High-Throughput Molecular Characterization of the Microbiome in Breast Implant-Associated Anaplastic Large Cell Lymphoma and Peri-Implant Benign Seromas

乳腺植入物相关间变性大细胞淋巴瘤和植入物周围良性血清瘤微生物组的高通量分子表征

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Abstract

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a mature T-cell lymphoma linked to textured breast implants. A leading hypothesis suggests that chronic inflammation, combined with immunological and genetic factors, drives its pathogenesis. Two previous studies investigating bacterial biofilms on breast implant capsules have produced conflicting results, particularly regarding the enrichment of Ralstonia spp. Methods: We analyzed the microbiota profiles in seroma samples from 10 BIA-ALCL patients and 12 patients with non-neoplastic effusion, subclassified into acute-, mixed-, and chronic-type based on cellular composition. We used two metagenomic approaches: 16S rRNA gene sequencing and Nanopore sequencing with the "What's in My Pot?" (WIMP) taxonomic classifier. Our analyses included alpha and beta diversity metrics, as well as comparisons of Gram status and oxygen requirements. Results: Both sequencing methods identified Staphylococcaceae, Propionibacteriaceae, and Bradyrhizobiaceae as the most prevalent bacterial families in both BIA-ALCL and benign seroma samples. Notably, the Burkholderiaceae family was more abundant in some of the benign seromas according to the 16S rRNA sequencing, but Ralstonia spp. were not detected. BIA-ALCL showed higher richness (based on Nanopore data) and higher evenness (based on 16S rRNA data) compared to acute-type seromas, indicating a more homogenous representation of the different taxa identified. BIA-ALCL seromas did not cluster together based on Nanopore data, but they did form a distinct cluster with 16S rRNA data. This cluster was differentiated from the other two clusters by a relatively balanced presence of multiple families without overt dominance. We observed no significant differences in Gram staining between BIA-ALCL and benign samples using either method. However, non-aerobic bacterial families were enriched in BIA-ALCL cases only when analyzed with the Nanopore pipeline. Conclusions: Overall, our findings did not identify a distinctive microbial signature specifically associated with BIA-ALCL.

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