Definition

A primary malignant epithelial tumour composed of epidermoid cells, which produce keratin and/or demonstrate intercellular bridges by light microscopy. It is essential to exclude the possibility of metastatic disease. By convention, the diagnosis of salivary squamous cell carcinoma is restricted to the major salivary glands, since minor salivary squamous carcinomas cannot be reliably distinguished from tumours of mucosal origin.

 ICD-O code 8070/3

 Synonym Epidermoid carcinoma

Epidemiology

Primary squamous cell carcinoma (PSCC) probably represents less than 1% of salivary gland tumours. PSCC occurs in patents over a wide age range, but the majority present in the 6th through 8th decades, with a mean of 60- 65 years. They are unusual in patients younger than 20 years, although several cases have been described in children {669}. There is a male to female ratio of approximately 2:1.

Etiology

In several studies, PSCC has been associated with a history of prior radiotherapy, with a latent period of 15-30 years {2329}.

 Localization

Roughly 80% of PSCC arise in the parotid gland and 20% in the submandibular gland. PSCC of the sublingual gland is quite unusual. Occasionally, cases arise from the mucosa lining Stensen’s duct.

Clinical features

Patients with PSCC present with a rapidly enlarging mass, which is frequently painful. Tumours are firm and fixed and may be associated with facial nerve weakness. PSCC is typically high stage at the time of diagnosis {2329,2468}.

Macroscopy

PSCC is an invasive neoplasm with illdefined margins. Most tumours are greater than 3 cm in size. The cut surface is typically solid, firm, and light grey or tan to white, sometimes with focal necrosis.

 Histopathology

 The histology of PSCC of salivary origin is similar to that of well- to moderately-differentiated squamous cell carcinoma originating elsewhere in the head and neck. The tumour infiltrates the salivary parenchyma in irregular nests and trabeculae, accompanied by a fibrous to desmoplastic stromal response. Squamous metaplasia and dysplasia of salivary ducts are occasionally identified in association with PSCC. Perineural invasion and extension into adjacent soft tissue are common findings. There is a significant incidence of cervical nodal metastases (both clinically apparent and occult) at the time of initial surgery {779, 869,1456,2329}.

Differential diagnosis

The most critical distinction in the differential diagnosis of PSCC is ruling out the possibility of metastatic squamous cell carcinoma, whose incidence is greater than true PSCC. PSCC must also be distinguished from mucoepidermoid carcinoma (MEC). MEC is typically composed of a variable cell population, including mucocytes, basaloid, and intermediate cells, in addition to epidermoid cells. However, prominent keratinization is not characteristic of MEC. MEC may exhibit cystic areas and focal clear cell differentiation, features not observed in PSCC. Histochemical stains for intracellular mucin to rule out high-grade MEC are recommended before making a definitive diagnosis of PSCC {669}. Squamous metaplasia in infarcted or surgically manipulated tumours can be misinterpreted as PSCC.

Keratocystoma is a recently described, rare lesion of salivary glands that may be confused with squamous cell carcinoma {1822}. It is characterized by multicytic spaces lined by stratified squamous cells containing keratotic lamellae and focal solid epithelial nests. The consistent absence of metastasis, necrosis or invasion, as well as the lack of cytological atypia and minimal cellular proliferative activity in keratocystoma is essential in distiguishing this lesion from PSCC.

Genetics

Cytogenetic studies in several cases of PSCC have yielded somewhat variable results, although it appears that various 6q deletions may be common, similar to the findings in other salivary carcinomas {1222}. Interestingly, this karyotype is unusual in squamous cell carcinoma of other head and neck sites {1222}.

Prognosis and predictive factors

PSCC is considered a relatively highgrade, aggressive salivary carcinoma. Five-year disease specific survival is approximately 25-30%. Local-regional recurrence develops in at least half of patients and distant metastases are found in 20-30% {2329}. Overall, 75% die of their disease, usually within 5 years {1456,2329}. In the largest published specific analysis of PSCC {2329}, tumour stage was the most important prognostic factor. Age greater than 60 years, ulceration, and fixation also had a significant negative impact on survival. Two additional series, which only considered parotid tumours, reported that age, facial nerve paralysis, deep fixation, and type of treatment were of statistical significance {869,1456}.