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

Br J Dermatol. 2015 Jul;173(1):93-105. doi: 10.1111/bjd.13832. Epub 2015 Jun 23.

Abstract

Background: Patients with erythrodermic disease are a diagnostic challenge regarding the clinical and histological differential diagnosis.

Objectives: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / metabolism*
  • Biopsy / methods
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism
  • Sezary Syndrome / immunology
  • Sezary Syndrome / mortality
  • Sezary Syndrome / pathology*
  • Skin / pathology*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology*

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor