From the Guidelines
Squamous cell carcinoma of the ocular surface is a malignancy that develops through a complex interplay of genetic mutations, environmental factors, and cellular transformation, ultimately leading to invasive cancer with potential for metastasis. The pathophysiology of this disease involves a multistep process, starting with dysplastic changes in the epithelial cells of the conjunctiva or cornea, which progress from mild to severe dysplasia before developing into carcinoma in situ and eventually invasive squamous cell carcinoma 1. Key risk factors for the development of ocular surface squamous cell carcinoma include ultraviolet radiation exposure, human papillomavirus infection, immunosuppression, and chronic inflammation 1.
Pathophysiological Mechanisms
The disease involves activation of oncogenes, inactivation of tumor suppressor genes, and dysregulation of cell cycle control mechanisms, leading to increased proliferation, resistance to apoptosis, and the ability to invade surrounding tissues 1. As the disease progresses, the transformed cells can break through the basement membrane, invade the substantia propria, and potentially metastasize to regional lymph nodes.
Clinical Manifestations
Clinically, ocular surface squamous cell carcinoma manifests as a raised, fleshy, gelatinous, or leukoplakic lesion on the ocular surface, often at the limbus where stem cells reside 1. Understanding the pathophysiology of this disease is crucial for guiding treatment approaches, which typically involve surgical excision with clear margins, supplemented by adjuvant therapies like topical chemotherapy or cryotherapy for more extensive disease 1. The optimal treatment should be tailored to the patient's and tumor's specific needs and should be managed by an experienced specialist.
From the Research
Pathophysiology of Squamous Cell Carcinoma
- Squamous cell carcinomas (SCCs) are highly heterogeneous tumors that arise from closely interconnected epithelial cell populations with intrinsic self-renewal potential inversely related to the stratified differentiation program 2
- The development and progression of SCC is a multistage process characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes 3
- SCCs can originate from simple or pseudo-stratified epithelia through activation of quiescent cells and/or a switch in cell-fate determination 2
Risk Factors
- Advanced age, cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses are significant risk factors for cutaneous squamous cell carcinoma (cSCC) 3
Treatment
- Surgical excision is the first-line treatment for invasive cSCC, and radiotherapy may be considered as a primary treatment in patients not candidates for surgery 3
- Concomitant radiation therapy, 5-fluorouracil infusion, and bolus mitomycin C is effective treatment for local control in esophageal squamous cell carcinoma, but not for distant hematogenous metastases 4
- Mitomycin and 5-fluorouracil regimen provides tumor control with acceptable tolerance and is an option for patients with metastatic SCC of the anal canal after failure of platinum-based chemotherapy 5
Diagnosis
- Dermoscopy and reflectance confocal microscopy have enhanced the diagnostic accuracy of cSCC 3
- A retrospective analysis of patients with squamous cell carcinoma of the oesophagus treated with radiation and 5-fluorouracil, with and without mitomycin C, showed that the treatment was well tolerated, but further studies are required to determine the most effective combination of radiation and chemotherapy or other radiation sensitizers for squamous cell carcinoma of the oesophagus 6