Track
Basic ScienceAbstract
Cutaneous squamous cell carcinoma (cSCC) of the auricular region demonstrates disproportionately high rates of perineural invasion (PNI), a critical prognostic factor associated with increased recurrence, metastasis, and mortality. While PNI is recognized as a high-risk feature, the extracellular matrix (ECM) alterations that facilitate tumor-nerve interactions in auricular SCC remain poorly characterized. This review systematically evaluated literature on ECM remodeling patterns associated with PNI in auricular SCC to identify mechanisms underlying this aggressive behavior. A PubMed search using terms including "auricular squamous cell carcinoma," "perineural invasion," "extracellular matrix," "laminin," and "collagen IV,” identified studies with histopathologic or immunohistochemical data on ECM alterations in cSCC with PNI. Across studies, PNI-positive auricular SCC consistently demonstrated loss or fragmentation of basement membrane components such as laminin and collagen IV. Increased peritumoral expression of matrix metalloproteinases-2 and -9 (MMP-2/MMP-9) was documented at tumor-nerve interfaces in cases with extensive PNI. Tenascin-C overexpression was significantly associated with nerve sheath disruption and tumor migration along perineurial spaces. Auricular location showed higher predisposition to these ECM changes than other cutaneous sites, likely due to proximity to complex sensory nerve networks, including branches of the trigeminal and facial nerves. Our review demonstrates a reproducible ECM remodeling pattern in PNI-positive auricular SCC, characterized by basement membrane degradation, MMP upregulation, and tenascin-C-mediated nerve sheath disruption. These findings suggest that auricular tumor microanatomy creates a permissive environment for PNI, providing a foundation for developing targeted diagnostic biomarkers and therapeutic interventions to prevent neural spread in high-risk cases.