A High Programmed Cell Death Protein 1 Hormone Receptor Score on Skin Biopsy is Associated with Sézary Syndrome Diagnosis: A Study of 91 Patients with Erythroderma


  • Camille Luherne Dermatology Department, CHU de Bordeaux, F-33000 Bordeaux, France
  • Sarah Menguy Pathology Department, CHU Bordeaux, F-33600 Pessac, France
  • Thomas Ferte Pole de Sante Publique, Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique, CHU de Bordeaux, F-33000 Bordeaux, France
  • Marie Beylot-Barry Dermatology Department, CHU de Bordeaux, F-33000 Bordeaux, France
  • Julien Seneschal Dermatology Department, CHU de Bordeaux, F-33000 Bordeaux, France
  • Brigitte Milpied Dermatology Department, CHU de Bordeaux, F-33000 Bordeaux, France
  • Jean-Philippe Vial Hematology Biology Department, CHU Bordeaux, F- 33600 Pessac, France
  • Audrey Gros Tumor Biology and Tumor Bank Department, CHU Bordeaux, F-33600 Pessac, France
  • Samuel Amintas Tumor Biology and Tumor Bank Department, CHU Bordeaux, F-33600 Pessac, France
  • Béatrice Vergier Pathology Department, CHU Bordeaux, F-33600 Pessac, France
  • Anne Pham-Ledard Dermatology Department, CHU de Bordeaux, Bordeaux, France




Sézary syndrome, programmed-death 1, erythrodermic mycosis fungoides, erythrodermic psoriasis, erythrodermic eczema, erythrodermic drug-induced erythroderma, programmed cell death protein 1


Erythroderma is challenging to diagnose. The aim of this single-centre retrospective study was to identify factors that can be used to improve the diagnosis of erythroderma. Among 91 patients with erythroderma, 21 were diagnosed with eczema, 17 with psoriasis, 20 with drug-induced erythroderma, 13 with erythrodermic mycosis fungoides and 20 with Sézary syndrome. Nail alterations, ear involvement, and severe scaling were significantly associated with psoriasis (p = 0.044). Fever and hypereosinophilia were associated with drug-induced erythroderma. Expression of programmed cell death protein 1 was observed in all skin biopsies. However, with Sézary syndrome, programmed cell death protein 1 expression was significantly higher than with other aetiologies. A programmed cell death protein 1 hormone receptor score (H-score) >50 was associated with Sézary syndrome (p < 0.001, sensitivity 75%, specificity 92%) as well as CXCL13 expression (p < 0.044). CD7 loss was more frequent with erythrodermic mycosis fungoides and Sézary syndrome (p = 0.022). This study reports the importance of programmed cell death protein 1 expression for the differential diagnosis of Sézary syndrome and other aetiologies, including erythrodermic mycosis fungoides.


Download data is not yet available.


Botella-Estrada R. Erythroderma. A clinicopathological study of 56 cases. Arch Dermatol 1994; 130: 1503-1507.


Yuan X-Y, Guo J-Y, Dang Y-P, Qiao L, Liu W. Erythroderma: a clinical-etiological study of 82 cases. Eur J Dermatol 2010; 20: 373-377.


Li J, Zheng H-Y. Erythroderma: a clinical and prognostic study. Dermatology 2012; 225: 154-162.


Khaled A, Sellami A, Fazaa B, Kharfi M, Zeglaoui F, Kamoun M. Acquired erythroderma in adults: a clinical and prognostic study: acquired erythroderma in adults. J Eur Acad Dermatol Venereol 2009; 24: 781-788.


Miyashiro D, Sanches JA. Erythroderma: a prospective study of 309 patients followed for 12 years in a tertiary center. Sci Rep 2020; 10: 9774.


César A, Cruz M, Mota A, Azevedo F. Erythroderma. A clinical and etiological study of 103 patients. J Dermatol Case Rep 2016; 10: 1-9.


Zip C, Murray S, Walsh NMG. The specificity of histopathology in erythroderma. J Cutan Pathol 1993; 20: 393-398.


Ram-Wolff C, Martin-Garcia N, Bensussan A, Bagot M, Ortonne N. Histopathologic diagnosis of lymphomatous versus inflammatory erythroderma: a morphologic and phenotypic study on 47 skin biopsies. Am J Dermatopathol 2010; 32: 755-763.


Kamarashev J, Burg G, Kempf W, Schmid MH, Dummer R. Comparative analysis of histologicai and immunohistological features in mycosis fungoides and Sezary syndrome. J Cutan Pathol 1998; 25: 407-412.


Klemke CD, Booken N, Weiss C, Nicolay JP, Goerdt S, Felcht M, et al. 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; 173: 93-105.


Willemze R, Cerroni L, Kempf W, Berti E, Facchetti F, Swerdlow SH, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood 2019; 133: 1703-1714.


Walsh NMG, Prokopetz R, Tron VA, Sawyer DM, Kevin Walters A, Murray S, et al. Histopathology in erythroderma: review of a series of cases by multiple observers. J Cutan Pathol 1994; 21: 419-423.


Mangold AR, Thompson AK, Davis MD, Saulite I, Cozzio A, Guenova E, et al. Early clinical manifestations of Sézary syndrome: a multicenter retrospective cohort study. J Am Acad Dermatol 2017; 77: 719-727.


Samimi S, Benoit B, Evans K, Wherry EJ, Showe L, Wysocka M, et al. Increased programmed death-1 expression on CD4+ T cells in cutaneous T-cell lymphoma: implications for immune suppression. Arch Dermatol 2010; 146: 1382.


Nguyen GH, Olson LC, Magro CM. Upregulation of inhibitory signaling receptor programmed death marker-1 (PD-1) in disease evolution from cutaneous lymphoid dyscrasias to mycosis fungoides and Sezary's syndrome. Ann Diagn Pathol 2017; 28: 54-59.


Kantekure K, Yang Y, Raghunath P, Schaffer A, Woetmann A, Zhang Q, et al. Expression patterns of the immunosuppressive proteins PD-1/CD279 and PD-L1/CD274 at different stages of cutaneous T-cell lymphoma/mycosis fungoides. Am J Dermatopathol 2012; 34: 126-128.


Çetinözman F, Jansen PM, Vermeer MH, Willemze R. Differential expression of programmed death-1 (PD-1) in Sézary syndrome and mycosis fungoides. Arch Dermatol 2012; 148: 1379.


Çetinözman F, Jansen PM, Willemze R. Expression of programmed death-1 in skin biopsies of benign inflammatory vs. lymphomatous erythroderma. Br J Dermatol 2014; 171: 499-504.


Saulite I, Ignatova D, Chang Y-T, Fassnacht C, Dimitriou F, Varypataki E, et al. Blockade of programmed cell death protein 1 (PD-1) in Sézary syndrome reduces Th2 phenotype of non-tumoral T lymphocytes but may enhance tumor proliferation. Oncoimmunology 2020; 9: 1738797.


Bosisio FM, Cerroni L. Expression of T-follicular helper markers in sequential biopsies of progressive mycosis fungoides and other primary cutaneous T-cell lymphomas. Am J Dermatopathol 2015; 37: 115-121.


Jogdand GM, Mohanty S, Devadas S. Regulators of Tfh cell differentiation. Front Immunol 2016; 7: 520.


Gaulard P, de Leval L. Follicular helper T cells: implications in neoplastic hematopathology. Semin Diagn Pathol 2011; 28: 202-213.


Lunning MA, Vose JM. Angioimmunoblastic T-cell lymphoma: the many-faced lymphoma. Blood 2017; 129: 1095-1102.


Hutloff A. Regulation of T follicular helper cells by ICOS. Oncotarget 2015; 6: 21785-21786.


Picchio MC, Scala E, Pomponi D, Caprini E, Frontani M, Angelucci I, et al. CXCL13 is highly produced by Sezary cells and enhances their migratory ability via a synergistic mechanism involving CCL19 and CCL21 chemokines. Cancer Res 2008; 68: 7137-7146.


Vergnolle I, Douat-Beyries C, Boulinguez S, Rieu J-B, Vial JP, Baracou R, et al. CD158k and PD-1 expressions define heterogeneous subtypes of Sezary syndrome. Blood 2022; 6: 1813-1825.


Park J, Daniels J, Wartewig T, G. Ringbloom K. Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity. Blood 2021; 138: 1225-1236.


Scarisbrick JJ, Prince HM, Vermeer MH, Quaglino P, Horwitz S, Porcu P, et al. Cutaneous lymphoma international consortium study of outcome in advanced stages of mycosis fungoides and Sézary syndrome: effect of specific prognostic markers on survival and development of a prognostic model. J Clin Oncol 2015; 33: 3766-3773.


Cohen DA, Dabbs DJ, Cooper KL, Amin M, Jones TE, Jones MW, et al. Interobserver agreement among pathologists for semiquantitative hormone receptor scoring in breast carcinoma. Am J Clin Pathol 2012; 138: 796-802.


Hirsch FR, Varella-Garcia M, Bunn PA, Di Maria MV, Veve R, Bremnes RM, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 2003; 21: 3798-3807.


Specht E, Kaemmerer D, Sänger J, Wirtz RM, Schulz S, Lupp A. Comparison of immunoreactive score, HER2/ neu score and H score for the immunohistochemical evaluation of somatostatin receptors in bronchopulmonary neuroendocrine neoplasms. Histopathology 2015; 67: 368-377.


Leclaire Alirkilicarslan A, Dupuy A, Pujals A, Parrens M, Vergier B, Robson A, et al. Expression of TFH markers and detection of RHOA p.G17V and IDH2 p.R172K/S mutations in cutaneous localizations of angioimmunoblastic T-cell lymphomas. Am J Surg Pathol 2017; 41: 1581-1592.


Ryu H-J, Kim S-I, Jang H-O, Kim S-H, Oh S-H, Park S, et al. Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the diagnosis of early mycosis fungoides. Cells 2021; 10: 2758.


Wada DA, Wilcox RA, Harrington SM, Kwon ED, Ansell SM, Comfere NI. Programmed death 1 is expressed in cutaneous infiltrates of mycosis fungoides and Sézary syndrome. Am J Hematol 2011; 86: 325-327.


Roncador G, Verdes-Montenegro J-FG, Tedoldi S, Paterson JC, Klapper W, Ballabio E, et al. Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma. Haematologica 2007; 92: 1059-1066.


Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood 2010; 116: 767-771.


Hawilo A, Zaraa I, Benmously R, Mebazaa A, Osman AB. Erythrodermic psoriasis: epidemiological clinical and therapeutic features about 60 cases. Tunis Med 2011; 89: 841-847.

Martin SJ, Duvic M. Prevalence and treatment of palmoplantar keratoderma and tinea pedis in patients with Sézary syndrome. Int J Dermatol 2012; 51: 1195-1198.


Rie MA, Catro I, Lier RAW, Bos JD. Expression of the T-cell activation antigens CD27 and CD28 in normal and psoriatic skin. Clin Exp Dermatol 1996; 21: 104-111.


Liu L, Abken H, Pfohler C, Rappl G, Tilgen W, Reinhold U. Accumulation of CD4+CD7- T cells in inflammatory skin lesions: evidence for preferential adhesion to vascular endothelial cells. Clin Exp Immunol 2000; 121: 94-99.


Delfau-Larue MH, Laroche L, Wechsler J, Lepage E, Lahet C, Asso-Bonnet M, et al. Diagnostic value of dominant T-cell clones in peripheral blood in 363 patients presenting consecutively with a clinical suspicion of cutaneous lymphoma. Blood 2000; 96: 2987-2992.


Diwan AH, Prieto VG, Herling M, Duvic M, Jones D. Primary Sézary syndrome commonly shows low-grade cytologic atypia and an absence of epidermotropism. Am J Clin Pathol 2005; 123: 510-515.


Decroos A, Giustiniani J, Pelletier L, Ingen-Housz-Oro S, Gaulard P, Ortonne N. PD1 in Sézary syndrome: a repressor of cell survival sometimes lost during progression, but a new target using depleting antibodies? Eur J Cancer 2021; 156: 14-15.





How to Cite

Luherne, C., Menguy, S., Ferte, T., Beylot-Barry, M., Seneschal, J., Milpied, B., Vial, J.-P., Gros, A., Amintas, S., Vergier, B., & Pham-Ledard, A. (2022). A High Programmed Cell Death Protein 1 Hormone Receptor Score on Skin Biopsy is Associated with Sézary Syndrome Diagnosis: A Study of 91 Patients with Erythroderma. Acta Dermato-Venereologica, 102, adv00773. https://doi.org/10.2340/actadv.v102.1062