Head and neck cancer technically refers to any malignancy

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1 Head and Neck Cancer Michael J. Walden, DO, MD, and Nafi Aygun, MD Cross sectional imaging fills a crucial role in the work up of squamous cell cancer of the head and neck. The radiologist can suggest important considerations in treatment planning and disease prognosis. Key areas of anatomy in radiologic staging are reviewed. Semin Roentgenol 48: Elsevier Inc. All rights reserved. Head and neck cancer technically refers to any malignancy arising in the skin, nasal cavity, paranasal sinuses, oral cavity, salivary glands, pharynx, and larynx. The majority of head and neck malignancies ( 90%) are squamous cell carcinoma of the mucosal surfaces of the head and neck (SCCHN), which is the focus of this review. Nasopharyngeal carcinoma (NPC) is somewhat unique in that squamous cell carcinoma is a minor subtype, with nonkeratinizing undifferentiated carcinoma, followed by keratinizing undifferentiated carcinoma, being more common. 1 The sinuses and salivary glands are best evaluated individually and are not addressed here. Epidemiology The overall incidence of cancer has declined in the United States, Canada, and western Europe within the past 20 years. 2,3 The same holds true for most subsites of head and neck cancer. During this same period, prevalence of smoking has declined, 4 and there appears to have been a decline in the impact of traditional risk factors, such as tobacco and alcohol consumption, on the development of squamous cell carcinoma of the head and neck. 5-8 However, there has been a marked increase in the incidence of oropharyngeal cancer (base of tongue and, to a lesser extent, tonsilar) over the same period in both America and Europe. 9 Numerous studies point to human papillomavirus (HPV) as the causative factor for this increase. 9,10 For nasopharyngeal cancer, there is a strong association with Epstein Barr virus. Ingestion of cured meats also appears to be a risk factor along with smoking. 11 For cancer of the oral cavity, chewing tobacco and, in some parts of the The Russell H. Morgan Department of Radiology and Radiological Sciences, the Johns Hopkins Medical Institutions, Baltimore, MD Address reprint requests to Nafi Aygun, MD, The Russell H. Morgan Department of Radiology and Radiological Sciences, the Johns Hopkins Medical Institutions, 600 North Wolfe Street, Phipps B-100F, Baltimore, MD naygun1@jhmi.edu. world, betel nuts, along with poor oral hygiene, are additional risk factors alongside smoking and alcohol consumption There is a strong male predilection for SCCHN, which accounts for approximately one-sixth of cancers worldwide and is the eighth commonest malignancy among male individuals in the United States. 16,17 Most patients present in advanced stages, that is, with large-sized metastatic lymph nodes. The incidence of SCCHN increases with age, with most patients presenting in the sixth through eighth decades. 12 However, patients with HPV-associated cancer tend to be younger and present in their 30s and 40s. Risk factors for HPV-related SCCHN suggest sexual transmission of the virus, for example, early intercourse, high number of sexual partners, and oral sex activity. This has led to discussion about targeting young men for HPV vaccination. 9,18,19 Overall survival rate in patients with SCCHN is poor and varies among subsites, although cure is often achievable in early-stage disease. Five-year survival rates range from 30% in the hypopharynx to 60% in portions of the oral cavity. Overall survival rate among patients with primary site as oropharynx and tonsil is 50%. 12 However, patients with HPV-related SCCHN have improved treatment response and 25%-30% improved 2-year survival compared with non- HPV related malignancies. 20,21 Imaging Modalities Imaging is complementary to clinical assessment, including endoscopy, for staging of SCCHN. In many cases, computed tomography (CT) and magnetic resonance imaging (MRI) are comparable in accuracy for staging initial tumors. However, CT has been the mainstay for initial imaging and staging because of its availability, cost, and tolerability by patients owing to ultrafast scan times. 22,23 The recent ability to combine diagnostic CT with positron emission tomography (PET) has also increased the utility of CT compared with MRI. Also, MRI is sometimes hampered by swallowing and motion artifacts. For evaluation of transglottic extension of X/13/$-see front matter 2013 Elsevier Inc. All rights reserved. 75

2 76 M.J. Walden and N. Aygun Table 1 Primary Tumor Staging of the Oral Cavity T1 T4a T4b Tumor <2 cm in greatest dimension Tumor >2 cmbut <4 cm in greatest dimension Tumor >4 cm in greatest dimension Tumor invades adjacent structures only; eg, mandible, maxilla, extrinsic tongue muscles, maxillary sinus, or skin of face Tumor invades masticator space, pterygoid plates, or skull base, and/or encases internal carotid artery Data from American Joint Committee on Cancer Staging. American Joint Committee on Cancer Staging Manual (7th ed). New York, NY, Springer, laryngeal disease, MRI is slightly more accurate owing to its better tissue contrast. For evaluation of laryngeal cartilage invasion, MRI is more sensitive than CT. However, CT is more specific than MRI. The combination of MRI and CT may be the most effective strategy to determine cartilage invasion in this area In the oral cavity and nasopharynx, MRI is preferable to CT because it is more sensitive than CT for demonstrating submucosal spread, perineural spread, and skull base involvement, although CT can be complementary in many cases MRI is also generally less hindered by dental metallic artifacts. Fluorodeoxyglucose (FDG)-PET/CT is a widely used modality that is often adjunctive to CT or MRI for initial staging of disease, although staging accuracy for PET is comparable with CT or MRI in most cases. However, the ability of PET to demonstrate distant metastases may be critical in evaluation of advanced-stage disease. In the setting of unknown (occult) primary tumor with nodal metastases, PET may help identify the primary tumor better than CT or MRI. It is used primarily as an adjunct to endoscopy and random biopsies of the tongue base and tonsils in this setting, where sensitivity for this modality approaches 40%. 32 FDG-PET/CT is often indispensable in evaluating posttreatment patients for recurrence, as the accuracy of anatomic imaging is somewhat limited in this setting. In addition, radiation oncologists use PET to plan radiation therapy, as studies have shown that PET/CT may be more accurate than CT alone or MRI in defining the radiation treatment field. 33 Consequent to its multiple indications, FDG-PET/CT use has grown substantially over the past decade as an adjunct to anatomic imaging. 34 Nonstandard techniques are sometimes used at some centers. These include MRI spectroscopy, MRI perfusion, diffusion-weighted imaging, and CT perfusion. These have shown some utility in differentiating between benign and malignant processes and evaluating treatment response in some studies, but are not yet widely used. Some of these applications are limited by artifact, as is the case for the MRI techniques, and often do not perform as well as PET/CT. Investigational biological techniques include perfusion CT or MRI, diffusion tensor imaging, fluorine-18 fluoromisonidazole imaging for hypoxia, fluorine F 18 fluorothymidine for imaging of tumor cell proliferation, 18 F-Galacto-RGD-PET for evaluation of neoangiogenesis inhibition, and PET/MR, which may help improve prognostication and customize treatments in the future. 35 Clinical Considerations The tumor staging system used for evaluating head and neck cancer is generally based on size and invasion of key anatomic structures, which vary according to the primary site (Tables 1-3). In general, most patients with SCCHN present with stage IV cancer because patients often remain asymptomatic or with very mild symptoms until the tumor grows to a size that causes compression of the aerodigestive tract, causing difficulty of swallowing or significant pain. A notable exception is glottic-type laryngeal cancer, where the majority of these patients present in stage I. 23 This is because even a small lesion causes noticeable voice changes leading to an early workup. Consequently, survival rates for glottic laryngeal cancer are better than most other types of SCCHN and with less morbidity. 24,36 Similarly, many oral cavity lesions Figure 1 (A) A small defect (arrow) is seen along the lingual cortex of the mandible adjacent to patient s floor of the mouth mass. Note that tumor is limited to the cortex and does not reach the medullary cavity. (B) Coronal computed tomography (CT) image of another patient with floor of the mouth cancer shows complete erosion of the inner cortex (arrow) of the mandible with soft tissue windows (not shown), demonstrating tumor in the medullary cavity of the bone.

3 Head and neck cancer 77 Figure 2 Axial (A) and coronal (B) CT images of a patient with left tongue cancer (white dot) that crosses (thick arrow) the midline defined by the fibrofatty raphe (arrowhead). Note that tumor encases the left lingual artery, which indicates lingual nerve involvement in the neurovascular bundle, involvement of the left geniohyoid muscle (extrinsic tongue muscle), and sparing of the right geniohyoid muscle (paired thin arrows). such as those with primary site in the gingiva have high 5-year survival rates because of early detection. 12 In more than half of patients, the presenting symptom for SCCHN is a lump in the neck. A solitary enlarged lymph node or more diffuse lymphadenopathy frequently accompanies head and neck primary malignancies because of the late stage of presentation. However, occasionally, the primary site may not be evident even after laryngoscopic and radiologic workup. Differences in TNM staging can mean profound differ- Figure 3 (A) Axial postcontrast fat-suppressed T1-weighted (T1W) image shows a small mucosal mass in the right fossa of Rosenmuller (lateral pharyngeal recess) in this patient with nasopharyngeal cancer. Note that the pharyngobasilar fascia is not breeched; thus, this is a stage T1 tumor (arrow). (B) Axial -weighted image of another patient with nasopharyngeal cancer shows a mass extending through the pharyngobasilar fascia (arrow) into the parapharyngeal space, making this a stage tumor.

4 78 M.J. Walden and N. Aygun Figure 4 Axial CT image (A) of a patient with nasopharyngeal cancer shows a mass (dot) infiltrating to the petroclival junction, with involvement of the pterygoid process and the clivus (arrows), making this a stage tumor. Progression of tumor toward the petroclival junction is a very common pattern of disease progression. Axial postcontrast T1W magnetic resonance images (MRIs) (B and C) of a different patient show a similar petroclival junction involvement, with abnormal enhancement in the clivus (short arrow) and further progression of disease intracranially into the posterior fossa through the clivus and into the cavernous sinus (long arrows). Intracranial extension is staged as T4. ences in treatment regimens and quality of life for the patient. Invasive surgery and extensive radiation fields have to be weighed against patient functionality. This is especially true in the laryngeal region, where surgeons try to spare critical portions of the voice apparatus, if possible, while still achieving curative treatment. Considerations in the oropharyngeal and hypopharyngeal regions include preservation of speech and swallowing and prevention of aspiration, which may be difficult depending on the level of involvement of the base of the tongue, constrictor muscles, and epiglottis. 24,37-39 Radiation also can have serious side effects that may render patients tracheostomy and/or gastrostomy dependent or lead to catastrophic complications such as carotid pseudoaneurysm and rupture. Imaging Oral Cavity The lips are often included as part of the oral cavity. For purposes of this article, cancer of the lips is excluded. The oral cavity includes the hard palate, the tongue anterior to the Figure 5 Axial postcontrast T1W image (A) shows a bulky nasopharyngeal mass that infiltrates through the clivus into the posterior fossa. (B) Coronal postcontrast T1W image of another patient shows tumor extending from right parapharyngeal space to the cavernous sinus via the foramen ovale (arrow).

5 Head and neck cancer 79 circumvallate papillae, including the undersurface, the floor of the mouth, and the gingival and buccal mucosa. For malignancy in the oral cavity, the radiologist s main role is to distinguish whether the lesion has features that make it a stage III or IV cancer (Table 1) because these lesions can no longer be treated with single-modality therapy (radiation or surgery). 39 Perhaps the most important feature is whether there is invasion of the mandible. When the tumor abuts but does not invade the mandible, surgeons usually perform a marginal mandibulectomy to ensure negative margins. When there is actual invasion of the cortex, which can be accurately assessed by CT (Fig. 1), a segmental mandibulectomy must be performed, which requires reconstructive measures. When the tumor is in the medullary cavity of the bone, it can spread to considerable length within the mandible and gain access to the inferior alveolar nerve, with subsequent spread along the nerve to the skull base and then intracranially. Spread of tumor in the medullary cavity of the mandible and beyond is better assessed using MRI compared with CT. Another important consideration is whether the tumor invades the intrinsic and/or extrinsic tongue muscles and whether it crosses the midline of the tongue. If the tumor crosses the midline, the entire oral tongue must be removed, and the patient s quality of life is dramatically reduced, whereas, partial glossectomy of the oral tongue can be better tolerated with some deficits in enunciation. Extension across midline can be assessed by paying attention to the fibrofatty structure (midline raphe) that defines the midline of the tongue. The midline raphe and its relation to tumor can be accurately assessed using both CT and MRI owing to its fatty content (Fig. 2). If the lesion extends into the base of the tongue, the swallowing mechanism will likely be compromised. 40 Other sites of invasion such as into the retromolar trigone, pterygomandibular raphe, or pterygoid muscles or perineural spread of the tumor can also dramatically alter treatment approach. MRI is more sensitive than CT in detecting most of these findings, with its superior representation of soft tissues, but is less specific for bone involvement. 39 Nasopharynx NPC often begins at the fossa of Rosenmuller. It is important to evaluate this area on MRI, especially if there is a mastoid effusion. Subtle abnormalities should be brought to the attention of clinicians, as this area is accessible to visual inspection. In contrast, NPC can often have extensive submucosal extension with minimal mucosal involvement, making imaging critical in the evaluation of this disease. The pharyngobasilar fascia, firmly attached to the skull base and pterygoid processes, invests the nasopharyngeal mucosa and provides a barrier for disease spread. NPC has a propensity to spread through the pharyngobasilar fascia into the parapharyngeal space and retropharyngeal space, which denotes stage (Fig. 3). From the parapharyngeal space, it can spread to the masticator and carotid spaces. Involvement of bones at the skull base indicates disease (Fig. 4). The most common site of bone involvement is the clivus and petroclival junction, from where tumor can extend intracranially through the foramen lacerum and carotid canal or directly through the bone (Fig. 5A). Low-resistance paths for intracranial tumor spread at the skull base include the foramen lacerum, jugular, and hypoglossal canals. Intracranial extension indicates T4 disease. Another route for intracranial extension is perineural spread, most commonly through the foramen ovale, along the V3 nerve, which can then extend into Meckel cave and cavernous sinus (Fig. 5B). Other routes of perineural spread include along the maxillary nerve through foramen rotundum. Lesions spreading along this route also frequently involve the pterygopalatine fossa and vidian canal. In addition to spread posteriorly and laterally, it is not uncommon for NPC to spread anteriorly and medially into the ethmoid sinuses and nasal cavity. 31 NPC is relatively treatable with ra- Table 2 Primary Tumor Staging of the Pharynx Nasopharynx T1 T4 Oropharynx T1 T4a T4b Hypopharynx T1 T4a T4b Tumor confined to nasopharynx or extends to orophayrnx and/or nasal cavity Tumor with parapharyngeal extension Tumor involves bony structures of skull base and/or paranasal sinuses Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit, or with extension to the infratemporal fossa/masticator space Tumor <2 cm in greatest dimension Tumor >2 cmbut <4 cm in greatest dimension Tumor >4 cm in greatest dimension or extension to lingual surface of epiglottis Tumor invades larynx, extrinsic tongue muscles, medial pterygoid, hard palate, or mandible Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base, or encases carotid artery Tumor limited to 1 subsite of hypopharynx and/or <2 cm in greatest dimension Tumor invades >1 subsite or an adjacent site, or measures >2 cmbut <4 cmin greatest dimension, without fixation of hemilarynx Tumor >4 cm in largest dimension, fixation of hemilarynx, or esophageal extension Invades thyroid/cricoids cartilage, hyoid bone, thyroid gland, or central compartment soft tissue Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures Data from American Joint Committee on Cancer Staging. American Joint Committee on Cancer Staging Manual (7th ed). New York, NY, Springer, 2010.

6 80 M.J. Walden and N. Aygun diation and chemotherapy despite its propensity for early lymph node metastasis, primarily to retropharyngeal and jugular lymph nodes. 12,31 For evaluation of NPC, MRI is the study of choice. It best delineates mucosal and submucosal spread, perineural spread, and/or intracranial extension Oropharynx The superior margin of the oropharynx is the soft palate. The inferior margin is the pharyngoepiglottic folds, and the anterior margin is the circumvallate papillae of the tongue. Thus, the pharyngeal mucosa within these boundaries, the faucial tonsils and tonsillar pillars, and the base of tongue are all parts of the oropharynx. The size of a primary oropharyngeal malignancy is an important part of staging in this area, with T4 lesions characterized by invasion of adjacent structures (Table 2). Although it is critical to determine whether a tongue base mass crosses the midline or extends inferiorly to involve the vallecula, this is better accomplished by visual inspection and biopsy, as necessary, than imaging in most cases. Likewise, the mucosal extent of tumor from the tonsillar fossa to the tongue base and vice versa is more accurately determined by endoscopic exam. Radiologists efforts, therefore, should be focused on evaluating the deep submucosal extent of tumor. Critical anatomic areas for the radiologist to evaluate for invasion include the parapharyngeal area, masticator muscles, and the mandible Fig. 6A; preepiglottic fat (Fig. 6B, C); prevertebral muscles; and pterygopalatine fossa If the vallecula is infiltrated, close inspection of the preepiglottic fat is warranted because invasion of this area often necessitates more extensive surgery that could involve a form of laryngectomy depending on the extent of invasion. If the mandible is invaded, portions of the mandible have to be resected, whereas prevertebral muscle invasion renders the disease unresectable. The possibility of perineural spread has to be raised when the tumor invades the pterygopalatine fossa. As mentioned earlier, involvement of the posterior tongue can severely affect patients quality of life by disrupting the swallowing mechanism, especially if the lesion crosses the midline, necessitating a large tongue base resection Hypopharynx The superior margin of the hypopharynx is the vallecula, and the inferior margin is the pharyngoesophageal junction, which corresponds to the inferior border of the cricoid cartilage. The 3 major subsites are the pyriform sinuses, lateral and posterior hypopharyngeal walls, and the postcricoid region. Hypopharyngeal cancers have a propensity for submucosal spread and nodal metastasis, with the majority presenting in later stages. Imaging is critical for evaluating extent of disease, with CT typically the frontline study. 23 Because of the proximity of the hypopharynx to the larynx, surgical treatment of hypopharyngeal tumors often requires a form of laryngectomy, which might have severe implications on quality of life. Tumors originating in the apex and medial wall of the pyriform sinus will often invade the adjacent paraglottic larynx (Fig. 7) and thyroid cartilage. If the apex of the pyriform sinus is involved in disease, a total laryngectomy is performed, whereas a hemilaryngectomy can be performed if the apex is not involved. If the tumor originates from the lateral wall of the pyriform sinus, it tends to invade the soft tissues of the neck. There is a tendency of craniocaudal submucosal spread in tumors originating in the posterior hypopharyngeal wall subsite, with possible extension into the nasopharynx superiorly or esophagus inferiorly. There is often laryngeal involvement in disease that originates in the postcricoid area. 22,23 Figure 6 Axial postcontrast T1W MRI (A) shows a bulky right tongue base mass (arrow) anteriorly extending into the intrinsic muscles of the tongue, laterally into the masticator space involving the medial pterygoid muscle (the normal contralateral medial pterygoid muscle is marked with a dot), and further laterally into the mandible (thin arrow). A metastatic lymph node is also demonstrated (arrowhead). Axial (B) and sagittal (C) CT images of a different patient with right tongue base cancer shows extension of the mass (short arrows) across midline and inferiorly into the preepiglottic space (long arrow), which is a submucosal space not accessible to visual inspection anterior to the epiglottis (arrowhead).

7 Head and neck cancer 81 Figure 7 Axial contrast-enhanced CT images of a left pyriform sinus squamous cell carcinoma (SCC; arrow on A) that involves the apex of the sinus (white arrow on B) and extends anteriorly into the paraglottic space, which is inaccessible to visual inspection, through the gap between the thyroid and cricoid cartilages (black arrow), which is widened compared with the normal right side. Tumors infiltrating the posterior pharyngeal wall, including hypopharyngeal posterior wall cancers, may infiltrate the prevertebral fascia, which would render the tumor unresectable. When the retropharyngeal fat plane is preserved between the prevertebral muscles and the tumor, there is no prevertebral fascia involvement and the negative predictive value of both CT and MRI is high (Fig. 8A). In contrast, the positive predictive value is poor in diagnosing involvement of the prevertebral fascia (Fig. 8B). Imaging features that suggest prevertebral fascia involvement include obliteration of the retropharyngeal fat Figure 8 Axial CT image (A) of hypopharyngeal SCC invading the paraglottic space. Note the intact retropharyngeal fat plane between the mass and the vertebra, indicating lack of prevertebral fascia involvement. Axial postcontrast T1W MRI (B) of a different patient with bulky hypopharyngeal SCC with loss of retropharyngeal fat plane and marked compression of the right prevertebral muscle (arrows), which was interpreted as suspicious for prevertebral fascia and which was proven to be a false-positive finding in surgery.

8 82 M.J. Walden and N. Aygun Figure 9 Axial CT image (A) of a right true vocal cord SCC shows minimal thickening of the anterior commissure (black arrow) compatible with tumor extension. This is staged at T1. There is no extension to the left cord. Sagittal CT image (B) of a different patient shows true vocal cord SCC involving the anterior commissure and tumor extension superiorly into the preepiglottic space, making this a stage tumor. Sagital CT image (C) of another patient demonstrates anterior commissure involvement as well as extension of tumor through the thyroid cartilage anteriorly into the prelaryngeal space, making this a stage T4 tumor. plane, asymmetric enlargement of the prevertebral muscles, and signal changes and enhancement on MRI. Larynx The larynx is divided into the supraglottis, glottis, and subglottis. The supraglottic subsites include the epiglottis, laryngeal aspect of the aryepiglottic folds, the arytenoids, and false cords. The glottis is composed of the true vocal cords to include the anterior and posterior commissures. The subglottis is the area that begins 1 cm inferior to the ventricle and extends inferiorly to superior margin of the first tracheal ring. Carcinoma arising in the larynx most often is centered in the glottis (65%), followed by the supraglottis (30%) and subglottis (5%). 23,41 Figure 10 Axial CT image (A) shows paraglottic extension of vocal cord SCC (black arrow) compatible with stage tumor. Note the normal fat-filled right paraglottic space (short arrow). Axial image (B) through the cricoid cartilage of a different patient with glottic SCC shows asymmetric soft tissue thickening within the cricoids ring (arrow), compatible with subglottic tumor extension, which precludes a voice-preserving surgery.

9 Head and neck cancer 83 Table 3 Primary Tumor Staging of the Larynx Supraglottis T1 T4a T4b Glottis T1a T1b T4a T4b Subglottis T1 T4a T4b Tumor limited to 1 subsite of supraglottis, with normal vocal cord mobility Invades mucosa of >1 subsite of supraglottis or glottis, without fixation of larynx Tumor limited to larynx, with vocal cord fixation, and/or invades postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage Tumor invades through the thyroid cartilage and/or tissues beyond the larynx (eg, trachea, soft tissues of neck, including deep extrinsic muscle of tongue, strap muscles, thyroid, or esophagus) Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures Tumor limited to 1 vocal cord Tumor involves both cords Tumor extends to supraglottis and/or subglottis, with/without impaired vocal cord mobility Limited to larynx, with cord fixation and/or invasion of paraglottic space and/or thyroid cartilage Invades through outer cortex of thyroid cartilage and/or invades tissues beyond larynx Invades prevertebral space, encases carotid artery, or invades mediastinal structures Tumor limited to the subglottis Tumor extends to vocal cord(s), with normal or impaired mobility Tumor limited to larynx, with vocal cord fixation Tumor invades cricoids or thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of neck, including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus) Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures Data from American Joint Committee on Cancer Staging. American Joint Committee on Cancer Staging Manual (7th ed). New York, NY, Springer, Evaluation of the preepiglottic (anterior) and paraepiglottic (lateral) fat is key in evaluating supraglottic tumors, as this space is submucosal and not reliably assessed by endoscopy. Both MRI and CT will show enhancing lesion replacing the fat in these regions. Lesions arising in the epiglottis often invade the preepiglottic space and have a propensity to spread to the glottis and subglottis via the anterior commissure (transglottic disease) if the lesion originates in the region of the petiole. Lateral lesions in the false cord, laryngeal ventricle, or aryepiglottic fold tend to infiltrate the paraglottic Figure 11 Axial CT image (A) of a left glottic SCC, which abuts the thyroid cartilage and focally invades it (arrow). Note that the outer cortex of the cartilage is intact, making this a stage tumor. Axial postcontrast T1W MRI (B) shows a left glottic SCC, with destruction of the thyroid cartilage (arrowhead) and extralaryngeal extension of tumor; stage T4.

10 84 M.J. Walden and N. Aygun space in a craniocaudal direction. Supraglottic cancer often presents with nodal metastasis and should prompt a careful search in the regional lymph node areas. Careful inspection of adjacent thyroid cartilage is also needed to evaluate cartilaginous involvement. 23,41 Glottic carcinoma most often arises from the anterior half of the vocal cord, where it tends to spread into the anterior commissure. If there is any thickening of the commissure, malignant spread should be assumed, although false positives are frequent, and this area can be best assessed with direct laryngoscopy using general anesthesia (Fig. 9A). 24 From there, it can spread into the contralateral cord and paraglottic space, as well as in a craniocaudal direction, causing transglottic disease just as in the petiole region tumors (Fig. 9B) or exhibit extralaryngeal spread through the thyroid cartilage (Fig. 9C). Using both CT and MRI, paraglottic extension of tumor can be accurately depicted secondary to the fat-filled submucosal tissue, which is readily seen (Fig. 10). Spread to the subglottic region (Fig. 10B) is often not apparent to the endoscopist, making imaging of this area with CT or MRI essential. Transglottic disease and extensive contralateral disease usually preclude partial voicesparing therapies, which include horizontal supraglottic laryngectomy, vertical hemilaryngectomy, and supracricoid laryngectomy along with either cricohyoidopexy or cricohyoidoepiglottopexy. 23,24,38,42 If disease is localized above the ventricle, the upper half of the larynx along with the epiglottis, aryepiglottic folds, false cords, preepiglottic space, a fraction of the thyroid cartilage, and possibly one arytenoid cartilage is removed (horizontal supraglottic laryngectomy). If the disease extends to the ventricle and invades the glottis or a very small area of thyroid cartilage, a supracricoid laryngectomy with cricohyoidopexy may be attempted, which involves removing the entire epiglottis. 24,42 If the tumor is localized to the true cord, on one side, a vertical hemilaryngectomy can be performed, which involves removing the ipsilateral true and false cords along with the ipsilateral ventricle and adjacent thyroid cartilage. For more advanced disease centered at the glottis, a supracricoid laryngectomy with cricohyoidoepiglottopexy may be performed, which is nearly the same as a supracricoid laryngectomy with a cricohyoidopexy, except that it spares a portion of the epiglottis. As mentioned earlier in the text, very extensive disease or recurrent disease may necessitate a total laryngectomy. 24,42 Fortunately, many of these present early secondary to voice changes. Careful inspection of adjacent cricoid and thyroid cartilage is needed in these cases, as invasion upgrades staging (Table 3; Fig. 11). MRI is more sensitive than CT in evaluation of cartilaginous invasion; however, CT is more specific. A combination of these modalities may be best in difficult cases for providing the maximum sensitivity and best chance of a cure combined with maximum specificity to optimize the chance of voice-sparing treatment ,38,41-43 Cancer arising from the subglottis is rare but difficult to detect by endoscopy in initial stages, making cross-sectional imaging invaluable for evaluation of this area. The mucosa should be uniformly thin, and any thickening is suspicious. 23,24 However, subglottic involvement in transglottic disease is not uncommon. When this area is involved, there is often extensive disease involving the glottis and supraglottis. Also, spread to the adjacent tissues to include the trachea, esophagus, and thyroid gland is not unusual. Also, lymphadenopathy in the lower jugular and upper mediastinum is often present. 23 Carotid Encasement Carotid encasement is a criterion that upstages head and neck cancer to stage 4b, and is typically considered unresectable. However, there may be some benefit to carotid dissection or resection, with reanastomosis in previously untreated patients. 44 Circumferential vessel wall involvement of 180 is often used as an indicator for vascular invasion on imaging. However, this is neither a sensitive nor a specific indicator. 38 In contrast, 270 circumferential wall involvement is highly specific for inability to peel the tumor off the affected artery. 45 A combination of imaging findings to include deformation of the carotid artery, encasement of 180, and segmental obliteration of the fat between the disease and carotid artery is highly predictive of massive arterial invasion. 46 Table 4 Regional Lymph Node Staging Nasopharynx N1 N2 N3a N3b All other sites N1 N2a N2b N2c N3 Unilateral metastasis in cervical lymph node(s), <6 cm in greatest dimension, above the supraclavicular fossa; and/or unilateral or bilateral metastasis in retropharyngeal lymph nodes, <6 cm in greatest dimension Bilateral metastasis in cervical lymph node(s), <6 cm, above the supraclavicular fossa Metastasis in lymph node(s), >6cmin dimension Extension to the supraclavicular fossa Metastasis in a single ipsilateral lymph node, <3 cm in greatest dimension Metastasis in a single ipsilateral lymph node, >3 cm but less than 6 cm in dimension Metastasis in multiple ipsilateral nodes, none >6 cm in greatest dimension Metastasis in bilateral or contralateral nodes, none >6 cm in greatest dimension Metastasis in a lymph node, >6cmin greatest dimension Data from American Joint Committee on Cancer Staging. American Joint Committee on Cancer Staging Manual (7th ed). New York, NY, Springer, 2010.

11 Head and neck cancer 85 Nodal Involvement Lymphadenopathy has very important prognostic implications. The presence of a single nodal metastasis reduces the patient s survival rate by 50%. Bilateral lymphadenopathy further reduces the survival rate by another 50%. Extracapsular spread and nodal fixation are also associated with reduced survival. 47 The TNM staging system for lymph nodes for the nasopharynx and remaining sites is noted in Table 4. Many radiologists use 10 mm as the cutoff for normal lymph node size in the head and neck area, with greater allowance (15 mm) for jugulodigastric nodes and a smaller cutoff (8 mm) for retropharyngeal nodes. This is somewhat arbitrary with a sensitivity of 88% and a specificity of 39% on CT using 10 mm as a cutoff. 48 The presence of central necrosis increases specificity. In general, surgeons err on the side of treating for lymphadenopathy, given the high propensity for metastatic lymphadenopathy in SCCHN. Many HPV-associated metastatic lymph nodes can be cystic, whereas most non-hpv related metastases are solid. 49 This can be problematic for radiologists when a patient presents with a solitary cystic neck mass, especially in the anterior triangle. There have been many cases where a cystic metastatic lymph node has been mistaken for a branchial cleft cyst and the patient dismissed clinically until returning with advanced disease with associated worse prognosis. 50,51 Patient age can be somewhat helpful in these circumstances. It would be very unusual for an initial presentation of branchial cleft cyst in a patient older than 35 years; therefore, any cystic neck mass in the nodal basins presenting after this age should be considered malignant until proven otherwise with appropriate biopsies, laryngoscopy, and imaging as indicated Conclusions The radiologist plays an important role in evaluation of head and neck cancer. Cross-sectional imaging is an indispensable part of the workup, and the radiologist can suggest important considerations in the treatment planning and prognosis of the disease. Knowledge of anatomy along with relevant epidemiologic and clinical historical factors and treatment considerations would help radiologists focus their attention on imaging features that have an impact on disease staging and treatment. References 1. Chan AT, Teo PM, Johnson PJ: Nasopharyngeal carcinoma. Ann Oncol 13: , Siegel R, Naishadham D, Jemal A: Cancer statistics. CA Cancer J Clin 62:10-29, Johnson-Obaseki S, McDonald JT, Corsten M, et al: Head and neck cancer in Canada: Trends Otolaryngol Head Neck Surg 2012, in press 4. 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