Bright PD-1 expression by flow cytometry is a powerful tool for diagnosis and monitoring of angioimmunoblastic T-cell lymphoma

Yabe, Mariko; Gao, Qi; Özkaya, Neval; Huet, Sarah; Lewis, Natasha; Pichardo, Janine; Moskowitz, Alison J.; Horwitz, Steven M.; Doğan, Ahmet; Roshal, Mikhail

doi:10.1038/s41408-020-0301-x

Cited by 12 publications

(11 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the contrary, FCI missed the involvement in only one sample due to hemodilution and focal involvement. Earlier studies have also reported similar findings ( 87 , 100 ). These observations highlighted the critical value of FCI for the assessment of BM involvement for correct clinical staging in T-NHL.…”

Section: Discussionsupporting

confidence: 85%

See 1 more Smart Citation

Critical Role of Flow Cytometric Immunophenotyping in the Diagnosis, Subtyping, and Staging of T-Cell/NK-Cell Non-Hodgkin’s Lymphoma in Real-World Practice: A Study of 232 Cases From a Tertiary Cancer Center in India

et al. 2022

View full text Add to dashboard Cite

BackgroundT-cell/NK-cell non-Hodgkin’s lymphoma (T/NK-NHL) is an uncommon heterogeneous group of diseases. The current classification of T/NK-NHL is mainly based on histopathology and immunohistochemistry. In practice, however, the lack of unique histopathological patterns, overlapping cytomorphology, immunophenotypic complexity, inadequate panels, and diverse clinical presentations pose a great challenge. Flow cytometric immunophenotyping (FCI) is a gold standard for the diagnosis, subtyping, and monitoring of many hematological neoplasms. However, studies emphasizing the role of FCI in the diagnosis and staging of T/NK-NHL in real-world practice are scarce.MethodsWe included T-cell non-Hodgkin’s lymphoma (T-NHL) patients evaluated for the diagnosis and/or staging of T/NK-NHL using FCI between 2014 and 2020. We studied the utility of FCI in the diagnosis and subtyping of T/NK-NHL and correlated the FCI findings with the results of histopathology/immunohistochemistry. For correlation purposes, patients were categorized under definitive diagnosis and subtyping, inadequate subtyping, inadequate diagnosis, and misdiagnosis based on the findings of each technique.ResultsA total of 232 patients were diagnosed with T/NK-NHL. FCI findings provided definitive diagnoses in 198 patients and subtyping in 187/198 (95.45%) patients. The correlation between FCI and histopathological/immunohistochemistry results (n = 150) demonstrated an agreement on the diagnosis and subtyping in 69/150 (46%) patients. Of the remaining cases, the diagnosis and subtyping were inadequate in 64/150 (42.7%), and 14/150 (9.33%) were misdiagnosed on histopathology/immunohistochemistry results. FCI provided definitive diagnosis and subtyping in 51/64 (79.7%) patients. Among these, 13 patients diagnosed with peripheral T-cell lymphoma not-otherwise-specified were reclassified (angioimmunoblastic T-cell lymphoma (AITL)-11 and prolymphocytic leukemia-2) on FCI. It corrected the diagnosis in 14 patients that were misdiagnosed (6 B-cell NHL (B-NHL), 3 Hodgkin’s lymphoma, 1 acute leukemia, and 1 subcutaneous panniculitis-like T-cell lymphoma) and misclassified (3 T-NHL) on histopathological results. AITL was the commonest T-NHL misclassified on histopathological results. FCI also confirmed the definite involvement in 7/83 (8.4%) and 27/83 (32.5%) bone marrow (BM) samples reported as suspicious and uninvolved, respectively, on histopathological evaluation.ConclusionAITL was the most frequently diagnosed T/NK-NHL in this study. FCI provided a distinct advantage in detecting BM involvement by T/NK-NHL, especially in patients with low-level involvement. Overall, our study concluded that FCI plays a critical role in the diagnosis, subtyping, and staging of T/NK-NHL in real-world practice.

show abstract

Section: Discussionsupporting

confidence: 85%

“…These markers are commonly included in the FCI panel. Hence, FCI can easily distinguish AITL tumor cells in the reactive lymphoid proliferations and helps in diagnosing AITL correctly (26,(85)(86)(87).…”

Section: Discussionmentioning

confidence: 99%

Critical Role of Flow Cytometric Immunophenotyping in the Diagnosis, Subtyping, and Staging of T-Cell/NK-Cell Non-Hodgkin’s Lymphoma in Real-World Practice: A Study of 232 Cases From a Tertiary Cancer Center in India

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Only 16% of patients with lung cancer are diagnosed in the early stages of the disease, 85% of the cases are of the non-small cell type (NSCLC), which promote the evasion strategy of the immune system to generate immunosuppressive environments to systemic level [ 78 ]. The expression of programmed cell death protein 1 (PD-1), by FCM, has been essential to establishing the initiation of therapy with blocking mAbs of PD-1 or PD-L1, and thus, improve the response of the immune system against tumour cells and improve the quality of life of patients [ 79 , 80 ].…”

Section: Use Of Flow Cytometry In the Diagnosis Of Respiratory Dismentioning

confidence: 99%

Flow Cytometry: From Experimental Design to Its Application in the Diagnosis and Monitoring of Respiratory Diseases

Flores‐González

Cancino‐Díaz

Chávez‐Galán

2020

IJMS

View full text Add to dashboard Cite

Recent advances in the field of flow cytometry (FCM) have highlighted the importance of incorporating it as a basic analysis tool in laboratories. FCM not only allows the identification of cell subpopulations by detecting the expression of molecules in the cell membrane or cytoplasm, but it can also quantify and identify soluble molecules. The proper functioning of the FCM requires six fundamental systems, from those related to the transport of events to the systems dedicated to the analysis of information. In this review, we have identified the main considerations that every FCM user must know for an optimal antibody panel design, the quality systems that must govern the FCM protocols to guarantee reproducible results in research or clinical laboratories. Finally, we have introduced the current evidence that highlights the relevance of FCM in the investigation and clinical diagnosis of respiratory diseases, establishing important advances in the basic and clinical study of diseases as old as Tuberculosis along with the recent proposals for the monitoring and classification of patients infected with the new SARS-CoV2 virus.

show abstract

“…It is expressed in T cells, some B cells and a subset of myeloid cells upon activation (Fife & Pauken, 2011; Francisco et al, 2010) and in certain cell types, like T follicular helper cells, at constitutively high levels (Crotty, 2011). Although studies have demonstrated increased PD‐1 expression in MF/SS (Bosisio & Cerroni, 2015; Cetinözman et al, 2012; Çetinözman et al, 2014; Horna et al, 2019; Kantekure et al, 2012; Murray et al, 2019; Nguyen et al, 2017; Novelli et al, 2015; Park et al, 2014; Samimi et al, 2010; Saulite et al, 2020; Wada et al, 2011; Yabe et al, 2020), most were limited to immunohistochemical evaluation of skin biopsies. Such studies suffered from difficulties in definitively characterizing tumor cells due to admixed reactive inflammatory cells and differing thresholds for defining positivity, consequently showing conflicting results (Bosisio & Cerroni, 2015; Cetinözman et al, 2012; Çetinözman et al, 2014; Kantekure et al, 2012; Nguyen et al, 2017; Park et al, 2014; Wada et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Such studies suffered from difficulties in definitively characterizing tumor cells due to admixed reactive inflammatory cells and differing thresholds for defining positivity, consequently showing conflicting results (Bosisio & Cerroni, 2015; Cetinözman et al, 2012; Çetinözman et al, 2014; Kantekure et al, 2012; Nguyen et al, 2017; Park et al, 2014; Wada et al, 2011). Large scale studies evaluating PD‐1 by flow cytometry in circulating Sezary cells identified by composite immunophenotype are rare (Horna et al, 2019; Murray et al, 2019; Novelli et al, 2015; Yabe et al, 2020) and none to our knowledge have comprehensively assessed the utility of PD‐1 in the context of established markers for accurate Sezary cell detection. In addition, a recent international guideline could not reach a consensus on whether to recommend PD‐1 for Sezary cell evaluation by flow cytometry, likely due to limited experience with this maker in many laboratories (Horna, Wang, et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

PD‐1 improves accurate detection of Sezary cells by flow cytometry in peripheral blood in mycosis fungoides/Sezary syndrome

Lewis

Gao

Petrova‐Drus

et al. 2022

Cytometry Part B Clinical

Self Cite

View full text Add to dashboard Cite

Background Accurate Sezary cell detection in peripheral blood of mycosis fungoides/Sezary syndrome (MF/SS) patients by flow cytometry can be difficult due to overlapping immunophenotypes with normal T cells using standard markers. We assessed the utility of programmed death‐1 (PD‐1/CD279), a transmembrane protein expressed in some hematopoietic cells, for identification and quantitation of circulating Sezary cells among established markers using flow cytometry. Methods 50 MF/SS and 20 control blood samples were immunophenotyped by flow cytometry. Principal component analysis (PCA) assessed contributions of antigens to separation of abnormal from normal T cell populations. PD‐1 was assessed over time in blood and bone marrow of available MF/SS cases. Results Normal CD4+ T cells showed dim/intermediate to absent PD‐1 expression. PD‐1 in Sezary cells was informatively brighter (≥1/3 log) than internal normal CD4+ T cells in 39/50 (78%) cases. By PCA, PD‐1 ranked 3rd behind CD7 and CD26 in population separation as a whole; it ranked in the top 3 markers in 32/50 (64%) cases and 1st in 4/50 (8%) cases when individual abnormal populations were compared to total normal CD4+ T cells. PD‐1 clearly separated Sezary from normal CD4+ T cells in 15/26 (58%, 30% of total) cases with few and subtle alterations of pan‐T cell antigens/CD26 and was critical in 6 (12% of total), without which identification and quantification were significantly affected or nearly impossible. PD‐1 remained informative in blood/bone marrow over time in most patients. Conclusions PD‐1 significantly contributes to accurate flow cytometric Sezary cell assessment in a routine Sezary panel.

show abstract

Bright PD-1 expression by flow cytometry is a powerful tool for diagnosis and monitoring of angioimmunoblastic T-cell lymphoma

Cited by 12 publications

References 13 publications

Critical Role of Flow Cytometric Immunophenotyping in the Diagnosis, Subtyping, and Staging of T-Cell/NK-Cell Non-Hodgkin’s Lymphoma in Real-World Practice: A Study of 232 Cases From a Tertiary Cancer Center in India

Critical Role of Flow Cytometric Immunophenotyping in the Diagnosis, Subtyping, and Staging of T-Cell/NK-Cell Non-Hodgkin’s Lymphoma in Real-World Practice: A Study of 232 Cases From a Tertiary Cancer Center in India

Flow Cytometry: From Experimental Design to Its Application in the Diagnosis and Monitoring of Respiratory Diseases

PD‐1 improves accurate detection of Sezary cells by flow cytometry in peripheral blood in mycosis fungoides/Sezary syndrome

Contact Info

Product

Resources

About