Association Between <scp><i>Moraxella catarrhalis</i></scp> and Nodular Lymphocyte‐Predominant Hodgkin Lymphoma

Nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) may be an antigen-driven malignancy. Recent studies demonstrated that in NLPHL patients, lymphoma B-cell receptor can bind proteins derived from Moraxella catarrhalis (MC) and Rothia mucilaginosa (RM). We examined whether MC and RM can be detected in NLPHL lymph nodes. The presence of MC DNA and RNA was tested by polymerase chain reaction (PCR) and RNAScope in situ hybridization (ISH), respectively. The presence of RM DNA was tested by PCR. We demonstrated the presence of MC DNA in 29 of 49 (59.2%) NLPHL patient tumor samples and RNA in 14 of 39 biopsies (35.9%), with good concordance between the assays, considering lower RNA stability in older biopsies and lower sensitivity of ISH compared to PCR. In comparison, 36 lymph nodes with follicular hyperplasia and a specimen with tubular adenoma were negative for MC by PCR, and only 6 of 37 non-NLPHL lymphoma tissues (16.2%) were positive for detection of MC by PCR, demonstrating a statistically higher detection rate of MC in patients with NLPHL (p = 0.00006). MC was detected in NLPHL samples at diagnosis and relapses, and there was no statistical difference in the detection rate for MC between IgD positive and negative samples. In contrast, RM was detected by PCR in 9 of 49 (18.4%) NLPHL patient tumor samples, always concomitantly with MC without statistical difference in comparison to other lymphomas. The high prevalence of MC in NLPHL tumor tissues provides direct evidence for its association with NLPHL.