Cutaneous T-cell lymphoma (CTCL): Current practices in blood assessment and the utility of T-cell receptor (TCR)-Vβ chain restriction

Abstract

Background Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T cell lymphoma (CTCL) is important for early detection, prognosis, and monitoring disease burden. Objective Determine the spectrum of current clinical practices; critically evaluate elements of current ISCL B1 and B2 staging criteria; and assess the potential role of TCR-Vβ analysis by flow cytometry. Methods We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, PPV, and NPV of parameters for ISCL B2 staging. Results There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture five Yale cohort patients with immunophenotypic abnormalities who later progressed. TCR-Vβ testing was more specific than PCR and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. Limitations Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. Conclusion We propose further study of “modified B1 criteria”: CD4/CD8 ratio ≥5, %CD4+/CD26- ≥ 20%, %CD4+/CD7- ≥ 20%, with evidence of clonality. TCR-Vβ testing should be considered in future diagnostic and staging algorithms.

Single-cell heterogeneity in Sézary syndrome

“…Malignant T cells were identified by their expression of a dominant TCRVb clone (SS6, SS8, SS9, SS10, and SS11) and their characteristic low expression of CD7 and/or CD26. 12,13 In accordance with the Declaration of Helsinki, the samples were obtained with informed consent after approval by the Committee on Health Research Ethics (H-16025331).…”

“…Dead cells were removed using 7-amino-actinomycin D, and after demultiplexing, malignant cells were gated based on low expression of CD7 and/or CD26. 12,13 The 240 screened surface markers were filtered as "expressed" by having at least 10% of cells from at least 1 patient expressing more than the median fluorescence intensity (MFI) of the isotype plus 10 standard deviations (SDs) of the isotype: MFI 90% quantile . (MFI Isotype 1 10 3 SD Isotype ).…”

“…[7][8][9][10][11] Malignant SS cells often exhibit abnormal expression of T-cell surface markers and can be isolated on the basis of their clonal T-cell receptor (TCR) or their characteristic low expression of CD7 and/or CD26. 12,13 On the basis of their presence in the blood and lymph nodes and their expression of distinct surface markers such as CD197 (CCR7), CD27, and CD62L (L-selectin), SS cells are suspected to derive from transformed central memory T (T CM ) cells. 14 However, studies have found that although the majority of malignant cells from most patients with SS do exhibit a T CM surface phenotype, some malignant cells express surface markers inconsistent with the T CM phenotype, such as high levels of CD45RA.…”

FISH Panel for Leukemic CTCL

“…FISH technology particularly suits CTCL, a cancer whose mutational landscape is characterized by a preponderance of gene copy number amplifications and deletions compared to single nucleotide variants relatively overrepresented in many other forms of cancer. In this study, we used the 11-probe panel to assess for genetic abnormalities in sorted or unsorted peripheral blood from 24 patients (patient characteristics in Supplementary Materials) with a range of disease presentations including SS, patch/plaque mycosis fungoides (MF), follicular mycosis fungoides (F-MF), tumor-stage mycosis fungoides, and follicular mucinosis –with evidence of blood involvement (Gibson et al , 2016). …”

Cutaneous T-cell lymphomas: modern data of pathogenesis, clinics and therapy

“…Впоследнеевремя,согласнорекомендациямНациональногоонкологическогообщества,дляпостанов-кидиагнозаТКЛКпроводитсябиопсияпатологических участковкожиспоследующимгистоморфологическим, иммуногистохимическимимолекулярно-генетическим анализом(трансформациягенаTCR).Осмотрипальпация кожи остаются основными при подозрении наТКЛК.ОбязательнойявляетсяпальпацияЛУ [24,81,84].Достаточночастодляпостановкиокончательного диагнозаТКЛКпоказанопроведениесериибиопсий, таккакморфологическиеифенотипическиепризнаки ТКЛКвариабельныиприоднократнойбиопсиисуществуетрискнеправильногодиагноза [32,33,81,84,85]. ИдентификациязлокачественныхклетоквПКпаци-ентовсТКЛКнеоценимадлядиагностикиипрогноза СС на ранних стадиях [86,87]. Однако анализ крови имеетограниченнуюценностьиз-заотсутствияточного высокочувствительного маркера для диагностики клетокСезари.Внастоящеевремяотсутствиемаркеров СD7и / илиCD26наСD4-клеткахявляетсясуррогатнымпоказателемзлокачественности.Лактатдегидрогеназаявляетсянеспецифическиммаркеромопухолевой нагрузки и указывает на неблагоприятный прогноз ТКЛК [24,29,88].…”