Immune-Enriched Versus Matrix-Remodeling Microenvironments in Psammoma Body-Rich and Psammoma Body-Poor WHO Grade I...

Psammoma bodies, which are characterized by concentric lamellated calcifications, are among the most recognizable histological features in field of neuropathology. However, reason why they form abundantly in some WHO grade I meningiomas (psammomatous subtype), not in others remains unanswered question that persisted for three decades. The predominant perspective attributes psammoma bodies to passive dystrophic calcification. However, ultrastructural evidence and a seminal hypothesis by Das (2009) suggest that they may instead represent an active biological process linked to tumor cell death and growth limitation. The molecular environment that sustains this process remains to be elucidated. The question of whether psammoma body-rich (PB-rich) and psammoma body-poor (PB-poor) WHO grade I meningiomas inhabit different molecular worlds remains a potential inquiry. Utilizing sole public expression dataset with explicit psammomatous annotation (GSE43290; 8 PB-rich vs. 24 PB-poor WHO grade I tumors), we conducted differential expression analysis via the GEO2R platform and a functional enrichment analysis via g:Profiler. Two remarkably divergent transcriptional programs were identified: PB-rich tumors were found to be predominantly influenced by immune and inflammatory pathways, chemokine signaling, leukocyte activation, NF-κB, and Toll-like receptor cascades. In contrast, PB-poor tumors were found to be characterized by extracellular matrix remodeling, elastic fiber assembly, and collagen organization. These findings are consistent with recent literature on inflammation-driven ectopic mineralization, immune-enriched meningioma subtypes, and DAMP-TLR-NF-κB positive-feedback loops. In complementary enrichment analyses, the PB-rich core genes were found to be associated with NK-cell and cytotoxic T-cell signatures, while PB-poor core genes exhibited a preferential enrichment in extracellular matrix, elastic fiber, and fibroblast-like stromal pathways. These findings suggest psammoma body formation may be morphological footprint of chronically inflamed tumor microenvironment. This exploratory study proposes mechanistic framework linking immune activation to calcification in meningiomas and identifies candidate pathways and genes for future immunohistochemical and functional validation.