Two cases suggest Tropheryma whipplei as a causative agent of pulmonary marginal zone lymphoma (original) (raw)
2024, Research Square (Research Square)
Background Marginal zone lymphomas of mucosa-associated lymphatic tissues (MZL of MALT) are a group of indolent B-cell neoplasms, which are thought to arise from chronic antigenic stimulation of B-cells either due to underlying chronic infection or autoimmune disease. Little is known about potential causative pathogens in pulmonary MZL (PMZL), although some data suggests a potential role of Achromobacter (A.) xylosoxidans. Methods An index case of chronic pulmonary colonisation with Tropheryma (T.) whipplei and subsequent development of PMZL was identi ed by T. whipplei speci c PCR and metagenomics whole genome sequencing (WGS). This case prompted a retrospectively conducted analysis of T. whipplei-speci c PCRs in lung tissue from PMZL patients (n = 22), other pulmonary lymphomas, and normal controls. Positive results were con rmed by metagenomics WGS. A systematic search for T. whipplei and A. xylosoxidans in our in-house metagenomics WGS dataset comprising autopsy lungs, lung biopsies and lung resection specimens (n = 181) was subsequently performed. Results A 69-year-old patient presented with weight loss and persistent pulmonary consolidation. Subsequent metagenomics WGS analysis detected T. whipplei in the resected lung specimen. An antibiotic regimen eventually eliminated the bacterium. However, the consolidation persisted, and the diagnosis of PMZL was made in a second lung resection specimen. A second case of T. whipplei-associated PMZL was subsequently detected in the retrospectively analysed PMZL cohort. Both cases showed comparatively few mutations and no mutations in genes encoding for NF-κB pathway components, suggesting that T. whipplei infection may substitute for mutations in these PMZL. None of the samples in our in-house dataset tested positive for T. whipplei. In contrast, A. xylosoxidans was frequently found in both autopsy lungs and lung biopsy / resection specimens that were not affected by PMZL (> 50%). Conclusions Our data suggests that T. whipplei colonisation of lungs may trigger PMZL as a potential driver. Systematic analyses with larger cohorts should be conducted to further support this hypothesis. The frequent detection of A. xylosoxidans in lung tissue suggests that it is a common component of the pulmonary microbiome and therefore less likely to trigger lymphomas.
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