The pharynx is the intermediate part of the upper aerodigestive tract in the head and neck region, connecting the nasal cavity to the lower airway thru the larynx and the oral cavity to the esophagus. It is divided into three contiguous anatomic regions: the nasopharynx, oropharynx, and hypopharynx ( Fig. 9.1 ). Each of these three divisions has distinct anatomic features and physiologic functions. The most frequently encountered neoplasm in the pharynx is squamous cell carcinoma. Although tobacco and alcohol consumption remain the most important etiologic factors, viral exposure (such as Epstein-Barr virus [EBV] for the nasopharynx and human papilloma virus [HPV]) for the oropharynx) frequently is associated with these tumors. These and other factors may account for geographic variations in the incidence of pharyngeal carcinomas. The worldwide incidence rates for cancer of the nasopharynx and other pharyngeal cancers are shown in Fig. 9.2 . In the United States the American Cancer Society estimates that approximately 17,000 new cases of cancer of the pharynx were diagnosed in 2017. Death-rate estimates vary depending on the stage of the tumor. However, overall, 3050 cause-specific deaths were estimated for 2017 ( Fig. 9.3 ).

Figure 9.1
Anatomic regions of the pharynx.

Figure 9.2
Worldwide incidence and mortality rates in males and females for cancer of the nasopharynx ( A ) and other pharynx sites ( B ).

(From Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France, International Agency for Research on Cancer, 2013. Available from http://gco.iarc.fr/today/home .)

Figure 9.3
American Cancer Society estimates of new cases and deaths for cancer of the pharynx in the United States in 2017.

The nasopharynx begins at the posterior choana of the nasal cavity and extends up to the level of the free edge of the soft palate. Various sites within the nasopharynx include the vault, the lateral walls, and the posterior wall. The lateral wall includes the fossa of Rosenmüller and the mucosa overlying the opening of the eustachian tube (torus tubarius). The posterior surface of the soft palate forms the floor of the nasopharynx. The mucosa of the pharynx is composed of squamous cells with varying degrees of keratinization and is interspersed with minor salivary glands in the submucosa. Primary neoplasms of the nasopharynx are squamous cell carcinomas; rarely, minor salivary gland tumors, chordomas, soft tissue tumors, and bone tumors may arise in the nasopharynx. Waldeyer's ring (which is composed of the lingual and pharyngeal tonsils, the adenoids, and mucosa covering the nasopharynx and oropharynx) has a rich lymphoid network. Waldeyer's ring also is a common site for involvement by lymphoma (particularly B-cell lymphoma); the tonsils and the base of the tongue are involved most frequently. Exposure to EBV (a gamma herpes virus) is frequently associated with nasopharyngeal carcinoma (NPC). EBV-associated NPC tumors have a unique histopathologic composition; they are undifferentiated carcinomas with a prominent lymphocytic infiltrate, and historically they were called “lymphoepitheliomas.” The interaction between cancer cells and lymphocytes is thought to contribute to the propagation of malignancy. Geographic variation in the incidence of NPC is observed, with the highest incidence in Southeast Asia and Africa. The precise reason for this geographic variation remains to be elucidated, but environmental factors, inherited genetic susceptibility, and EBV exposure may be contributory. Serologic screening for EBV-specific antibody titers are used for early diagnosis and to monitor response to therapy in select high-risk populations. Genetic predisposition also is suggested by the high incidence of NPC in Chinese men (especially Cantonese men) regardless of where they live. Environmental cofactors, such as consumption of salted fish, also may contribute to geographic variations in incidence.

The oropharynx begins at the anterior aspect of the faucial arch and extends posteriorly. It includes the soft palate and tonsillar fossae on each side, as well as the posterior pharyngeal wall and the posterior third of the tongue (the base of the tongue). Historically, the base of the tongue was the most frequent site of primary tumors in the oropharynx, followed by the tonsils and soft palate. However, during the past two decades in the United States, the tonsils are observed to be the most predominant site of primary carcinomas in the oropharynx. This shift in site distribution is attributed to the steep rise in the incidence of HPV-associated squamous cell carcinomas in the oropharynx. Tobacco and alcohol consumption as etiologic factors for cancers in the oropharynx is declining, whereas HPV-associated squamous cell carcinoma in the nonsmoking younger population is continuing to rise. The carcinogenic role of HPV in cancer pathogenesis is well established based on studies of cervical carcinomas in women. Although similar, the precise role of HPV infection in the pathogenesis of head and neck cancer is not analogous to cervical cancer, because infection appears to be neither necessary nor sufficient for development of these tumors. Epidemiologic and molecular studies have, however, identified HPV as a causative agent of oropharyngeal carcinoma. Moreover, lending further support to their being distinct clinical entities, the clinical course of HPV-positive oropharyngeal carcinomas appears to be different from that of HPV-negative tobacco- or alcohol-related tumors. Demographically, HPV-associated oropharyngeal cancer occurs more often in younger males with little or no tobacco exposure. Clinically, the primary tumor is often small and the presenting symptom is lymphadenopathy. HPV-associated oropharyngeal cancer is highly responsive to treatment and carries an excellent prognosis, in contrast to its HPV-negative counterpart. The impact of these improved outcomes has generated debate on selection of treatment for oropharynx cancer, with a focus on de-escalation to reduce treatment-related morbidities. Several clinical trials of de-escalation of treatment programs are currently under way. The site distribution for primary tumors of the oropharynx observed at Memorial Sloan Kettering Cancer Center is shown in Fig. 9.4 . Although squamous cell carcinomas are the most frequently encountered primary tumors of epithelial origin in the oropharynx, lymphomas often are seen because of the abundance of lymphoid tissue in the oropharynx, which is a significant component of Waldeyer's ring. A primary lymphoma of the tonsil, pharyngeal wall, or base of the tongue therefore can present as a surface lesion with ulceration because of rapid proliferation. Physiologically, the oropharynx is important as an entry portal to the pharyngoesophageal region during the pharyngeal phase of deglutition. Transport of the food bolus from the oral cavity to the hypopharynx requires that the velopharyngeal sphincter be competent, preventing regurgitation of the bolus into the nasopharynx and nasal cavity. Similarly, elevation of the larynx during the pharyngeal phase of deglutition requires that the muscles of the tongue and the hyomandibular complex be intact. Disturbance in any of these well-coordinated muscular functions will produce swallowing dysfunction, including nasal regurgitation and aspiration.

Figure 9.4
Site distribution of primary carcinoma of the oropharynx at Memorial Sloan Kettering Cancer Center, 1985 to 1999, 2000 to 2009, and 2010 to 2017.

The hypopharynx is the lowermost part of the pharynx, beginning at the level of the tip of the epiglottis and ending at the level of the lower border of the cricoid cartilage. At that point the upper aerodigestive tract continues into the cervical esophagus. The pyriform sinuses on each side, the posterior pharyngeal wall, and the postcricoid region form the three designated anatomic sites within the hypopharynx. However, their boundaries overlap because their demarcation is somewhat arbitrary. The site distribution of primary squamous cell carcinomas of the hypopharynx is shown in Fig. 9.5 . Physiologically, the hypopharynx is a critically important anatomic site because it is a component of the upper aerodigestive tract, contiguous with the supraglottic larynx. The pharyngeal phase of deglutition requires a well-coordinated process controlled by the glossopharyngeal, vagus, and hypoglossal nerves. Normal mucosal sensations of the oropharynx, supraglottic larynx, and hypopharynx are essential in initiating the swallowing reflex. Similarly, coordinated action of muscles of the tongue, pharynx, and intrinsic muscles of the larynx is required for successful passage of the food bolus into the cervical esophagus without aspiration into the airway. Thus surgical treatment of any tumor arising in the hypopharynx will, by necessity, produce disturbance in swallowing, with risk of aspiration into the respiratory tract. In the Western world, primary malignant tumors within the hypopharynx are seen most frequently in the pyriform sinuses, followed by the posterior pharyngeal wall. The least frequent site is the postcricoid region. In other parts of the world, distribution of primary tumors of the hypopharynx is somewhat different.

Figure 9.5
Site distribution of primary carcinoma of the hypopharynx at Memorial Sloan Kettering Cancer Center, 1985 to 1999, 2000 to 2009, and 2010 to 2017.

The cervical esophagus begins where the hypopharynx ends, at the level of the lower border of the cricoid cartilage. The exact lower extent of the cervical esophagus is somewhat arbitrary. It is generally accepted that the cervical esophagus ends at the thoracic inlet. The most common site of origin for primary cancers of the esophagus is in its lower third, followed by the middle third, and last in the cervical esophagus. Although primary tumors of the cervical esophagus are infrequent, direct extension of postcricoid or pharyngeal wall tumors to the cervical esophagus is quite common. Because of its contiguity to the postcricoid region cephalad and to the larynx and proximal trachea anteriorly, surgical treatment of cancer of the cervical esophagus requires consideration of management of the larynx and proximal trachea along with the primary tumor. The most frequently seen malignant tumor in the hypopharynx and cervical esophagus is squamous cell carcinoma, although adenocarcinoma of minor salivary gland origin does occur infrequently. Melanomas, soft tissue tumors, and occasionally metastatic tumors also may be seen.

Staging

Staging for primary nasopharynx cancer (NPC) depends on local extension to the adjacent soft tissues (parapharyngeal space) and bone (skull base). Tumors of the nasopharynx commonly invade adjacent muscles, including medial pterygoid, lateral pterygoid, and prevertebral muscles. In contrast to oral cavity cancers, these are still considered in early T stages in the AJCC/UICC staging system. In addition, because of the rich lymphatic network of the nasopharynx, regional lymph node metastases occur early and often, and a neck mass may be the presenting symptom in many patients. Nodal metastases occur in a predictable fashion with involvement of retropharyngeal and parapharyngeal lymph nodes, the deep jugular chain, and posterior triangle lymph nodes, in that order. Bilateral metastases are common.

The most recent revision of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system (eighth edition) has introduced separate staging for “high-risk HPV (p16-positive)”–associated oropharynx cancer (OPC) from the “non-HPV (p16-negative)—,” tobacco-, and alcohol- associated OPC due to the distinctly improved prognosis for HPV-positive cancers. T classification in both HPV-positive and HPV-negative oropharyngeal cancer remains the same and is staged on the basis of the surface dimensions of the primary tumor. On the other hand, the impact of regional lymph node metastases in HPV-positive tumors is not the same. Regional lymph node metastases are quite common and may be the first manifestation of the disease. Nodal metastases occur in a predictable and sequential manner, with lymph nodes in the anterior triangle of the neck (levels I to IV) being at highest risk. Nodal staging for HPV-negative oropharynx cancer remains the same as that for other sites. Extranodal extension is an adverse risk feature that upstages N staging for all mucosal squamous cell carcinomas, including HPV-negative oropharynx tumors. This finding has not been found to be prognostic in HPV-positive cancer and therefore is not included in the N staging. Laterality and size of metastatic nodes are the only factors included in the N staging for HPV-positive OPC (see Chapter 11 ). These changes will more accurately classify HPV-positive oropharynx cancers, improve prognostication, and enhance stratification for clinical trials and outcome reporting.

Staging of primary tumors of the hypopharynx is not dependent on the surface dimensions of the tumor but is related to local extent and invasion of various sites within the hypopharynx or to adjacent regions such as the oropharynx and larynx. Fixation of the vocal cord implies deep invasion into the musculature of the larynx, putting it in an advanced stage category. Because of its anatomic location, a small primary tumor of the hypopharynx is seldom symptomatic and is diagnosed infrequently. The majority of symptomatic tumors, therefore, have an advanced T stage at presentation. In addition, the lymphatic network of the hypopharynx is quite rich, and dissemination of the primary lesion to the regional lymph nodes occurs often and early in the course of the disease. The T stage distribution of hypopharyngeal tumors at diagnosis is shown in Fig. 9.6 . Nearly two-thirds of patients present with clinically apparent cervical lymph node metastases ( Fig. 9.7 ).

Figure 9.6, Clinical T stage distribution at presentation of squamous cell carcinoma of the hypopharynx (MSKCC data).

Figure 9.7, Incidence of nodal metastases at presentation for squamous cell carcinoma of the hypopharynx (MSKCC data).

Evaluation

Patients with lesions of the nasopharynx present with symptoms of nasal obstruction, epistaxis, otalgia, unilateral or bilateral middle ear effusion, or cranial neuropathy as a result of the location and extent of the primary tumor. On the other hand, cervical lymph node metastases may be the first and occasionally the only clinical manifestation in patients with carcinoma of the nasopharynx. Clinical diagnosis requires adequate evaluation of the primary tumor through flexible or rigid nasal endoscopy and/or examination of the nasopharynx through the oral cavity with a 30-degree and 70-degree rigid telescope if the nasopharynx is obstructed. The surface appearance of the lesion often provides a clue to the diagnosis. Smooth, submucosal lesions such as a retention cyst (Thornwaldt cyst), meningocele, craniopharyngioma, or minor salivary gland tumor have normal overlying mucosa. Several examples of lesions in the nasopharynx are shown in Figs. 9.8 through 9.10 . On the other hand, mucosal lesions have a characteristic appearance with irregular, cauliflower-like growth. These lesions should be differentiated from enlarged adenoids, which can be seen in patients with human immunodeficiency virus ( Figs. 9.11 through 9.14 ). Tissue diagnosis of exophytic mucosal lesions can be established easily by a transnasal or peroral biopsy under topical anesthesia. However, a biopsy of submucosal and highly vascular lesions should not be performed before appropriate radiographic imaging and only under controlled circumstances in the operating room. Radiologic imaging of the nasopharynx and neck with computed tomography (CT) and magnetic resonance imaging (MRI) is essential for accurate assessment of the extent of the lesion and staging of malignant tumors.

Figure 9.8, A Thornwaldt cyst of the nasopharynx, nasal endoscopic view (A) and T2 weighted sagittal MRI showing the cyst in the posterior wall of the nasopharynx (B) .

Figure 9.9, A hemangioma of the nasopharynx.

Figure 9.10, A plasmacytoma of the nasopharynx.

Figure 9.11, A hypertrophic adenoid in the nasopharynx.

Figure 9.12, A squamous cell carcinoma of the roof of the nasopharynx.

Figure 9.13, A squamous cell carcinoma of the lateral wall of the nasopharynx.

Figure 9.14, A melanoma of the nasopharynx.

Tumors of the oropharynx are readily assessed by clinical examination through the oral cavity and by flexible fiberoptic nasolaryngoscopy under topical anesthesia in the office setting. Some examples of peroral view of tumors of the oropharynx are shown in Figs. 9.15 through 9.18 . Cervical lymph node metastases occur often in patients with oropharyngeal primary tumors. It is not uncommon to see a small primary tumor with bulky lymph node metastases ( Fig. 9.19 ). This is particularly true in patients with HPV-positive oropharynx cancers. It is the volume and extent of nodal metastases that will determine the treatment approach. For example, a patient with a small primary and bulky nodal metastases is likely to be treated with chemoradiotherapy, in contrast to a patient with a small primary and low-volume neck metastases ( Fig. 9.20 ). Metastatic lymph nodes from primary carcinomas of the tonsil often have cystic degeneration and may be misinterpreted clinically and radiologically as a branchial cleft cyst. Radiologic imaging with CT and MRI is necessary for assessment of these features and regional lymph nodes. Flexible fiberoptic laryngoscopy provides excellent visual assessment of the surface extent of the tumor, but digital palpation is essential to estimate the depth of infiltration in the pharyngeal wall and deep muscles of the base of the tongue. Some examples of endoscopic views of lesions of the base of the tongue are shown in Fig. 9.21 . Clinical differentiation between a hypertrophic lingual tonsil, exophytic squamous cell carcinoma, and lymphoma can sometimes be difficult. For primary tumors of the tonsil, extension to the nasopharynx, soft palate, and base of the tongue are crucial determinants in accurate staging and treatment planning. On the other hand, for primary tumors of the base of the tongue, assessment of extension to the supraglottic larynx and deep infiltration into the extrinsic musculature of the tongue is necessary for accurate staging. Endoscopy, palpation, and biopsy under general anesthesia are usually required for accurate assessment of tumors of the base of the tongue.

Figure 9.15, Squamous cell carcinomas of the soft palate. A , Early stage. Two separate lesions of the hard and soft palate. B , Advanced stage.

Figure 9.16, Squamous cell carcinomas of the tonsil. A , An exophytic lesion of the left tonsil. B , A submucosal lesion of the right tonsil.

Figure 9.18, Ulcerated endophytic carcinoma of the base of the tongue (A) . Exophytic carcinoma of the base of the tongue; lateral (B) and midline (C) .

Figure 9.17, A carcinoma of the posterior pharyngeal wall.

Figure 9.19, Bulky lymph node metastases to the neck from a small primary cancer of the right tonsil.

Figure 9.20, Carcinoma of the right tonsil (T1) with low volume (N1) nodal metastases.

Figure 9.21, Endoscopic view of lesions of the base of the tongue. A , Hypertrophic lingual tonsil. B , Squamous cell carcinoma. C , Adenocarcinoma.

Patients with primary tumors of the hypopharynx usually present with the complaints of discomfort in the throat, dysphagia, odynophagia, sensation of something stuck in the throat, otalgia (referred pain in the ipsilateral ear), hemoptysis, hoarseness of voice, or shortness of breath. A significant proportion of patients have clinically palpable cervical lymph nodes at presentation. In most instances, diagnosis is made by a thorough clinical examination, which would include mirror examination of the hypopharynx and larynx as well as either rigid telescopic or flexible fiber-optic nasolaryngopharyngoscopic examination for adequate clinical assessment of the primary tumor. Several examples of the presenting features of primary tumors of the hypopharynx are shown in Figs. 9.22 through 9.27 . Although clinical examination permits the establishment of the diagnosis of a primary tumor of the hypopharynx, direct laryngoscopy and esophagoscopy under general anesthesia are essential for accurate assessment of the extent of the tumor and to obtain a biopsy specimen for histologic diagnosis to facilitate treatment planning. The important features to be assessed during endoscopic examination under anesthesia include the site of origin of the primary tumor and its local extension to the other sites within the hypopharynx and adjacent regions, including the larynx, oropharynx, and cervical esophagus. For a primary tumor of the pyriform sinus, it is essential to assess its lateral and cephalocaudad extents, particularly as they relate to the apex of the pyriform sinus ( Fig. 9.28 ).

Figure 9.22, A carcinoma of the medial wall of the left pyriform sinus with extension to the arytenoid.

Figure 9.23, An advanced carcinoma of the right pyriform sinus with transglottic invasion.

Figure 9.24, A carcinoma of the left pyriform sinus extending to its apex.

Figure 9.25, An advanced carcinoma of the right pyriform sinus with extension to the larynx.

Figure 9.26, A postcricoid carcinoma.

Figure 9.27, A localized tumor of the medial wall of the right pyriform sinus.

Figure 9.28, Surgical specimen of locally advanced carcinoma of the pyriform sinus extending into cervical esophagus.

Radiographic Evaluation

The lining of the upper aerodigestive tract, including the nasopharynx, oropharynx, and hypopharynx, is radiographically termed the pharyngeal mucosal space. Radiographic imaging is crucial for delineating the third dimension of the primary tumor and the extent of its local invasion, whereas clinical examination is more reliable for assessment of its surface extent. Although MRI is superior for assessment of the soft tissue extent of the tumor, its utility is limited by motion artifact if the patient cannot control swallowing during the examination because of a bulky tumor at the base of the tongue or hypopharynx. In contrast, new generation CT scanners allow rapid acquisition of data that can be reconstructed in coronal and sagittal planes, which is particularly useful in patients who are unable to tolerate an adequate MRI examination.

When evaluating the nasopharynx, MRI is the modality of choice. Although CT is excellent for assessment of cortical bone and foramina at the skull base, nasopharyngeal tumors have a tendency to invade the medullary space of the clivus, and bone involvement therefore is detected earlier on MRI than on CT. Benign lesions of the nasopharynx such as a Thornwaldt cyst and retention cysts have characteristic imaging features that are helpful in making a diagnosis. Thornwaldt cysts arise from the notochord remnant and are located submucosally in the midline. They are very well defined and generally are bright on T2-weighted MRI ( Fig. 9.29 ). Retention cysts, generally located paramedian or laterally, are also bright on T2-weighted MRI and do not enhance with contrast ( Fig. 9.30 ).

Figure 9.29, A Thornwaldt cyst of the nasopharynx. A , A T1-weighted magnetic resonance imaging scan showing a well-defined midline submucosal lesion of the nasopharynx located between the longus colli muscles. The lesion is T1 bright because of its high protein content. B , This lesion has an intermediate signal on T2-weighted MRI, but the signal can vary depending on the protein content of the lesion.

Figure 9.30, A T2-weighted magnetic resonance imaging scan showing a well-defined hyperintense retention cyst in the right fossa of Rosenmüller.

The presence of an asymmetric mass in the nasopharynx is an obvious feature that should raise suspicion for a tumor in adults, especially if unilateral opacification of the ipsilateral mastoid air cells is noted. However, adenoidal tissue can be a source of confusion, especially in children. The presence of certain other features such as skull base invasion can point to the diagnosis of malignancy in these situations. Invasion of the skull base is seen frequently in patients with NPC, because the pharyngobasilar fascia acts as a barrier to lateral spread and funnels the tumor cephalad toward the central skull base. Early clival invasion is nicely seen on precontrast T1-weighted MRI, because normal bright adult fatty marrow provides contrast for grayish tumor infiltration. The tumor generally has a high signal on T2-weighted MRI and enhances on postcontrast images ( Fig. 9.31 ). Another feature of NPC is infiltration of the petroclival fissure, which is best demonstrated on bone windows of a CT scan ( Fig. 9.32 ). Gross extension into the parapharyngeal space occurs with breach of the pharyngobasilar fascia ( Fig. 9.33 ). The tumor can directly involve the lower cranial nerves, or perineural spread of tumor can occur along the branches of the trigeminal nerve. A tumor also can extend into the pterygopalatine fossa, gaining access to the vidian nerve and V2 ( Fig. 9.34 ), and it can involve the muscles of mastication in the masticator space ( Fig. 9.35 ), although this happens rarely.

Figure 9.31, Invasion of the clivus by a nasopharyngeal carcinoma seen on a magnetic resonance imaging (MRI) scan. A , An axial precontrast T1-weighted MRI scan showing a grayish tumor infiltrating normal bright adult fatty marrow. B , The tumor has a high signal on T2-weighted MRI. C , The tumor enhances on a postcontrast T1-weighted MRI scan.

Figure 9.32, A computed tomography scan. A , Soft tissue. B , Bone window showing widening of the petroclival fissure by a nasopharyngeal carcinoma ( arrow ).

Figure 9.33, An axial postcontrast computed tomography scan showing invasion of the right parapharyngeal space by a nasopharyngeal carcinoma.

Figure 9.34, An axial postcontrast computed tomography scan. A , Arrow shows abnormal soft tissue in the right pterygopalatine fossa on the soft-tissue window. B , Arrow shows widening of the bony right pterygopalatine fossa on the bone window.

Figure 9.35, A T2-weighted magnetic resonance imaging scan showing involvement of the left masticator space by a nasopharyngeal carcinoma. Arrow indicates tumor extension.

Small and superficial tumors of the base of the tongue can be difficult to differentiate from lingual tonsillar tissue. The diagnosis of malignancy is obvious if infiltration into the base of tongue musculature is seen, but tumors of minor salivary gland origin can be well defined and difficult to differentiate from benign lesions ( Fig. 9.36 ). Imaging for lesions of the base of the tongue can be helpful in delineating the relationship of the tumor to the neurovascular bundles and for assessment of submucosal spread to the tonsillar fossa, soft palate, and pharyngeal wall ( Fig. 9.37 ). Sagittal T1-weighted precontrast MRI is useful for assessment of preepiglottic space invasion by a base of tongue tumor. Tumors of the tonsil also can spread submucosally to the base of the tongue via the glossotonsillar fold or to the soft palate ( Fig. 9.38 ). More advanced tumors can extend into the masticator space, involve the mandible, or encase the internal carotid artery.

Figure 9.36, A minor salivary gland tumor of the right base of the tongue. A , Endoscopic view. B , Postcontrast, T1-weighted magnetic resonance imaging scan shows contrast-enhancing tumor of the right base of the tongue.

Figure 9.37, A contrast-enhanced computed tomography scan showing spread of a tumor ( A ) at the left base of the tongue ( arrowhead ) and ( B ) laterally to the lateral pharyngeal wall ( arrow ).

Figure 9.38, Patterns of spread of a tonsillar carcinoma shown on a computed tomography scan. A , Invasion of the right soft palate. B , Involvement of the base of the tongue. Note the location of the right internal carotid artery shown by the arrow between the primary tumor and the necrotic right level II lymph node. The artery is at risk for encasement or involvement by advanced tonsil cancer.

Early staged carcinomas of the hypopharynx are rare but are evident on CT scans as an area of thickened, enhancing mucosa ( Fig. 9.39 ). Tumors of the medial wall of the pyriform sinus can extend into the paraglottic space and cause vocal cord fixation ( Fig. 9.40 ). Laterally, the thyroid cartilage is located immediately beneath the pyriform mucosa and is at risk for invasion by cancer. Involvement of the apex of the pyriform sinus places the cricoid cartilage at risk for invasion, and the adjacent recurrent laryngeal nerve can be directly invaded by tumor in the upper tracheoesophageal groove ( Fig. 9.41 ). Early carcinomas of the posterior pharyngeal wall appear as an area of subtle thickening with enhancement on contrast-enhanced CT, but more advanced tumors are readily apparent because of asymmetry ( Fig. 9.42 ). Imaging can be useful in delineating the relationship of these tumors to the prevertebral musculature if obvious infiltration is present, but early invasion often is difficult to define. Postcricoid tumors can spread submucosally to involve the circumference of the hypopharynx and often extend caudally into the cervical esophagus ( Fig. 9.43 ). Involvement of the cervical esophagus appears as asymmetric thickening of its wall, which is more easily seen on T2-weighted MRI. Extraluminal spread is indicated by obliteration of fat in the upper tracheoesophageal groove.

Figure 9.39, A contrast-enhanced axial computed tomography scan showing thickened, enhancing reverse-C–shaped lesion of the left pyriform sinus ( arrow ). Note the pencil-thin mucosa of the normal contralateral pyriform sinus for comparison.

Figure 9.40, A postcontrast T1-weighted fat-saturated magnetic resonance imaging scan showing extension of a left pyriform sinus tumor into the left paraglottic space ( arrow ).

Figure 9.41, A contrast-enhanced computed tomography scan showing ( A ) a locally advanced tumor of the right pyriform sinus that has ( B ) destroyed the posterior aspect of the lamina of the right thyroid cartilage and ( C ) the right half of the cricoid cartilage with obvious extralaryngeal soft-tissue extension.

Figure 9.42, A carcinoma of the posterior pharyngeal wall seen on a contrast-enhanced computed tomography scan. A , Early tumor of the left posterior pharyngeal wall. B , Obvious abnormal thickening and enhancement of the posterior pharyngeal wall in a more advanced tumor. Note the presence of a fat plane ( arrows ) overlying the prevertebral musculature.

Figure 9.43, A contrast-enhanced computed tomography scan showing ( A ) abnormal soft tissue thickening of the postcricoid hypopharynx ( arrow ) and ( B ) circumferential extension caudad into the cervical esophagus ( arrow shows esophageal lumen).

Radiographic imaging with CT or MRI is especially important in the evaluation of the regional lymph nodes in patients with cancer of the pharynx, because retropharyngeal lymph nodes are not amenable to clinical evaluation or ultrasound examination. The lateral retropharyngeal lymph nodes (which have a normal size of less than 8 mm in adults) are located between the prevertebral musculature (longus colli and capitis muscles) and the internal carotid artery. These lymph nodes are at risk for involvement by tumors of the nasopharynx and tonsil ( Fig. 9.44 ). Cystic cervical nodal metastases are a hallmark of primary cancer of Waldeyer's ring and should not be confused with “branchial cleft cyst.” A cystic neck mass in an adult always should be considered indicative of metastatic disease unless proven otherwise. Branchial cleft cysts have homogeneous content and a thin and smooth wall that does not enhance unless the cyst is infected. Cystic metastases, on the other hand, usually have a thick wall with rim enhancement, may be multiple, and are most often associated with a demonstrable primary tumor ( Fig. 9.45 ).

Figure 9.44, Lateral retropharyngeal lymphadenopathy. A , Contrast-enhanced computed tomography scan showing a cystic right lateral retropharyngeal lymph node from a primary tonsil squamous cell carcinoma. Note the location of the lymph node ( * ) between the prevertebral musculature ( black arrow ) and the internal carotid artery ( white arrow ). B , A postcontrast axial T1-weighted fat-saturated magnetic resonance imaging scan showing a metastatic left retropharyngeal node from a nasopharyngeal primary tumor. The prevertebral musculature ( white arrow ) is infiltrated by extracapsular spread from the retropharyngeal lymph node.

Figure 9.45, A , A contrast-enhanced computed tomography scan showing a cystic homogeneous mass with a thin nonenhancing rim ( arrow ) in a young male patient indicative of a branchial cleft cyst of the right neck. B , A computed tomography simulation film showing a cystic mass with an enhancing rim ( * ) in the left side of the neck consistent with cystic nodal metastasis. This patient had bilateral cystic nodal metastases from a primary carcinoma of the left tonsil evident on a positron emission tomography scan ( C ).

Positron emission tomography (PET) scanning has become essential in pretreatment assessment of the extent of primary tumor and regional lymph node metastases ( Fig. 9.46 ). It is regularly used for radiation treatment planning and is an essential imaging study for evaluating response to therapy in cancers of the oropharynx and other sites treated by chemoradiotherapy. Generally, PET scan assessment should be done at least 3 months following completion of treatment.

Figure 9.46, Pretreatment imaging with a contrast-enhanced CT scan and a PET scan for carcinoma of the tonsil.

Pathologic Evaluation

Nasopharynx

Nasopharyngeal squamous cell carcinoma is classified by the World Health Organization into keratinizing, nonkeratinizing, and undifferentiated types ( Table 9.1 ). Nonkeratinizing carcinoma is further subclassified into differentiated and undifferentiated subtypes. The undifferentiated subtype of nonkeratinizing carcinoma is particularly common in southeast Asia, where it represents 15% to 20% of all cancers and is thought to be associated with EBV infection. EBV can be detected in the tumor cells of almost all nonkeratinizing carcinoma but rarely in keratinizing NPC ( Fig. 9.47 ).

Table 9.1
The World Health Organization (WHO) Classification of Nasopharyngeal Carcinoma (2005)
WHO 1978 WHO 1991 WHO 2005
  • I

    Squamous cell carcinoma

  • I

    Squamous cell carcinoma

  • Keratinizing squamous cell carcinoma

  • II

    Nonkeratinizing carcinoma

  • III

    Undifferentiated carcinoma

  • II

    Nonkeratinizing carcinoma

    • a

      Differentiated nonkeratinizing carcinoma

    • b

      Undifferentiated carcinoma

  • Nonkeratinizing carcinoma

  • Differentiated

  • Undifferentiated

  • Basaloid squamous cell carcinoma

Figure 9.47, Epstein-Barr virus–encoded ribonucleic acid in situ hybridization showing strong nuclear labeling of tumor for Epstein-Barr virus in nasopharyngeal carcinoma.

Differentiated nonkeratinizing nasopharyngeal carcinomas display a stratified appearance and distinct cell margins. By contrast, undifferentiated tumors exhibit clusters of poorly delineated or syncytial cells bearing large vesicular oval nuclei and scant eosinophilic cytoplasm. The undifferentiated variant often features a conspicuous lymphoid infiltrate, accounting for the obsolete (and misleading) term “lymphoepithelioma” ( Fig. 9.48 ). Both subtypes are immunoreactive with cytokeratin. The epithelial nature of this tumor is underscored by the fact that tumor cells express cytokeratin but no hematologic or lymphoid markers.

Figure 9.48, Undifferentiated nasopharyngeal carcinoma. A , Tumor cells growing in a nested, syncytial pattern with indistinct cell borders, open chromatin, and prominent nucleoli. (Hematoxylin-eosin stain; ×400.) B , Abundant lymphoid infiltrate that obscures nests of tumor cells ( arrow ). (Hematoxylin-eosin stain; ×100.)

Oropharynx

Worldwide, up to 25% of head and neck squamous cell carcinomas are associated with high-risk HPV, the great majority of which are HPV 16. However, HPV serotypes 18, 31, 33, and 35 also have been associated with oropharyngeal squamous cell carcinoma. The HPV oncoproteins (E6 and E7) transform oral squamous epithelial cells. These proteins bind with p53 and Rb, respectively, interfering with their tumor suppressor functions and leading to cell cycle dysregulation and genetic instability. Immunohistochemistry for p16 is commonly used as a surrogate marker to identify HPV infection. Diffuse (>70%) and strong nuclear and cytoplasmic immunoreactivity is required to label a tumor as positive for that marker. In situ hybridization for HPV DNA ( Fig. 9.49 ) and RNA are now available. The latter has high sensitivity and specificity and localizes to the nucleus and cytoplasm.

Figure 9.49, Oropharyngeal squamous cell carcinoma. A , Islands of squamous cell carcinoma involving the tonsil. (Hematoxylin-eosin stain.) B , Low-power view of human papillomavirus in situ hybridization with a probe that covers multiple high-risk serotypes, including human papillomavirus 16 and 18. C , Higher magnification demonstrates dot-like nuclear positivity.

In the United States approximately 80% of oropharyngeal squamous cell carcinomas are associated with high-risk HPV. The tonsil is the most frequent site for these tumors, which have a basaloid morphologic appearance, are usually moderately to poorly differentiated, and have minimal to no associated keratin production. HPV-associated carcinomas in general carry a better prognosis than do their non-HPV–related counterparts. The histologic distinction between these tumors and the classic basaloid squamous cell carcinoma is not clear.

HPV-positive oropharyngeal squamous cell carcinomas are seen in a younger patient population, two to three decades earlier than the usual head and neck squamous cell carcinoma population. Patients usually do not have a history of smoking or heavy alcohol consumption. These patients have a better response to treatment with superior outcomes. On the other hand, heavy smokers and drinkers who also are HPV positive do not have the same favorable outcomes.

Hypopharynx

The majority of patients with hypopharyngeal squamous cell carcinoma have a history of tobacco and alcohol consumption. The risk is especially increased in patients with heavy alcohol consumption, as is observed in southern Europe. Historically, nutritional deficiency and anemia were said to be associated with postcricoid carcinoma, as reported from Scandinavia (Plummer-Vinson syndrome). Histologically, these tumors are moderate to poorly differentiated carcinomas with significant proclivity for submucosal spread, especially distally ( Fig. 9.50 ). Skip areas of tumor spread with additional lesions often are seen in the cervical esophagus. The hypopharynx is the most frequent site for synchronous primary tumors in the upper aerodigestive tract. Lymphatic drainage of the hypopharynx to the regional lymph nodes is profuse, and lymph node metastasis is a common feature at presentation. Consequently, management of cervical lymph nodes is integral in treatment planning.

Figure 9.50, Submucosal extension of tumor in a hypopharyngeal squamous cell carcinoma (hematoxylin-eosin stain).

Treatment

Nasopharyngeal squamous cell carcinomas, by virtue of their anatomic location and relative inaccessibility for a curative surgical resection, are generally managed by nonsurgical treatment. In addition, these tumors are highly responsive to radiotherapy and chemotherapy. Thus a combination of chemotherapy and radiotherapy remains the choice of initial definitive treatment (see Chapter 19 for details). Surgical intervention may be considered in a select group of patients for whom previous chemoradiation therapy has failed and who have a localized, well-defined, residual or recurrent cancer (confined to the mucosa and underlying soft tissues only). Similarly, neck dissection for regional metastases is considered only in the setting of residual or recurrent nodal metastases that have failed to respond to chemoradiotherapy. However, minor salivary gland tumors, angiofibromas, and other benign and malignant lesions of the nasopharynx do require surgical intervention with or without postoperative radiation therapy.

Treatment of oropharyngeal cancer is evolving with improved understanding of tumor biology, technical advances in instrumentation, and emerging data from retrospective studies and clinical trials. In general, oropharyngeal squamous cell carcinomas are responsive to primary radiation approaches with the addition of concurrent chemotherapy for advanced stage tumors. There has also been a renewed interest in surgery as a definitive treatment with or without postoperative radiation therapy with technologic advancements in transoral robotic surgery (TORS) and transoral laser microsurgery (TOLM). Traditional open approaches via mandibulotomy are reserved for recurrent disease, advanced tumors in patients who are not candidates for chemoradiation therapy, minor salivary gland tumors, and other neoplasms that are not sensitive to primary radiation approaches.

The ultimate goal for the treatment of tumors of the hypopharynx is control of the cancer. However, when feasible, preservation of the functions of speech and normal swallowing and avoidance of a tracheostomy are other desirable goals. Small and superficial lesions of the hypopharynx can be managed by external radiation therapy or endoscopic resection as definitive treatment. In select patients requiring a laryngectomy for advanced pharyngeal cancers, nonsurgical means of treatment with the aim of preservation of the larynx, using a multimodal treatment program consisting of chemotherapy and radiation therapy, should be considered. In the past two decades, an increasing number of patients with hypopharyngeal cancers requiring total laryngectomy are being treated with a larynx preservation treatment program of neoadjuvant or concurrent chemoradiotherapy, except for those with gross thyroid cartilage destruction by cancer (see Chapter 20 for details).

For patients presenting with advanced disease for whom a pharyngolaryngectomy is essential, the goals of treatment are directed at reestablishing the anatomic continuity of the alimentary tract with restoration of the patient's ability to swallow by mouth as soon as possible. However, in patients in whom the larynx is uninvolved but the extent of pharyngeal resection requires the need for immediate reconstruction, significant clinical judgment needs to be exercised for the successful outcome of such an undertaking, because postoperative aspiration becomes a major problem. In patients requiring a circumferential pharyngolaryngectomy, restoration of the continuity of the alimentary tract becomes an integral part of initial surgical treatment planning. Most patients with advanced primary tumors require multimodality treatment to enhance the chances of control of the cancer. Because of the aggressive nature of this tumor and its increased proclivity to early involvement of regional lymph nodes by metastatic disease, a combined treatment program of surgical excision of the primary tumor with or without neck dissection followed by postoperative radiation therapy with or without chemotherapy for the primary site and regional lymphatics is currently considered the standard of care.

Factors Affecting Choice of Treatment

The anticipated response to chemoradiation therapy is a key factor in the selection of initial definitive treatment. In general, early staged pharyngeal squamous cell carcinomas are responsive to radiation, with only a small proportion of patients requiring salvage surgery. Therefore most of these cancers, and particularly those where the larynx is at risk, are currently treated with radiation or chemoradiation therapy. This approach is supported by several prospective trials (see Chapter 20 ) and has become the standard of care.

Current treatment guidelines for oropharynx squamous cell carcinoma are in a state of evolution in light of the favorable prognostic influence of HPV status and with the goal of reducing treatment-related morbidity. Quantifying risk in this patient population has affected the choice of treatment. Specifically, risk stratification studies have attempted to identify “low-risk” patients who may be candidates for de-escalation of treatment. In the Radiation Therapy and Oncology Group trial (RTOG–0129), HPV-positive patients who were nonsmokers or with a smoking history of less than 10 pack-years and/or N0–N2a were considered “low risk” with a 3-year overall survival rate of 93%. T1-T3N0-N2b HPV-positive patients were identified as having a very low risk of distant metastases and therefore could be possible candidates for radiation alone. Surgery as a de-escalation strategy is also under evaluation. In 2009 the US Food and Drug Administration approved transoral robotic surgery for the treatment of T1–T2 oropharyngeal carcinoma. Proponents of surgery argue that TORS may achieve better functional outcomes compared with primary radiation approaches by reducing radiotherapy doses or eliminating chemotherapy. This is being tested in a randomized controlled trial at this time. TORS represents an attractive option in highly selected patients in whom surgery as a single modality of treatment may be all that is required for disease control. On the other hand, utilizing primary surgery as a deintensifying approach may be counterproductive if adjuvant radiation with possible concurrent chemotherapy is required based on the pathologic results of the resected primary tumor and neck nodes. This may be the case with a positive margin resection or if metastatic lymph nodes are found to have extranodal spread. Several de-escalation strategies are currently being evaluated in ongoing clinical trials, and they will need to show long-term better functional outcomes and at least equally good tumor control rates. Although concurrent chemoradiation is recommend for advanced stage tumors, selected deeply infiltrating endophytic tumors have a lower probability of complete response to chemoradiation and may be better treated with initial surgical resection. Very advanced tumors of the oropharynx with invasion of the mandible also are best treated with initial surgery. The factors that influence the choice of treatment for squamous cell carcinoma of the hypopharynx are related to the tumor, the patient, and the treatment team. Primary site, T stage, local extension, circumferential extent, cephalo-caudad extent, multifocality, extent of laryngeal invasion, histology, and involvement of regional lymph nodes are important tumor factors that would influence the decision regarding initial treatment. Invasion of the larynx with fixation of the vocal cords clearly puts the larynx in jeopardy. Early staged tumors of the hypopharynx may be treated by external beam radiation therapy alone or endoscopic laser resection with or without neck dissection and postoperative radiation therapy. Lesions that are not suitable for endoscopic resection where the larynx is not involved may be candidates for a partial laryngopharyngectomy. Patients in whom a laryngectomy is required for resection of a hypopharyngeal carcinoma are candidates for organ preservation treatment with chemoradiation given sequentially or concurrently. Very advanced tumors of the hypopharynx with invasion of the thyroid or cricoid cartilage require a pharyngolaryngectomy with appropriate reconstruction and postoperative adjuvant treatment. Tumors of the postcricoid region or lesions of the pharyngeal wall with circumferential involvement have a high risk of development of stricture following chemoradiation and should be considered for initial surgery.

With regard to patient factors, general status of health, airway compromise, and pulmonary function are vitally important. Patients with chronic obstructive pulmonary disease are poor candidates for consideration of an endoscopic or open partial laryngopharyngectomy because their ability to handle resulting postoperative aspiration is poor. Thus the possibility of extended pharyngeal resections with a partial laryngectomy is exceedingly small in patients who have poor pulmonary reserve. Similarly, the choice of reconstructive procedures for restoration of the anatomic continuity of the alimentary tract depends on various patient factors. These factors include availability of regional cutaneous and myocutaneous flaps, the status of peripheral vessels to permit the use of microvascular composite free flaps, and the availability of the stomach in patients who require a pharyngolaryngoesophagectomy for large tumors with extension to the cervical esophagus. In addition, a patient's habits, lifestyle, compliance, and preference are other factors to be considered.

Availability of a multidisciplinary surgical and comprehensive head and neck oncology team is the most important physician-related factor that influences the successful outcome of a comprehensive treatment program. These factors include surgical skills, especially endoscopic diagnostic capabilities; skills in laser resection and robotic surgery; experience in open conservation surgery; and experience in contemporary reconstructive techniques, including microvascular surgery as well as the availability of a postoperative swallowing and speech rehabilitation team. On the other hand, for nonsurgical organ preservation treatments, excellence in multidisciplinary management, including expertise in medical oncology and radiation oncology and availability of a speech and swallowing rehabilitation team, is essential for a successful outcome.

Surgical Treatment

During the past two decades, the role of initial definitive surgery in the management of oropharyngeal and hypopharyngeal carcinomas has diminished considerably. Primary surgery is reserved for highly selected patients as mentioned previously. However, surgery remains the only effective option for salvage of patients who do not respond to initial nonsurgical treatment. The management of these patients is challenging, both from the perspective of the cancer and the patient. Tumors that are resistant to chemotherapy and radiation are biologically more aggressive than those that respond, leading to higher rates of recurrence even after complete surgical resection. In addition, chemoradiated tissues heal poorly, leading to increased risk for surgical complications. Accordingly, surgical treatment planning in these patients should include the judicious use of nonirradiated vascularized regional or free flaps for reconstruction and to promote healing of radiated mucosal suture lines.

In preparing the patient for surgical resection, preoperative evaluation to assess the anatomic extent of the tumor and the functional integrity of the upper aerodigestive tract is crucial. Velopharyngeal competence and mobility of the vocal cords are best assessed by careful clinical examination and flexible nasolaryngoscopy. However, to assess the anatomic extent of the tumor; detailed radiographic imaging; examination under anesthesia; and nasopharyngoscopy, laryngoscopy, and esophagoscopy are required. Palpation of the base of the tongue and pharyngeal wall for lesions of the oropharynx provides valuable information regarding the third dimension of the tumor. Similarly, evaluation of the apex of the pyriform sinus and pharyngoesophageal junction is crucial in planning surgical resection for hypopharyngeal tumors.

Surgical Anatomy

The nasopharynx begins at the posterior choana of the nasal cavity and extends up to the free border of the soft palate. The oropharynx extends from the plane of the superior surface of the soft palate to the plane of the superior surface of the hyoid bone. The hypopharynx extends from the plane of the superior surface of the hyoid bone to the plane corresponding to the lower border of the cricoid cartilage (C6 vertebra), where it continues into the cervical esophagus. The musculature of the pharynx consists of the pharyngeal constrictors and the pharyngeal elevators. The three pharyngeal constrictor muscles are oriented in a “cup within a cup” fashion, and their fibers insert posteriorly into a midline fibrous raphe, which is attached superiorly to the pharyngeal tubercle of the occipital bone. The pharyngeal mucosa immediately superior to the level of the superior constrictor muscle is in direct contact with and is supported by a thickened pharyngobasilar fascia. This fascia is attached at the skull base to the basilar portion of the occipital bone, the petrous temporal bone along the medial border of the pharyngotympanic tube, and the posterior border of the medial pterygoid plate and pterygomandibular raphe. The pharyngeal elevators attach to the skull base and help elevate the pharynx during swallowing and breathing.

The branches of the external carotid artery provide blood supply to the pharynx via the ascending pharyngeal artery, the ascending palatine and tonsillar branches of the facial artery, the greater palatine and pharyngeal branches of the maxillary artery, and the dorsal lingual branches of the lingual artery. The pharyngeal veins drain into the internal jugular vein and lymphatics drain into the retropharyngeal and parapharyngeal nodes and the nodes at levels II, III, and IV in the neck. The branches of the pharyngeal plexus (from the IX and X cranial nerves) provide sensory and motor innervation to the pharynx. The anatomic location of the major nerves and blood vessels in relation to the pharynx is shown in Fig. 9.51 .

Figure 9.51, Anatomic relation of the major nerves and blood vessels to the pharynx.

Nasopharynx

The mucosal surface of the nasopharynx can be divided into its roof, the posterior wall, and two lateral walls. The dome-shaped roof consists of the mucosa that overlies the body of the sphenoid bone and the basilar part of the occipital bone up to the pharyngeal tubercle (clivus). Inferiorly, the mucosa of the posterior wall covers the pharyngobasilar fascia and the anterior arch of the atlas. The nasopharyngeal tonsil or adenoid is a midline lymphoid mass that is located in the roof of the nasopharynx as it curves into the posterior wall. The adenoid is relatively large at birth and generally atrophies by preadolescence. However, the adenoid may persist even as late as the seventh decade of life and can cause confusion with a nasopharyngeal tumor. The eustachian (pharyngotympanic) tube connects the tympanic cavity of the ear to the nasopharynx and serves the important function of equilibrating pressure in the middle ear. The trumpet-shaped bony part of the tube arises from the anterior tympanic wall and narrows down to the junction of the squamous and petrous parts of the temporal bone, where it lies medial to the carotid canal. The cartilaginous portion arises at this isthmus and flares out to open onto the lateral wall of the nasopharynx through a triangular opening that lies immediately anterior to the small mound of lymphoid tissue (torus tubarius) and the pharyngeal recess (fossa of Rosenmüller). The petrous portion of the temporal bone and the levator veli palatini muscle are located posteromedial, while the salpingopharyngeus muscle is attached to the inferior lip of the tube underlying the mucosal fold that bounds the tubal opening. The tensor veli palatini muscle separates the eustachian tube anterolaterally from the otic ganglion, V3 and its branches, the middle meningeal artery, and the chorda tympani. The superior surface of the soft palate constitutes the floor of the nasopharynx, which is deficient posteriorly as it continues into the oropharynx. The lateral wall of the nasopharynx is in close anatomic proximity to the lower cranial nerves (IX–XII), which are at risk for involvement not only by tumor but also from long-term sequelae of radiation.

Oropharynx

The soft palate is a musculoaponeurotic curtain that hangs down from the posterior border of the hard palate and maintains velopharyngeal competence during speech and swallowing. The midline uvula is located on the free inferior border, and the sides blend into the faucial arches that attach to the lateral pharyngeal walls. The mucosa of the soft palate is of the stratified squamous type, and the submucosa contains minor salivary glands that mainly secrete mucus. The muscles of the soft palate include the palatopharyngeus, palatoglossus, tensor veli palatini, levator veli palatini, and musculus uvulae. Resection of the musculature of the soft palate often will lead to dysfunction of the eustachian tube and middle ear effusion, requiring placement of ventilation tubes. Passavant's ridge, which is formed by contraction of the fibers of the superior constrictor muscle, often compensates for the loss of the soft palate and provides velopharyngeal competence. The pterygomandibular raphe provides attachment to the superior constrictor and buccinator muscles. It extends from the pterygoid hamulus, which is located immediately posterior and medial to the upper alveolar process, to the posterior end of the mylohyoid line on the lingual aspect of the mandible. The inferior alveolar nerve lies underneath the mucosal fold formed by the raphe and is at risk for involvement by tumors.

The pharyngeal tonsils are located in the tonsillar fossae, which are bounded by the anterior and posterior tonsillar pillars and contain the palatoglossus and palatopharyngeus muscles, respectively. The pharyngeal tonsils blend inferiorly into the lingual tonsils at the base of the tongue. These tonsils, together with nasopharyngeal adenoid tissue, form Waldeyer's ring. The deep or lateral boundary of the tonsillar fossa is composed of the superior constrictor and stylopharyngeus muscles, and the tonsil is separated from the pharyngeal wall by loose areolar tissue. The arterial supply to the tonsils is provided primarily by the superior and inferior tonsillar arteries, which are branches of the facial and palatine arteries. The pharyngeal tonsils are lined by squamous mucosa that forms crypts within aggregations of lymphoid tissue. These crypts can harbor a “clinically occult” primary squamous cell carcinoma that may be asymptomatic. Larger tumors extend beyond the tonsil and may involve the pharyngeal wall, base of the tongue, larynx, or parapharyngeal space.

The base of the tongue is demarcated by the circumvallate papillae anteriorly and the valleculae (pharyngoepiglottic folds) posteriorly and is bounded laterally by the tonsillar fossae. The muscles of the base of the tongue consist of the extrinsic muscles (hyoglossus, styloglossus, and genioglossus) and the intrinsic muscles. Minor salivary glands and aggregates of lymphoid tissue (lingual tonsil) are dispersed throughout its submucosa. The base of the tongue, along with other suprahyoid muscles, have an important function in laryngeal elevation during the pharyngeal phase of deglutition. Therefore resection of any part of the base of the tongue has the potential to alter swallowing. The sensory supply of the base of the tongue is from the glossopharyngeal nerve. Reconstruction of surgical defects of the base of tongue therefore ideally is accomplished with primary closure, because insensate flaps may increase the risk for aspiration.

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