Ocular surface squamous cell neoplasia: risk factors for aggressive growth behaviour and the role of Ki-67

Objective: Analyzing characteristics of ocular surface squamous cell neoplasia (OSSN) at first diagnosis and potential risk factors for aggressive growth behaviour. Design: Retrospective. Methods: Including patients with first diagnosis of OSSN at a tertiary center from 2013 until 2022. Cases were analyzed regarding demographics, clinical findings, and histopathological findings, including Ki-67 expression. Results: A total of 153 patients with first diagnosis of histopathological confirmed OSSN were included. Mean age was 72 years (36–98), with a slight male predominance (66%; n = 101). Most patients had invasive squamous cell carcinoma (SCC; 45.8%, 70), followed by carcinoma in situ (CIS; 37.9%, 58) and epithelial dysplasia (ED; 16.3%, 25). Duration of symptoms varied significantly: ED 6 months (0–36), CIS 1.5 (0–48), SCC 3 (0–36) (p = 0.048). 44.3% (51/115) of cases were previously misdiagnosed, and, therefore, inadequately treated. Orbital involvement was observed in 8.5% (13), intraocular in 1.3% (2), metastasis in 2.7% (4) at initial diagnosis. Ki-67 labeling index (LI) varied significantly across subtypes: ED 35% (2–87%), CIS 45% (11–85%), SCC 50% (18–93%) (p = 0.007) and was higher with involvement of the caruncle, lower fornix, lower eyelid margin, or tarsus (p = 0.023). Patients with globe or orbit invasion had significantly longer median symptom duration (6 months (0–48) vs 2 (0–48); p = 0.01). Patients with metastasis exhibited significantly higher Ki-67 LI (p = 0.027). Conclusions: Our study found extended time intervals from first symptoms to first correct diagnosis correlate with higher risk for advanced SCC. Further, elevated Ki-67 LI correlated with more invasive tumor entities, such as SCC and CIS, and indicate an increased risk of metastasis.