eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery

Malignant Tumors of the Larynx: Workup

Author: Jonas T Johnson, MD, FACS, Chairman, Department of Otolaryngology, The Eugene N Myers, MD, Professor and Chairman of Otolaryngology, Professor, Department of Radiation Oncology, University of Pittsburgh School of Medicine; Professor, Department of Oral Maxillofacial Surgery, University of Pittsburgh School of Dental Medicine
Coauthor(s): Apostolos Christopoulos, MD, MSc, FRCSC, Fellow in Head and Neck Oncologic Surgery, Department of Otolaryngology, University of Pittsburgh; Emiro E Caicedo-Granados, MD, Fellow in Head and Neck Oncology/Anterior Endoscopic Skull Base Surgery, Department of Otolaryngology, University of Pittsburgh
Contributor Information and Disclosures

Updated: Jan 7, 2009

Workup

Laboratory Studies

• Arterial blood gas analysis
  • The patient's symptoms or clinical findings may indicate the need to obtain arterial blood gases.
  • This analysis may be preformed preoperatively to provide a baseline to monitor the patient's course.
• Blood studies for clotting parameters
  • These studies might be ordered when surgery is a consideration.
  • Include a platelet count.
  • Blood typing and cross matching are also prudent.
  • Every experienced head and neck surgeon or trauma physician is aware of the tremendous potential for hemorrhage in this area. Anomalous blood vessels often yield unexpected complications.
• Thyroid function studies
  • These studies may be indicated, as may tests of serum calcium levels, because the results are occasionally anomalous after surgery. Having baseline data for reference is ideal.
  • In some cases, especially with cases of fibrosis, either radiation or tumor induced, the thyroid may be biopsied during laryngectomy to assess for occult carcinoma.
• Studies of renal and hepatic function
  • These studies are necessary before any informed discussion of chemotherapeutic regimens can occur.
  • Many chemotherapeutic agents are metabolized by the liver and/or kidneys.
• Nutrition studies: Albumin and transferrin serum levels are important to establish nutritional status.

Imaging Studies

• CT scanning
  • Contrast-enhanced CT scans obtained with appropriate section thickness aid in the evaluation of neck masses.
  • CT scans and MRIs may demonstrate the extension of tumor into vital structures such as the surrounding soft tissue, the preepiglottic space. They may also show invasion though the thyrohyoid-ligament and cartilage invasion.
• Plain radiography of the chest
  • Plain films of the chest may be useful in planning surgery.
  • If metastases are already present in the chest, the therapeutic decision tree changes entirely.
• Positron emission tomography-computerized tomography scan (PET-CT)
  • This is a radiologic tool that detects metabolic signals from cells with high metabolic activity like cancer cells. The patient receives intravenously a glucose analog called fluorodeoxyglucose (FDG) that is tagged with a radioisotope. This analog is taken up by cells with high metabolic activity. A CT scanner is used to correlate the nuclear medicine image with anatomic abnormality.
  • This is the most sensitive test available to detect metastasis or second primary tumors. The clinician must be aware, however, that some tumors do not take FDG and that small tumors (<5 mm) are not be identified.

Other Tests

Pulmonary function tests are necessary before one decides whether the patient is a suitable candidate for radical surgery that involves airway function.

Diagnostic Procedures

• Direct laryngoscopy provides an opportunity for examination under general anesthesia, palpation and biopsy. Suspension laryngoscopy provides an excellent view of the extent of the tumor and the overall condition of the airway mucosa.
• Fine needle aspiration (FNA) of a neck mass may yield a positive result when the certainty of a malignant lymph node is not 100%.
• Single, well-targeted biopsy reveals the nature (type and perhaps grade) of the tumor. Several biopsy procedures may be extremely useful in mapping the tumor to optimally plan surgery.
• Reminders
  • The rationale behind the entire work-up is to have as much staging information available as possible to present to a tumor board before definitive study is performed. Treatment options are frequently discussed in a multidisciplinary format called a tumor board. Although a tumor board may comprise only a few physicians, the ideal head and neck tumor board is a powerful ally. Diverse experts on these boards widely expand and exchange knowledge, such as awareness of new open clinical trials (on the part of radiation or medical oncologists); the patient in question may be ideal for such a trial. Likewise, the surgeon may know of a new technique that may obviate postoperative therapy or considerably decreases disfigurement, and the pathologist may know that certain histologic features suggest an improved prognosis or a different responds to therapy. This level of information is impossible for any one individual to know, and well-earned CME credits are a natural outcome.
  • The value of this tumor board is greater than the sum of its parts. Therefore, the tumor board approach is strongly advocated. In the United States, such tumor boards may include the following members:
    • Surgeons
    • Anesthesiologists
    • Radiologists
    • Pathologists
    • Radiation oncologists
    • Medical oncologists
    • Psychiatrists and or the patients' spiritual advisors
    • Speech and swallowing therapists
    • Nursing staff
    • Relevant clinical research teams
    • Social workers and placement teams
    • Reconstructive, plastic, and cosmetic surgeons

Histologic Findings

The vast majority of laryngeal cancers are of the squamous cell carcinoma variety. Variations include standard squamous cell carcinoma (in situ or invasive, well, moderately or poorly differentiated), verrucous carcinoma, spindle cell carcinoma, basaloid-squamous cell carcinoma, and papillary squamous cell carcinoma. Other types of carcinoma are neuroendocrine carcinoma, lymphoepitheliomatous carcinoma, adenocarcinoma, and rare tumors (including sarcomas, lymphomas, adenocarcinomas, and metastases).

Because 96% of laryngeal carcinomas in the United States are squamous cell carcinomas, the following discussion is limited to this neoplasm.

Laryngeal squamous cell carcinoma histology is similar in many ways to squamous cell carcinoma found elsewhere in the body.

It arises in stages from hyperplasia, dysplasia of various degrees, in situ carcinoma, and invasive squamous cell carcinoma. At times, these stages cannot be observed in an invasive carcinoma. In addition, some squamous cell carcinomas of the larynx arise de novo without an in situ stage. This process was demonstrated for oral tumors, and some indications suggest that this may be true in laryngeal tumors as well.

About 5-7 cell layers line the normal larynx. In some regions, this lining is stratified squamous epithelium, and in others (eg, ventricle, false cord, and subglottis), this is pseudostratified respiratory epithelium.

The nuclei at the base are elongated, with their long axis perpendicular to the basement membrane. Normal mitotic figures are present in the basal layer, which is 1 layer above the parabasal layer. Mitotic figures should be absent above this second layer. As the cells move toward the surface, the nuclei become oval, then full circles. By the fourth to fifth layer from the bottom, all of the squamous cells should have circular nuclei. The nuclei then continue upward and elongate again, first to ovals then to flattened variants. However, this time, the elongated nuclei have their long axis parallel to the surface and are therefore parallel to the basement membrane. Surface keratinization may or may not be present.

In situ carcinoma is simply full-thickness atypia of the squamous cells. The basal nuclei have round, oval, and elongated forms. The long axes of the elongated forms are haphazardly arranged and not perpendicular to the basement membrane except by occasional chance. Typical and atypical mitotic figures are observed throughout the epithelial surface, with some at the surface or 1 layer below. These figures are usually but not always abundant.

The individual cells themselves are bizarre in appearance, with angulated nuclei, multipoled mitotic figures, apoptotic cells (individually necrotic cells), hyperchromasia, and high nuclear-to-cytoplasmic ratios.

Invasive squamous cell carcinoma simply means that the wild-appearing squamous cells, and often keratin, are beneath the area where the usual basement membrane lies. The cells may extend deeply into soft tissue, and they may invade cartilage, nerves, blood vessels, and lymphatics. They may invade as nests, broad and pushing fronts, as individual cells, or as any combination of these.

The pathologists classify the degree of atypicality as follows: well, moderately, or poorly differentiated or undifferentiated. Use of the undifferentiated classification is best avoided. The term undifferentiated carcinoma is an oxymoron in that an undifferentiated neoplasm cannot show any morphologic features of epithelium (ie, carcinoma). In addition, the pathologist may subtype the tumor according to the types of tumors listed at the beginning of this section (eg, papillary carcinoma or verrucous carcinoma).

Staging

The 2002 AJCC classification for laryngeal tumors is determined by the following 3 main factors:¹

• Number of subsites involved
• Vocal fold mobility
• Presence of cervical or distant metastases

Furthermore, one must pay attention to specific factors who are essential for initial staging and can help determine the optimal therapeutic option(s) for the patient. These factors are as follows:

• Involvement of the base of tongue
• Involvement of the preepiglottic space, ie, the tissue anterior to the epiglottis, posterior to the thyrohyoid membrane, superior to the petiole, and inferior to the hyoepiglottic ligament
• Paraglottic space
• Thyroid cartilage
• Soft tissue, including strap muscles
• Carotid artery and sheath
• Esophagus
• Neck lymph nodes, their location, involvement (ipsilateral, bilateral, contralateral), size, and extranodal spread
• Distant metastases and location

American Joint Committee on Cancer Sixth Edition Larynx Staging Schema

• TX: Primary tumor cannot be assessed.
• T0: No evidence of primary tumor T is carcinoma in situ .

Supraglottis

• T1: Tumor is 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 (eg, mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx.
• T3: Tumor is 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 (eg, inner cortex).
• T4a: Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus).
• T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.

Glottis

• T1: Tumor is limited to the vocal cord or cords (may involve anterior or posterior commissure) with normal mobility.
• T1a: Tumor is limited to one vocal cord.
• T1b: Tumor involves both vocal cords.
• T2: Tumor extends to the supraglottis and/or subglottis, and/or with impaired vocal cord mobility.
• T3: Tumor is limited to the larynx with vocal cord fixation and/or invades paraglottic space, and or minor thyroid cartilage erosion (eg, inner cortex).
• T4a: Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of the neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus).
• T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.

Subglottis

• T1: Tumor is limited to the subglottis.
• T2: Tumor extends to the vocal cord(s), with normal or impaired mobility.
• T3: Tumor is limited to the larynx with vocal cord fixation.
• T4a: Tumor invades the cricoid 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).
• T4b: Tumor invades the prevertebral space, encases carotid artery, or invades mediastinal structures.

Regional lymph nodes (N)

• NX: Regional lymph nodes cannot be assessed.
• N0: No regional lymph node metastasis exists.
• N1: Metastasis is in a single ipsilateral lymph node, 3 cm or less in greatest dimension.
• N2: Metastasis is in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension.
• N2a: Metastasis is in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension.
• N2b: Metastasis is in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension.
• N2c: Metastasis is in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension.
• N3: Metastasis is in a lymph node, more than 6 cm in greatest dimension.

Distant Metastasis (M)

• MX: Distant metastasis cannot be assessed.
• M0: No distant metastasis.
• M1: Distant metastasis.

Stage Grouping 

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