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

Schuh, Anna ; Ettl, Medea; Priglinger, Siegfried ; Messmer, Elisabeth M. ; Ohlmann, Andreas und Hintschich, Christoph (19. April 2025): Ocular surface squamous cell neoplasia: risk factors for aggressive growth behaviour and the role of Ki-67. In: Canadian Journal of Ophthalmology

Abstract

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.

Ocular surface squamous cell neoplasia (OSSN) include epithelial dysplasia (ED), carcinoma in situ (CIS) and invasive squamous cell carcinoma (SCC).1 Most lesions are located in the conjunctiva or limbal cornea of the intrapalpebral fissure, while forniceal or palpebral conjunctiva is less frequently involved.2,3 By invading the corneoscleral lamella or the orbital septum SCC can involve intraocular structures, such as the anterior chamber or iris, or spread to adjacent orbital structures, like extraocular muscles, lacrimal gland, or bone, respectively.4,5 In the course of the disease SCC may metastasize trough lymphatics or blood vessels.6 Because of their aggressiveness, they are potentially both sight and life threatening.2,6 The worldwide published incidence of OSSN varies tremendously between 0.02 and 3.5/100,000.7–9 Even if it is a rare entity overall, SCC is the most common malignant tumour of the ocular surface.

Ki-67 is a nuclear protein that is expressed in all active phases of the cell cycle, but not in resting cells and is, therefore, closely associated with cellular proliferation.10 The proportion of Ki-67-positive cells is commonly used as a marker to determine the growth fraction of a given cell population. High levels of Ki-67-positive cells are associated with a high mitotic activity and have been used as a prognostic indicator in various cancers, including breast,11,12 prostate,12 and brain tumours.10,13 Ki-67 labeling index (LI) is valuable in clinical diagnostics to estimate the aggressiveness of tumors and the efficiency of potential treatment strategies.14

The purpose of this study was to investigate clinical characteristics, histopathology, (including Ki-67 labeling index), and epidemiology of OSSN at initial diagnosis to identify potential indicators for aggressive growth behaviour (e.g., orbit invasion, globe invasion, and metastasis).

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Klinikum der LMU München > Augenklinik und Poliklinik
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 00084182
• Bemerkung: Online first
• Sprache: Englisch