Clinical and Laboratory Investigations

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

Corresponding Author

C.D. Klemke

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

Correspondence

Claus-Detlev Klemke.

E-mail:[email protected]

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N. Booken,

N. Booken

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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C. Weiss,

C. Weiss

Division of Statistics, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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J.P. Nicolay,

J.P. Nicolay

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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S. Goerdt,

S. Goerdt

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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M. Felcht,

M. Felcht

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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C. Géraud,

C. Géraud

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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W. Kempf,

W. Kempf

Department of Dermatology and Venereology, University of Zurich, Zurich, Switzerland

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C. Assaf,

C. Assaf

Department of Dermatology, Helios Clinic Krefeld, Krefeld, Germany

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N. Ortonne,

N. Ortonne

Department of Pathology, Hôpital Henri-Mondor, Créteil, France

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M. Battistella,

M. Battistella

Department of Pathology, AP-HP, Hôpital Saint Louis, Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1165, F-75010 Paris, France

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M. Bagot,

M. Bagot

Department of Dermatology, Hôpital Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, Inserm U976, 1 Avenue Claude Vellefaux, 75010 Paris, France

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R. Knobler,

R. Knobler

Department of Dermatology, University of Vienna, Vienna, Austria

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P. Quaglino,

P. Quaglino

Dermatologic Clinic, Department of Medical Science, University of Torino, Torino, Italy

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B. Arheiliger,

B. Arheiliger

Department of Dermatology, Johannes Wesling Klinikum, Minden, Germany

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M. Santucci,

M. Santucci

Division of Pathological Anatomy, University of Florence, Florence, Italy

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P. Jansen,

P. Jansen

Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands

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M.H. Vermeer,

M.H. Vermeer

Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands

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R. Willemze,

R. Willemze

Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands

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C.D. Klemke,

Corresponding Author

C.D. Klemke

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

Correspondence

Claus-Detlev Klemke.

E-mail:[email protected]

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N. Booken,

N. Booken

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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C. Weiss,

C. Weiss

Division of Statistics, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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J.P. Nicolay,

J.P. Nicolay

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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S. Goerdt,

S. Goerdt

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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M. Felcht,

M. Felcht

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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C. Géraud,

C. Géraud

Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany

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W. Kempf,

W. Kempf

Department of Dermatology and Venereology, University of Zurich, Zurich, Switzerland

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C. Assaf,

C. Assaf

Department of Dermatology, Helios Clinic Krefeld, Krefeld, Germany

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N. Ortonne,

N. Ortonne

Department of Pathology, Hôpital Henri-Mondor, Créteil, France

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M. Battistella,

M. Battistella

Department of Pathology, AP-HP, Hôpital Saint Louis, Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1165, F-75010 Paris, France

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M. Bagot,

M. Bagot

Department of Dermatology, Hôpital Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, Inserm U976, 1 Avenue Claude Vellefaux, 75010 Paris, France

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R. Knobler,

R. Knobler

Department of Dermatology, University of Vienna, Vienna, Austria

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P. Quaglino,

P. Quaglino

Dermatologic Clinic, Department of Medical Science, University of Torino, Torino, Italy

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B. Arheiliger,

B. Arheiliger

Department of Dermatology, Johannes Wesling Klinikum, Minden, Germany

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M. Santucci,

M. Santucci

Division of Pathological Anatomy, University of Florence, Florence, Italy

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P. Jansen,

P. Jansen

Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands

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M.H. Vermeer,

M.H. Vermeer

Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands

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R. Willemze,

R. Willemze

Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands

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First published: 09 April 2015

https://doi.org/10.1111/bjd.13832

Citations: 72

Funding sources

Wilhelm Sander Stiftung (C. Assaf, Förderprojekt no. 2011.066.1).

Conflicts of interest

None declared.

C.D.K., N.B., P.J., M.H.V. and R.W. contributed equally to this work.

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Summary

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.

Supporting Information

References

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Citing Literature

Volume173, Issue1

July 2015

Pages 93-105

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

Summary

Background

Objectives

Methods

Results

Conclusions

Supporting Information

References

Citing Literature

References

Information

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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

Summary

Background

Objectives

Methods

Results

Conclusions

Supporting Information

References

Citing Literature

References

Related

Information