5
Larynx

(Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included.)

ANATOMY
RULES FOR CLASSIFICATION
DEFINITION OF TNM
STAGE GROUPING
HISTOPATHOLOGIC TYPE
HISTOPATHOLOGIC GRADE (G)
PROGNOSTIC FACTORS
BIBLIOGRAPHY
Manual for Staging of Cancer; Fifth Edition; Edited by Irvin D. Fleming, M.D., Jay S. Cooper, M.D., Donald Earl Henson, M.D., Robert V.P. Hutter, M.D., B.J. Kennedy, M.D., Gerald Murphy, M.D., D.S.c., Brian O'Sullivan, M.B., F.R.C.P.C., F.R.C.P.I., Leslie H. Sobin, M.D., John W. Yarbro, M.D., Ph.D.; Copyright 1997, the American Joint Committee on Cancer. Published by Lippincott-Raven Publishers. Chapter 5, pp. 41 - 46.

C10.1Anterior (lingual) surface of epiglottis
C32.0Glottis
C32.1Supraglottis (laryngeal surface)
C32.2Subglottis
C32.3Laryngeal cartilage
C32.8Overlapping lesion
C32.9Larynx, NOS

ANATOMY

Primary Site. The following anatomic definition of the larynx allows classification of carcinomas arising in the encompassed mucous membranes but excludes cancers arising on the lateral or posterior pharyngeal wall, pyriform fossa, postcricoid area, or base of tongue.

The anterior limit of the larynx is composed of the anterior or lingual surface of the suprahyoid epiglottis, the thyrohyoid membrane, the anterior commissure, and the anterior wall of the subglottic region, which is composed of the thyroid cartilage, the cricothyroid membrane, and the anterior arch of the cricoid cartilage.

The posterior and lateral limits include the laryngeal aspect of aryepiglottic folds, the arytenoid region, the interarytenoid space, and the posterior surface of the subglottic space, represented by the mucous membrane covering the surface of the cricoid cartilage.

The superolateral limits are composed of the tip and the lateral borders of the epiglottis. The inferior limits are made up of the plane passing through the inferior edge of the cricoid cartilage.

For purposes of this clinical stage classification, the larynx is divided into three regions: supraglottis, glottis, and subglottis. The supraglottis is composed of the epiglottis (both its lingual and laryngeal aspects), aryepiglottic folds (laryngeal aspect), arytenoids, and ventricular bands (false cords). The epiglottis is divided for staging purposes into suprahyoid and infrahyoid positions by a plane at the level of the hyoid bone. The inferior boundary of the supraglottis is a horizontal plane passing through the lateral margin of the ventricle at its junction with the superior surface of the vocal cord. The glottis is composed of the true vocal cords, including the anterior and posterior commissures, superior and inferior surfaces. It occupies a horizontal plane, 1 cm in thickness, extending inferiorly from the lateral margin of the ventricle. The subglottis is the region extending from the lower boundary of the glottis to the lower margin of the cricoid cartilage.

The division of the larynx is summarized in the following table:

Site Subsite
SupraglottisSuprahyoid epiglottis
Infrahyoid epiglottis
Aryepiglottic folds (laryngeal aspect)
Arytenoids
Ventricular bands (false cords)
GlottisTrue vocal cords including anterior and posterior commissures
SubglottisSubglottis

Regional Lymph Nodes. The incidence and distribution of cervical nodal metastases from cancer of the larynx varies with the site of origin and the "T" classification of the primary tumor. The true vocal cords are nearly devoid of lymphatics and tumors of that site alone rarely spread to regional nodes. On the contrary, the supraglottis has a rich and bilaterally interconnected lymphatic network and primary supraglottic cancers are commonly accompanied by regional nodal spread. Glottic tumors may spread directly to adjacent soft tissues and pre laryngeal, pretracheal, paralaryngeal and paratracheal nodes as well as upper, mid and lower jugular nodes. Supraglottic tumors commonly spread to upper and midjugular nodes, considerably less commonly to submental or submandibular nodes, but occasionally to retropharyngeal nodes. The rare subglottic primary tumors spread first to adjacent soft tissues and prelaryngeal, pretracheal, paralaryngeal and para tracheal nodes, then to mid and lower jugular nodes. Contralateral lymphatic spread is common.

In clinical evaluation the physical size of the nodal mass should be measured. It is recognized that most masses over 3 cm in diameter are not single nodes but are confluent nodes or tumor in soft tissues of the neck. There are three categories of clinically positive nodes: N1, N2, and N3. The use of subgroups a, b, and c is not required but is recommended. Midline nodes are considered ipsilateral nodes. In addition to the components to describe the N-category, regional lymph nodes should also be described according to the level of the neck that is involved. Pathologic examination is necessary for documentation of such disease extent. Imaging studies showing amorphous spiculated margins of involved nodes or involvement of internodal fat resulting in loss of normal oval-to-round nodal shape strongly suggest extracapsular (extranodal) tumor spread. No imaging study (as yet) can identify microscopic foci in regional nodes or distinguish between small reactive nodes and small malignant nodes without central radiographic inhomogeneity.

For pN, a selective neck dissection will ordinarily include 6 or more lymph nodes and a radical or modified radical neck dissection will ordinarily include 10 or more lymph nodes.

Metastatic Sites. Distant spread is common only for patients who have bulky adenopathy. When distant metastases occur spread to the lungs is most common; skeletal or hepatic metastases occur less often. Mediastinal lymph node metastases are considered distant metastases.

RULES FOR CLASSIFICATION

Clinical Staging. The assessment of the larynx is accomplished primarily by inspection, using indirect mirror and direct endoscopic examination. The tumor must be confirmed histologically, and any other data obtained by biopsies may be included. Cross-sectional imaging in laryngeal carcinoma is recommended when the primary tumor extent is in question based upon clinical examination. Radiologic nodal staging should be done simultaneously to supplement clinical examination.

Complete endoscopy, usually under general anesthesia, is generally performed after completion of other diagnostic studies to accurately assess, document and biopsy the tumor.

Pathologic Staging. All information used in clinical staging and in histologic studies of the surgically resected specimen is used for pathologic staging. The surgeon's evaluation of gross unresected residual tumor must also be included. The pathologic description of any lymphadenectomy specimen should describe the size, number, and level of involved lymph nodes.

DEFINITION OF TNM

Primary Tumor (T)

TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ

Supraglottis

T1Tumor limited to one subsite of supraglottis with normal vocal cord mobility
T2Tumor 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
T3Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre-epiglottic tissues
T4Tumor invades through the thyroid cartilage, and/or extends into soft tissues of the neck, thyroid, and/or esophagus

Glottis

T1Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility
    T1aTumor limited to one vocal cord
    T1bTumor involves both vocal cords
T2Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility
T3Tumor limited to the larynx with vocal cord fixation
T4Tumor invades through the thyroid cartilage and/or to other tissues beyond the larynx (e.g., trachea, soft tissues of neck, including thyroid, pharynx)

Subglottis

T1Tumor limited to the subglottis
T2Tumor extends to vocal cord(s) with normal or impaired mobility
T3Tumor limited to larynx with vocal cord fixation
T4Tumor invades through cricoid or thyroid cartilage and/or extends to other tissues beyond the larynx (e.g., trachea, soft tissues of neck, including thyroid, esophagus)

Regional Lymph Nodes (N)

NXRegional lymph nodes cannot be assessed
N0No regional lymph node metastasis
N1Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2Metastasis 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
N2aMetastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension
N2bMetastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2cMetastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3Metastasis 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

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 T4 N0 M0
  T4 N1 M0
  Any T N2 M0
Stage IVB Any T N3 M0
Stage IVC Any T Any N M1

HISTOPATHOLOGIC TYPE

The predominant cancer type is squamous cell carcinoma. Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone and cartilage are not included. Histologic diagnosis is required to use this classification. Tumor grading of squamous carcinoma is recommended. The grade is subjective and uses a descriptive, as well as a numerical form; i.e., well, moderately well, and poorly differentiated, depending upon the degree of closeness to or deviation from squamous epithelium in normal mucosal sites. Also recommended where feasible is a quantitative evaluation of depth of invasion of the primary tumor and the presence or absence of vascular/perineural invasion.

HISTOPATHOLOGIC GRADE (G)

GX Grade cannot be assessed
G1 Well differentiated
G2 Moderately differentiated
G3 Poorly differentiated

PROGNOSTIC FACTORS

In addition to the importance of the TNM factors outlined previously, the overall health of these patients clearly influences outcome. Co-morbidity can be classified by more general measures, such as the Karnofsky performance score, or more specific measures, such as the Kaplan-Feinstein Index.

Continued exposure to carcinogens, such as alcohol and tobacco smoke, likely also affects patients' outcome adversely.

BIBLIOGRAPHY

Archer CR, Yeager VL, Herbold DR: CT versus histology of laryngeal cancer: the value in predicting laryngeal cartilage invasion. Laryngoscope 93:140-147, 1983

Cooper JS, Farnan NC, Asbell SO, et al: Recursive partitioning analysis of 2105 patients treated in Radiation Therapy Oncology Group studies of head and neck cancer. Cancer 77:1905-1911, 1996

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Eibaud JD, Elias EG, Suter CM, et al: Prognostic factors in squamous cell carcinoma of the larynx. Am J Surg 158:314-317, 1989

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Isaacs JJ, Mancuso AA, Mendenhall WM, et al: Deep spread patterns in CT staging of T2-4 squamous cell laryngeal carcinoma. Otolaryngol Head Neck Surg 99:455-464, 1988

Kaplan MH, Feinstein AR: The importance of classifying initial co-morbidity in evaluating the outcome of diabetes mellitus. J Chron Dis 27:387-404, 1974

Karnofsky DA, Abelman WH, Craver LF, Burchenal JH: The use of the nitrogen mustards in the palliative treatment of carcinoma. Cancer 1:634-656, 1948

Mafee MF, Schield JA, Valvassori GE, et al: CT of the larynx: correlation with anatomic and pathologic studies in cases of laryngeal carcinoma. Radiology 147:123-128, 1983

Mendenhall WM, Parsons JT, Stringer SP, et al: Carcinoma of the supraglottic larynx: a basis for comparing the results of radiotherapy and surgery. Head Neck 12:204-209, 1990

Piccirillo, JF. Inclusion of comorbidity in a staging system for head and neck cancer. Oncology 9:831-836, 1995

Rozack MS, Maipang T, Sabo K, et al: Management of advanced glottic carcinomas. Am J Surg 158:318-320, 1989

Strong EW: Cancer of the larynx and hypopharynx. Prob Gen Surg 5:166-189, 1988

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Veterans Administration Laryngeal Study Group. Induction chemotherapy plus radiation compared to surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 324:1685-1690, 1991

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