Squamous Cell Carcinoma

In common with squamous cancers at other upper aerodigestive sites, chronic abuse of tobacco is the most important etiologic factor, and alcohol abuse may potentiate its carcinogenic effect synergisti-cally. Other factors such as genetic, environmental and dietary influences also play a part, and may explain some of the geographic variations in incidence. The disease is more common in men than in women (2.5:1) and is most frequently seen between the sixth and seventh decades of life. Premalignant lesions such as leukoplakia and erythroplakia do not seem to have the same significance in predisposition for oropharyngeal cancer as they do for squamous carcinoma of the oral cavity.

The most common sites for carcinoma in the oropharynx are the base of the tongue and the tonsil, while tumors of the soft palate and posterior wall are less common (Figure 6-6). Most squamous cancers initially expand along the mucosal surface and eventually invade the deeper structures, spreading along fascial planes and neurovascular structures. The base of the tongue is an exception because tumors tend to invade its musculature early, resulting in decreased mobility or fixation of the tongue and nodal metastasis. The anterior surface of the soft palate is affected more frequently than its posterior surface and delineation of the lesion from leukoplakia and keratinization may be difficult in heavy smokers. Tumors of the pharyngeal wall are commonly associated with extensive submucosal spread and so-called skip lesions.

Pharyngeal

Wall

Soft Palate

\

Base of Tongue

r

Tonsil

Figure 6-6. Site distribution of tumors of the oropharynx.

Figure 6-6. Site distribution of tumors of the oropharynx.

The majority of patients present with locoregion-ally-advanced tumors (Figure 6-7). Between 30 and 80 percent of patients develop nodal metastases at some stage of their disease (Table 6-2) and various characteristics of the primary tumor may be respon-sible.7 Tumors arising in areas of rich lymphatics such as the tongue base and tonsillar fossae have a high risk of metastatic nodal disease at presentation compared with those in other areas such as the soft palate and anterior faucial pillar.8 Levels II, III and IV are at greatest risk of metastasis. Involvement of levels I and V is rare (1.4% each) in the clinically N0 neck but the risk is higher (12.6% for level I and 9.7% for level V) in the clinically positive neck. Level V involvement occurs only in presence of metastasis at other levels and isolated skip metastasis to level I is also extremely rare (0.4%).9Although the risk of nodal involvement is generally proportional to the size of the primary tumor, early-stage oropharyngeal tumors, especially those of the tonsil and tongue base, can give rise to massive nodal disease. The grade of the primary lesion does not seem to influence the risk of nodal metastases. Risk factors for bilateral nodal metastases include tumors of the base of tongue or soft palate, tumors approaching or involving the midline, and alteration of the cervical lymphatics either by tumor or treatment (previous surgery, or irradiation or both).

Distant metastases, most often to the lungs, bones and liver, occur in up to 20 percent of patients with oropharyngeal tumors. The majority of these patients have active locoregional disease, primary or recurrent, at the time of detection of metastases.

34%

31%

25%

10%

Stage 1

Stag« II

Stage III

Stage IV

Figure 6-7. Stage distribution of oropharyngeal tumors.

Figure 6-7. Stage distribution of oropharyngeal tumors.

Table 6-2. NODAL METASTASES IN OROPHARYNGEAL CARCINOMA

Site Node Positive (%) Bilateral Nodes (%)

Table 6-2. NODAL METASTASES IN OROPHARYNGEAL CARCINOMA

Site Node Positive (%) Bilateral Nodes (%)

Base of tongue

78

34

Tonsil

76

21

Soft palate

44

19

Anterior faucial pillar

45

7

Posterior wall

37

Patients with oropharyngeal tumors, especially posterior pharyngeal wall tumors10 are at high risk to develop second and subsequent primary tumors.

Lymphoepithelioma or undifferentiated carcinoma of nasopharyngeal type (UCNT) is a variant of squamous cell carcinoma that is characterized by an increased propensity to metastasize and by its extreme radiosensitivity. While the squamous component of the tumor may be extremely undifferenti-ated, a non-neoplastic lymphocytic infiltrate often permeates widely throughout the tumor. Nodal metastases consist of squamous cells similar to those of the primary tumor and usually lack the reactive lymphoid component of the primary tumor.

Lymphoma, especially the non-Hodgkin's type, accounts for about 8 percent of oropharyngeal tumors.11 The tonsil and base of tongue are the most frequently involved sites and B-cell lymphoma is the most common type. Although the lesion arises in the submucosa, it can ulcerate the mucosa and present like a squamous cancer. An adequate biopsy specimen must be submitted to avoid confusion with lymphoid hyperplasia. If a lymphoma is suspected, the clinician must have the foresight to consult the pathologist and submit fresh tissue for special studies which may include immunohistochemical stains, flow cytometry, and molecular genetic techniques.

Salivary gland tumors arise from the minor salivary glands of the soft palate and tongue base, and account for about 5 percent of oropharyngeal tumors.12 The majority of these tumors are malignant and adenoid cystic carcinoma is the most common histologic variant. As with other sites in the head and neck, the tumor has a tendency to spread along nerve sheaths in the perineural lymphatics and metastasizes late to lymph nodes, lung and bone. Although the short-term prognosis for these tumors is excellent, eventually about 60 to 80 percent of patients die from or with metastatic disease.

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