Histopathological and immunophenotypical criteria for the diagnosis of Sézary syndrome in differentiation from other erythrodermic skin diseases

TY - JOUR

T1 - Histopathological and immunophenotypical criteria for the diagnosis of Sézary syndrome in differentiation from other erythrodermic skin diseases

T2 - a European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force Study of 97 cases

AU - Klemke, C D

AU - Booken, N

AU - Weiss, C

AU - Nicolay, J P

AU - Goerdt, S

AU - Felcht, M

AU - Géraud, C

AU - Kempf, W

AU - Assaf, C

AU - Ortonne, N

AU - Battistella, M

AU - Bagot, M

AU - Knobler, R

AU - Quaglino, P

AU - Arheiliger, B

AU - Santucci, M

AU - Jansen, P

AU - Vermeer, M H

AU - Willemze, R

N1 - © 2015 British Association of Dermatologists.

PY - 2015/7

Y1 - 2015/7

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antigens, CD/metabolism

KW - Biomarkers, Tumor/metabolism

KW - Biopsy/methods

KW - Diagnosis, Differential

KW - Female

KW - Follow-Up Studies

KW - Forkhead Transcription Factors/metabolism

KW - Humans

KW - Immunohistochemistry

KW - Lymphocytes/pathology

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Prognosis

KW - Programmed Cell Death 1 Receptor/metabolism

KW - Sezary Syndrome/immunology

KW - Skin/pathology

KW - Skin Neoplasms/immunology

U2 - 10.1111/bjd.13832

DO - 10.1111/bjd.13832

M3 - SCORING: Journal article

C2 - 25864856

VL - 173

SP - 93

EP - 105

JO - BRIT J DERMATOL

JF - BRIT J DERMATOL

SN - 0007-0963

IS - 1

ER -