<i>MYD88</i> and <i>CD79B</i> Mutation Analysis in Primary Pharyngeal Diffuse Large B‐Cell Lymphomas: Expanding the MCD‐Like Subtype From the Sinonasal Region to the Upper Airway

We recently identified a high prevalence of the MCD-like subtype in primary sinonasal DLBCL, defined by MYD88 L265P and/or CD79B Y196 mutations, which is associated with poor prognosis and preferred relapse sites. In this study, we characterized 56 primary pharyngeal DLBCLs and compared them with 55 sinonasal cases from our prior cohort, assessing mutations by droplet digital PCR and immunophenotype by immunohistochemistry. Pharyngeal and sinonasal DLBCLs exhibited site-specific heterogeneity, with pharyngeal cases showing lower frequencies of MYD88 L265P (15/56 [26.8%] vs. 29/55 [52.7%], p = 0.007) and CD79B Y196 mutations (15/56 [26.8%] vs. 20/55 [36.4%], p = 0.312), and correspondingly fewer MCD-like cases (20/56 [35.7%] vs. 32/55 [58.2%], p = 0.023). Nevertheless, MCD-like pharyngeal cases shared similar features with sinonasal MCD-like cases, including high tendencies for non-GCB phenotype (75% vs. 96.9%), inferior prognosis, and specific site relapse (CNS, testis, and/or skin). Across the entire upper airway cohort (n = 111), MCD-like status consistently correlated with site-specific relapse and adverse clinical outcomes. These findings support expanding the utility of simplified MCD-like classification as a practical tool for prognostic prediction, relapse site estimation, and therapeutic guidance in upper airway DLBCL, with potential for broader application to anatomically diverse DLBCL-NOS cases.