Clinicopathologic and Genomic Characteristics of Minute Pulmonary Meningothelial-like Nodules

Minute pulmonary meningothelial-like nodules (MPMNs) are benign lung lesions with histologic characteristics similar to meningeal epithelium. MPMNs often lead to misdiagnosis for their similar radiologic characteristics to malignant nodules. The pathogenesis of MPMNs remains unclear, and this research primarily focused on mutations in a limited number of genes, lacking a comprehensive analysis of their mutational landscape. We collected 134 MPMNs from 88 patients with pathologic examinations at Peking Union Medical College Hospital in the past 5 years. We performed whole-exome sequencing on 12 MPMNs and 7 adenocarcinoma lesions from 6 patients. In our PUMCH-MPMN cohort, we provided clinical, pathologic, radiologic, and follow-up characteristics of patients with MPMNs. Our study demonstrated the pathologic diagnostic value of 3 classic MPMN diagnostic markers (epithelial membrane antigen, progesterone receptor, and vimentin) and the novel marker somatostatin receptor 2. It also suggested the preoperative differential diagnostic value of positron emission tomography/computed tomography. We also classified MPMNs into 4 types based on different discovery methods and verified the diagnostic value of traditional and novel immunohistochemical markers. We performed whole-exome sequencing and revealed that MPMNs harbor mutations enriched in cell cycle and cytoskeleton assembly pathways. On the other hand, classical meningioma-related mutations, such as NF2 mutations, were not detected. These findings provide new evidence for the hypothesis that MPMNs arise from reactive proliferation rather than share a common origin with meningiomas, contributing to a better understanding of MPMNs among clinicians and pathologists, reducing misdiagnosis, and improving patient care.