Laryngeal Carcinoma
Laryngeal carcinoma is a malignant neoplasm arising from the epithelial lining of the larynx, most commonly squamous cell carcinoma, strongly associated with smoking and alcohol use, presenting with hoarseness, dysphagia, or stridor.
Laryngeal Carcinoma
Laryngeal carcinoma ("larynx" = Greek for "upper windpipe"; "carcinoma" = Greek karkinos = crab, referring to a malignant epithelial tumour) is a primary malignant neoplasm arising from the mucosal lining of the larynx.
- Squamous cell carcinoma (SCC) is the MOST common malignancy of the larynx [1], accounting for approximately 95% of all laryngeal malignancies.
- Benign tumours of the larynx are extremely rare [2].
- The larynx is part of the upper aerodigestive tract, and laryngeal carcinoma is therefore a subtype of head and neck squamous cell carcinoma (HNSCC).
Why 'squamous'?
The entire mucosal surface of the larynx (except the true vocal folds, which are stratified squamous from the start) is lined by respiratory (pseudostratified ciliated columnar) epithelium. Chronic irritation by tobacco smoke and alcohol causes squamous metaplasia → dysplasia → carcinoma in situ → invasive SCC. This is the classic metaplasia-dysplasia-carcinoma sequence.
2. Epidemiology
| Parameter | Detail |
|---|---|
| Male predominance | M:F ≈ 5–10:1 (reflects higher prevalence of smoking and alcohol use in males) [1][2] |
| Age | Predominantly a disease of the elderly (age > 60) [2]; peak incidence 55–70 years |
| Incidence trend | Declining in many Western countries due to falling smoking rates; in Hong Kong, laryngeal carcinoma accounts for ~1–2% of all new cancers, with a similar declining trend |
| Subsite | Glottic carcinoma is the MOST common form of laryngeal cancer [2], especially in Western and East Asian populations |
| Global incidence | ~180,000 new cases/year worldwide (GLOBOCAN 2022) |
| Subsite | Relative Frequency | Key Epidemiological Feature |
|---|---|---|
| Glottic | ~60–65% | Earlier presentation (hoarseness); better prognosis |
| Supraglottic | ~30–35% | Late presentation; more aggressive; higher nodal metastasis |
| Subglottic | ~2–5% | Rarest; late presentation; poorest prognosis |
In countries with higher alcohol consumption (e.g., Southern Europe, parts of South America), the proportion of supraglottic tumours is relatively higher because alcohol appears to have a predilection for supraglottic mucosa.
3. Anatomy and Function of the Larynx
Understanding the anatomy is absolutely critical for understanding the clinical behaviour, lymphatic drainage, staging, and management of laryngeal carcinoma. Let's build it from first principles.
3.1 Structural Overview
The larynx extends from the tip of the epiglottis superiorly to the inferior border of the cricoid cartilage inferiorly [2]. It is divided into three anatomical regions:
- From the tip of the epiglottis to the laryngeal ventricle (not including the ventricle floor, i.e., the true vocal cord)
- Structures: epiglottis (both lingual and laryngeal surfaces), aryepiglottic folds, arytenoid cartilages, false vocal cords (ventricular bands), and the ventricle
- Embryologically derived from buccopharyngeal anlage (branchial arches 3 and 4)
- Key clinical relevance: Rich lymphatic network → drains bilaterally → higher incidence of lymph node metastasis (30–50%) [2]
- The true vocal cords, anterior commissure, posterior commissure, and the region extending ~1 cm below the free edge of the vocal fold
- Embryologically derived from tracheobronchial anlage (branchial arch 6)
- Key clinical relevance: Very sparse lymphatic drainage (the true vocal fold is nearly devoid of lymphatics) → limited glottic cancers typically do NOT spread to regional lymph nodes [2]
- This is also why early glottic tumours present with hoarseness — any mass on the vocal fold immediately affects vibration
- From 1 cm below the free edge of the vocal fold to the inferior border of the cricoid cartilage
- Key clinical relevance: relatively poor lymphatic drainage but propensity for local extension (especially circumferentially and into the trachea); lymphatic drainage ~40% at presentation [2]
Why does the glottis have sparse lymphatics?
The true vocal folds are essentially a muscle (thyroarytenoid/vocalis) covered by a thin mucosa with a unique layered microstructure (epithelium → superficial lamina propria [Reinke's space] → intermediate and deep lamina propria → vocalis muscle). Reinke's space is a potential space with very few lymphatic vessels and blood vessels — this is great for voice quality (allows mucosal wave propagation) but also means early glottic cancers are "trapped" locally and have less access to lymphatics.
| Subsite | Drainage Pathway | First Echelon Nodes |
|---|---|---|
| Supraglottic | Pierce thyrohyoid membrane alongside the superior laryngeal artery, vein, and nerve [2] | Subdigastric (Level II) and superior jugular nodes |
| Glottic | Very sparse; exit via cricothyroid ligament | Prelaryngeal node (Delphian node), paratracheal nodes, deep cervical nodes along inferior thyroid artery [2] |
| Subglottic | Exit via cricothyroid ligament | Prelaryngeal (Delphian) node, paratracheal nodes, deep cervical nodes along inferior thyroid artery [2] |
The Delphian node (named after the Oracle of Delphi — it "predicts" or portends the presence of cancer) is a prelaryngeal lymph node located anterior to the cricothyroid membrane. Its involvement is a sign of subglottic or transglottic extension.
Understanding the functions explains why laryngeal cancer causes the symptoms it does:
-
Phonation [2]
- Production of a primary vocal tone at the level of the vocal folds
- The vocal folds adduct (come together) and the subglottic air pressure builds up until it blows them apart → the Bernoulli effect pulls them back together → this cycle repeats rapidly (100–250 Hz in normal speech) = mucosal wave
- The fundamental tone then resonates in the pharynx and nose, adding harmonics and timbre
- Fine motor control of the tongue, palate, and lips provides articulation
- Why does a tumour on the vocal fold cause hoarseness? → The mass disrupts the mucosal wave and prevents complete glottic closure → irregular vibration → rough, breathy voice
-
Airway patency and protection during swallowing [2]
- During swallowing: laryngeal elevation, posterior deflection of the epiglottis, inhibition of respiration, and closure of the vocal folds → prevents aspiration
- Why does advanced laryngeal cancer cause aspiration? → Tumour bulk prevents complete glottic closure; destruction of sensory innervation (superior laryngeal nerve) impairs the cough reflex
-
Valsalva manoeuvre [2]
- Generation of increased intrathoracic pressure against a closed glottis
- Enables coughing, throat clearing, straining, and defecation
- Why do patients with laryngeal cancer have a weak cough? → Incomplete glottic closure means they cannot generate sufficient intrathoracic pressure
| Nerve | Origin | Motor Function | Sensory Function |
|---|---|---|---|
| Superior laryngeal nerve (SLN) — external branch | Vagus (CN X) | Cricothyroid muscle (tensor of vocal fold) | — |
| SLN — internal branch | Vagus (CN X) | — | Supraglottic larynx (above vocal folds) |
| Recurrent laryngeal nerve (RLN) | Vagus (CN X) | All intrinsic muscles EXCEPT cricothyroid | Glottic and subglottic larynx |
- Vocal fold fixation in laryngeal carcinoma can be caused by:
- Tumour infiltration of the thyroarytenoid muscle (vocalis)
- Tumour infiltration of the cricoarytenoid joint
- Invasion of the recurrent laryngeal nerve
- Any of these → immobile vocal fold → T3 staging (see later)
| Cartilage | Type | Clinical Relevance |
|---|---|---|
| Thyroid | Hyaline | Tumour invasion through thyroid cartilage → T4a; ossification occurs with age making invasion easier through non-ossified areas |
| Cricoid | Hyaline | Complete ring; subglottic extension may invade cricoid |
| Epiglottis | Elastic | Perforated (contains small fenestrations) → supraglottic tumours can penetrate through to pre-epiglottic fat space |
| Arytenoid | Hyaline | Tumour involvement → vocal fold fixation |
Pre-epiglottic and Paraglottic Spaces
These are two important "deep" spaces in the larynx filled with fat:
- Pre-epiglottic space: Between epiglottis posteriorly, thyrohyoid membrane/hyoid anteriorly, and hyoepiglottic ligament superiorly. Supraglottic tumours can invade this space (especially through the fenestrated epiglottic cartilage).
- Paraglottic space: Lateral to the ventricle and vocal fold, medial to the thyroid cartilage. Acts as a "highway" for tumour spread from supraglottis to glottis (transglottic spread).
Involvement of these spaces is a key feature on imaging and upstages tumours.
4. Aetiology and Risk Factors
Smoking is the primary risk factor [1][3]. Let me emphasise this:
Smoking, Smoking, Smoking [3] — this is repeated three times in the lecture slides for emphasis. It is the single most important modifiable risk factor.
| Risk Factor | Mechanism / Explanation |
|---|---|
| Smoking [1][2][3] | Tobacco smoke contains >70 known carcinogens (polycyclic aromatic hydrocarbons, nitrosamines, benzene). These cause direct DNA damage (adduct formation), oxidative stress, and chronic mucosal inflammation → squamous metaplasia → dysplasia → carcinoma. Tumours in smokers present more frequently in the floor of the mouth, hypopharynx, and larynx [2]. Dose-response relationship: risk increases with pack-years. |
| Alcohol — synergistic effect with smoking [3][4] | Alcohol itself is metabolised to acetaldehyde (a Group 1 carcinogen). Alcohol also acts as a solvent for tobacco carcinogens, increasing mucosal penetration. The synergistic (multiplicative, not just additive) effect of smoking + alcohol is well established for HNSCC [2][4]. Particularly associated with hypopharyngeal carcinoma [3]. |
| Previous irradiation / malignancy [3] | Prior radiotherapy to the head and neck region increases the risk of second primary malignancy in the radiation field, including laryngeal carcinoma, due to radiation-induced DNA damage. |
| GERD / Laryngopharyngeal reflux (LPR) [2] | Chronic acid and pepsin exposure to the posterior larynx causes chronic inflammation (posterior laryngitis) → metaplasia → potential dysplasia. The posterior glottis and interarytenoid area are most affected. |
| Chronic laryngitis [2] | Chronic inflammation from any cause (infection, irritants, reflux) provides a chronic proliferative stimulus to the mucosal epithelium. |
| Immunocompromised [3] | Impaired immune surveillance allows escape of dysplastic/neoplastic cells. |
| Poor oral hygiene with chronic infection [3] | Chronic bacterial/fungal infection creates a pro-inflammatory microenvironment with cytokine release and reactive oxygen species. |
| Family history of CA larynx [2] | Genetic susceptibility (polymorphisms in carcinogen-metabolising enzymes such as CYP1A1, GSTM1, and others). |
| Irradiation [2][3] | As above — radiation is both a treatment for and a cause of laryngeal cancer (field cancerisation effect). |
Diffuse and chronic exposure of the mucosa of the upper aerodigestive tract to carcinogenic substances (especially tobacco and alcohol) leads to widespread changes in the mucosal epithelium [2].
- This leads to an increased risk of synchronous or metachronous tumours [2]:
- Patients who develop tumours in the larynx are more likely to develop a second primary tumour in the lung [2] (same carcinogen exposure — inhaled tobacco smoke affects both larynx and lung)
- Panendoscopy is ALWAYS recommended [2]: includes direct laryngoscopy, bronchoscopy, and OGD — to look for synchronous primaries in the upper aerodigestive tract
Field Cancerisation — Clinical Implication
A common exam pitfall: When you find a laryngeal SCC, you must search for synchronous primaries. The entire aerodigestive tract mucosa has been "primed" by the same carcinogens. This is why panendoscopy (triple endoscopy) is standard of care at initial evaluation.
While HPV (types 16 and 18) is primarily associated with oropharyngeal carcinoma (especially tonsils and base of tongue) [3], its role in laryngeal SCC is less well-established and controversial:
- HPV has been detected in a subset of laryngeal SCCs, but the aetiological role is not as clear-cut as in the oropharynx.
- HPV-associated H&N cancers [2][3]:
- More common in younger male patients with higher lifetime number of sexual partners and oral sex
- HPV oncoproteins E6 and E7 inactivate tumour suppressors p53 and Rb respectively → loss of cell cycle control → tumour promotion
- Define a distinct subset with: frequent LN metastasis, higher response to induction chemotherapy, better prognosis, and deintensification of treatment can be considered [2][3]
- For laryngeal carcinoma specifically, smoking and alcohol remain far more important than HPV
5Ss: Smoking + Spirits + Sharp teeth + Sex (male/oral) + Spicy food [2]
5. Pathophysiology
Key molecular events:
- TP53 mutation (~50–70% of laryngeal SCCs): Loss of the "guardian of the genome" → failure of apoptosis and cell cycle arrest
- CDKN2A (p16) loss: Inactivation of another tumour suppressor → unchecked CDK4/6 activity → uncontrolled cell proliferation
- EGFR overexpression (~80–90%): Epidermal growth factor receptor drives proliferation via RAS-MAPK and PI3K-AKT pathways (therapeutic target for cetuximab)
- Cyclin D1 amplification: Drives G1→S transition
- NOTCH1 mutations: Loss of differentiation signals
5.2 Patterns of Local Spread (Subsite-Dependent)
Understanding local spread patterns is critical for staging and surgical planning:
- Usually arises on the free edge of the true vocal fold (anterior two-thirds)
- Tends to remain localised initially (sparse lymphatics, cartilage framework acts as barrier)
- Can spread:
- Anteriorly → anterior commissure → contralateral vocal fold (anterior commissure has no cartilage, only Broyles' ligament, which is a weak point)
- Superiorly → ventricle → false cord (transglottic)
- Inferiorly → subglottis
- Laterally → paraglottic space → through thyroid cartilage (T4a)
- Posteriorly → arytenoid → cricoarytenoid joint fixation (T3)
- Often arises on the epiglottis (most common) or the aryepiglottic folds
- Can spread:
- Through epiglottic fenestrations → pre-epiglottic space
- Laterally → paraglottic space
- Inferiorly → glottis (transglottic spread)
- Superiorly → base of tongue / vallecula
- Bilateral lymph node metastasis is common (midline structures drain bilaterally)
- Rare but aggressive
- Spread:
- Circumferential submucosal spread
- Inferiorly → trachea
- Through cricothyroid membrane → extralaryngeal
- Paratracheal lymph nodes
- Overall uncommon at presentation (~5–10% of all laryngeal cancers)
- More common in advanced disease (T3/T4, N2/N3)
- Most common sites: Lung (most common), bone, liver
- The lung is the most common site because of haematogenous spread via pulmonary capillary bed and shared carcinogen exposure (field cancerisation)
6. Classification
| Type | Frequency | Notes |
|---|---|---|
| Squamous Cell Carcinoma | ~95% | Conventional, verrucous, basaloid, spindle cell variants |
| Verrucous carcinoma | ~1–3% | Well-differentiated, warty, locally aggressive but rarely metastasises ("Ackerman's tumour") |
| Minor salivary gland tumours | Rare | Adenoid cystic carcinoma, mucoepidermoid carcinoma |
| Neuroendocrine tumours | Very rare | Small cell carcinoma, typical/atypical carcinoid |
| Sarcoma | Very rare | Chondrosarcoma (arises from cricoid cartilage) |
| Lymphoma | Very rare |
As detailed above:
- Supraglottic — from tip of epiglottis to floor of ventricle (not including true vocal fold)
- Glottic — true vocal folds, anterior and posterior commissures, extending 1 cm below the free edge
- Subglottic — from 1 cm below vocal fold free edge to inferior border of cricoid cartilage
- Transglottic — tumour crosses from one subsite to another (e.g., supraglottis to glottis); this is a clinical descriptor rather than a formal anatomical subsite but has important staging and prognostic implications
6.3 TNM Staging (AJCC 8th Edition, 2017)
| Stage | Definition |
|---|---|
| T1 | Tumour limited to ONE subsite of supraglottis with normal vocal fold mobility |
| T2 | Tumour invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., base of tongue mucosa, vallecula, medial wall of pyriform sinus) WITHOUT fixation of the larynx |
| T3 | Tumour limited to larynx with vocal fold fixation AND/OR invasion of postcricoid area, pre-epiglottic space, paraglottic space, AND/OR inner cortex of thyroid cartilage |
| T4a | Moderately advanced: tumour invades through thyroid cartilage AND/OR invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of tongue, strap muscles, thyroid, oesophagus) |
| T4b | Very advanced: tumour invades prevertebral space, encases carotid artery, or invades mediastinal structures |
| Stage | Definition |
|---|---|
| T1a | Tumour limited to ONE vocal fold (may involve anterior or posterior commissure) with normal mobility |
| T1b | Tumour involves BOTH vocal folds with normal mobility |
| T2 | Tumour extends to supraglottis and/or subglottis AND/OR impaired vocal fold mobility |
| T3 | Tumour limited to larynx with vocal fold fixation AND/OR invasion of paraglottic space AND/OR inner cortex of thyroid cartilage |
| T4a | As above (through thyroid cartilage or beyond larynx) |
| T4b | As above (prevertebral space, carotid encasement, mediastinum) |
| Stage | Definition |
|---|---|
| T1 | Tumour limited to subglottis |
| T2 | Tumour extends to vocal fold(s) with normal or impaired mobility |
| T3 | Tumour limited to larynx with vocal fold fixation |
| T4a/T4b | As above |
| Stage | Definition |
|---|---|
| N0 | No regional LN metastasis |
| N1 | Metastasis in single ipsilateral LN ≤ 3 cm and ENE (−) [2] |
| N2a | Single ipsilateral LN ≤ 3 cm with ENE (+), OR single ipsilateral LN > 3 cm but ≤ 6 cm and ENE (−) [2] |
| N2b | Multiple ipsilateral LN, all ≤ 6 cm and ENE (−) [2] |
| N2c | Bilateral or contralateral LN, all ≤ 6 cm and ENE (−) [2] |
| N3a | LN > 6 cm and ENE (−) [2] |
| N3b | Any node(s) with ENE (+) [clinically overt, > 2mm on pathology] [2] |
ENE = Extranodal extension (previously called extracapsular spread). Its presence is a major adverse prognostic factor and upstages the N category in AJCC 8th edition. This is a key change from previous editions.
| Stage | Definition |
|---|---|
| M0 | No distant metastasis |
| M1 | Distant metastasis present |
| Stage | T | N | M |
|---|---|---|---|
| I | T1 | N0 | M0 |
| II | T2 | N0 | M0 |
| III | T3 | N0 | M0; or T1-T3, N1, M0 |
| IVA | T4a, N0-N2; or T1-T4a, N2, M0 | ||
| IVB | T4b, any N; or any T, N3, M0 | ||
| IVC | Any T, any N, M1 |
7. Clinical Features
7.1 Symptoms
The symptoms depend heavily on the subsite of the tumour.
- The earliest and most common symptom of glottic carcinoma
- Pathophysiological basis: Any mass on the true vocal fold disrupts the mucosal wave and prevents complete glottic closure → irregular vibration → dysphonia (hoarse, rough, breathy voice)
- Even a tiny (T1a) glottic tumour causes hoarseness because the vocal fold edge is exquisitely sensitive to any mass effect
- Any hoarseness persisting > 3 weeks in a smoker warrants urgent laryngoscopy — this is a clinical pearl
- In supraglottic carcinoma, hoarseness is a late symptom because the tumour must extend inferiorly to involve the true vocal folds or paraglottic space (causing fixation) before voice changes occur
- In subglottic carcinoma, hoarseness is also late for the same reason
- Stridor (inspiratory or biphasic): indicates significant narrowing of the laryngeal airway
- Pathophysiological basis: Tumour bulk physically narrows the glottic or subglottic lumen; additionally, vocal fold fixation (from tumour invasion of the cricoarytenoid joint or recurrent laryngeal nerve) prevents abduction of the cord during inspiration
- Dyspnoea on exertion progressing to dyspnoea at rest
- More common in subglottic and transglottic tumours (the subglottis is the narrowest part of the adult airway within the larynx, and any circumferential growth rapidly compromises the lumen)
- This is a late symptom — the laryngeal airway must be reduced to < 4–5 mm before stridor becomes clinically apparent at rest
ALWAYS protect the airway
ALWAYS protect the airway for all H&N cancer [2]. Airway compromise is the most immediately life-threatening presentation of laryngeal carcinoma. If a patient presents with stridor, urgent assessment and potential tracheostomy/intubation are required before any further workup.
- Pathophysiological basis:
- Supraglottic tumours (especially those involving the epiglottis or aryepiglottic folds) directly obstruct the hypopharyngeal inlet or fix the laryngeal framework, preventing normal laryngeal elevation during swallowing
- Pain from tumour invasion of the pharyngeal mucosa or deep muscle → odynophagia
- More common in supraglottic carcinoma and tumours with hypopharyngeal extension
- Globus sensation progressing to dysphagia [4] — the sequence described in the lecture slides for hypopharyngeal/pharyngeal carcinoma applies here too for supraglottic tumours extending to the pharynx
- Pathophysiological basis: The internal branch of the superior laryngeal nerve (from vagus, CN X) provides sensory innervation to the supraglottic larynx. The auricular branch of the vagus (Arnold's nerve) supplies the ear (external auditory canal, tympanic membrane). Tumour invasion of supraglottic mucosa causes pain signals that travel via the vagus nerve → referred pain is perceived in the ear (this is referred otalgia via CN X)
- This is a classic clinical feature of supraglottic and pyriform sinus tumours
- An adult with unexplained unilateral otalgia and a normal ear examination should have their larynx and pharynx examined
- Persistent unilateral sore throat, especially in a smoker/drinker, should raise suspicion for malignancy
- Pathophysiological basis: Direct mucosal involvement by tumour → inflammation, ulceration, secondary infection
- Coughing up blood-streaked sputum
- Pathophysiological basis: Tumour neovascularisation is fragile; the friable tumour surface ulcerates and bleeds, especially during coughing
- Pathophysiological basis: Loss of laryngeal protective function — the tumour prevents complete glottic closure during swallowing → aspiration of food/saliva into the trachea → chronic cough, recurrent aspiration pneumonia
- More common in advanced disease with vocal fold fixation
- A feature of advanced disease
- Pathophysiological basis: Combination of dysphagia (reduced oral intake), cancer cachexia (cytokine-mediated [TNF-α, IL-6] → hypermetabolic state with muscle wasting), and pain
- Patient may present with a cervical lymph node metastasis [1] as the first noticeable symptom, especially for supraglottic tumours (30–50% nodal rate at presentation)
- Less likely in early glottic tumours
| Symptom | Supraglottic | Glottic | Subglottic |
|---|---|---|---|
| Hoarseness | Late | Early (cardinal symptom) | Late |
| Dysphagia/odynophagia | Early-moderate | Late | Late |
| Referred otalgia | Common | Uncommon | Uncommon |
| Stridor/dyspnoea | Late | Late (unless bilateral fixation) | Relatively earlier (narrow lumen) |
| Neck lump | Early-moderate | Late | Late |
| Sore throat | Common | Uncommon | Uncommon |
Why supraglottic and subglottic cancers present late
Supraglottic cancer presents as advanced disease due to paucity of symptoms [2]. The supraglottic larynx is a spacious region — a tumour can grow to significant size before impinging on the vocal folds (causing hoarseness) or the airway (causing stridor). Similarly, subglottic cancer presents as advanced disease due to paucity of symptoms [2]. It often grows circumferentially and submucosally before becoming clinically apparent.
7.3 Signs
- Palpable neck nodes: Hard, non-tender, fixed or mobile depending on extent
- Level II (subdigastric) most common for supraglottic tumours
- Level VI (central compartment/paratracheal) for subglottic/glottic tumours
- Bilateral nodes suggest midline tumour or supraglottic primary
- Normal finding: The larynx can be rocked gently from side to side over the cervical vertebral column, producing a palpable (and sometimes audible) crepitus
- Abnormal (loss of crepitus): Indicates one of the following:
- Postcricoid/hypopharyngeal tumour interposed between the larynx and the vertebral column
- Tumour fixation of the larynx to the prevertebral fascia (T4b disease)
- This is a classic clinical sign in pharyngolaryngeal malignancy
- Exophytic/ulcerative/infiltrative mass on the vocal fold, supraglottic structures, or subglottis
- Leukoplakia (white patch) or erythroplakia (red patch) — premalignant lesions
- Vocal fold immobility (fixation): the affected cord does not abduct during inspiration or adduct during phonation
- Pathophysiological basis: Tumour invasion of the thyroarytenoid muscle, cricoarytenoid joint, or recurrent laryngeal nerve
- Fixed vocal fold = at least T3 disease
- Pooling of saliva in the pyriform sinus on the affected side — suggests hypopharyngeal or supraglottic tumour causing obstruction
- Also known as Plummer-Vinson syndrome
- Triad of: iron deficiency anaemia + postcricoid dysphagia + upper oesophageal/postcricoid web
- Associated with increased risk of postcricoid carcinoma and hypopharyngeal carcinoma
- Pathophysiological basis: Chronic iron deficiency leads to mucosal atrophy and web formation in the postcricoid region → chronic mucosal irritation → increased risk of malignant transformation
- More common in middle-aged women
- Relevant because postcricoid carcinoma can present similarly to subglottic laryngeal carcinoma (location is adjacent)
- Inspiratory stridor suggests supraglottic obstruction
- Biphasic stridor suggests glottic or subglottic obstruction
- Indicates advanced/bulky disease
- Hoarseness, breathiness, roughness
- "Hot potato voice" (muffled voice) — suggests supraglottic mass (particularly base of tongue or epiglottic tumour)
- Complete aphonia — suggests bilateral vocal fold fixation or very large tumour
- Cachexia: Muscle wasting, temporal wasting
- Supraclavicular lymphadenopathy (Virchow's node / left supraclavicular = Troisier's sign) — may indicate distant metastatic spread
- Hepatomegaly: Liver metastases (less common)
| Feature | Supraglottic | Glottic | Subglottic |
|---|---|---|---|
| Frequency | 30–35% | Most common (60–65%) [2] | 2–5% |
| Presentation | Advanced (late) [2] | Early (hoarseness) [2] | Advanced (late) [2] |
| Aggressiveness | More aggressive [2] | Less aggressive (early stage) | Aggressive |
| Lymphatics | Rich → higher LN metastasis (30–50%) [2] | Sparse → limited LN metastasis [2] | Moderate (~40%) [2] |
| Local extension | Pre-epiglottic/paraglottic space, base of tongue | Anterior commissure, contralateral cord, subglottis | Propensity for local extension [2], circumferential |
| Recurrence | Moderate | Lower (early stage) | Higher rates of local recurrence [2] |
| Survival | Moderate | Best (early stage ≈ 90% 5-year) | Poorer survival rates [2] |
High Yield Summary
-
Definition: Laryngeal carcinoma = malignant epithelial neoplasm of the larynx; ~95% are SCC [1].
-
Epidemiology: Male predominance; predominantly elderly > 60 [2]; glottic carcinoma is the most common subsite [2].
-
Anatomy: The larynx is divided into supraglottic, glottic, and subglottic regions. The glottis has sparse lymphatics (early tumours rarely metastasise to nodes), while the supraglottis has rich lymphatics (30–50% nodal disease at presentation) [2].
-
Risk factors: Smoking is THE primary risk factor [1][3]. Alcohol has a synergistic effect [3]. Other: GERD/LPR, prior radiation, immunosuppression, chronic laryngitis, family history.
-
Field cancerisation: The entire upper aerodigestive tract mucosa is at risk → panendoscopy (direct laryngoscopy + bronchoscopy + OGD) is mandatory [2].
-
Clinical features:
- Glottic → early hoarseness (cardinal symptom) [1]
- Supraglottic → late symptoms; sore throat, dysphagia, referred otalgia, neck lump [4]
- Subglottic → late symptoms; stridor
- Cervical lymph node metastasis [1] — especially supraglottic
- Loss of laryngeal crepitus [4] — suggests tumour between larynx and vertebral column
- Airway obstruction [1] — always protect the airway
-
TNM staging: Key points — vocal fold fixation = T3; cartilage invasion = T4a; ENE is now incorporated into N staging (AJCC 8th edition) [2].
-
Paterson-Brown-Kelly syndrome [4] = iron deficiency anaemia + postcricoid web + dysphagia → risk of postcricoid/hypopharyngeal carcinoma.
Active Recall - Laryngeal Carcinoma (Definition to Clinical Features)
[1] Lecture slides: GC 216. Dysphonia Laryngitis, voice abuse, tumour and laryngeal cancer.pdf (p19) [2] Senior notes: felixlai.md (sections on Laryngeal carcinoma, Head and neck cancer overview, field cancerisation, anatomy, TNM staging) [3] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p41 — Etiology) [4] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p39 — History and Examination of pharyngeal/hypopharyngeal carcinoma)
Differential Diagnosis of Laryngeal Carcinoma
When a patient presents with hoarseness, stridor, dysphagia, or a laryngeal mass, the clinician must think systematically: "Is this really laryngeal carcinoma, or could it be something else?" The differential diagnosis is broad and spans benign vocal cord pathologies, other malignancies, neurological causes, and systemic conditions. Let me walk you through this from first principles.
The key clinical question is: What can cause a visible lesion on the larynx, hoarseness, or airway compromise?
We can organise differentials using the aetiological framework from the lecture slides [1]:
1. Benign Local Vocal Cord Pathologies
These are the conditions that most commonly mimic early glottic carcinoma because they also cause hoarseness and may appear as visible lesions on laryngoscopy.
- What it is: Acute inflammation of the laryngeal mucosa, usually viral (URI) or from voice abuse
- Why it mimics carcinoma: Causes hoarseness, erythema, and oedema of the vocal folds
- How to distinguish: Self-limiting ( < 3 weeks), associated with URTI symptoms, bilateral and diffuse mucosal changes rather than a discrete mass. Persistent hoarseness (> 3 weeks) warrants further investigation to exclude malignancy [1]
- What they are: Bilateral, symmetrical, small fibrotic nodules at the junction of the anterior 1/3 and posterior 2/3 of the true vocal folds ("singer's nodules" or "screamer's nodules")
- Pathophysiological basis: Chronic voice abuse → repeated collision of the vocal folds at the point of maximal vibration amplitude → localised oedema → fibrosis → nodule
- Why it mimics carcinoma: Discrete lesion on the vocal fold causing persistent hoarseness
- How to distinguish: Always bilateral and symmetrical (carcinoma is almost always unilateral initially); associated with voice abuse/high vocal demand; smooth surface (carcinoma is irregular/ulcerated); responds to voice therapy. Occupation and voice demand are key history points [1]
- What it is: Usually a unilateral, pedunculated or sessile, smooth, translucent/haemorrhagic mass on the vocal fold
- Pathophysiological basis: Often follows a single episode of voice strain → submucosal haemorrhage in Reinke's space → organisation → polyp
- Why it mimics carcinoma: Unilateral lesion on the vocal fold causing hoarseness — this can look very similar to an early exophytic glottic SCC
- How to distinguish: Smooth, well-circumscribed, often translucent or vascular appearance; no surrounding leukoplakia. However, biopsy is essential to exclude malignancy — you cannot distinguish a polyp from an early carcinoma on appearance alone
Clinical Pearl
A unilateral vocal cord "polyp" in a smoker is guilty until proven innocent. Biopsy!!! [5] — always obtain tissue for histology. Many early glottic carcinomas are initially mistaken for benign polyps.
- What it is: Diffuse, bilateral oedema of the subepithelial layer (Reinke's space) of the vocal folds
- Pathophysiological basis: Chronic irritation (smoking, voice abuse, LPR) → increased vascular permeability → fluid accumulation in the loose connective tissue of Reinke's space → polypoid degeneration of both vocal folds
- Why it mimics carcinoma: Causes significant dysphonia (low-pitched, rough voice); the swollen vocal folds can look alarming on laryngoscopy
- How to distinguish: Bilateral and diffuse (not a discrete mass); translucent/gelatinous appearance; strongly associated with smoking. However, given the shared risk factor of smoking, coexistent dysplasia/carcinoma must be actively excluded with biopsy
- What it is: Multiple warty (papillomatous) growths on the laryngeal mucosa caused by HPV types 6 and 11 (the low-risk types, NOT the oncogenic 16/18 types that cause oropharyngeal SCC)
- Pathophysiological basis: HPV infection of the basal epithelial cells → proliferative squamous papillomas; "recurrent" because the virus persists in adjacent normal-appearing mucosa and lesions regrow after removal
- Why it mimics carcinoma: Exophytic lesions that can cause hoarseness and airway obstruction; in adults, can occasionally undergo malignant transformation (especially with HPV 11, smoking, or prior radiation)
- How to distinguish: Multiple, bilateral, papillomatous (not ulcerated); history of recurrence after excision; bimodal age distribution (juvenile form: < 5 years; adult form: 20–40 years). Biopsy confirms squamous papilloma
2. Premalignant Lesions
These sit on the continuum between benign and malignant disease. They are critical differentials because they may represent the precursor to or coexist with laryngeal SCC.
- Definition: A white patch or plaque on the mucosal surface that cannot be scraped off and cannot be characterised clinically or pathologically as any other definable lesion [2]
- Pathophysiological basis: Represents hyperkeratosis or epithelial hyperplasia, often with underlying dysplasia; caused by chronic irritation (smoking, alcohol, voice abuse)
- Clinical significance: Premalignant (dysplasia) or already malignant (SCC) [5]. Malignant transformation rate varies widely (1–40% depending on grade of dysplasia and location — leukoplakia of the floor of the mouth has a particularly high risk [2])
- Management: Biopsy!!! [5] — Microlaryngoscopy + biopsy [5] is mandatory to determine the grade of dysplasia or exclude invasive carcinoma
- Definition: A bright red plaque of the oral/laryngeal mucosa that cannot be characterised clinically or pathologically as any other definable condition
- Pathophysiological basis: The red colour comes from thin, atrophic epithelium overlying a highly vascularised, dysplastic submucosa — the blood vessels "show through" the thinned epithelium
- Clinical significance: Premalignant (dysplasia) or malignant (SCC) [5]. Erythroplakia has a MUCH higher rate of malignant transformation than leukoplakia (~50% harbour invasive carcinoma or carcinoma in situ at initial biopsy)
- Management: Biopsy!!! [5]
Leukoplakia vs Erythroplakia
Think of it this way: White = hyperkeratosis (thickened surface layer); Red = thin, atrophic epithelium with underlying dysplasia showing the vasculature beneath. Erythroplakia is far more dangerous than leukoplakia — if you see a red patch, be very worried. Both require biopsy.
While SCC accounts for ~90–95% of laryngeal malignancies [1][6], other histological types must be considered:
| Malignancy | Key Distinguishing Features |
|---|---|
| Verrucous carcinoma | Well-differentiated, warty exophytic growth; locally aggressive but rarely metastasises; may be confused with papilloma on biopsy (needs adequate deep biopsy to show pushing invasion) |
| Minor salivary gland tumours [2] | May present as submucosal masses [2] — smooth overlying mucosa (submucosal rather than mucosal origin); includes adenoid cystic carcinoma (perineural invasion), mucoepidermoid carcinoma |
| Lymphoma [2][7] | Tonsils and tongue base may be the presenting site for a lymphoma [2]; can also rarely involve the larynx; suspect if rapidly growing, rubbery mass; constitutional B symptoms (fever, night sweats, weight loss); bilateral cervical lymphadenopathy |
| Neuroendocrine tumours | Rare; small cell carcinoma of the larynx (supraglottis most common) — very aggressive; typical/atypical carcinoid |
| Chondrosarcoma | Arises from laryngeal cartilage (usually cricoid); slow-growing, submucosal mass; endoscopy shows smooth, firm expansion |
4. Neurological Causes of Hoarseness (Mimicking Laryngeal Cancer)
A vocal cord that does not move on laryngoscopy could be due to tumour invasion (T3 laryngeal carcinoma) or a neurological lesion affecting the recurrent or superior laryngeal nerve.
- Causes: Thyroid surgery (most common iatrogenic cause), thyroid carcinoma, lung apex tumour (Pancoast), aortic arch aneurysm (left RLN loops under the aortic arch), mediastinal lymphadenopathy, oesophageal carcinoma, idiopathic
- Why it mimics carcinoma: Unilateral vocal fold immobility → hoarseness; on laryngoscopy, the cord appears immobile in the paramedian position
- How to distinguish: No visible mass on the vocal fold; the cord itself looks normal but does not move. CT neck and chest is needed to identify the cause of the nerve palsy. A vocal fold that is immobile but appears normal mandates investigation of the entire course of the RLN from skull base to mediastinum
- Causes: Thyroid surgery, viral neuritis
- Effect: External branch paralysis → cricothyroid muscle weakness → loss of vocal fold tension → breathy, weak voice, inability to project or hit high notes
- How to distinguish: Vocal fold is mobile but may appear bowed; subtle and often missed on routine laryngoscopy
- Parkinsonism: Hypophonia (soft, monotone voice), not typically a mass lesion
- Vocal tremor: Rhythmic oscillation of vocal folds
- Spasmodic dysphonia: Involuntary spasms of the laryngeal muscles during speech (adductor type → strained, strangled voice; abductor type → breathy breaks)
5. Functional and Psychogenic Causes
- What it is: Excessive tension in the extrinsic and/or intrinsic laryngeal muscles during phonation
- Pathophysiological basis: Compensatory hyperfunction in response to an underlying laryngeal pathology (secondary MTD) or primary psychosocial stress
- How to distinguish: No structural lesion on laryngoscopy; may see supraglottic hyperadduction ("false fold phonation"); voice improves with manual laryngeal manipulation or voice therapy
- Why it matters: Can coexist with organic pathology — don't assume hoarseness is "just functional" without thorough laryngoscopy
- What it is: Loss of voice without organic cause, typically in the setting of psychological stress
- How to distinguish: Complete aphonia but with a normal cough (the cough reflex requires vocal fold adduction, proving the folds can move); laryngoscopy shows normal vocal fold structure and mobility (though folds may not adduct during phonation)
6. Other Important Differentials to Consider in the H&N Region
These are relevant because tumours from adjacent sites can extend to involve the larynx or present with similar symptoms:
- Level of hyoid to lower border of cricoid [8]
- 3 sites: 60% piriform fossa, 30% postcricoid, 10% posterior pharyngeal wall [8]
- Can invade the larynx secondarily → hoarseness, vocal fold fixation
- Paterson-Brown-Kelly syndrome [4] — associated with postcricoid carcinoma
- 30% LN metastases at presentation [4]; loss of laryngeal crepitus [4] on examination
- History: Sore throat → globus → dysphagia [4]; otalgia, hoarseness [4]
- Subsites: Tonsil (commonest), tongue base, soft palate, posterior wall [7]
- Histology: SCC (epithelial) vs lymphoma / minor salivary gland tumours [7]
- HPV-associated subset (younger patients, better prognosis) [2]
- Can refer pain to the ear and cause "hot potato" voice — symptoms overlapping with supraglottic laryngeal cancer
- Risk of synchronous cancer: 8–10% [9] due to field change effect from carcinogen exposure [9]
- Patients with laryngeal carcinoma are more likely to develop a second primary in the lung [2]
- This is why panendoscopy (bronchoscopy + oesophagoscopy) [9] is mandatory — you must actively look for a second tumour
- A thyroid mass can invade the larynx/trachea and cause hoarseness via RLN invasion
- Distinguished by thyroid nodule on examination/USG, thyroid function tests, and FNAC
- Can extend superiorly to involve the postcricoid region or compress/invade the RLN
- Distinguished by dysphagia as the predominant symptom and by OGD findings
Here is a practical clinical approach when a patient presents with hoarseness ± a laryngeal lesion:
The Golden Rule
Any visible lesion on the vocal fold in a smoker must be biopsied. You cannot distinguish early SCC from a benign polyp or leukoplakia on appearance alone. This is why the lecture slides emphatically state: Biopsy!!! [5]. The standard approach is microlaryngoscopy + biopsy [5] under general anaesthesia.
The lecture slides specifically highlight these associated "red flag" symptoms for malignancy [1]:
| Red Flag | Why It Suggests Malignancy |
|---|---|
| Bleeding [1] | Friable, neovascularised tumour surface ulcerates and bleeds; benign lesions rarely bleed spontaneously |
| Shortness of breath [1] | Significant airway narrowing from tumour bulk or bilateral cord fixation; benign polyps/nodules rarely cause this |
| Dysphagia [1] | Suggests tumour extension beyond the glottis (supraglottic, hypopharyngeal, or oesophageal involvement) |
| Persistent hoarseness (> 3 weeks) [1] | Persistent = organic lesion; fluctuating = functional [1]. Organic lesions include SCC, polyp, nodule |
| Progressive course [1] | Benign lesions tend to be stable; progressive worsening suggests growing malignancy |
| Referred otalgia [4] | CN IX/X-mediated referred pain from pharyngolaryngeal tumour |
| Weight loss | Cancer cachexia; not expected with benign vocal cord pathology |
| Cervical lymphadenopathy | Nodal metastasis from SCC; not seen with benign lesions |
| Differential | Typical Patient | Laryngoscopy Appearance | Key Distinguishing Feature |
|---|---|---|---|
| Laryngeal SCC | Elderly male smoker/drinker | Irregular, ulcerated, exophytic mass; leukoplakia; fixed cord | Biopsy confirms SCC |
| Vocal cord polyp | Any age; voice strain history | Smooth, unilateral, pedunculated | Biopsy needed to exclude SCC |
| Vocal cord nodules | Voice professional; high vocal demand | Bilateral, symmetrical, anterior 1/3–2/3 junction | Bilateral = almost never cancer |
| Reinke's oedema | Smoker; middle-aged woman | Bilateral, diffuse, translucent swelling | Bilateral + diffuse; still biopsy |
| RRP | Bimodal: child or young adult | Multiple, bilateral, warty | HPV 6/11; recurrence after excision |
| Leukoplakia | Smoker | White patch, cannot scrape off | Biopsy — may be dysplasia/SCC [5] |
| Erythroplakia | Smoker | Red patch | Biopsy — ~50% harbour SCC [5] |
| RLN palsy | Post-thyroidectomy, lung cancer | Immobile cord but normal-looking | No mass; CT to find cause |
| Hypopharyngeal CA | Elderly male smoker/drinker | Pyriform fossa/postcricoid mass | Loss of laryngeal crepitus [4] |
| Lymphoma | Any age; constitutional symptoms | Submucosal mass, tonsil/tongue base | B symptoms; biopsy shows lymphoid |
| Minor salivary gland tumour | Any age | Submucosal, smooth mucosa overlying | Submucosal mass [2] |
High Yield Summary — Differential Diagnosis
-
Aetiologies of voice disorders are classified as Organic (local pathology / neurological / poor breath support), Functional (muscle tension dysphonia), and Psychogenic (conversion disorder) [1].
-
Benign mimics of glottic SCC: vocal cord polyp, nodules, Reinke's oedema, recurrent respiratory papillomatosis, laryngitis. Key distinguishing features: bilateral (nodules, Reinke's), smooth and pedunculated (polyp), self-limiting (laryngitis), multiple and warty (papillomatosis).
-
Leukoplakia and erythroplakia are premalignant — Biopsy!!! [5]. Erythroplakia carries a much higher malignant transformation rate.
-
Persistent hoarseness = organic lesion; fluctuating = functional [1]. Any hoarseness > 3 weeks in a smoker requires urgent laryngoscopy.
-
Red flag symptoms for malignancy: bleeding, shortness of breath, dysphagia [1], otalgia, progressive course, weight loss, cervical lymphadenopathy.
-
Immobile vocal fold with no visible mass → think RLN palsy → investigate the entire nerve course (neck + chest CT).
-
Adjacent H&N malignancies: Hypopharyngeal carcinoma (piriform fossa > postcricoid > posterior wall) [8], oropharyngeal carcinoma (tonsil commonest) [7], and synchronous primary from field cancerisation (8–10% risk) [9].
-
Panendoscopy is mandatory [9] to detect synchronous lesions in the upper aerodigestive tract.
Active Recall - Differential Diagnosis of Laryngeal Carcinoma
References
[1] Lecture slides: GC 216. Dysphonia Laryngitis, voice abuse, tumour and laryngeal cancer.pdf (p4, p7) [2] Senior notes: felixlai.md (sections on Laryngeal carcinoma, Head and neck cancer overview, CA Oropharynx differential diagnosis, field cancerisation) [4] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p39 — History and Examination) [5] Lecture slides: GC 216. Dysphonia Laryngitis, voice abuse, tumour and laryngeal cancer.pdf (p18 — Leukoplakia, erythroplakia) [6] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p40 — Histology) [7] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p36 — Oropharyngeal Malignancy) [8] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p38 — Hypopharyngeal carcinoma) [9] Lecture slides: GC 216. Dysphonia Laryngitis, voice abuse, tumour and laryngeal cancer.pdf (p20 — Principle of investigation in HN cancers)
Diagnosis of Laryngeal Carcinoma
When we approach the diagnosis of laryngeal carcinoma, we have three simultaneous objectives, as outlined in the lecture slides [9]:
Principle of investigation in H&N cancers [9]:
- Determine tumour staging — T = Local tumour stage (Endoscopy, CT/MRI); N = Regional lymph node (USG neck + FNA); M = Distant metastasis (CXR, Blood test, PET) [9]
- Detect synchronous lesion — Risk of synchronous cancer: 8–10% due to field change effect from carcinogen exposure → Panendoscopy (bronchoscopy + oesophagoscopy) [9]
There is no single "diagnostic criterion" like the Jones criteria for rheumatic fever. Instead, the diagnosis of laryngeal carcinoma is confirmed by histopathological examination of biopsied tissue. Everything else — history, examination, endoscopy, imaging — serves to (a) raise clinical suspicion, (b) obtain tissue, and (c) stage the disease.
Laryngeal carcinoma is fundamentally a histopathological diagnosis. The diagnostic "criteria" are:
| Step | Requirement |
|---|---|
| 1. Clinical suspicion | Hoarseness > 3 weeks in a smoker/drinker; red flag symptoms (bleeding, dyspnoea, dysphagia); visible lesion on laryngoscopy |
| 2. Tissue diagnosis | Biopsy to obtain histological diagnosis [1] — this is the gold standard and definitive step |
| 3. Staging | TNM staging via endoscopy + imaging (CT/MRI) + nodal assessment (USG ± FNA) + distant metastasis workup (CXR/CT chest, PET-CT) |
No Biopsy = No Diagnosis
You cannot diagnose laryngeal carcinoma on clinical or radiological grounds alone. Biopsy!!! [5] — a tissue specimen showing invasive squamous cell carcinoma (or other malignant histology) with breach of the basement membrane is the definitive diagnostic criterion. Imaging and endoscopy guide you to the lesion and stage it, but the pathologist makes the diagnosis.
What the Pathologist Reports
The biopsy specimen (usually obtained via microlaryngoscopy) is assessed for:
- Histological type: SCC (conventional, verrucous, basaloid, spindle cell), adenocarcinoma, neuroendocrine, etc.
- Grade of differentiation: Well / moderately / poorly differentiated SCC
- Depth of invasion: Superficial (carcinoma in situ / microinvasive) vs deeply invasive
- Margins: If excisional biopsy — clear vs involved
- Lymphovascular invasion (LVI) and perineural invasion (PNI): Adverse prognostic features
- p16 immunohistochemistry (surrogate marker for HPV): Particularly relevant for oropharyngeal SCC; less established for laryngeal SCC but increasingly reported
3. Investigation Modalities — Detailed Breakdown
Let me walk through each investigation, explaining why we do it, what we look for, and how to interpret the findings.
Before any investigation, a thorough history and examination directs the workup.
History — from lecture slides [1][4]:
- Smoking [1][3] — quantify in pack-years; the single most important risk factor
- Occupation, voice demand [1] — professional voice users (teachers, singers) are more likely to have benign voice pathology; but smoking history overrides this
- Details of hoarseness [1]:
- Acute vs chronic [1] — acute suggests infection; chronic ( > 3 weeks) demands investigation
- Progression [1] — progressive worsening suggests growing malignancy
- Persistent (organic lesion) vs fluctuating (functional) [1] — this is a critical distinction. A carcinoma causes persistent hoarseness that does not improve day-to-day. Functional dysphonia fluctuates
- Associated "red flag" symptoms for malignancy [1]:
- Sore throat, globus → dysphagia, otalgia [4] — classic progression for pharyngolaryngeal malignancy
- Risk factors: alcohol, smoking [4]
- Alcohol consumption (units/week) — synergistic with smoking
- Cervical lymphadenopathy [2]: Systematic palpation of all cervical lymph node levels (I–VI). Note size, consistency (hard = malignancy), fixation, tenderness
- 30% LN metastases [4] — a significant proportion present with palpable nodes (especially supraglottic and hypopharyngeal tumours)
- Loss of laryngeal crepitus [4] — gently rock the larynx against the vertebral column. Loss of the normal side-to-side grating sensation suggests a tumour mass interposed between the larynx and the prevertebral fascia (postcricoid/hypopharyngeal tumour) or direct fixation
- Paterson-Brown-Kelly syndrome [4] — look for signs of iron deficiency anaemia (pallor, koilonychia, angular stomatitis, glossitis) in patients with postcricoid symptoms
- Oral cavity and oropharynx examination with tongue depressor and headlight
- General examination: cachexia, hepatomegaly, supraclavicular nodes (distant metastasis)
When to Refer Urgently
EARLY REFERRAL to ENT Surgeons when suspecting malignancy [10]:
- Persistent 2–4 weeks after conservative/empirical treatment [10]
- Clinically suspicious: irregular, induration, > 2 cm, associated cervical LN enlargement [10]
This is a key take-home message from the lecture slides. Do not wait months to refer a hoarse smoker — 2–4 weeks of persistent symptoms is enough to trigger urgent ENT referral.
| Parameter | Detail |
|---|---|
| What it is | A thin, flexible fibreoptic scope passed through the nose to directly visualise the larynx. Can also use a rigid 70° or 90° laryngoscope transorally |
| Setting | Outpatient clinic; no general anaesthesia required |
| Why we do it | Flexible laryngoscopy to assess extent [1] — first-line investigation for any patient with hoarseness > 3 weeks; allows real-time assessment of vocal fold mobility, mucosal lesions, and airway |
| What to look for | See table below |
Key findings on flexible laryngoscopy [2]:
| Finding | Interpretation | Staging Implication |
|---|---|---|
| Discrete mass on one vocal fold | Likely glottic carcinoma (or polyp — needs biopsy) | T1a if limited to one fold, mobile |
| Mass involving both vocal folds | Bilateral glottic involvement | T1b if both mobile |
| Mass extending to supraglottis/subglottis | Transglottic tumour | At least T2 |
| Impaired vocal fold mobility | Tumour infiltration of vocalis muscle, paraglottic space, or cricoarytenoid joint beginning | T2 (impaired mobility) |
| Fixed vocal fold (immobile) | Full invasion of thyroarytenoid muscle, cricoarytenoid joint ankylosis, or RLN invasion | T3 |
| Leukoplakia / erythroplakia | Premalignant or malignant — Biopsy!!! [5] | — |
| Pooling of saliva in pyriform sinus | Suggests hypopharyngeal/supraglottic obstruction | — |
| Epiglottic mass | Supraglottic carcinoma | T staging depends on extent |
Key areas to note for tumour extension [2]:
- Supraglottic tumour: Vallecula / base of tongue / ventricle / arytenoid / anterior commissure [2]
- Glottic tumours: False cord / arytenoid / anterior commissure / subglottic extension [2]
| Parameter | Detail |
|---|---|
| What it is | Direct laryngoscopy using a rigid laryngoscope with the patient under GA, combined with an operating microscope for magnified visualisation and tissue biopsy |
| Why we do it | Biopsy to obtain histological diagnosis [1] — the gold standard for definitive tissue diagnosis. Also allows detailed assessment of tumour extent that may not be possible with flexible scope alone |
| What to look for | Precise tumour extent (anterior commissure involvement, subglottic extension, arytenoid involvement); biopsy of the lesion for histopathology |
| Interpretation | Histology confirms SCC (or other malignancy) and provides grade of differentiation, presence of LVI/PNI |
This is typically combined with panendoscopy (see below) in a single GA session — efficient use of theatre time.
| Parameter | Detail |
|---|---|
| What it is | A "triple endoscopy" performed under GA to examine the entire upper aerodigestive tract |
| Components | Direct laryngoscopy + Bronchoscopy + Oesophagoscopy (OGD) [2][9] |
| Why we do it | 10% risk of synchronous/metachronous tumour (field cancerisation) [9][10]. The same carcinogens (tobacco + alcohol) affect the entire mucosal field |
| What to look for | Synchronous primary tumours in: bronchial tree (especially in laryngeal cancer patients — laryngeal cancer → second primary in lung [2]), oesophagus, or other pharyngeal subsites |
| Interpretation | Any suspicious lesion identified during panendoscopy is biopsied. A positive finding means the patient has two primary cancers requiring coordinated management |
Why Panendoscopy is Non-Negotiable
Staging examination is recommended at the initial evaluation of ALL patients with primary cancers of the upper aerodigestive tract [2]. Missing a synchronous primary can lead to inadequate treatment and worse survival. The 8–10% risk is too high to ignore.
| Parameter | Detail |
|---|---|
| What it is | High-frequency ultrasound probe applied to the neck to assess cervical lymph nodes, followed by FNA of suspicious nodes under USG guidance |
| Why we do it | N staging: USG neck + FNA [9]; Ultrasound neck +/- FNAC [1][10] — the primary modality for assessing regional lymph node metastasis |
| What to look for | See table below |
USG features of a suspicious (malignant) lymph node:
| Feature | Benign (Reactive) Node | Malignant (Metastatic) Node |
|---|---|---|
| Shape | Oval (L:S ratio > 2) | Round (L:S ratio < 2) |
| Hilum | Preserved, echogenic | Absent or eccentric |
| Cortex | Thin, uniform | Thickened, eccentric, or replaced |
| Echogenicity | Hypoechoic, homogeneous | Heterogeneous, may have cystic/necrotic areas |
| Border | Well-defined, smooth | Irregular, may show extranodal extension |
| Vascularity | Hilar flow pattern | Peripheral or mixed flow pattern |
| Size | < 1 cm (generally) | > 1 cm; but size alone is unreliable |
FNA interpretation:
- Positive for SCC: Confirms nodal metastasis → at least N1 disease
- Negative/non-diagnostic: Does not exclude metastasis (false negative rate ~5–10%); may need repeat FNA or core needle biopsy
- FNA of a suspected LN in the setting of an established primary tumour may provide relevant information when clinical and imaging evaluation of neck LNs is equivocal and a positive or negative finding will change the treatment approach [2]
FNA vs Excisional Biopsy of Neck Nodes
Never do an excisional biopsy of a cervical lymph node suspected to be metastatic SCC as the first step — this can cause field contamination, disrupt tissue planes, and compromise subsequent neck dissection. Always use FNA first. Excisional biopsy is reserved for suspected lymphoma (where architecture is needed for subtyping) [2].
| Parameter | Detail |
|---|---|
| What it is | Computed tomography of the neck with intravenous contrast |
| Why we do it | Contrast CT neck to assess extent [1]; T staging: Local tumour stage (CT/MRI) [9]; evaluates local tumour invasion and nodal disease |
| What to look for | See table below |
Key CT findings and their interpretation:
| CT Finding | Interpretation | Staging Relevance |
|---|---|---|
| Enhancing mucosal mass | Primary tumour | Determines T stage based on extent |
| Pre-epiglottic space invasion | Fat stranding/obliteration in the pre-epiglottic space | T3 for supraglottic tumours [2] |
| Paraglottic space invasion | Fat stranding lateral to the ventricle/vocal fold | T3 [2] |
| Cartilage erosion/invasion | Sclerosis, lysis, or frank destruction of thyroid/cricoid cartilage | Inner cortex = T3; through-and-through = T4a [2] |
| Extralaryngeal spread | Tumour extending beyond the laryngeal framework into strap muscles, thyroid gland, trachea, oesophagus | T4a |
| Prevertebral fascia involvement | Obliteration of the fat plane between larynx and prevertebral muscles | T4b (unresectable) |
| Carotid artery encasement | Tumour surrounding > 270° of the carotid artery circumference | T4b (unresectable) |
| Enlarged cervical lymph nodes | Size > 1 cm, central necrosis, heterogeneous enhancement, irregular border | N staging; central necrosis is highly specific for metastatic SCC |
| Contralateral nodes | Bilateral lymphadenopathy | N2c or higher |
Why CT over MRI for initial assessment?
- CT is faster, more widely available, cheaper, and better at detecting cartilage invasion (sclerosis and erosion patterns)
- CT also provides good assessment of airway patency (critical in patients with stridor)
- CT chest can be done in the same session for distant metastasis workup
| Parameter | Detail |
|---|---|
| What it is | Magnetic resonance imaging of the neck |
| Why we do it | Provides important staging information and is crucial for identifying cartilage erosion or invasion and extension into pre-epiglottic or paraglottic spaces [2]; MRI provides optimal visualisation of soft-tissue infiltration [2] |
| When to use | Complements CT; particularly useful for: (1) assessing soft-tissue extent (pre-epiglottic/paraglottic space invasion), (2) differentiating tumour from post-treatment fibrosis, (3) patients with contrast allergy or renal impairment (gadolinium vs iodinated contrast) |
Key MRI sequences and findings:
| Sequence | What It Shows |
|---|---|
| T1-weighted | Anatomical detail; tumour appears isointense to muscle; fat (pre-epiglottic, paraglottic) is bright — loss of bright signal = tumour invasion |
| T2-weighted | Tumour appears hyperintense (bright); good for delineating tumour extent from surrounding tissues |
| T1 post-gadolinium (with fat suppression) | Enhancing tumour within pre-epiglottic/paraglottic fat; helps define tumour margins |
| DWI (Diffusion-weighted imaging) | Restricted diffusion in malignant tissue (high cellularity) — useful for differentiating recurrent tumour from post-treatment changes |
CT vs MRI — when to use which:
| Feature | CT | MRI |
|---|---|---|
| Cartilage invasion | ✅ Superior (sclerosis, erosion) | Moderate |
| Pre-epiglottic/paraglottic space | Good | ✅ Superior (fat signal loss on T1) |
| Soft-tissue detail | Good | ✅ Superior |
| Nodal assessment | ✅ Good | ✅ Good |
| Speed | ✅ Fast (seconds) | Slow (20–40 min) |
| Motion artefact | Less affected | More affected (swallowing, breathing) |
| Post-treatment surveillance | Moderate | ✅ Superior (DWI for recurrence) |
| Availability | ✅ Widely available | Less available |
| Parameter | Detail |
|---|---|
| What it is | Plain radiograph of the chest |
| Why we do it | M staging: Distant metastasis (CXR, blood test, PET) [9]; CXR [10] — baseline screening for pulmonary metastasis and synchronous lung primary |
| What to look for | Pulmonary nodules (metastasis); hilar/mediastinal lymphadenopathy; lung mass (synchronous primary — remember field cancerisation: laryngeal cancer → second primary in lung [2]) |
| Interpretation | Any suspicious finding warrants CT chest for further characterisation |
| Parameter | Detail |
|---|---|
| What it is | 18F-FDG PET combined with CT; FDG (fluoro-deoxyglucose) is a glucose analogue taken up avidly by metabolically active (i.e., malignant) cells |
| Why we do it | PET scan if necessary [10]; M staging: Distant metastasis (PET) [9]; used for: (1) detecting distant metastasis, (2) identifying the unknown primary in patients presenting with cervical metastatic SCC of unknown primary, (3) assessing treatment response |
| What to look for | Focal areas of increased FDG uptake (SUVmax) in the larynx (primary), neck nodes (N staging), and distant sites (lung, liver, bone) |
| When to use | Not routine for all laryngeal carcinomas. Indicated for: advanced disease (stage III/IV), suspected distant metastasis, unknown primary, post-treatment surveillance with equivocal CT/MRI |
| Limitations | False positives: inflammation, infection, recent biopsy. False negatives: small tumours ( < 1 cm), low-grade tumours. Not good for brain metastasis (high background brain FDG uptake) |
| Test | Purpose |
|---|---|
| Full blood count (FBC) | Baseline; assess for anaemia (iron deficiency in Paterson-Brown-Kelly syndrome; anaemia of chronic disease in malignancy) |
| Liver function tests (LFTs) | Baseline hepatic function; elevated ALP/GGT may suggest liver metastasis; also relevant as many patients have alcohol-related liver disease |
| Renal function (U&E, creatinine) | Baseline before CT contrast; before chemotherapy (cisplatin is nephrotoxic) |
| Calcium | Hypercalcaemia of malignancy (PTHrP-mediated) in advanced disease |
| Thyroid function tests (TFTs) | If thyroid pathology suspected; also baseline before potential radiation to neck (which can cause hypothyroidism) |
| Coagulation screen | Pre-operative assessment |
| Nutritional markers (albumin, pre-albumin) | Assess nutritional status — many H&N cancer patients are malnourished |
| EBV serology | If nasopharyngeal carcinoma is in the differential (endemic in Hong Kong) [2] |
| HPV/p16 testing | Primarily for oropharyngeal SCC; increasingly performed on laryngeal specimens though clinical significance is less established |
| Parameter | Detail |
|---|---|
| What it is | Laryngoscopy combined with a strobe light synchronised to the vocal fold vibration frequency, allowing visualisation of the mucosal wave in "slow motion" |
| Why we do it | Assesses mucosal wave propagation. In early glottic carcinoma, the mucosal wave is absent or reduced over the mass (tumour stiffens the vocal fold cover). Helps differentiate neoplastic from functional lesions |
| Interpretation | Absent mucosal wave over a discrete lesion = high suspicion for malignancy (tumour infiltrates the superficial lamina propria/Reinke's space). Normal mucosal wave over a lesion suggests a superficial/benign process |
| Staging Component | Investigation | What It Determines |
|---|---|---|
| T — Local tumour stage [9] | Endoscopy (flexible + microlaryngoscopy) [9] | Mucosal extent, vocal fold mobility, subsite involvement |
| CT/MRI neck [9] | Deep invasion: pre-epiglottic space, paraglottic space, cartilage, extralaryngeal spread | |
| N — Regional lymph nodes [9] | USG neck + FNA [9] | Size, morphology, and cytology of cervical nodes |
| CT/MRI neck | Nodal size, necrosis, extranodal extension | |
| M — Distant metastasis [9] | CXR [9][10] | Pulmonary metastasis/synchronous lung primary |
| Blood tests [9] | LFTs (liver mets), calcium (hypercalcaemia) | |
| PET-CT [9][10] | Distant metastatic disease; unknown primary | |
| Synchronous primary | Panendoscopy [9][10] | Synchronous tumour in bronchial tree, oesophagus, or other pharyngeal subsite |
5. Special Diagnostic Scenarios
Sometimes the first presentation is a neck lump (metastatic cervical LN) without an obvious primary tumour.
Approach:
- USG-guided FNAC [10] — confirms SCC (or other histology)
- Flexible nasolaryngoscopy — look for primary in larynx, pharynx
- CT/MRI neck [9] — identify primary and assess nodes
- PET-CT [9][10] — highly sensitive for identifying occult primary
- Panendoscopy + directed biopsies [9] — bilateral tonsillectomy, base of tongue biopsies, nasopharyngeal biopsies
- If still no primary found → classified as "carcinoma of unknown primary" (CUP) and managed accordingly
- ALWAYS protect the airway [2]
- Secure airway first (awake fibreoptic intubation or emergency tracheostomy) before any diagnostic workup
- Do NOT attempt to pass a rigid laryngoscope in an awake patient with stridor — risk of complete obstruction
- Once airway is secured → proceed with staging investigations
- MRI with DWI is superior to CT
- PET-CT useful — FDG uptake in recurrent tumour but not in fibrosis/scar
- EUA + biopsy remains definitive
High Yield Summary — Diagnosis of Laryngeal Carcinoma
-
Diagnosis is histopathological — Biopsy to obtain histological diagnosis [1] via microlaryngoscopy + biopsy [5] is the gold standard.
-
First-line investigation: Flexible laryngoscopy to assess extent [1] — done in clinic; assesses mucosal disease and vocal fold mobility.
-
Staging workup follows the TNM framework [9]:
-
Synchronous tumour detection: Panendoscopy (direct laryngoscopy + bronchoscopy + OGD) [2][9] — mandatory; 8–10% risk of synchronous cancer [9].
-
CT is superior for cartilage invasion; MRI is superior for soft-tissue extent (pre-epiglottic/paraglottic spaces) and post-treatment surveillance.
-
Urgent referral criteria: Persistent 2–4 weeks after conservative treatment; clinically suspicious: irregular, induration, > 2 cm, associated cervical LN enlargement [10].
-
USG features of malignant node: Round shape, absent hilum, heterogeneous, central necrosis, peripheral vascularity. Never do excisional biopsy of suspected metastatic SCC node — use FNA first [2].
Active Recall - Diagnosis of Laryngeal Carcinoma
References
[1] Lecture slides: GC 216. Dysphonia Laryngitis, voice abuse, tumour and laryngeal cancer.pdf (p7 — Salient history; p19 — Cancer of Larynx; p22 — Investigations) [2] Senior notes: felixlai.md (sections on Laryngeal carcinoma diagnosis, Head and neck cancer overview, field cancerisation, TNM staging, oropharyngeal diagnosis) [3] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p41 — Etiology) [4] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p39 — History and Examination) [5] Lecture slides: GC 216. Dysphonia Laryngitis, voice abuse, tumour and laryngeal cancer.pdf (p18 — Leukoplakia, erythroplakia — Biopsy!!!) [9] Lecture slides: GC 216. Dysphonia Laryngitis, voice abuse, tumour and laryngeal cancer.pdf (p20 — Principle of investigation in HN cancers) [10] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p42 — Workup and Investigation; p48 — Take Home Message)
Management of Laryngeal Carcinoma
Before diving into specific treatment modalities, let's establish the philosophy of managing laryngeal carcinoma. The lecture slides lay out a clear framework [11][12]:
Management Framework — General Principle [12]:
- Tumour clearance with long-term survival benefit
- Organ and function preservation
- When surgery is indicated → Resection with adequate margins → Reconstruction for Form and Function → Rehabilitation always — swallowing, voice, and hearing
The larynx is not just a tube — it is the organ of voice, airway protection, and swallowing. Removing it (total laryngectomy) permanently disconnects the upper airway from the digestive tract and eliminates normal speech. Therefore, the overarching goal in modern laryngeal cancer management is larynx preservation whenever oncologically safe, meaning we try to cure the cancer while keeping the larynx functioning.
Based on TNM staging [11]:
| Stage | Approach | Rationale |
|---|---|---|
| Early stage (I, II) | Single modality of treatment — Surgery or radiotherapy alone [11] | Small tumours can be cured with one treatment; adding a second modality increases toxicity without survival benefit |
| Late stage (III, IV) | Combined modality of treatment — Concurrent chemo-irradiation OR Surgery with adjuvant radiotherapy ± chemotherapy [11] | Advanced tumours have higher risk of local recurrence and distant metastasis; combined modalities improve locoregional control and survival |
General rule [11]:
- Early stage: Radiotherapy or minimally invasive surgery (laser/robotic) [11]
- Late stage: Surgery with adjuvant treatment [11]
BUT — Site-specific exceptions [11]:
- Oral cavity and thyroid: Surgery in early stage [11] (because oral cavity tumours don't respond as well to RT as laryngeal tumours do, and thyroid cancers require surgical excision)
- NPC: Chemo-irradiation in late stage [11] (NPC is exquisitely radiosensitive due to its undifferentiated histology and EBV association)
For laryngeal carcinoma specifically, the approach differs from oral cavity in that radiotherapy is a very effective single modality for early-stage glottic cancer and is often preferred over surgery for voice preservation [2].
3. Treatment of Early-Stage Disease (Stage I and II)
Patients with early cancer should be treated with the intent to preserve the larynx [2].
The two main options are:
- Definitive radiotherapy
- Larynx-preserving surgery (TOLM or partial open laryngectomy)
Both achieve excellent oncological outcomes (~90–95% local control for T1 glottic, ~80–85% for T2 glottic). The choice depends on tumour-specific factors, patient preference, institutional expertise, and functional considerations.
| Parameter | Detail |
|---|---|
| What it is | External beam radiation therapy (EBRT) delivered to the primary tumour ± elective nodal irradiation |
| Typical regimen | Conventional fractionation: 66–70 Gy in 33–35 fractions over 6.5–7 weeks; or hypofractionated regimens for T1 glottic (e.g., 63 Gy in 28 fractions) |
| When to use | Radiotherapy is often preferred because of better functional outcomes, particularly voice quality, while avoiding GA and other risks associated with surgery [2]; Radiation therapy is equally as effective as surgery in controlling disease for early-stage cancers of the glottis [2] |
Why RT is preferred for early glottic cancer:
- The vocal fold is an ideal RT target: small volume, well-defined boundaries, and laryngeal cartilage acts as a natural border
- RT treats the entire mucosal surface (important for field change) while preserving the layered microstructure of the vocal fold → better voice quality than excisional surgery
- No GA required for each fraction (daily outpatient visits)
- Salvage surgery (total laryngectomy) remains an option if RT fails
When RT is NOT preferred:
- Anterior commissure involvement with cartilage abutment (higher local failure rates with RT alone)
- Very superficial T1a lesions that can be easily excised by TOLM with excellent voice outcomes
- Patient unable to comply with a 6–7 week daily RT course
- Prior head and neck irradiation (re-irradiation carries significant toxicity)
Complications of RT [2]:
- Radiation dermatitis — erythema, desquamation of neck skin (direct radiation effect on rapidly dividing basal keratinocytes)
- Hoarseness — radiation-induced oedema and fibrosis of the vocal fold
- Dysphagia / Odynophagia — radiation mucositis of the pharyngeal and laryngeal mucosa (inflammation of rapidly dividing mucosal epithelium); usually peaks at weeks 3–4 and resolves 2–4 weeks after completing RT
- Xerostomia — if salivary glands are in the field (less of an issue with modern IMRT techniques that spare parotids)
- Laryngeal oedema — can persist for weeks to months; may require short-course corticosteroids
- Laryngeal/pharyngeal stenosis — late complication from fibrosis
- Hypothyroidism — thyroid gland often receives incidental radiation; TSH monitoring required
- Osteoradionecrosis — of the mandible (if included in field) or hyoid
- Radiation-induced second malignancy — very late risk ( > 10 years)
Why not chemotherapy alone for early-stage laryngeal cancer?
Chemotherapy alone does NOT have a role in the treatment of early-stage cancer [2]. Chemotherapy is a systemic treatment designed to address micrometastatic disease or radiosensitise tumours; it cannot achieve the local tumour control needed for cure when used alone. It is only added to radiotherapy in selected early T2 cancers or advanced disease.
3.3 Larynx-Preserving Surgery [2]
| Parameter | Detail |
|---|---|
| What it is | Endoscopic excision of the tumour through the mouth using a CO2 laser under general anaesthesia with operating microscope magnification |
| Why CO2 laser? | CO2 laser is used because its frequency of light is absorbed by water, thus minimising tissue damage [2] — the laser energy is absorbed by intracellular water, causing precise vaporisation with minimal thermal spread to adjacent tissue |
| When to use | Early-stage glottic and supraglottic tumours (T1–selected T2); surgeon must be confident of achieving clear margins |
| Key principle | All larynx-preserving surgery should be undertaken only when the surgeon is confident that tumour-free margins can be obtained because post-operative RT may compromise functional outcomes, particularly after open surgical procedures [2] |
| Prerequisite | At least one functional arytenoid complex must be preserved so that function of the larynx is maintained [2] — if both arytenoids are destroyed, the patient cannot protect their airway during swallowing |
Advantages of TOLM over partial open laryngectomy [2]:
- Decreased morbidity such as need for tracheostomy and nasogastric feeding [2]
- Improved preservation of laryngeal function [2]
- Lower cost [2]
- Shorter hospital stay [2]
Limitations of TOLM:
- Requires adequate endoscopic exposure (limited by anatomy — narrow mouth opening, prominent teeth, stiff neck, bulky tongue)
- Not suitable for tumours with extensive subglottic extension, cartilage invasion, or extralaryngeal spread
- Requires highly specialised surgical expertise
| Parameter | Detail |
|---|---|
| What it is | Open surgical procedures that remove the tumour-bearing portion of the larynx while preserving the remaining functional larynx |
| Types | Vertical partial laryngectomy (laryngofissure + cordectomy) for glottic tumours; Supraglottic laryngectomy (horizontal partial) for supraglottic tumours; Supracricoid partial laryngectomy (SCPL) for selected transglottic tumours |
When to use:
- Early-stage tumours not amenable to TOLM (e.g., poor endoscopic exposure)
- Selected T2–T3 tumours where the surgeon can preserve at least one cricoarytenoid unit
Complications of partial open laryngectomy [2]:
- Laryngocutaneous fistula — abnormal communication between the neopharynx and the neck skin; occurs when the mucosal closure breaks down
- Aspiration pneumonia — the most dangerous complication; partial laryngectomy removes part of the sphincteric mechanism, and patients need to "re-learn" swallowing
- Swallowing difficulties — due to altered anatomy
- Bleeding and infection — standard surgical complications
Post-operative RT is only indicated in selected patients with resected early-stage cancer [2]:
- Compromised resection margins (close < 2mm or positive)
- Lymphovascular or perineural invasion
- Upstaging to Stage III or IV cancer (pathological stage higher than clinical stage)
4. Treatment of Advanced-Stage Disease (Stage III and IV)
The goals here are balancing cure vs function. There are two main strategies [2]:
Strategy 1: Functional Organ-Preservation (Preferred for most) [2]
- Patients with good performance status should be treated with a functional organ-preservation strategy including chemoradiotherapy or larynx-preserving surgery with post-operative RT [2]
Strategy 2: Total Laryngectomy (When organ preservation is not feasible) [2]
- Patients who are not candidates for functional organ-preservation strategy should be treated with total laryngectomy with post-operative RT and voice rehabilitation [2]
- This includes:
- Elderly patients or patients with poor functional status that cannot tolerate the associated toxicities of chemoradiotherapy [2]
- Patients with resectable tumours with destruction of both vocal cords or extensive cartilage destruction such that vocal or airway protective function cannot be recovered [2]
When to Abandon Organ Preservation
Organ preservation is NOT appropriate when the organ has already been destroyed by the tumour. If the larynx is non-functional (both cords destroyed, extensive cartilage destruction, aspiration), preserving it serves no purpose — it's a functionless, cancer-harbouring structure. These patients are better served by total laryngectomy, which actually protects them from aspiration [2].
| Parameter | Detail |
|---|---|
| What it is | Radiotherapy (70 Gy in 35 fractions / 7 weeks) delivered concurrently with radiosensitising chemotherapy |
| Standard chemotherapy | Cisplatin 100 mg/m² IV on days 1, 22, and 43 of RT (every 3 weeks × 3 cycles) — this is the most evidence-based regimen (VA Larynx Trial, RTOG 91-11) |
| Alternative | Weekly cisplatin 40 mg/m² (less emetogenic, easier to administer but less robust evidence); cetuximab (anti-EGFR monoclonal antibody) for patients unfit for cisplatin |
| When to use | Concurrent chemo-irradiation [11] — for advanced-stage laryngeal cancer in patients with good performance status who are candidates for organ preservation |
Why add chemotherapy to RT?
- Cisplatin is a radiosensitiser — it inhibits DNA repair mechanisms (cross-links DNA strands), making tumour cells more susceptible to radiation-induced DNA damage
- Concurrent CRT improves locoregional control and larynx preservation rates compared to RT alone (RTOG 91-11 trial: 88% larynx preservation with concurrent CRT vs 75% with induction chemo then RT vs 70% with RT alone)
- Does NOT improve overall survival significantly vs total laryngectomy + post-op RT, but achieves comparable survival with organ preservation
Cisplatin ("cis" = same side; "platin" = platinum) — a platinum-based alkylating agent:
- Mechanism: Forms intrastrand and interstrand DNA cross-links → prevents DNA replication and transcription → apoptosis
- Major toxicities: Nephrotoxicity (requires aggressive hydration), ototoxicity (sensorineural hearing loss), nausea/vomiting (highly emetogenic), myelosuppression, peripheral neuropathy
Cetuximab ("ce" = chimeric; "tu" = tumour; "ximab" = chimeric monoclonal antibody):
- Mechanism: Monoclonal antibody targeting EGFR (which is overexpressed in ~80–90% of laryngeal SCCs) → blocks ligand binding → inhibits downstream RAS-MAPK and PI3K-AKT signalling → reduces proliferation
- Used when cisplatin is contraindicated (renal impairment, hearing loss, poor performance status)
- BONNER trial showed cetuximab + RT improves locoregional control vs RT alone, but is generally considered inferior to cisplatin-based CRT
| Strategy | Description |
|---|---|
| Induction chemotherapy followed by radiotherapy alone [2] | Chemotherapy given first (usually TPF: docetaxel + cisplatin + 5-FU × 3 cycles) to shrink the tumour, followed by RT. Responders proceed with RT (organ preservation); non-responders undergo total laryngectomy |
| Sequential therapy: Induction chemotherapy followed by concurrent CRT [2] | Induction chemo (TPF) → then concurrent CRT for responders. More intensive; higher toxicity |
The induction approach allows an "in vivo chemosensitivity test" — if the tumour responds to chemotherapy, it is likely to also respond to RT, and organ preservation is pursued. If not, surgery is performed.
Surgery with adjuvant radiotherapy ± chemotherapy [11]:
| Component | Detail |
|---|---|
| Surgery | Larynx-preserving surgery (TOLM/partial) for selected T3 or total laryngectomy for T4a/non-organ-preservation candidates |
| Post-operative RT | Post-operative RT is generally recommended for all patients with resected advanced-stage cancer following larynx-preservation surgery or total laryngectomy [2] |
| Post-operative concurrent chemo-RT | Added when high-risk pathological features are present: positive/close margins, extranodal extension (ENE), lymphovascular invasion, perineural invasion, pT3/T4 |
Indications for post-operative RT (applicable to both early and advanced resected disease) [2][11]:
- Compromised resection margins
- Lymphovascular or perineural invasion
- pT3/T4 disease
- Nodal metastasis (especially multiple nodes or ENE)
- Subglottic extension
5. Surgical Procedures — Detailed
This is the most radical surgical option and is reserved for when organ preservation is not feasible.
Procedure [2]:
- Remaining trachea is brought out onto the lower neck as a permanent tracheal stoma after the larynx is removed [2]
- Hypopharynx, which is opened at the time of operation, is subsequently closed to restore continuity for swallowing [2]
- Upper aero-tract and digestive tract are permanently disconnected [2]
- Part or all of the thyroid gland and associated parathyroid glands may also be removed depending on the extent of disease [2]
What this means for the patient:
- Breathing: Through the permanent tracheal stoma — no air passes through the nose/mouth
- Swallowing: Via the reconstructed neopharynx → oesophagus (swallowing is preserved, though stricture can occur)
- Speech: Normal speech is impossible (no air passes through the vocal folds). Voice rehabilitation is critical (see below)
- Smell: Significantly reduced (air no longer passes through the nose during normal breathing — anosmia/hyposmia)
Advantages [2]:
- Protection from aspiration pneumonia [2] — the airway is completely separated from the digestive tract. This is actually an advantage for patients whose larynx was non-functional (e.g., bilateral cord fixation with chronic aspiration)
Disadvantages [2]:
- Stigmatisation with the presence of permanent tracheostomy [2] — psychosocial impact is significant
Complications [2]:
- Loss of ability to speak [2]
- Loss of coughing effort [2] — because the patient cannot build up intrathoracic pressure against a closed glottis (there is no glottis)
- Swallowing dysfunction [2]: Stricture of neopharynx or anastomosis / Regurgitation [2]
- Endocrine dysfunction [2]: Hypothyroidism / Hypoparathyroidism [2] — because the thyroid and parathyroid glands may be partially or completely removed
- Pharyngocutaneous fistula — the most common early post-operative complication (~15–25%); communication between the neopharynx and the neck skin
- Stomal recurrence — tumour recurrence at the tracheostomy site
- Wound infection, haematoma
- Carotid blow-out — rare but catastrophic; erosion of the carotid artery, usually related to pharyngocutaneous fistula + radiation + wound breakdown
Reconstruction for pharyngeal extension [2]:
- Reconstruction by means of a pectoralis major flap or free flap reconstruction is required for lesions with pharyngeal extension [2]
- Pectoralis major myocutaneous flap: pedicled flap based on the thoracoacromial artery; used to reconstruct pharyngeal defects
- Free flaps: radial forearm free flap (fasciotcutaneous) or anterolateral thigh (ALT) flap; for larger defects
- Free jejunal flap: for circumferential pharyngeal defects (replaces the entire pharynx with a segment of jejunum)
Since the patient has lost their vocal folds, alternative methods of voice production are essential:
| Method | How It Works | Pros | Cons |
|---|---|---|---|
| Tracheoesophageal puncture (TEP) with voice prosthesis | A one-way valve is placed through a surgically created fistula between the trachea and the oesophagus. The patient occludes the stoma with a finger → air is diverted through the valve into the oesophagus → vibration of the pharyngo-oesophageal segment → voice | Best voice quality; most commonly used; ~80–90% success | Requires maintenance (valve needs replacement every few months); risk of aspiration through the valve; candida colonisation |
| Oesophageal speech | Patient swallows air into the oesophagus and releases it, causing the pharyngo-oesophageal segment to vibrate | No device needed; hands-free | Difficult to learn (~30% mastery); low volume; short phrases |
| Electrolarynx | External vibrating device held against the neck or cheek; transmits vibration through tissue | Easy to use immediately post-op | Robotic quality; requires hand to hold device; socially conspicuous |
Management of the neck is integral to laryngeal cancer treatment:
| Clinical Scenario | Neck Management |
|---|---|
| N0 glottic (T1–T2) | Observation — very low risk of occult nodal metastasis ( < 5%) |
| N0 supraglottic | Elective neck dissection (selective: levels II–IV) or elective RT to neck — because of 20–40% risk of occult nodal disease |
| N0 subglottic | Bilateral paratracheal (level VI) dissection + ipsilateral lateral neck dissection |
| N+ (any subsite) | Therapeutic neck dissection: modified radical or radical neck dissection + post-operative RT to neck |
Types of neck dissection [2]:
| Type | What Is Removed | When Used |
|---|---|---|
| Selective neck dissection | Only the levels at highest risk of metastasis (e.g., levels II–IV for supraglottic) | Elective (N0 but high risk of occult disease) |
| Modified radical neck dissection | Levels I–V LN; preserves one or more of: internal jugular vein, spinal accessory nerve, sternocleidomastoid | Therapeutic (N+); organ preservation when possible |
| Radical neck dissection | Levels I–V LN + internal jugular vein + spinal accessory nerve + SCM | Bulky N2/N3 disease with gross involvement of these structures |
Subglottic tumours are the least common and are commonly asymptomatic until locally advanced [2].
Higher rates of local recurrence and poor survival when compared with lesions involving the supraglottis or glottis [2].
Treatment is aggressive with initial surgical treatment consisting of either total laryngectomy or partial laryngectomy in very selected cases [2]:
- Thyroidectomy and bilateral paratracheal node dissection are usually performed [2] — because subglottic tumours drain to paratracheal nodes (level VI) and can directly invade the thyroid gland through the cricothyroid membrane
7. Non-Pharmacological Management
- Smoking cessation — mandatory; continued smoking increases the risk of treatment failure, second primary cancers, and complications of RT (impaired wound healing, increased mucositis)
- Alcohol cessation — reduces the synergistic carcinogenic effect and improves nutritional status
- These are not optional "lifestyle suggestions" — they are critical components of cancer treatment
- Many patients with laryngeal cancer are malnourished at presentation (dysphagia, cancer cachexia, alcohol-related malnutrition)
- Pre-treatment nutritional assessment and supplementation improve treatment tolerance
- Prophylactic percutaneous endoscopic gastrostomy (PEG) or nasogastric tube may be placed before CRT to maintain nutrition during treatment-induced mucositis
- Dietitian involvement from the start
- Rehabilitation always — swallowing, voice, and hearing [12]
- Speech and language therapist (SLT) assessment pre- and post-treatment
- Swallowing assessment to evaluate swallowing techniques and evaluate for the appropriate diet consistency [2]
- Allows initiation of oral intake of nutrition while minimising the risk of aspiration [2]
- Fibreoptic endoscopic evaluation of swallowing (FEES) or videofluoroscopy to objectively assess swallowing function
- The diagnosis of laryngeal cancer and its treatment (especially total laryngectomy) profoundly impacts quality of life, self-image, social interaction, and mental health
- Psychological counselling, support groups (laryngectomy support groups), and occupational therapy are essential
For patients with:
- Stage IVC (distant metastasis)
- Unresectable T4b disease (carotid encasement, prevertebral invasion)
- Poor performance status precluding curative treatment
Options include:
- Palliative radiotherapy: Symptom relief (pain, bleeding, airway obstruction)
- Palliative chemotherapy: Cisplatin + 5-FU, or pembrolizumab/nivolumab (immune checkpoint inhibitors targeting PD-1; approved for recurrent/metastatic HNSCC)
- Immunotherapy: Pembrolizumab ("pem" = programmed; "brolizumab" = humanised monoclonal antibody) — anti-PD-1; now first-line for recurrent/metastatic HNSCC with PD-L1 CPS ≥ 1 (KEYNOTE-048 trial)
- Tracheostomy: For airway obstruction
- PEG tube: For nutrition if swallowing is impossible
- Best supportive care: Pain management, psychological support, end-of-life care
While not a primary focus of the undergraduate curriculum, it is worth noting:
| Agent | Target | Indication |
|---|---|---|
| Pembrolizumab | PD-1 | First-line for recurrent/metastatic HNSCC with PD-L1 CPS ≥ 1; or second-line after platinum failure |
| Nivolumab | PD-1 | Second-line for recurrent/metastatic HNSCC after platinum-based chemotherapy (CheckMate 141 trial) |
These work by blocking the PD-1/PD-L1 checkpoint, which tumour cells exploit to evade immune surveillance. By blocking this interaction, T cells are "unleashed" to attack the tumour.
Post-treatment follow-up is essential because of:
- Local recurrence risk
- Metachronous second primary risk (field cancerisation)
- Treatment-related complications (hypothyroidism, dysphagia, osteoradionecrosis)
| Time Post-Treatment | Frequency | Investigations |
|---|---|---|
| Year 1–2 | Every 1–3 months | Clinical examination, flexible laryngoscopy, TSH (if neck RT) |
| Year 3–5 | Every 3–6 months | As above + annual CXR or CT chest (lung surveillance) |
| Year 5+ | Every 6–12 months | As above; lifelong follow-up recommended |
| Scenario | Primary Treatment | Neck Management | Adjuvant Treatment |
|---|---|---|---|
| T1a N0 glottic | RT (preferred) or TOLM | Observation | None (unless adverse pathology) |
| T1b N0 glottic | RT or TOLM | Observation | None |
| T2 N0 glottic | RT (preferred) or TOLM/partial laryngectomy | Observation or elective RT to neck | RT if adverse pathology; selected T2 may get CRT [2] |
| T1–T2 N0 supraglottic | RT or supraglottic laryngectomy (TOLM or open) | Elective bilateral neck dissection or RT to neck | None (unless adverse pathology) |
| T3 N0/N1 any subsite | CRT (organ preservation) or larynx-preserving surgery + post-op RT | Included in CRT field or neck dissection | Post-op RT ± chemo if surgical route |
| T4a N0–N2 | Total laryngectomy + post-op RT ± chemo (organ preservation less feasible) | Neck dissection | Post-op CRT if ENE, positive margins |
| T4b or N3 | Definitive CRT (unresectable) or palliative | Included in CRT field | — |
| Subglottic | Total laryngectomy + thyroidectomy + bilateral paratracheal dissection | As above | Post-op RT |
| Recurrent/metastatic | Salvage surgery (if feasible) or immunotherapy (pembrolizumab/nivolumab) ± chemo | — | Palliative RT |
High Yield Summary — Management of Laryngeal Carcinoma
-
Management is based on TNM staging [11]: Early stage (I, II) = single modality (RT or surgery); Late stage (III, IV) = combined modality (CRT or surgery + adjuvant RT ± chemo) [11].
-
General principles [12]: Tumour clearance + organ/function preservation. When surgery is indicated → resection with adequate margins → reconstruction → rehabilitation (swallowing, voice, hearing) [12].
-
Early glottic cancer: RT is equally effective as surgery and is preferred for voice preservation [2]. TOLM is an alternative with advantages of less morbidity, shorter hospital stay, and better function preservation [2].
-
Advanced disease: Organ preservation with CRT is the standard for patients with good performance status [2]. Total laryngectomy is reserved for those with destruction of both vocal cords, extensive cartilage destruction, or poor performance status [2].
-
Total laryngectomy permanently disconnects the airway from the digestive tract → permanent tracheostomy, voice rehabilitation (TEP, oesophageal speech, electrolarynx) [2]. Complications include loss of speech, loss of cough effort, swallowing dysfunction, hypothyroidism, and hypoparathyroidism [2].
-
Subglottic tumours: Aggressive treatment — total laryngectomy + thyroidectomy + bilateral paratracheal node dissection [2].
-
Chemotherapy alone has NO role in early-stage cancer [2]. Cisplatin-based CRT is the backbone of organ-preservation protocols.
-
Neck management: N0 glottic = observe; N0 supraglottic = elective dissection/RT; N+ = therapeutic neck dissection.
-
Immunotherapy (pembrolizumab, nivolumab) is now first/second-line for recurrent/metastatic HNSCC.
Active Recall - Management of Laryngeal Carcinoma
References
[2] Senior notes: felixlai.md (sections on Laryngeal carcinoma treatment — general approach, treatment modalities, surgical treatment, non-pharmacological treatment, medical treatment, complications of total laryngectomy, neck dissection types) [11] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p43 — Management Framework: staging-based approach, general rule, site-specific exceptions) [12] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p44 — Management Framework: general principles — tumour clearance, organ preservation, reconstruction, rehabilitation)
Complications of Laryngeal Carcinoma
Complications of laryngeal carcinoma arise from three main sources: the disease itself (tumour-related), the treatment (surgery, radiotherapy, chemotherapy), and long-term sequelae affecting function and quality of life. Let me walk through each systematically, explaining the pathophysiological basis of every complication from first principles.
1. Complications of the Disease Itself (Tumour-Related)
These are complications that arise from the natural progression of untreated or advancing laryngeal carcinoma.
- Pathophysiology: Tumour bulk progressively narrows the laryngeal lumen. The subglottis is the narrowest portion of the adult laryngeal airway (~6 mm radius), so even moderate tumour growth here causes critical stenosis. Additionally, bilateral vocal fold fixation (from tumour invasion of both cricoarytenoid joints or bilateral paraglottic space involvement) prevents abduction during inspiration → fixed adducted cords → near-complete obstruction
- Clinical presentation: Progressive dyspnoea on exertion → dyspnoea at rest → stridor (inspiratory if supraglottic; biphasic if glottic/subglottic) → respiratory failure
- Management: ALWAYS protect the airway [2] — emergency tracheostomy or awake fibreoptic intubation. This must be addressed BEFORE any oncological workup in a patient presenting with stridor
- Pathophysiology: The larynx is the primary sphincter protecting the airway during swallowing. Tumour disrupts this mechanism in two ways:
- Mechanical: Tumour bulk prevents complete glottic closure → food/saliva enters the trachea
- Neurological: Invasion of the superior laryngeal nerve (internal branch) abolishes the supraglottic sensory reflex → the patient does not sense aspirated material and does not trigger a protective cough
- Motor: Vocal fold fixation prevents adduction → absent protective cough reflex (cannot generate intrathoracic pressure against a closed glottis)
- Recurrent aspiration → chemical pneumonitis → bacterial superinfection → aspiration pneumonia
- This is a major source of morbidity and mortality in advanced disease
- Pathophysiology: Supraglottic and transglottic tumours obstruct the pharyngeal inlet or fix the laryngeal framework, preventing normal laryngeal elevation during swallowing. Pain (odynophagia) further reduces oral intake. Cancer cachexia (TNF-α, IL-6 driven hypermetabolism) compounds the problem
- Many patients are already malnourished at presentation due to combined dysphagia, alcohol-related malnutrition, and cancer cachexia
- Pathophysiology: Tumour neovascularisation produces fragile, disorganised blood vessels (driven by VEGF). Ulceration of the tumour surface exposes these vessels → haemoptysis. In very advanced disease (T4a/T4b), tumour can erode into the carotid artery → catastrophic "carotid blow-out" (see below)
- Pathophysiology: Tumour cells access lymphatic channels → regional nodal disease. Haematogenous spread (via pulmonary capillary bed) → distant metastasis to lung (most common), bone, liver
- Supraglottic tumours have 30–50% nodal metastasis; subglottic ~40%; early glottic < 5% [2]
- Distant metastasis is uncommon at presentation (~5–10%) but increases with advancing stage
- Pathophysiology: Chronic carcinogen exposure (smoking + alcohol) causes widespread mucosal dysplasia across the entire upper aerodigestive tract → patients with laryngeal cancer are more likely to develop a second primary tumour in the lung [2]
- This is a lifelong risk that persists even after cure of the index tumour — mandates surveillance
2. Complications of Treatment
Radiation works by causing double-strand DNA breaks in rapidly dividing cells. Unfortunately, normal rapidly dividing tissues (mucosa, skin, bone marrow) are also affected — this is the basis of all RT side effects.
| Complication | Timing | Pathophysiology |
|---|---|---|
| Radiation dermatitis [2] | Acute (weeks 2–4) | Direct radiation damage to basal keratinocytes → erythema → dry desquamation → moist desquamation. Skin in the radiation field becomes erythematous, then peels |
| Radiation mucositis | Acute (weeks 2–5) | Mucosal epithelium turns over every 5–7 days; radiation kills proliferating basal cells → ulceration, pain, pseudomembrane formation → odynophagia and dysphagia [2] |
| Hoarseness [2] | Acute/subacute | Radiation-induced oedema of the vocal folds → stiffened mucosal wave → voice change. Usually temporary but may persist |
| Laryngeal oedema [2] | Subacute (weeks to months) | Radiation damages lymphatic endothelium → impaired lymphatic drainage → fluid accumulation in the supraglottic tissues. Can cause airway compromise if severe; may require short-course steroids or rarely tracheostomy |
| Xerostomia | Acute → chronic | Radiation damages salivary acinar cells (particularly serous acini of the parotid). Modern IMRT spares the contralateral parotid to reduce this. Dry mouth → difficulty swallowing, increased dental caries, oral candidiasis |
| Laryngeal or pharyngeal stenosis [2] | Late (months to years) | Radiation-induced fibrosis of the submucosal tissue → progressive narrowing of the laryngeal or pharyngeal lumen. Presents with progressive dysphagia or stridor long after treatment completion |
| Osteoradionecrosis | Late (months to years) | Radiation causes endarteritis obliterans (intimal fibrosis of small blood vessels) → hypoxic, hypovascular, hypocellular bone → susceptible to necrosis, especially after trauma (e.g., dental extraction). Primarily affects the mandible if in the RT field |
| Hypothyroidism | Late (months to years) | The thyroid gland is often within the radiation field for laryngeal cancer. Radiation damages thyroid follicular cells → progressive gland failure → ↓ T4 → ↑ TSH. Occurs in 20–50% of patients receiving neck RT. Requires lifelong TSH monitoring |
| Carotid artery stenosis | Very late ( > 5 years) | Radiation-induced accelerated atherosclerosis of the carotid arteries → increased risk of stroke. Radiation damages the vascular endothelium → inflammatory cascade → intimal thickening → stenosis |
| Radiation-induced second malignancy | Very late ( > 10 years) | Radiation itself is mutagenic → can induce new cancers (typically sarcomas) in the radiation field. Risk is low but real |
| Dental caries | Late | Secondary to xerostomia — saliva normally buffers oral pH and contains antimicrobial enzymes; without it, dental decay accelerates. Patients need lifelong fluoride application and dental follow-up |
Chondroradionecrosis of the Larynx
A dreaded late complication of laryngeal RT. Radiation damages the perichondrial blood supply to the laryngeal cartilages (especially the arytenoids and cricoid) → avascular necrosis → cartilage exposure → secondary infection → abscess → potential airway compromise. Clinically presents with persistent pain, dysphagia, and progressive hoarseness months to years after RT. May require surgical debridement or even salvage laryngectomy.
Cisplatin is the backbone of concurrent chemoradiotherapy. Its toxicity profile reflects its mechanism — it forms DNA crosslinks in ALL rapidly dividing cells, not just tumour cells.
| Complication | Pathophysiology |
|---|---|
| Nephrotoxicity | Cisplatin is concentrated in the renal tubular epithelium → direct tubular cell death and oxidative stress → acute tubular necrosis. Dose-limiting toxicity. Requires aggressive IV hydration (pre- and post-infusion) and monitoring of creatinine/GFR |
| Ototoxicity | Cisplatin damages outer hair cells of the cochlea (particularly the basal turn, which encodes high-frequency sound) → irreversible, bilateral, high-frequency sensorineural hearing loss. Cumulative and dose-dependent |
| Nausea/vomiting | Highly emetogenic. Cisplatin triggers 5-HT3 receptors on vagal afferents in the GI tract and CTZ in the area postrema → requires triple antiemetic prophylaxis (5-HT3 antagonist + dexamethasone + NK1 antagonist) |
| Myelosuppression | Bone marrow suppression → neutropenia (nadir ~10–14 days), anaemia, thrombocytopenia → increased risk of infection and bleeding |
| Peripheral neuropathy | Cisplatin damages dorsal root ganglia → sensory neuropathy (numbness, tingling in hands and feet); cumulative and potentially irreversible |
| Enhanced mucositis | When combined with RT, chemotherapy acts as a radiosensitiser — this amplifies the mucosal damage → more severe mucositis, odynophagia, and dysphagia than RT alone |
2.3 Complications of Surgery
| Complication | Pathophysiology |
|---|---|
| Laryngocutaneous fistula [2] | Breakdown of the pharyngeal/laryngeal mucosal closure → abnormal communication between the neopharynx/larynx and the neck skin. Saliva and food leak through the wound. Risk factors: prior RT (impairs wound healing), poor nutrition, diabetes. Management: conservative (NPO, wound care, antibiotics) initially; may need surgical repair if persistent |
| Aspiration pneumonia [2] | Partial laryngectomy removes part of the laryngeal sphincteric mechanism → food and saliva are aspirated during swallowing. The most dangerous functional complication. Requires pre-operative swallowing counselling and post-operative speech-language pathology (SLP) rehabilitation |
| Swallowing difficulties [2] | Altered anatomy → impaired laryngeal elevation, reduced pharyngeal squeeze, and sensory deficits → dysphagia. Needs dietary modification and swallowing therapy |
| Bleeding and infection [2] | Standard surgical complications. Post-operative haematoma can compromise the airway — analogous to post-thyroidectomy haematoma. Infection can lead to wound breakdown and fistula |
These are the most significant complications in the entire topic because they fundamentally alter the patient's physiology and quality of life.
| Complication | Pathophysiology | Management |
|---|---|---|
| Loss of ability to speak [2] | Removal of the vocal folds eliminates the sound source for speech. The upper airway is permanently disconnected from the lower airway, so air no longer passes through the vocal tract | Voice rehabilitation: TEP with voice prosthesis (most common), oesophageal speech, electrolarynx [2] |
| Loss of coughing effort [2] | The Valsalva mechanism requires closing the glottis to build intrathoracic pressure. Without a glottis, the patient cannot generate an effective cough → difficulty clearing tracheal secretions | Humidification of inspired air (HME filter over stoma), regular suctioning, chest physiotherapy |
| Swallowing dysfunction [2] — Stricture of neopharynx or anastomosis / Regurgitation [2] | The hypopharynx is closed primarily to create a neopharynx. Scar tissue formation at the closure site → progressive narrowing (stricture) → dysphagia. Regurgitation occurs when the neopharyngeal reservoir is small or the swallowing mechanism is uncoordinated | Endoscopic dilation for stricture; dietary modification; may need PEG if severe |
| Endocrine dysfunction — Hypothyroidism / Hypoparathyroidism [2] | Part or all of the thyroid and parathyroid glands may be removed during laryngectomy (especially if thyroid is invaded by tumour or in subglottic cancers requiring thyroidectomy). Hypothyroidism: loss of T4 production → fatigue, weight gain, cold intolerance. Hypoparathyroidism: loss of PTH → hypocalcaemia → perioral numbness, carpopedal spasm, Chvostek's/Trousseau's signs, potentially laryngospasm (though the patient no longer has a larynx, hypocalcaemic tetany can still cause respiratory muscle spasm) | Monitor TSH and calcium post-operatively. Thyroxine replacement for hypothyroidism. Calcium + calcitriol for hypoparathyroidism. Acute hypocalcaemia: IV 10–20 mL of 10% calcium gluconate over 10 min [2] |
| Pharyngocutaneous fistula | Most common early post-operative complication (~15–25%). Breakdown of the neopharyngeal closure → saliva leaks into the neck → can track to skin. Risk factors: prior RT, poor nutrition, diabetes, positive margins, large pharyngeal defect | NPO, wound care, antibiotics, negative pressure wound therapy. Surgical repair if persistent ( > 4–6 weeks). If carotid artery is exposed → risk of carotid blow-out |
| Stigmatisation with permanent tracheostomy [2] | Psychosocial rather than physical — the patient has a permanent hole in the lower neck through which they breathe. This is visible, requires daily care (stoma cleaning, HME filter), and fundamentally changes social interaction | Psychosocial support, laryngectomy support groups, stoma covers/scarves, heat and moisture exchange (HME) devices |
| Stomal recurrence | Tumour recurrence at the tracheostomy stoma site. Risk factors: subglottic extension, paratracheal nodal disease, emergency pre-operative tracheostomy through tumour-involved tissue | Post-operative RT reduces risk; surveillance; may require revision surgery |
| Carotid blow-out | The most feared complication. Erosion of the carotid artery wall by a combination of: wound infection/fistula + radiation-induced vessel wall weakening + direct tumour recurrence. Presents as massive haemorrhage from the neck/stoma. Mortality ~40% | Emergency: direct pressure, call vascular surgery. Definitive: endovascular stenting or carotid ligation (risks stroke). Prevention: adequate soft tissue coverage of the carotid during surgery; prompt management of fistulae |
Carotid Blow-Out — The 'Warning Bleed'
Carotid blow-out does not always present as a sudden torrential haemorrhage. There is often a "sentinel" or "warning bleed" — a small-volume arterial bleed from the neck wound or stoma that precedes the catastrophic rupture by hours to days. Any unexplained arterial bleeding from the neck of a post-laryngectomy (especially post-RT) patient must be treated as a potential carotid blow-out and investigated urgently with CT angiography [2].
| Complication | Pathophysiology |
|---|---|
| Spinal accessory nerve (CN XI) injury | Damaged during modified radical or radical neck dissection → trapezius muscle weakness/paralysis → "shoulder syndrome" (shoulder drop, winged scapula, difficulty with arm abduction above 90°). More common in radical neck dissection where CN XI is deliberately sacrificed |
| Internal jugular vein thrombosis | Ligation or injury → ipsilateral facial/cerebral venous congestion. Usually well-tolerated if unilateral (contralateral IJV compensates). Bilateral IJV ligation → raised intracranial pressure, facial oedema (rare, only in bilateral radical neck dissection) |
| Chyle leak | Thoracic duct injury (left neck dissection, level IV) → chyle leaks into the surgical field → chylous fistula. Diagnosis: milky output from the drain, triglycerides > 110 mg/dL. Management: NPO + TPN + pressure dressing; octreotide; surgical exploration if > 1 L/day |
| Marginal mandibular nerve injury | Branch of CN VII; runs superficial to the submandibular gland. Damaged during level I dissection → ipsilateral lower lip weakness → asymmetric smile |
| Hypoglossal nerve injury | Rare unless involved by tumour. Injury → ipsilateral tongue deviation, difficulty with speech and swallowing |
3. Long-Term Functional Sequelae
Head and neck cancer poses special challenges in both resection and reconstruction [13]. The lecture slides emphasise that management must be individualised: individualise the option of surgery to achieve the best functional and cosmetic result [13].
The three key functional domains requiring rehabilitation always — swallowing, voice, and hearing [12] are:
- Phonation — post-laryngectomy [13]: As discussed, total laryngectomy eliminates the vocal source. Voice rehabilitation (TEP, oesophageal speech, electrolarynx) is essential but results in a fundamentally altered voice quality
- Articulation — post-glossectomy / nasal / paranasal sinus surgery [13]: Less relevant to laryngeal cancer specifically, but important in the broader context of H&N cancer where combined resections may affect both phonation and articulation
- Even after partial laryngectomy or RT, voice quality is often altered — patients may have a permanently hoarse, breathy, or rough voice
- Dysphagia is common after treatment (surgery or CRT) due to altered anatomy, fibrosis, reduced laryngeal sensation, and impaired pharyngeal motility
- Radiation-induced fibrosis of the pharyngeal constrictors → reduced pharyngeal squeeze → pharyngeal residue → aspiration
- May require long-term dietary modification, swallowing exercises, or in severe cases, permanent PEG dependence
- Depression and anxiety: Very common (~30–40% of H&N cancer patients). Related to disfigurement, loss of voice, social isolation, inability to eat normally, altered appearance (tracheostomy stoma)
- Social isolation: Difficulty communicating (voice change/loss), eating in public (dysphagia, drooling), visible stoma
- Body image disturbance: Permanent tracheostomy, neck scars, potential facial asymmetry from neck dissection
- Alcohol dependence: Many patients have pre-existing alcohol dependence that needs to be addressed
- Chronic dysphagia → inadequate oral intake → weight loss, muscle wasting
- Xerostomia (post-RT) → difficulty with dry foods, dental caries
- May require long-term PEG tube or dietary supplementation
| Source | Complication | Key Mechanism |
|---|---|---|
| Disease | Airway obstruction | Tumour bulk / bilateral cord fixation |
| Aspiration pneumonia | Loss of laryngeal sphincter function | |
| Dysphagia/malnutrition | Mechanical obstruction + cachexia | |
| Haemorrhage | Tumour neovascularisation / carotid erosion | |
| Metastasis | Lymphatic/haematogenous spread | |
| Second primary | Field cancerisation | |
| Radiotherapy | Mucositis / odynophagia / dysphagia [2] | Basal cell death in mucosal epithelium |
| Radiation dermatitis [2] | Basal keratinocyte damage | |
| Laryngeal oedema [2] | Lymphatic damage → impaired drainage | |
| Laryngeal/pharyngeal stenosis [2] | Fibrosis | |
| Hypothyroidism | Thyroid follicular cell destruction | |
| Xerostomia | Salivary acinar cell damage | |
| Osteoradionecrosis | Endarteritis obliterans → hypovascular bone | |
| Chemotherapy | Nephrotoxicity | Cisplatin → tubular cell death |
| Ototoxicity | Cisplatin → outer hair cell loss | |
| Myelosuppression | Bone marrow progenitor cell kill | |
| Partial laryngectomy | Laryngocutaneous fistula [2] | Mucosal closure breakdown |
| Aspiration pneumonia [2] | Reduced sphincteric function | |
| Total laryngectomy | Loss of speech [2] | Vocal fold removal |
| Loss of cough [2] | Loss of glottis for Valsalva | |
| Neopharyngeal stricture [2] | Scar tissue formation | |
| Hypothyroidism / hypoparathyroidism [2] | Thyroid/parathyroid removal | |
| Pharyngocutaneous fistula | Closure breakdown | |
| Carotid blow-out | Vessel wall erosion (infection + RT + tumour) | |
| Neck dissection | CN XI injury | Nerve sacrifice/damage in dissection |
| Chyle leak | Thoracic duct injury |
High Yield Summary — Complications of Laryngeal Carcinoma
-
Disease complications: Airway obstruction (the most immediately life-threatening), aspiration pneumonia (loss of laryngeal sphincter), haemorrhage, metastasis, and second primary tumour from field cancerisation.
-
RT complications [2]: Acute — radiation dermatitis, mucositis (odynophagia/dysphagia), hoarseness, laryngeal oedema. Late — laryngeal/pharyngeal stenosis, hypothyroidism, xerostomia, osteoradionecrosis, carotid stenosis, second malignancy.
-
Cisplatin toxicity: Nephrotoxicity (dose-limiting), ototoxicity (irreversible high-frequency SNHL), nausea/vomiting (highly emetogenic), myelosuppression, peripheral neuropathy.
-
Partial laryngectomy complications [2]: Laryngocutaneous fistula, aspiration pneumonia, swallowing difficulties, bleeding and infection.
-
Total laryngectomy complications [2]: Loss of speech, loss of coughing effort, swallowing dysfunction (neopharyngeal stricture/regurgitation), endocrine dysfunction (hypothyroidism/hypoparathyroidism), stigmatisation with permanent tracheostomy. Also pharyngocutaneous fistula, stomal recurrence, and the dreaded carotid blow-out (sentinel bleed → catastrophic haemorrhage).
-
Voice rehabilitation after laryngectomy [13]: TEP with voice prosthesis (best quality), oesophageal speech, electrolarynx.
-
Rehabilitation is ALWAYS required — swallowing, voice, and hearing [12].
-
Psychosocial complications are significant: depression, social isolation, body image disturbance — a multidisciplinary support team is essential.
Active Recall - Complications of Laryngeal Carcinoma
References
[2] Senior notes: felixlai.md (sections on Laryngeal carcinoma — treatment modalities, surgical complications, total laryngectomy complications, radiotherapy complications, field cancerisation, neck dissection, thyroidectomy complications) [12] Lecture slides: GC 219. Infections and tumours in pharynx and oral cavity.pdf (p44 — Management Framework: rehabilitation always — swallowing, voice, hearing) [13] Lecture slides: GC 187. Head and neck cancer problems Function and shape.pdf (p10 — Speech: phonation post-laryngectomy, articulation post-glossectomy; p27 — Summary: special challenges in resection and reconstruction, individualise surgery for best functional and cosmetic result)
High Yield Summary
-
Definition: Laryngeal carcinoma = malignant epithelial neoplasm of the larynx; ~95% are SCC [1].
-
Epidemiology: Male predominance; predominantly elderly > 60 [2]; glottic carcinoma is the most common subsite [2].
-
Anatomy: The larynx is divided into supraglottic, glottic, and subglottic regions. The glottis has sparse lymphatics (early tumours rarely metastasise to nodes), while the supraglottis has rich lymphatics (30–50% nodal disease at presentation) [2].
-
Risk factors: Smoking is THE primary risk factor [1][3]. Alcohol has a synergistic effect [3]. Other: GERD/LPR, prior radiation, immunosuppression, chronic laryngitis, family history.
-
Field cancerisation: The entire upper aerodigestive tract mucosa is at risk → panendoscopy (direct laryngoscopy + bronchoscopy + OGD) is mandatory [2].
-
Clinical features:
- Glottic → early hoarseness (cardinal symptom) [1]
- Supraglottic → late symptoms; sore throat, dysphagia, referred otalgia, neck lump [4]
- Subglottic → late symptoms; stridor
- Cervical lymph node metastasis [1] — especially supraglottic
- Loss of laryngeal crepitus [4] — suggests tumour between larynx and vertebral column
- Airway obstruction [1] — always protect the airway
-
TNM staging: Key points — vocal fold fixation = T3; cartilage invasion = T4a; ENE is now incorporated into N staging (AJCC 8th edition) [2].
-
Paterson-Brown-Kelly syndrome [4] = iron deficiency anaemia + postcricoid web + dysphagia → risk of postcricoid/hypopharyngeal carcinoma.
High Yield Summary — Differential Diagnosis
-
Aetiologies of voice disorders are classified as Organic (local pathology / neurological / poor breath support), Functional (muscle tension dysphonia), and Psychogenic (conversion disorder) [1].
-
Benign mimics of glottic SCC: vocal cord polyp, nodules, Reinke's oedema, recurrent respiratory papillomatosis, laryngitis. Key distinguishing features: bilateral (nodules, Reinke's), smooth and pedunculated (polyp), self-limiting (laryngitis), multiple and warty (papillomatosis).
-
Leukoplakia and erythroplakia are premalignant — Biopsy!!! [5]. Erythroplakia carries a much higher malignant transformation rate.
-
Persistent hoarseness = organic lesion; fluctuating = functional [1]. Any hoarseness > 3 weeks in a smoker requires urgent laryngoscopy.
-
Red flag symptoms for malignancy: bleeding, shortness of breath, dysphagia [1], otalgia, progressive course, weight loss, cervical lymphadenopathy.
-
Immobile vocal fold with no visible mass → think RLN palsy → investigate the entire nerve course (neck + chest CT).
-
Adjacent H&N malignancies: Hypopharyngeal carcinoma (piriform fossa > postcricoid > posterior wall) [8], oropharyngeal carcinoma (tonsil commonest) [7], and synchronous primary from field cancerisation (8–10% risk) [9].
-
Panendoscopy is mandatory [9] to detect synchronous lesions in the upper aerodigestive tract.
High Yield Summary — Diagnosis of Laryngeal Carcinoma
-
Diagnosis is histopathological — Biopsy to obtain histological diagnosis [1] via microlaryngoscopy + biopsy [5] is the gold standard.
-
First-line investigation: Flexible laryngoscopy to assess extent [1] — done in clinic; assesses mucosal disease and vocal fold mobility.
-
Staging workup follows the TNM framework [9]:
-
Synchronous tumour detection: Panendoscopy (direct laryngoscopy + bronchoscopy + OGD) [2][9] — mandatory; 8–10% risk of synchronous cancer [9].
-
CT is superior for cartilage invasion; MRI is superior for soft-tissue extent (pre-epiglottic/paraglottic spaces) and post-treatment surveillance.
-
Urgent referral criteria: Persistent 2–4 weeks after conservative treatment; clinically suspicious: irregular, induration, > 2 cm, associated cervical LN enlargement [10].
-
USG features of malignant node: Round shape, absent hilum, heterogeneous, central necrosis, peripheral vascularity. Never do excisional biopsy of suspected metastatic SCC node — use FNA first [2].
High Yield Summary — Management of Laryngeal Carcinoma
-
Management is based on TNM staging [11]: Early stage (I, II) = single modality (RT or surgery); Late stage (III, IV) = combined modality (CRT or surgery + adjuvant RT ± chemo) [11].
-
General principles [12]: Tumour clearance + organ/function preservation. When surgery is indicated → resection with adequate margins → reconstruction → rehabilitation (swallowing, voice, hearing) [12].
-
Early glottic cancer: RT is equally effective as surgery and is preferred for voice preservation [2]. TOLM is an alternative with advantages of less morbidity, shorter hospital stay, and better function preservation [2].
-
Advanced disease: Organ preservation with CRT is the standard for patients with good performance status [2]. Total laryngectomy is reserved for those with destruction of both vocal cords, extensive cartilage destruction, or poor performance status [2].
-
Total laryngectomy permanently disconnects the airway from the digestive tract → permanent tracheostomy, voice rehabilitation (TEP, oesophageal speech, electrolarynx) [2]. Complications include loss of speech, loss of cough effort, swallowing dysfunction, hypothyroidism, and hypoparathyroidism [2].
-
Subglottic tumours: Aggressive treatment — total laryngectomy + thyroidectomy + bilateral paratracheal node dissection [2].
-
Chemotherapy alone has NO role in early-stage cancer [2]. Cisplatin-based CRT is the backbone of organ-preservation protocols.
-
Neck management: N0 glottic = observe; N0 supraglottic = elective dissection/RT; N+ = therapeutic neck dissection.
-
Immunotherapy (pembrolizumab, nivolumab) is now first/second-line for recurrent/metastatic HNSCC.
High Yield Summary — Complications of Laryngeal Carcinoma
-
Disease complications: Airway obstruction (the most immediately life-threatening), aspiration pneumonia (loss of laryngeal sphincter), haemorrhage, metastasis, and second primary tumour from field cancerisation.
-
RT complications [2]: Acute — radiation dermatitis, mucositis (odynophagia/dysphagia), hoarseness, laryngeal oedema. Late — laryngeal/pharyngeal stenosis, hypothyroidism, xerostomia, osteoradionecrosis, carotid stenosis, second malignancy.
-
Cisplatin toxicity: Nephrotoxicity (dose-limiting), ototoxicity (irreversible high-frequency SNHL), nausea/vomiting (highly emetogenic), myelosuppression, peripheral neuropathy.
-
Partial laryngectomy complications [2]: Laryngocutaneous fistula, aspiration pneumonia, swallowing difficulties, bleeding and infection.
-
Total laryngectomy complications [2]: Loss of speech, loss of coughing effort, swallowing dysfunction (neopharyngeal stricture/regurgitation), endocrine dysfunction (hypothyroidism/hypoparathyroidism), stigmatisation with permanent tracheostomy. Also pharyngocutaneous fistula, stomal recurrence, and the dreaded carotid blow-out (sentinel bleed → catastrophic haemorrhage).
-
Voice rehabilitation after laryngectomy [13]: TEP with voice prosthesis (best quality), oesophageal speech, electrolarynx.
-
Rehabilitation is ALWAYS required — swallowing, voice, and hearing [12].
-
Psychosocial complications are significant: depression, social isolation, body image disturbance — a multidisciplinary support team is essential.
Head And Neck Cancer
Head and neck cancer refers to a group of malignancies arising from the squamous epithelial lining of the mucosal surfaces of the oral cavity, pharynx, larynx, nasal cavity, and paranasal sinuses, often associated with tobacco, alcohol use, and HPV infection.
Nasopharyngeal Carcinoma
Nasopharyngeal carcinoma is a malignant epithelial neoplasm arising from the nasopharyngeal mucosa, strongly associated with Epstein-Barr virus infection, and characterized by early lymph node metastasis and high radiosensitivity.