Giant Basal Cell Carcinomas Express Neuroactive Mediators and Show a High Growth Rate: A Case-Control Study and Meta-Analysis of Etiopathogenic and Prognostic Factors

Giant basal cell carcinomas (GBCCs), (BCC ≥ 5 cm), are often painless, destructive tumors resulting from poorly understood patient neglect.To elucidate etiopathogenic factors distinguishing GBCC from basal cell carcinoma (BCC) and identify predictors for disease-specific death (DSD).Case-control study examining clinicopathologic and neuroactive factors (β-endorphin, met-enkephalin, serotonin, adrenocorticotropic hormone, and neurofilament expression) in GBCC and BCC. Systematic literature review to determine DSD predictors.Thirteen GBCCs (11 patients) were compared with 26 BCCs (25 patients). GBCC significantly differed in size, disease duration, and outcomes; patients were significantly more likely to live alone, lack concern, and have alcoholism. GBCC significantly exhibited infiltrative/morpheic phenotypes, perineural invasion, ulceration, and faster growth. All neuromediators were similarly expressed. Adenoid phenotype was significantly more common in GBCC. Adenoid tumors expressed significantly more β-endorphin (60% vs. 18%, P = 0.01) and serotonin (30% vs. 4%, P = 0.02). In meta-analysis (n ≤ 311: median age 68 years, disease duration 90 months, tumor diameter 8 cm, 18.4% disease-specific mortality), independent DSD predictors included tumor diameter (cm) (hazard ratio (HR): 1.12, P = 0.003), bone invasion (HR: 4.19, P = 0.015), brain invasion (HR: 8.23, P = 0.001), and distant metastases (HR: 14.48, P = 0.000).GBCC etiopathogenesis is multifactorial (ie, tumor biology, psychosocial factors). BCC production of paracrine neuromediators deserves further study.