SCC arises from the epidermal prickle and squamous cells. Although it may develop de novo, actinic keratosis, Bowen’s disease, and radiation dermatoses are all precursors to the development of SCC [10, 11].

SCC of the eyelid usually begins with an early epithelial phase referred to as actinic keratosis (senile keratosis, solar keratosis), with subtotal replacement of the epidermis by atypical cells (intraepithelial squamous dysplasia). Intraepithelial squamous cell carcinoma or squamous cell carcinoma in situ is diagnosed when there is complete disorganization of the epidermis, with numerous atypical cells that are rounded, large, and with homogeneous, eosinophilic cytoplasm. Invasion of the dermis is the hallmark for the histopathologic diagnosis of invasive SCC (Fig. 5.2) [1].

The invading cells show different degrees of differentiation leading to variable histologic features. In well-differentiated tumors the cells are polygonal, with abundant acidophilic cytoplasm and prominent hyperchromatic nuclei that vary in size and staining properties. Characteristic findings are of abnormal keratinization with dyskeratotic cells and keratin pearls and intercellular bridges. Poorly differentiated lesions show an increased degree of cellular anaplasia, with irregularly shaped and sized cells, enlarged nuclei, abnormal mitoses, little or no evidence of keratinization, and loss of intercellular bridges (Fig. 5.3).

Prevention by minimizing sun exposure, especially in childhood and adolescence, remains of prime importance in minimizing the morbidity and mortality associated with SCC.

The main treatment modality used for eyelid SCC is surgical excision, with microscopic monitoring of the margins or Mohs’ microsurgery. A variety of other forms of therapy were suggested, such as radiation therapy, cryotherapy, chemotherapy, curettage with carbon dioxide laser, photodynamic therapy, and treatment with retinoids or

α-interferon. When used alone, these therapies have high recurrence rates, which are not acceptable for SCC of the eyelid, where recurrent tumors can be more aggressive and invasive. However, they may be appropriate for patients who cannot tolerate or who decline surgery [11].

High-risk eyelid SCC lesions are those larger than 2 cm, with poor histological differentiation, deep invasion, and the presence of perineural invasion [22]. Recurrent tumors and tumors developing in scars or in immunocompromised patients also imply a poor prognosis [23, 24]. The histologic variant of adenoid SCC is associated with a better prognosis [1].

According to the applied practical review of the American Joint Committee on Cancer (AJCC) 7th edition [25], primary SCC is classified into stages I, II, III, and IV stages according to size, adjacent invasion, complete resection that requires enucleation, exenteration or bone resection, involvement of regional lymph nodes, extensive invasion making the tumor not resectable, and evidence of distant metastasis. This classification was found to be a practical tool for staging of carcinoma of the eyelids [26].

Eyelid SCC is potentially fatal and responsible for considerable morbidity [9]. Aggressive or neglected cases of eyelid SCC may spread into the lacrimal passages, the orbit, and the intracranial cavity. SCC is by far the most frequent of the secondary epithelial neoplasms in the orbit [1]. However, orbital invasion is a rare complication that has been reported to occur in 2.5 % of all eyelid BCC and SCC [27]. Orbital invasion of eyelid SCC may take years to occur, often preceded by several surgical interventions, irradiations, and recurrences of the tumor. If left unattended, the entire orbital region and a major portion of the face are destroyed in an ulcerating fungating crater [1]. Orbital spread is usually associated with complete ptosis, ophthalmoplegia, and proptosis. Eventually, involvement of the orbital nerves and bones causes severe and constant pain [1, 10].

Perineural spread of SCC occurs in up to 14 % of facial lesions [28]. The perineural infiltration of SCC of the eyelids along branches of the trigeminal nerve, the extraocular motor nerves, and the facial nerve facilitates its spread into the orbit, periorbital structures, and intracranial cavity [29]. Once clinical signs or symptoms of perineural spread have developed, the prognosis is poor, with around 50 % recurrence after simple excision [28].