The value of five blood markers in differentiating mycosis fungoides and Sézary syndrome: a validation cohort*

Abstract

Summary Background Clinical and histological diagnosis of Sézary syndrome (SS) and mycosis fungoides (MF) is challenging in clinical routine. Objectives We investigated five blood markers previously described for SS (T‐plastin, Twist, KIR3DL2, NKp46 and Tox) in a prospective validation cohort of patients. Methods We included 447 patients in this study and 107 patients were followed up for prognosis. The markers were analysed by reverse transcriptase quantitative real‐time polymerase chain reaction (RT‐qPCR) on peripheral blood leucocytes and CD4+ T cells in a cohort of consecutive patients with early MF, erythrodermic MF and SS and compared with patients presenting with benign inflammatory dermatoses (BID) and erythrodermic BID. The markers were assessed in parallel to gold standard values such as CD4/CD8 ratio, loss of CD7 and CD26 membrane expression and CD4 absolute values. Sensitivity and specificity were analysed by receiver operator characteristic curves. The prognostic value of selected markers was analysed on a subset of patients. This study was conducted in one centre. Results We defined cut‐off values for each marker. T‐plastin, Twist and KIR3DL2 had the best validity. SS may be overrepresented. The combination of T‐plastin and Twist was able to differentiate between erythrodermic MF or BID and SS. The additional analysis of KIR3DL2 may be useful to predict the prognosis. Conclusions We propose T‐plastin, Twist and KIR3DL2 measured by RT‐qPCR as new diagnostic markers for Sézary syndrome.

Mycosis fungoides and Sézary syndrome

“…In addition to circulating Sézary cells, the blood also shows an increased absolute number of CD4 + T lymphocytes resulting in a shifted/increased CD4 + :CD8 + ratio. The percentage of CD4 + /CD7 – and CD4 + /CD26 – circulating T cells is determined to assess tumor blood burden, and recently threshold values for absolute tumor cell counts have been discussed – especially for evaluating therapeutic success [ 63 , 64 ]. Since the clinical presentation and histopathology may sometimes be non‐specific, it is essential to evaluate peripheral blood involvement and the medical history in order to differentiate between erythrodermic MF and SS.…”

“…Recent studies have described new biomarkers such as PD‐1 (CD279), KIR3DL2 (CD158k), T‐plastin and Twist. These should facilitate differentiation between SS and benign erythrodermic dermatoses both in the skin and peripheral blood [ 5 , 64 ].…”

Mycosis fungoides und Sézary‐Syndrom

“…Zusätzlich zu zirkulierenden Sézary‐Zellen im Blut finden sich auch eine absolut erhöhte CD4 + T‐Lymphozytenzahl und eine daraus resultierende erhöhte CD4 + /CD8 + ‐Ratio. Einerseits wird der Prozentsatz CD4 + /CD7 – und CD4 + /CD26 – zirkulierender T‐Zellen ermittelt, um das Ausmaß der Blutbeteiligung zu erfassen und seit kurzem werden hierfür auch Schwellenwerte absoluter Zellzahlen (auch in Hinblick auf die Beurteilung des therapeutischen Erfolges) diskutiert [63, 64]. Für die Differenzierung zwischen erythrodermatischer MF und SS bei mitunter unspezifischer Klinik und Histopathologie ist die Erfassung der peripheren Blutbeteiligung und die Anamnese für die Diagnose des SS entscheidend.…”

“…Laut aktueller Klassifikation muss mindestens eines der folgenden Kriterien vorhanden sein, um ein SS zu diagnostizieren: eine absolute Sézary‐Zellzahl von > 1000/μl oder eine erhöhte CD4 + ‐T‐Zellpopulation, ein CD4 + /CD8 + ‐Verhältnis ≥ 10, CD4 + /CD7 – ‐Zellen ≥ 40 % oder CD4 + /CD26 – ‐Zellen ≥ 30 %. Rezente Studien haben neue Biomarker beschrieben wie PD‐1 (CD279), KIR3DL2 (CD158k), T‐Plastin und Twist, die wiederum eine Differenzierung zwischen SS und benignen erythrodermatischen Dermatosen sowohl in der Haut als auch in peripherem Blut erleichtern sollen [5, 64].…”

The time for new biomarkers in mycosis fungoides/Sézary syndrome is here

“…In this issue, Dobos et al . publish a large study of almost 450 patients with early MF, eMF, SS, BID and eBID 9 . Definition of the cases is at least controversial, as patients with eMF were defined as ‘having tumoral stage (T3 involvement) or at least 80% of body surface area affected and B0–B1 involvement’, and patients with SS as ‘having B2 involvement by the time of blood sampling’.…”