Laryngeal Carcinoma

Anatomy & Pathophysiology:

Laryngeal carcinoma is classified into three subtypes depending on whether the tumor originates in the supraglottis, glottis, or subglottis. Briefly, the supraglottis comprises the epiglottis, aryepiglottic folds, arytenoid cartilages, and false vocal cords. The glottis extends from the apex of the laryngeal ventricle between the false and true vocal cords to 0.5 cm inferior to the free edge of the true cords; it includes the anterior commissure. From the inferior glottic margin, the subglottis extends inferiorly to the inferior border of the cricoid cartilage. Because of the differing embryologic origin of the laryngeal subdivisions, cancers in the three regions behave differently with regard to lymphatic drainage and patterns of locoregional spread. Glottic cancers are slower to spread outside of the glottis and have a lower propensity for lymphatic metastasis compared to supraglottic malignancies. In the United States, glottic cancers outnumber supraglottic cancers 1.5:1. Primary subglottic cancer is extremely rare, and most tumors in the subglottis are actually extensions of tumors originating in the glottis or supraglottis.

Over 90% of laryngeal malignancies are squamous cell carcinomas (SCC); thus, references to laryngeal cancer in this chapter should be interpreted as referring to SCC unless otherwise noted. Both tobacco and alcohol use are risk factors for the development of laryngeal cancer; the combined usage of tobacco and alcohol produces a risk that is even greater than the additive risk of each individual factor. Other risk factors include laryngeal papillomatosis/human papillomavirus infection, occupational exposures (such as asbestos), and prior irradiation.

Involvement of the larynx by malignancy can result in impairment of some or all laryngeal functions, depending on tumor size and extent. Supraglottic tumors may cause airway obstruction, while glottic tumors are more likely to produce changes in voice quality. Swallowing may also be affected, resulting in aspiration.

Epidemiology:

Laryngeal carcinoma has an incidence of 11,000 cases diagnosed per year in the United States, accounting for 1% of all cancer diagnoses. As with other head and neck malignancies, there is a male predominance, with a 4:1 male to female ratio, although the incidence in women has been rising. Peak incidence occurs during the sixth and seventh decades of life. The majority of cases are associated with tobacco or alcohol use.

Natural History:

The histologic progression of laryngeal cancer typically involves the development of mucosal dysplasia, followed by carcinoma in situ, which then progresses to invasive carcinoma. Supraglottic cancers are more likely than glottic cancers to exhibit locoregional spread and regional nodal metastasis. Glottic cancers generally cause symptoms earlier in the disease course than supraglottic cancers due to involvement of the vocal cords, which produces dysphonia.

Presentation:

Presenting symptoms of laryngeal cancer vary depending on tumor site and size. Glottic cancers can produce changes in voice quality even when very small, due to the sensitivity of vocal cord vibrations to the presence of any lesions. In advanced stages, glottic cancer causing fixation of both vocal cords or airway obstruction can cause stridor and respiratory compromise. Supraglottic tumors can also cause dysphonia, along with dysphagia, odynophagia, referred otalgia, and airway obstruction. Rarely, cervical lymphadenopathy may be the presenting sign in patients without significant laryngeal complaints. Subglottic tumors most commonly present with dyspnea and stridor but are often not detected until advanced stages due to their insidious nature.

Laryngeal cancer spreads most commonly to cervical lymph nodes in levels 2 to 4, but may spread hematogenously to the lung, liver, and bone. However, distant metastasis is not common at the time of initial presentation.

Differential Diagnosis of Laryngeal Mass:

Evaluation:

History

In addition to any presenting symptoms, the patient should be asked about tobacco and alcohol use history and any prior irradiation.

Physical Examination

Examination should include inspection and palpation of the oral cavity, flexible fiberoptic laryngoscopic (FFL) examination, and palpation of the neck for cervical lymphadenopathy.

FFL findings vary and may include ulcerative, polypoid, nodular, or friable lesions. In some cases of early stage disease, findings may be more subtle, such as change in mucosal color or vocal cord contour. Assessment of vocal cord function during FFL is necessary for proper staging of glottic tumors. In addition, airway patency should be evaluated and the need for emergent intervention determined. Large tumors causing significant airway obstruction may require tracheostomy or tumor debulking in order to temporize symptoms while definitive management is considered.

Biopsy

Pathologic diagnosis is achieved by biopsy during a direct laryngoscopy under general anesthesia. A panendoscopy, including bronchoscopy and esophagoscopy, is performed at the same time to exclude a second primary.

Imaging Studies

Radiographic evaluation is necessary to stage the tumor by determining the extent of the primary tumor and the presence of regional or distant metastases. Computed tomography (CT) is most commonly used, although magnetic resonance imaging (MRI) may refine assessment of certain structures, such as cartilage. Positron emission tomography (PET) is generally performed concurrently with CT to evaluate for regional and distant metastases. Imaging of the chest should be performed as part of the PET-CT scan, with a dedicated CT thorax, or even with a plain radiograph, as the lungs are the most common site of distant metastasis.

Staging

Staging of laryngeal cancer is according to the American Joint Committee on Cancer (AJCC) TNM (tumor, node, metastasis) system.

AJCC TNM Staging for Laryngeal Carcinoma
Supraglottis
T1	Tumor limited to one subsite of supraglottis with normal vocal cord mobility
T2	Tumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx
T3	Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre-epiglottic tissues, paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex)
T4a	Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus)
T4b	Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
Glottis
T1	Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility
T1a	Tumor limited to one vocal cord
T1b	Tumor involves both vocal cords
T2	Tumor extends to supraglottis and/or subglottis, or with impaired vocal cord mobility
T3	Tumor limited to the larynx with vocal cord fixation, and/or invades paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex)
T4a	Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx, (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus)
T4b	Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
Subglottis
T1	Tumor limited to the subglottis
T2	Tumor extends to vocal cord(s) with normal or impaired mobility
T3	Tumor limited to larynx with vocal cord fixation
T4a	Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus)
T4b	Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures
Nodal Metastasis (N)
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension
N2a	Metastasis in a single ipsilateral lymph node, >3 cm but not >6 cm in greatest dimension
N2b	Metastasis in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension
N2c	Metastasis in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension
N3	Metastasis in a lymph node, >6 cm in greatest dimension
Distant Metastasis (M)
MX	Distant metastasis cannot be assessed
M0	No distant metastasis
M1	Distant metastasis present
Staging Groups
Stage	T	N	M
I	T1	N0	M0
II	T2	N0	M0
III	T3	N0	M0
	T1-3	N1	M0
IVA	T4a	N0-1	M0
	T1-4	N2	M0
IVB	T4b	Any N	M0
	Any T	N3	M0
IVC	Any T	Any N	M1

Treatment:

The treatment approach for laryngeal SCC depends on staging. Early stage cancer (AJCC stages I and II) can be treated either with surgical excision or radiotherapy alone. The advantages of surgical therapy are shorter treatment time, avoidance of radiation-related side effects, and the ability to use radiation in the future, should the tumor recur. Radiotherapy, on the other hand, may afford better voice outcomes in select cases, while providing a safer treatment option in patients whose comorbidities would entail significant risk from general anesthesia. For supraglottic cancers, both necks may be treated with radiation or neck dissection even in early stage disease, due to the high risk of occult nodal metastasis.

Advanced stage laryngeal cancer usually requires treatment with multiple modalities. In recent years, organ preserving protocols employing concurrent chemoradiation have become more common. However, under certain circumstances, surgery may still be the first-line approach; these include patients with T4a tumors, extensive or high volume disease, and patients with T3 tumors with a poorly functioning larynx (aspiration and poor anticipated functional outcome). Most T3 and T4 tumors require total laryngectomy to achieve adequate surgical margins. Adjuvant radiotherapy is generally given post-operatively. N0 necks may be treated with a selective neck dissection or radiation alone, whereas N1 to 3 should be treated with modified radical dissection (depending on feasibility of structure preservation) with adjuvant radiotherapy for N2 and 3. With smaller tumors, partial laryngectomy may be performed without postoperative radiotherapy in an effort to preserve the voice. These procedures include transoral laser excision, vertical hemilaryngectomy with vocal cord reconstruction, supraglottic laryngectomy, supracricoid laryngectomy, and near-total laryngectomy.

Complications, Prognosis & Follow-Up:

Survival rates for laryngeal cancer depend on disease stage and tumor site. Early stage glottic cancers have the best prognosis, with 5-year disease-free survival rates as high as 74-100% for stage I tumors. Subglottic tumors have the worst prognosis, although statistics are limited due to the rarity of this tumor subtype. Stage IV tumors have 5-year survival rates below 60% regardless of site.

Complications of surgical treatments for laryngeal cancer include dysphonia or aphonia, dysphagia, fistula development, aspiration, cranial nerve injury, and vascular injury. Speech production after total laryngectomy can be achieved through various strategies. Tracheoesophageal puncture (TEP) with placement of a one-way valve device allows air to be directed from the lungs into the neopharynx during exhalation. An electrolarynx produces external vibration that substitutes for vocal fold vibration. Alternatively, some patients may learn esophageal speech, wherein air is ingested and regurgitated from the esophagus, the oscillation of which produces a source of vibration for phonation. Preoperative counseling and postoperative speech therapy are essential for patients undergoing procedures anticipated to result in voice loss.

Radiotherapy carries additional complication risks, including mucositis , xerostomia (dry mouth), hypothyroidism, pharyngoesophageal stricture, and odynophagia. Nutritional assessment and monitoring are essential for patients undergoing treatment because of the impact of radiotherapy on swallowing.