Blood classification and blood response criteria in mycosis fungoides and Sézary syndrome using flow cytometry: recommendations from the EORTC cutaneous lymphoma task force

Scarisbrick, Julia; Hodak, Emmilia; Bagot, Martine; Stranzenbach, René; Stadler, Rudolf; Ortiz‐Romero, Pablo L.; Papadavid, Evangelia; Evison, Felicity; Knobler, Robert; Quaglino, Pietro; Vermeer, Maarten H.

doi:10.1016/j.ejca.2018.01.076

Cited by 115 publications

(193 citation statements)

References 27 publications

(30 reference statements)

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“…In this prospective study, patients with clinical features consistent with CTCL were referred to our laboratory at the time of initial diagnosis by the dermatology department at Hospital Saint‐Louis between March 2014 and February 2019. Diagnosis was made using ISCL/EORTC criteria and the recently published EORTC criteria, after correlation of the clinical, histological and molecular characteristics . ‘Sézary’ refers here to T4 and B2 (stage IV), namely the presence of an identical T‐cell clone evidenced in blood and skin with: (i) expanded CD4 + T cells with either CD4 + CD26 – ≥ 30%, or CD4 + CD7 – ≥ 40%, or CD4/CD8 ratio ≥ 10; (ii) SCs ≥ 1000 μL −1 on blood smear; or (iii) either CD4 + CD7 – or CD4 + CD26 – T cells ≥ 1000 μL −1 .…”

Section: Methodsmentioning

confidence: 99%

Revisiting the initial diagnosis and blood staging of mycosis fungoides and Sézary syndrome with the KIR 3 DL 2 marker

et al. 2019

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Summary Background The early diagnosis of Sézary syndrome (SS) is challenging. Loss of CD7 and CD26 expression on CD4+ T cells is the currently used criterion in the initial diagnosis and staging of patients with SS. Objectives Our aim was to evaluate the respective value of CD26, CD7 and KIR3DL2 expression on CD4+ T cells and total lymphocytes at initial diagnosis of SS. Methods This prospective study included 254 patients with clinical features consistent with cutaneous T‐cell lymphoma seen at our institution between March 2014 and February 2019. Peripheral blood analysis by flow cytometry was performed for each patient at the time of diagnosis and during follow‐up. The diagnosis of SS was based on ISCL/EORTC criteria. Results The presence of KIR3DL2+ Sézary cells (SCs) ≥ 200 μL−1 correlated with the diagnosis of SS, with sensitivity of 88·6% and specificity of 96·3%. All 154 patients with either inflammatory skin disease or other haematological disease had KIR3DL2+ cells < 200 μL−1, while eight of them had CD4+ CD26− T cells ≥ 1000 μL−1. Of five patients with SS and lymphopenia, four had CD4+ CD7− T cells < 1000 μL−1 and three had CD4+ CD26− T cells < 1000 μL−1. However, all of them had KIR3DL2+ CD4+ T cells ≥ 200 μL−1. Among patients with available samples during evolution, all B1‐staged patients with ≥ 200 μL−1 KIR3DL2+ SCs at diagnosis evolved to B2 stage within 7 months. Conclusions KIR3DL2 expression on T cells is highly specific and helps the early diagnosis of SS, especially in those patients with lymphopenia. What's already known about this topic? In the ISCL/EORTC cutaneous T‐cell lymphoma (CTCL) categorization of blood involvement (B0–B2), B2 is defined as a T‐cell receptor clonal rearrangement in blood, associated with high blood‐smear Sézary cell (SC) count. Flow cytometry was developed to circumvent interobserver variability of SC manual counts; however, it mostly relies on detection of cells lacking CD7 and/or CD26 expression. We previously reported the reliability of KIR3DL2 as the first positive SC marker. What does this study add? Based on our analysis of 254 patients, we propose that KIR3DL2 be added to the ISCL/EORTC criteria for initial diagnosis of Sézary syndrome (SS) and B2 staging. This marker improved sensitivity of SS B2‐stage CTCL diagnosis with a specificity > 95%, especially for patients with lymphopenia. We found KIR3DL2 helped early diagnosis of SS and was more reliable than CD26 in assessing blood tumour burden during therapy. What is the translational message? SC quantification is the major means of staging at initial diagnosis and monitoring blood tumour burden in a clinical trials setting. We recommend using a threshold value of KIR3DL2+ SCs ≥ 200 μL−1 or KIR3DL2+ SCs/lymphocytes ≥ 10% in the diagnostic criteria of SS and propose a novel algorithm for CTCL B2 blood staging.

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Section: Methodsmentioning

confidence: 99%

Revisiting the initial diagnosis and blood staging of mycosis fungoides and Sézary syndrome with the KIR 3 DL 2 marker

et al. 2019

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“…Our cases raise the question whether immunosuppression related to advanced CTCL 26 may be associated with increased risk of MCC, as has been shown for other forms of immunosuppression .2 One patient in our series developed MCC in the setting of stage IVA 1 SS. [27][28][29][30][31] This patient's advanced CTCL may have been associated with immunosuppression . 2 The other patient in our case series had low stage MF at the time of MCC diagnosis, therefore an association with immunosuppression is less clear in this case.…”

Section: Discussionmentioning

confidence: 99%

Merkel cell carcinoma arising in association with cutaneous T‐cell lymphoma: A potential diagnostic pitfall

et al. 2019

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Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma with increased prevalence in patients with immunosuppression or B‐cell neoplasms. To the best of our knowledge, an association with cutaneous T‐cell lymphoma (CTCL) has not been previously described. In this report, we present two cases of MCC arising in the setting of CTCL. The first case was a female during her 70s with previously diagnosed stage IVA1 Sezary syndrome. Biopsy of a scaly patch showed two distinct abnormal cell populations. The first population consisted of hyperchromatic dermal and epidermotropic lymphocytes, expressing CD3 and CD4 with diminished CD7. The second population consisted of intraepidermal clusters of larger atypical cells that expressed synaptophysin, neurofilament, CK20, and Merkel cell polyomavirus transcript. The combination of findings was consistent with intraepidermal MCC in a background of CTCL. Excision showed residual intraepidermal MCC without dermal involvement. The second case was a male during his 50s with a longstanding history of mycosis fungoides, who presented with a new lesion on his right thigh. Biopsy and excision showed dermal MCC without secondary involvement by CTCL. Our cases show that MCC may rarely occur in the setting of T‐cell lymphoma, and that intraepidermal MCC may mimic epidermotropic T‐cells.

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“…One established criterion for B2 is an absolute count of 1000 Sézary cells/μL plus evidence of a T‐cell clone to exclude occasional erythrodermic inflammatory dermatoses (EID) with high numbers of non‐neoplastic atypical lymphocytes. Other criteria are based on flow cytometry and include an expanded population of clonal T‐cells resulting in a CD4/CD8 ratio ≥10 or an absolute count of CD4 + CD7− or CD4 + CD26− lymphocytes ≥1000/μL . In addition to molecular genetic evidence of a clone, blood involvement can be confirmed by the presence of very large Sézary cells (cell diameter >14 μm), cytogenetic abnormalities, and T‐cells with diminished expression levels of CD3 or restricted expression of T‐cell receptor Vβ …”

Section: Introductionmentioning

confidence: 99%

“…population of clonal T-cells resulting in a CD4/CD8 ratio ≥10 or an absolute count of CD4 + CD7− or CD4 + CD26− lymphocytes ≥1000/μL. [3][4][5] In addition to molecular genetic evidence of a clone, blood involvement can be confirmed by the presence of very large Sézary cells (cell diameter >14 μm), cytogenetic abnormalities, and Tcells with diminished expression levels of CD3 or restricted expression of T-cell receptor Vβ. 6 The histopathologic features of E-CTCL have been extensively studied with comparison of SS to pre-SS,* 7 E-CTCL to typical MF, 8,9 and E-CTCL to EID.…”

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confidence: 99%

A histo‐immunopathologic and prognostic study of erythrodermic cutaneous T‐cell lymphoma

Vonderheid

Kantor²,

Telang

et al. 2019

J Cutan Pathol

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Background Sézary syndrome (SS) and erythrodermic mycosis fungoides (E‐MF) represent two expressions of erythrodermic cutaneous T‐cell lymphoma (E‐CTCL). Methods Histopathologic features were compared on skin specimens from 41 patients with SS and 70 patients with E‐MF. Immunopathologic findings were compared on 42 SS and 79 E‐MF specimens. Results Specimens of SS usually showed band‐like dermal infiltrates with intermediate‐sized lymphoid cells and few plasma cells; on the other hand E‐MF more often had a perivascular infiltrative pattern, predominance of small/mixed lymphoid cells and eosinophils. SS also had lower numbers of CD8+ cells and higher numbers of CD62L+ cells compared to E‐MF. For E‐MF patients, the presence of large Pautrier collections, infiltrates with intermediate‐sized cells, increased number of mitotic figures and ≥50% CD62L+ cells in the dermal infiltrate correlated with a relatively poor disease‐specific survival. However, only the presence of mitotic figures retained prognostic significance with clinical stage as a covariate. Conclusions Clinical stage provides the most important prognostic information for patients with E‐CTCL. However, mitotic activity for E‐MF and CD8+ cells <20% for SS have additional value. We hypothesize that observed differences in plasma cell and eosinophil numbers may reflect the influence of CD62L+ central memory T‐cells in the microenvironment.

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Blood classification and blood response criteria in mycosis fungoides and Sézary syndrome using flow cytometry: recommendations from the EORTC cutaneous lymphoma task force

Cited by 115 publications

References 27 publications

Revisiting the initial diagnosis and blood staging of mycosis fungoides and Sézary syndrome with the KIR 3 DL 2 marker

Revisiting the initial diagnosis and blood staging of mycosis fungoides and Sézary syndrome with the KIR 3 DL 2 marker

Merkel cell carcinoma arising in association with cutaneous T‐cell lymphoma: A potential diagnostic pitfall

A histo‐immunopathologic and prognostic study of erythrodermic cutaneous T‐cell lymphoma

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