H&N Evaluation and management of laryngeal cancer Flashcards
What patient demographic is at highest risk for
laryngeal cancer?
● Males (3.8:1)
● Associated with tobacco exposure
● Age younger than 40 years
What are the strongest risk factors for laryngeal
carcinoma?
● Tobacco smoking (packs per day and years of use)
● Alcohol use (amount consumed and duration of use)
What is the role of laryngopharyngeal reflux in
laryngeal cancer?
Controversial. It is unclear whether it is an independent or
associated risk factor.
What percentage of laryngeal cancers have been
associated with high-risk HPV (HPV 16 > HPV 18)?
~ 25%. Clinical significance is unclear.
What are four primary premalignant laryngeal
lesions as defined by the WHO?
● Hyperplasia
● Keratosis
● Dysplasia: Mild, moderate, severe
● Carcinoma in situ
What significance does laryngeal leukoplakia have?
Leukoplakia means “white plaque” and without a biopsy
gives no information relevant to management.
What is the approximate rate of dysplasia in
laryngeal leukoplakia?
40%
What is the approximate rate of malignant trans-
formation of mild dysplasia? Severe dysplasia or
carcinoma in situ?
● 11%
● 30%
Note: It may take up to 10 years for malignant conversion
(average 3 years).
What percentage of laryngeal tumors are squamous cell carcinomas?
85 to 95%
According to WHO, what are the possible subtypes
of squamous cell carcinoma found in the larynx?
● Verrucous
● Spindle cell carcinoma (also called sarcomatoid carcinoma, carcinosarcoma, pseudosarcoma)
● Adenoid (acantholytic) Basaloid squamous cell carcinoma
● Clear cell carcinoma
● Adenosquamous carcinoma
● Giant cell carcinoma
● Lymphoepithelial carcinoma
What laryngeal lesion is characterized by prolifer-
ation of the squamous mucosa, elongated rete
ridges that appear worrisome for carcinoma and
show no evidence of cytologic abnormalities
consistent with malignancy?
Pseudoepitheliomatous hyperplasia. It can be associated with
infection (e.g., tuberculosis, syphilis, blastomycosis), trauma,
granular cell tumor, and chronic irritation. It is easily mistaken
for squamous cell carcinoma and requires proper orientation
of specimens and periodic-acid Schiff stain.
What pathology in the larynx is associated with
trauma and infarction of salivary gland tissue
(ducts and acini of seromucinous glands), is often
misdiagnosed as squamous cell carcinoma or
mucoepidermoid carcinoma, and requires immu-
nohistochemistry for diagnosis?
Necrotizing sialometaplasia
What subtype of squamous cell carcinoma results
in largely exophytic growth, pushing margins,
does not metastasize, is associated with HPV-16
and -18, and has an indolent course?
Verrucous carcinoma. It is the second most common site in
the head and neck (to oral cavity).
What epithelial laryngeal cancer contains both
basaloid and squamous components (biphasic),
cystic spaces, results in frequent regional and
distant metastases, occurs most commonly in the
supraglottis, and has a worse prognosis than
standard squamous cell carcinoma?
Basaloid squamous cell carcinoma
What epithelial laryngeal cancer contains malignant squamous epithelium on its surface associated with a deeper malignant spindle cell
carcinoma (biphasic), is associated with tobacco
and alcohol use, results in common regional
metastases, and is relatively radioresistant?
Spindle cell carcinoma
What is the most common location for adenosquamous carcinoma, a biphasic tumor arising
from the basal layer of the epithelium and
demonstrating behavior more aggressive than
conventional squamous cell carcinoma, in the
upper aerodigestive tract?
Larynx
What is the key pathologic difference between laryngeal verrucous carcinoma and papillary
squamous cell carcinoma, which demonstrates
exophytic papillary growth with cores of fibrovas-
cular stroma?
Significantly abnormal cytology
According to the WHO, what are the possible
subtypes of malignant salivary gland tumors found
in the larynx, which make up less than 1% of all
laryngeal tumors?
● Mucoepidermoid carcinoma ● Adenoid cystic carcinoma ● Adenocarcinoma ● Acinic cell carcinoma ● Carcinoma ex-pleomorphic adenoma ● Epithelial-myoepithelial cell carcinoma ● Salivary duct carcinoma
What are the cells of origin for supraglottic
adenocarcinoma?
Minor salivary glands
Are salivary gland carcinomas of the larynx more
common in men or women?
Men (2:1). However, adenoid cystic carcinoma has no
gender bias.
What are the two most common laryngeal
malignant salivary gland cancers?
Mucoepidermoid carcinoma and adenoid cystic carcinoma,
constituting one-third of malignant laryngeal salivary gland
tumors
What laryngeal tumor is composed of squamous,
mucin-secreting, and intermediate-type cells and likely forms in the intercalated ducts of seromucinous glands?
Mucoepidermoid carcinoma
What percentage of supraglottic cancers arising from minor salivary glands will be mucoepidermoid carcinoma on pathological analysis?
35%. They are less common than adenoid cystic (46%),
more common than adenocarcinoma (12%).
Adenoid cystic carcinoma is defined by uniform
basaloid cells that grow in what three distinct
patterns?
● Cribriform
● Tubular
● Solid
According to the WHO, what are the possible
subtypes of neuroendocrine tumors found in the
larynx, which are the second most common
tumors of the larynx next to squamous cell
carcinoma?
● Atypical carcinoid tumor (54%)
● Small cell carcinoma (28%)
● Malignant paraganglioma (12%)
● (Typical) carcinoid tumor (7%)
What is the relative occurrence of supraglottic
neuroendocrine tumors in men and women?
They occur three times more commonly in women than in
men.
What is the 5-year survival rate for laryngeal
neuroendocrine carcinoma?
Although it is one of the most common extrapulmonary sites for neuroendocrine carcinoma, laryngeal neuroendocrine carcinoma is extremely rare. It is also most often lethal, with 2- and 5-year survival rates of 16% and 5%,
respectively.
What subsite of the larynx is most commonly
involved by both typical and atypical carcinoid tumors, which present as submucosal and polypoid masses?
Supraglottis
To what unusual locations do atypical carcinoids
commonly metastasize?
Skin and subcutaneous tissue
What percentage of patients with laryngeal small
cell carcinoma will develop distant metastases?
90%
According to the WHO, what are the possible
subtypes of malignant soft tissue tumors found in
the larynx?
● Fibrosarcoma ● Malignant fibrous histiocytoma ● Liposarcoma ● Leiomyosarcoma ● Rhabdomyosarcoma ● Angiosarcoma ● Kaposi sarcoma ● Malignant hemangiopericytoma ● Malignant nerve sheath tumor ● Alveolar soft part sarcoma ● Synovial sarcoma ● Ewing sarcoma
According to the WHO, what are the possible
subtypes of malignant bone and cartilage tumors
in the larynx?
● Chondrosarcoma (most common)
● Osteosarcoma
What laryngeal tumors arise from ossified hyaline cartilage, most commonly from the cricoid cartilage?
Chondrosarcomas
What is the distant metastasis rate in laryngeal
chondrosarcoma?
8.5%
According to the WHO, what are the possible
subtypes of malignant hematolymphoid tumors
found in the larynx?
● Extramedullary plasmacytoma (most common)
● Lymphoma
According to the WHO, what tumors most
commonly metastasize from a distant site to the
larynx?
● Kidney ● Skin (melanoma) ● Breast ● Lung ● Prostate ● Gastrointestinal tract
What is the most common site of second
primaries in patients with larynx cancer?
Lung. Consider a pulmonary lesion a second primary tumor
until proven otherwise.
What are the clinical risk factors that may increase
the likelihood of stomal recurrence?
● Primary subglottic tumor
● Glottic tumor invading subglottis by > 1 cm
● T4 glottic primary tumor
What are the proposed causes of stomal recurrence after total laryngectomy for laryngeal cancer?
● Positive tracheal margin
● Paratracheal nodal metastases
● Thyroid gland invasion
● Seeding of the stoma at initial operation
What is the most common initial symptom
associated with supraglottic carcinoma?
Dysphagia. It can also manifest with dysphonia, odynophagia, otalgia, stridor, dyspnea, hemoptysis, and neck mass.
What is the most common initial symptom
associated with early versus late glottic carcinoma?
● Early disease: Dysphonia
● Advanced disease: Stridor, dyspnea
What are the most common initial symptoms
associated with subglottic carcinoma?
Dyspnea and stridor
Patients with what symptoms may require urgent
or emergent management of their laryngeal
tumor?
Dyspnea and stridor
On endoscopy, which of the following lesions may
be suspicious for a laryngeal carcinoma: ulceration, sessile lesion, polypoid lesion, submucosal fullness, or exophytic friable mass?
All should suggest possible malignant process.
What laryngoscopy adjunct should be used in the
clinic to evaluate a patient in whom you are
concerned about a laryngeal malignancy?
Flexible fiberoptic laryngoscopy and/or video stroboscopy
To evaluate a patient with laryngeal carcinoma for posterior invasion of the prevertebral fascia, you grasp the larynx and rock it back and forth.
Inability to rock the larynx and lack of what sound/tactile feedback suggest invasion?
Laryngeal crepitus (movement of laryngopharyngeal framework across the prevertebral and vertebral structures)
What is the most commonly used imaging
modality for the initial workup of laryngeal
cancer?
CT with contrast using fine cuts through the larynx
~ 1 mm
Which offers better evaluation of cartilage invasion: CT or MRI?
MRI
When using MRI for the evaluation of a patient
with laryngeal cancer, what modality or sequences
would be most useful to determine invasion of the
preepiglottic and/or paraglottic spaces?
T1-weighted gadolinium enhanced MRI with fat suppres-
sion. High negative predictive value. False-positive results are caused by inflammation.
During direct endoscopic examination of the
upper aerodigestive tract in the operating room
for laryngeal cancer, what maneuver should be
performed if there is concern for fixation of the
larynx or immobility of a vocal cord?
Palpation of the laryngeal structures
Describe microflap excision for laryngeal biopsy.
Microflap surgery requires dissection of the superficial
lamina propria as opposed to excision. This allows for
sparing of the vocal ligament and affords a better
postoperative mucosal wave.
Why is detection of recurrence after radiation
more difficult in laryngeal cancer?
Persistent edema and fibrosis are common post-treatment
sequelae that obscure visualization of (often submucosal)
tumor growth.
Although deep biopsies are often necessary to
diagnose a recurrent laryngeal tumor after radiation therapy, what adverse outcomes are associated with biopsy in this setting?
Increased risk of infection, perichondritis, and chondroradionecrosis
Describe the “T” staging system for epithelial
supraglottic malignancies according to the AJCC.
● T1: Tumor limited to one supraglottic subsite, normal
vocal cord mobility.
● T2: Tumor invasion of more than one subsite of the
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 the 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: Moderately advanced local disease: tumor invades
through the thyroid cartilage and/or invades tissue
beyond the larynx (e.g., trachea, soft tissues of neck
including deep extrinsic muscles of the tongue, strap
muscles, thyroid, or esophagus).
● T4b: Very advanced local disease: Tumor invades pre-
vertebral space, encases carotid artery, or invades mediastinal structures.
What differentiates T2 from T3 supraglottic
tumors?
T2 tumors do not invade the parilaryngeal spaces; T3
tumors present with vocal cord fixation.
What differentiates T1 from T2 supraglottic
tumors?
● T1 tumors are limited to one subsite with normal vocal
cord mobility.
● T2 tumors may involve multiple supraglottic subsites or
adjacent regions (tongue base, glottis).
Describe the “T” staging system for epithelial
glottic malignancies according to the AJCC).
● T1: Tumor is limited to the vocal cord(s); may involve anterior or posterior commissure; normal vocal cord
mobility.
● T1a: Tumor is 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 (some authors divide
T2 into T2a and T2b; see below).
● T3: Tumor is limited to the larynx with vocal cord fixation
and/or invades the paraglottic space, and/or minor
thyroid cartilage erosion (e.g., inner cortex).
● T4a: Moderately advanced local disease: Tumor invades
through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck
including deep extrinsic muscle of the tongue, strap muscles, thyroid or esophagus).
● T4b: Very advanced local disease: Tumor invades pre-
vertebral space, encases carotid artery, or invades mediastinal structures.
Although the AJCC, (7th edition) does not differentiate T2 into T2a and T2b, some authorities do. How are these stages defined?
Tumor extends to the supraglottis and/or subglottis:
● T2a: Without impaired vocal cord mobility
● T2b: With impaired vocal cord mobility
What is the rate of nodal metastases in T1 glottic
carcinoma?
5%
What differentiates T3 from T4 glottic tumors?
T3 tumors are confined to the larynx, whereas T4 have
spread extralaryngeally (into strap musculature, thyroid
gland, trachea, esophagus).
Describe the “T” staging system for epithelial
subglottic malignancies according to the AJCC.
● T1: Tumor is limited to the subglottics.
● T2: Tumor extends to vocal cord(s) with normal or
impaired mobility.
● T3: Tumor is limited to the larynx with vocal cord fixation.
● T4a: Moderately advanced local disease. Tumor invades
cricoid or thyroid cartilage and/or invades tissues beyond
the larynx (e.g., trachea, soft tissues of the neck including
deep extrinsic muscles of the tongue, strap muscles,
thyroid or esophagus)
● T4b: Very advanced local disease: Tumor invades pre-
vertebral space, encases carotid artery, or invades mediastinal structures.
Describe the stages of stomal recurrence after
total laryngectomy for laryngeal cancer (Sisson,
1989).
● Stage I: Superior to the stoma, at 9 to 3 o’clock position.
Normal swallowing and esophagoscopy
● Stage II: Above or below the stoma, 9 to 3 o’clock. Most
have dysphagia and esophageal invasion.
● Stage III: Below the stoma, at 9 to 3 o’clock. Esophagus is
always involved. High risk of upper mediastinal disease
● Stage IV: Lateral extension of the tumor under the
clavicle, dysphagia, and esophageal invasion
What is the overall 5-year survival rate for
laryngeal cancer, and what subsite has the best overall survival?
● 64%
● Glottic (79%) > supraglottic (47%) > subglottic (30 to 50%)
During the initial workup of a patient with
laryngeal cancer, you identify cartilage invasion.
How does this impact prognosis and manage-
ment?
● Upstages tumor (T3 or T4a)
● Poorer response to radiation therapy
● Decreased local control rates
● Higher risk of chondroradionecrosis
What is the incidence of distant metastasis in
glottic carcinoma?
4%
What are the most important clinical prognostic
factors in order of importance?
● Clinical stage (most important to least: M > N > T)
● Location of the primary (best to worst: glottic > supra-
glottic > subglottic)
Why does involvement of the anterior commissure decrease prognosis (local control rates) for both surgery and radiation therapy?
Inadequate recognition of deep extension