Oral Cavity and Oropharynx Malignancy

1

The oral cavity extends from the lip to the circumvallate papillae inferiorly and the junction of the hard and soft palate superiorly. Name the eight subsites within the oral cavity.

• 1.

  Mucosal lip

• 2.

  Buccal mucosa

• 3.

  Lower (mandibular) alveolar ridge/gingiva

• 4.

  Upper (maxillary) alveolar ridge/gingiva

• 5.

  Retromolar trigone

• 6.

  Hard palate

• 7.

  Floor of mouth

• 8.

  Oral tongue (anterior two-thirds)

2

What is the most common type of malignancy within the oral cavity?

Squamous cell carcinoma: As in all head and neck sites, squamous cell carcinoma (SCC) is by far the most common type of tumor seen. More than 90% of oral cavity cancers are SCC. Other malignant tumors include minor salivary gland malignancies, Kaposi’s sarcoma, other sarcomas, melanoma, and, rarely, lymphoma.

3

Where in the oral cavity are minor salivary gland malignancies most commonly seen? What is the most common type?

Within the oral cavity, minor salivary gland malignancies most commonly occur on the hard palate. Adenoid cystic carcinoma is the most common tumor of the minor salivary glands.

4

What are the most common subsites for oral cavity SCC?

• a.

  Lips: Overall, 15% to 30% of oral cancers arise from mucosal (wet) and external vermilion (dry) lip combined. The lower lip is much more common a site than the upper lip (>90% arise in the lower lip). American Joint Committee on Cancer (AJCC) staging and National Comprehensive Cancer Network (NCCN) guidelines now separate mucosal lip squamous carcinoma (included as oral cavity) and vermilion dry lip carcinoma (included with cutaneous squamous cell carcinoma). The external vermilion (dry) lip is exposed to external environmental factors, such as ultraviolet radiation from the sun, and thus a tumor in this area behaves more like cutaneous SCC. Current classifications of lip cancers make the true mucosal lip a less common subsite, although much of the historical data are based on all lip cancers being staged within the oral cavity.

• b.

  Oral tongue: 20% to 30% of oral cavity cancers. The lateral tongue is more common than the dorsal tongue.

5

Discuss three premalignant clinical lesions or conditions of the oral cavity

• a.

  Leukoplakia: Defined as a white keratotic plaque or patch that cannot be rubbed off. Often seen due to chronic trauma or irritation of oral mucosa. Most are benign, but malignant potential/transformation rate is very difficult to predict. Baseline biopsy and follow-up or excision are recommended depending on pathologic findings.

• b.

  Erythroplakia (red plaque/lesion): Red mucosal plaque not arising from an obvious mechanical or inflammatory cause. Has much higher malignant potential than leukoplakia (estimated to be seven times more malignant potential). Can be seen in conjunction with leukoplakia. More aggressive therapy recommended than that for leukoplakia.

• c.

  Oral lichen planus: Lacy white lines primarily noted on buccal mucosa, known as Wickham’s striae (buccal mucosa is classic location, but changes can be seen throughout the oral cavity). Exact cause is unknown but thought to be immune-mediated (lymphocytic infiltration of epithelial layers seen). Associated with pain and burning, and the clinical course waxes and wanes. Treated with topical steroids, systemic steroids, and sometimes other immunosuppressants. Lifetime malignant transformation risk is 5% to 10%.

Note: The above are clinical , rather than pathologic , descriptions of premalignant conditions. Dysplasia, which can be seen in any of these lesions, is the pathologic description of premalignant change describing degrees of cellular change. Dysplasia can be described as mild, moderate, and severe. Severe dysplasia and carcinoma in situ are often utilized interchangeably by pathologists.

6

Are oral cavity SCCs commonly caused by human papillomavirus (HPV)?

No. Whereas oropharynx SCC is very commonly driven by HPV, only a small percentage (<3%) of oral cavity cancers are truly HPV-associated.

7

Where in the neck do regional metastases of oral cavity SCC most commonly appear and how is this clinically significant?

Regional nodal disease from oral cavity SCC most commonly presents in the upper cervical lymph nodes – level I (submental and submandibular) and levels II and III (upper and middle jugular nodes). This relatively predictable nodal drainage of oral cavity subsites has led to the use of what is termed supraomohyoid neck dissection (includes levels I, II, and III) being utilized for elective nodal dissection in oral cavity cancers. The finding of microscopic nodal disease in levels III and IV without level I and II disease in more than 15% of patients with oral tongue cancer in a 1997 study has led to some recommending inclusion of level IV in elective neck dissections for oral tongue cancer.

8

How is cancer of the oral cavity staged?

SCC of the oral cavity is staged according to the tumor, node, metastasis (TNM) system by the AJCC, currently in its eighth edition, utilized since 2017. Within the oral cavity, size and depth of invasion (DOI) are major factors determining T stage (eighth edition AJCC included DOI in T staging for the first time).

T staging

• Tx: Primary tumor cannot be assessed

• Tis: Carcinoma in situ

• T1: Tumor ≤ 2 cm with DOI ≤ 5 mm

• T2: Tumor ≤ 2 cm with DOI > 5 mm or tumor > 2 cm and ≤ 4 cm with DOI ≤ 10 mm

• T3: Tumor > 2 cm and ≤ 4 cm with DOI > 10 mm or tumor > 4 cm with DOI ≤ 10 mm

• T4a: Moderately advanced local disease.

• Tumor > 4 cm, with DOI > 10 mm or tumor invades adjacent structures only (e.g., through cortical bone of the mandible or maxilla, or involves the maxillary sinus or skin of the face). Note: Superficial erosion of bone or tooth socket by a gingival primary is not sufficient to classify a tumor as T4.

• T4b: Very advanced local disease.

• Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery

• Nodal staging was previously the same for most head and neck squamous cell cancers. However, the eight edition of AJCC staging has changed nodal staging such that it differs between head and neck sites. Clinical (cN) nodal staging for oral cavity cancers now includes a clinical (based upon exam/imaging) assessment of extranodal extension (ENE). cN staging for oral cavity cancers is as follows:

Clinical N staging

• Nx: Regional lymph nodes cannot be assessed

• N0: No regional lymph node metastasis

• N1: Metastasis in a single ipsilateral lymph node, 3 centimeters or smaller in greatest dimension, and ENE(-)

• N2a: Metastasis in a single ipsilateral lymph node larger than 3 centimeters but not larger than 6 centimeters in greatest dimension and ENE(-)

• N2b: Metastases in multiple ipsilateral lymph nodes, none greater than 6 centimeters in greatest dimension, and ENE(-)

• N2c: Metastases in bilateral or contralateral lymph nodes, none larger than 6 centimeters in greatest dimension, and ENE(-)

• N3a: Metastasis in a lymph node larger than 6 centimeters in greatest dimension and ENE(-)

• N3b: Metastasis in any node(s) and clinically overt ENE(+)

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