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Malignant Tumors of the Larynx Workup

  • Author: Jonas T Johnson, MD, FACS; Chief Editor: Arlen D Meyers, MD, MBA  more...
 
Updated: Dec 22, 2015
 

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 performed 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.

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Imaging Studies

CT scanning

See the list below:

  • Contrast-enhanced CT scans obtained with appropriate section thickness (1-2mm thick sections through the larynx) 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. See the image below.
    Axial view on CT scan of an advanced right larynge Axial view on CT scan of an advanced right laryngeal tumor invading through the thyroid cartilage.

Plain radiography of the chest

See the list below:

  • Plain films of the chest may be useful in planning surgery.
  • If metastases are present in the chest, the therapeutic decision tree changes entirely. However, chest CT or PET-CT are more sensitive for metastasis that plain films

Positron emission tomography-computerized tomography scan (PET-CT)

See the list below:

  • This is a radiologic tool that detects metabolic signals from cells with high metabolic activity like cancer cells. The patient intravenously receives a glucose analog called fluorodeoxyglucose (FDG) that is tagged with a radioisotope. This analog is taken up by cells with high metabolic activity, and the decay of the radioisotope is detected. 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 tumor FDG uptake may vary, normal tissues may display FDG avidity (eg, tonsillar tissue, active muscle tissue), and that PET cannot detect very small tumors (< 5 mm). See the image below.
    PET/CT image of a laryngeal cancer showing increas PET/CT image of a laryngeal cancer showing increased FDG avidity.
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Other Tests

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

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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. When coupled with appropriate imaging such as a CT scan, the direct laryngoscopy provides the best information for tumor staging and surgical planning. The direct laryngoscopy also provides an opportunity for biopsies of the tumor to be obtained. Well-targeted biopsies will typically reveal the type and perhaps grade of the tumor. Multiple biopsies may also be used to map out the tumor extent in cases where the tumor margins are unclear; this may be important to optimally plan surgical treatment.

Fine needle aspiration (FNA) of a neck mass may be useful to diagnose malignant lymphadenopathy from a laryngeal tumor, and may be an alternative means of establishing a diagnosis rather than direct biopsy via direct laryngoscopy.

Reminders

The rationale behind the entire work-up is to have as much staging information available as possible to present to a tumor board in order to determine a treatment plan. 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 decrease disfigurement, and the pathologist may know that certain histologic features suggest an improved prognosis or a different response to therapy.

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
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Histologic Findings

The vast majority of laryngeal cancers are squamous cell carcinoma. 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 malignancies of the larynx are neuroendocrine carcinoma,[3] 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. The spectrum ranges from hyperplasia, mild to severe dysplasia, 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 may 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, and should be absent above the 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, with the long axis parallel to the surface (parallel to the basement membrane). Surface keratinization may or may not be present.

Dysplasia is present when the ovoid, basal-appearing nuclei and mitotic figures persist higher in the epithelium, beyond the second layer. In mild dysplasia these atypical cells extend about one third of the way to the surface, in moderate dysplasia they reach two thirds of the way to the surface, and in severe dysplasia they encompass the entire thickness of the epithelium. Severe dysplasia is similar to carcinoma in situ, which is full-thickness atypia of the squamous cells with typical and atypical mitosis present. 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 means that abnormal-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).

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Staging

The 2002 AJCC classification for laryngeal tumors is determined by the following 3 main factors:[4]

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

Furthermore, one must pay attention to specific factors that 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 involvement
  • Thyroid cartilage invasion
  • Soft tissue invasion, including strap muscles
  • Carotid artery and sheath involvement
  • Esophageal invasion
  • Neck lymph nodes, their location, involvement (ipsilateral, bilateral, contralateral), size, and extranodal spread
  • Distant metastases and location

The American Joint Committee on Cancer Sixth Edition Larynx Staging Schema is discussed below.

Primary tumor (T)

Criteria for primary tumor staging depends on tumor location in either the supraglottis, glottis, or subglottis.

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

See the list below:

  • 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.
  • N2a: Metastasis is in a single ipsilateral lymph node, more than 3 cm but less 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)

See the list below:

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

Stage Grouping

Stage groupings can be seen in the table below.

Table 1. Stage Tumor, Node, and Metastasis Groupings (Open Table in a new window)

Stage Grouping
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
  T1 N1 M0
  T2 N1 M0
  T3 N1 M0
Stage IVA T4a N0 M0
  T4a N1 M0
  T1 N2 M0
  T2 N2 M0
  T3 N2 M0
  T4a N2 M0
Stage IV B T4b Any N M0
  Any T N3 M0
Stage IV C Any T Any N M1
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Contributor Information and Disclosures
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

Jonas T Johnson, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Association for Cancer Research, American Bronchoesophagological Association, American College of Surgeons, American Head and Neck Society, American Laryngological Association, The Triological Society, American Medical Association, American Rhinologic Society, Allegheny County Medical Society, American Society of Clinical Oncology, Pennsylvania Medical Society, Society of University Otolaryngologists-Head and Neck Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel Clayburgh, MD, PhD Clinical Instructor, Head and Neck Surgery Fellow, Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Karen H Calhoun, MD, FACS, FAAOA Professor, Department of Otolaryngology-Head and Neck Surgery, Ohio State University College of Medicine

Karen H Calhoun, MD, FACS, FAAOA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Head and Neck Society, Association for Research in Otolaryngology, Southern Medical Association, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Medical Association, American Rhinologic Society, Society of University Otolaryngologists-Head and Neck Surgeons, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;SymbiaAllergySolutions<br/>Received income in an amount equal to or greater than $250 from: Symbia<br/>Received from Allergy Solutions, Inc for board membership; Received honoraria from RxRevu for chief medical editor; Received salary from Medvoy for founder and president; Received consulting fee from Corvectra for senior medical advisor; Received ownership interest from Cerescan for consulting; Received consulting fee from Essiahealth for advisor; Received consulting fee from Carespan for advisor; Received consulting fee from Covidien for consulting.

Additional Contributors

Jack A Coleman, MD Consulting Staff, Franklin Surgical Associates

Jack A Coleman, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Sleep Medicine, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American Bronchoesophagological Association, American College of Surgeons, The Triological Society, American Society for Laser Medicine and Surgery, Association of Military Surgeons of the US

Disclosure: Received honoraria from Accarent, Inc. for speaking and teaching.

Acknowledgements

Emiro E Caicedo-Granados, MD Assistant Professor, Department of Otolaryngology, University of Minnesota Medical School

Emiro E Caicedo-Granados, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery

Disclosure: Nothing to disclose.

Apostolos Christopoulos, MD, MSc, FRCSC Assistant Professor of Otolaryngology-Head and Neck Surgery, Department of Surgery, Universite de Montreal Faculty of Medicine, Canada

Disclosure: Nothing to disclose.

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Fiberoptic endolaryngeal view of an early glottic lesion of the right true vocal cord extending to the anterior commissure.
Axial view on CT scan of an advanced right laryngeal tumor invading through the thyroid cartilage.
PET/CT image of a laryngeal cancer showing increased FDG avidity.
Tracheostoma and skin flap reconstruction following total laryngectomy for a locally advanced laryngeal cancer invading the skin of the neck.
Table 1. Stage Tumor, Node, and Metastasis Groupings
Stage Grouping
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
  T1 N1 M0
  T2 N1 M0
  T3 N1 M0
Stage IVA T4a N0 M0
  T4a N1 M0
  T1 N2 M0
  T2 N2 M0
  T3 N2 M0
  T4a N2 M0
Stage IV B T4b Any N M0
  Any T N3 M0
Stage IV C Any T Any N M1
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