIONS
  PC-ENKTL is rare and aggressive. These cases strongly demonstrate the importance of consultation/referral to experienced hematopathologists and the inclusion of EBER in the initial diagnostic work-up for patients with nonmycosis fungoides CTCL to avoid erroneous diagnosis and subsequent inadequate treatment of the patients.
authors.affiliation: *Department of Pathology, Chi-Mei Medical Center, Tainan †Department of Pathology ‡Graduate Institute of Pathology, National Taiwan University College of Medicine #Tai-Cheng Stem Cell Therapy Center, National Taiwan University Hospital §Department of Pathology, Taipei Medical University Hospital ¶Taiwan Cytoscreen Diagnostic Center **Department of Anatomical Pathology, Cheng Hsin General Hospital ††Department of Pathology, Taipei Medical University, Taipei, Taiwan ∥Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Khin Than
authors.initials: KT
authors.lastname: Win
authors.forename: Jau-Yu
authors.initials: JY
authors.lastname: Liau
authors.forename: Bo-Jung
authors.initials: BJ
authors.lastname: Chen
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.forename: Chiao-Yun
authors.initials: CY
authors.lastname: Chen
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Li
authors.forename: Cheng-Hsiang
authors.initials: CH
authors.lastname: Hsiao
authors.forename: Shih-Sung
authors.initials: SS
authors.lastname: Chuang
mesh_terms: D000328:Adult; D000368:Aged; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007694:Killer Cells, Natural / Q000502:physiology*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis*; D016410:Lymphoma, T-Cell, Cutaneous / Q000175:diagnosis*; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012017:Referral and Consultation; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000175:diagnosis*