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.

Bhausaheb Bagal,Dhanalaxmi Shetty,Sweta Rajpal,Tushar Agrawal,Gaurav Chatterjee,Twinkle Khanka,Hasmukh Jain,Niharika Dasgupta,Anumeha Chaturvedi,Papagudi Ganesan Subramanian ,Karishma Girase,Nilesh Deshpande,Tanuja Shet,Prashant Tembhare ,Nikhil Patkar,Shefali Verma,Sumeet Gujral,Manju Sengar,Sridhar Epari,Sitaram Ghogale

doi:10.3389/fonc.2022.779230

Abstract

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.

Highlights

T-cell non-Hodgkin’s lymphoma (T-NHL) is a heterogeneous group of aggressive NHL arising from T-cell and NK-cell subsets accounting for approximately 10%–15% of all NHLs [1–3]
Patients diagnosed with mature T-/NK-cell neoplasms were identified from the electronic medical records (EMRs) of Tata Memorial Center (TMC), India
The final diagnosis and subtyping were made in accordance with WHO 2008 and 2016 hematolymphoid classification based on the available details on clinical presentation, cytomorphological and histopathological features, immunophenotypic data, radiological features, and genetic findings [66, 67]

Summary

Introduction

T-cell non-Hodgkin’s lymphoma (T-NHL) is a heterogeneous group of aggressive NHL arising from T-cell and NK-cell subsets accounting for approximately 10%–15% of all NHLs [1–3]. The diagnosis and subtyping of T-cell/NK-cell NHL (T/NK-NHL) heavily rely on a multifactorial approach that includes clinical presentation, morphology, immunophenotype, and chromosomal abnormalities [4]. The treatment regimens for T-NHL has seen great improvements with the availability of newer agents such as denileukin diftitox, brentuximab vedotin, pralatrexate, alemtuzumab, vorinostat, and romidepsin [5–8]. In middle- or low-income countries with limited resources, the prognosis of lymphoma, which can vary between the subtypes of T/NK-NHL, can help in prioritizing the available resources [11, 12]. T-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. The lack of unique histopathological patterns, overlapping cytomorphology, immunophenotypic complexity, inadequate panels, and diverse clinical presentations pose a great challenge. Studies emphasizing the role of FCI in the diagnosis and staging of T/NK-NHL in real-world practice are scarce

Methods

Results

Conclusion