IL-10, IL-13, Eotaxin and IL-10/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas

Arianna Di Napoli,Marshall E Kadin,Adriana Bonifacino,Enrico Giarnieri,Giorgia Scafetta,Alessandro Gulino,Daniele Greco,Luigi Aurisicchio,Francesca Ascenzi,John Morgan,Fabio Santanelli Di Pompeo,Rita Mancini

doi:10.1007/s00262-020-02778-3

Abstract

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is an uncommon peripheral T cell lymphoma usually presenting as a delayed peri-implant effusion. Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo/monoclonal expansion of CD30 + cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL.

Highlights

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a provisional entity recently introduced in the revised version of the WHO classification of lymphoid malignancy [1]
We simultaneously analyzed the concentrations of 45 different cytokines, chemokines and growth factors in the supernatant of 32 late seromas, including 12 BI-ALCL and 20 benign reactive seromas (RS), and in the supernatant of 7 T-cell lymphoma cell lines (T-TCL) using a multiplex assay
Only IL-10, IL-13 and Eotaxin remained significantly more expressed in BI-ALCL when compared to each of the three different types of RS (Fig. 2b–d)

Summary

Introduction

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a provisional entity recently introduced in the revised version of the WHO classification of lymphoid malignancy [1]. Aspirated effusions must undergo microbiological culture, cytomorphological examination, immunocytochemistry for CD30 expression and sometimes analysis of T-cell receptor genes rearrangement to confirm clonality of the T-cell population. This approach allows an early diagnosis and avoids local and lymph node metastasis of tumor cells [3, 4]. Higher levels of soluble interleukin (IL) 9, IL-10, IL-13, IL-22, and/or IFN-γ have been detected in malignant seromas than in benign seromas [8] This prompted us to further validate these results and to investigate the existence of a possible BI-ALCL-associated cytokine signature by applying a highly multiplex immuno-based assay to late seromas, including, besides BI-ALCL, different types of reactive effusions

Methods

Results

Conclusion