Stromal α-smooth muscle actin-positive myofibroblasts in odontogenic keratocyst: A systematic review and network meta-analysis.

Objective

To systematically review and meta-analyze the available evidence on stromal α-SMA expression in odontogenic keratocyst/keratocystic odontogenic tumour (OKC/KCOT), with dentigerous cyst and ameloblastoma considered as prespecified comparator lesions for contextual interpretation of the stromal myofibroblast phenotype.

Design

MEDLINE/PubMed, Scopus, and Web of Science were searched from inception to August 2026. Human studies assessing stromal α-SMA-positive myofibroblasts by immunohistochemistry were eligible. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Heterogeneous outcomes were synthesized qualitatively, while comparable continuous outcomes were analyzed using a frequentist random-effects network meta-analysis with standardized mean differences (SMDs).

Results

Twenty-two studies comprising 429 OKC/KCOT specimens were included. Several studies reported higher stromal α-SMA-positive myofibroblasts expression in OKC than in DC, although findings were inconsistent. Comparisons between OKC and ameloblastoma were heterogeneous. The three-node network included seven studies comparing ameloblastoma with DC, eight comparing OKC with DC, and seven comparing ameloblastoma with OKC/KCOT. Large standardized differences were observed for ameloblastoma versus DC (SMD 15.37) and OKC versus DC (SMD 13.88), whereas the direct ameloblastoma-OKC comparison showed a smaller difference (SMD 2.34). Significant global heterogeneity was present (Q=28.75, df=13, P = 0.0071).

Conclusions

Higher stromal α-SMA-positive myofibroblast expression in OKC than DC, with no significant pooled difference from ameloblastoma, suggests a distinct contractile stromal phenotype. Their roles in matrix remodeling, contraction, and epithelial-stromal signaling provide biological rationale for further investigation. However, methodological heterogeneity and limited clinicopathological evidence preclude interpreting α-SMA expression as a marker or determinant of aggressive behavior or recurrence.