title: Histopathological and immunophenotypical criteria for the diagnosis of Sézary syndrome in differentiation from other erythrodermic skin diseases: a European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force Study of 97 cases.
abstract: BACKGROUND
  Patients with erythrodermic disease are a diagnostic challenge regarding the clinical and histological differential diagnosis.
  
  
  OBJECTIVE
  To evaluate histopathological and immunohistochemical diagnostic markers for Sézary syndrome.
  
  
  METHODS
  Ninety-seven erythrodermic cases [Sézary syndrome (SS), n = 57; erythrodermic inflammatory dermatoses (EIDs), n = 40] were collected by the EORTC Cutaneous Lymphoma Task Force histopathology group. Evaluation criteria were (i) epidermal and dermal changes; (ii) morphology of the infiltrate; (iii) immunohistochemical analysis of marker loss (CD2, CD3, CD4, CD5 and CD7); (iv) bystander infiltrate by staining for CD8, FOXP3 and CD25; and (v) expression of Ki-67, CD30, PD-1 and MUM-1.
  
  
  RESULTS
  The workshop panel made a correct diagnosis of SS in 51% of cases (cutaneous T-cell lymphoma 81%) and of EID in 80% without clinical or laboratory data. Histology revealed a significantly increased degree of epidermotropism (P < 0.001) and more intraepidermal atypical lymphocytes (P = 0.0014) in SS biopsies compared with EID. Pautrier microabscesses were seen only in SS (23%) and not in EID (P = 0.0012). SS showed significantly more dermal cerebriform and blastic lymphocytes than EID. Immunohistochemistry revealed a significant loss of CD7 expression (< 50%) in 33 of 51 (65%) cases of SS compared with two of 35 (6%) EID (P < 0.001). The lymphocytic infiltrate in SS skin samples was found significantly to express PD-1 (P = 0.0053), MUM-1 (P = 0.0017) and Ki-67 (P < 0.001), and showed less infiltration of CD8(+) lymphocytes (P < 0.001). A multivariate analysis identified CD7 loss, increased numbers of small cerebriform lymphocytes, low numbers of CD8(+) lymphocytes and increased proliferation (Ki-67(+) lymphocytes) as the strongest indicators for the diagnosis of SS.
  
  
  CONCLUSIONS
  A number of different histological and immunophenotypical criteria are required to differentiate between SS and EIDs.
authors: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors: C D
authors: CD
authors: Klemke
authors: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors: N
authors: N
authors: Booken
authors: Division of Statistics, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors: C
authors: C
authors: Weiss
authors: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors: J P
authors: JP
authors: Nicolay
authors: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors: S
authors: S
authors: Goerdt
authors: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors: M
authors: M
authors: Felcht
authors: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany.
authors: C
authors: C
authors: Géraud
authors: Department of Dermatology and Venereology, University of Zurich, Zurich, Switzerland.
authors: W
authors: W
authors: Kempf
authors: Department of Dermatology, Helios Clinic Krefeld, Krefeld, Germany.
authors: C
authors: C
authors: Assaf
authors: Department of Pathology, Hôpital Henri-Mondor, Créteil, France.
authors: N
authors: N
authors: Ortonne
authors: Department of Pathology, AP-HP, Hôpital Saint Louis, Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1165, F-75010, Paris, France.
authors: M
authors: M
authors: Battistella
authors: Department of Dermatology, Hôpital Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, Inserm U976, 1 Avenue Claude Vellefaux, 75010, Paris, France.
authors: M
authors: M
authors: Bagot
authors: Department of Dermatology, University of Vienna, Vienna, Austria.
authors: R
authors: R
authors: Knobler
authors: Dermatologic Clinic, Department of Medical Science, University of Torino, Torino, Italy.
authors: P
authors: P
authors: Quaglino
authors: Department of Dermatology, Johannes Wesling Klinikum, Minden, Germany.
authors: B
authors: B
authors: Arheiliger
authors: Division of Pathological Anatomy, University of Florence, Florence, Italy.
authors: M
authors: M
authors: Santucci
authors: Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
authors: P
authors: P
authors: Jansen
authors: Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
authors: M H
authors: MH
authors: Vermeer
authors: Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
authors: R
authors: R
authors: Willemze
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy / Q000379:methods; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012751:Sezary Syndrome / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor