Carcinoma of the Larynx

Laryngeal carcinoma is among the commonest head-and-neck malignancies and a perennial NEET PG favourite because the three subsites (glottis, supraglottis, subglottis) behave so differently in presentation, spread, prognosis, and treatment. Master the anatomy-driven logic and the rest follows.

Definition & epidemiology

Carcinoma of the larynx is a malignant epithelial tumour arising from the laryngeal mucosa. Squamous cell carcinoma (SCC) accounts for >90–95% of cases. It is predominantly a disease of men over 50 years with a strong dose-dependent link to tobacco and alcohol. In India and worldwide the glottis is the commonest subsite affected.

High-yield: Most common laryngeal malignancy = squamous cell carcinoma. Most common site within the larynx = glottis (true vocal cords).

Surgical/anatomical subsites

The larynx is divided by anatomical landmarks. The key dividing planes are the laryngeal ventricle (separates supraglottis from glottis) and a line 1 cm below the free edge of the vocal cord (separates glottis from subglottis).

Subsite	Boundaries	Frequency	Lymphatics	Typical presentation	Prognosis
Glottis	Vocal cords + 1 cm below; anterior & posterior commissures	Commonest (~60%)	Sparse (cords are almost avascular for lymph)	Early hoarseness	Best
Supraglottis	Epiglottis, aryepiglottic folds, false cords, ventricle	~30%	Rich, bilateral	Late — throat pain, referred otalgia, node, dysphagia	Worst (early nodes)
Subglottis	1 cm below cords to lower border of cricoid	Rare (<5%)	To paratracheal & lower deep cervical (level VI) nodes	Late stridor, airway obstruction	Poor

High-yield: Vocal cords have a poor lymphatic supply, so early glottic cancer rarely metastasises to nodes → excellent prognosis and presents EARLY with hoarseness. Supraglottis has rich bilateral lymphatics → presents LATE with nodal disease.

Etiology & risk factors

• Tobacco smoking — the single most important risk factor (also chewing).
• Alcohol — synergistic/multiplicative with smoking, especially for supraglottic cancer.
• Human papillomavirus (HPV 16/18) — increasingly implicated, more in oropharynx but relevant.
• Chronic laryngitis, gastro-oesophageal reflux (laryngopharyngeal reflux).
• Asbestos, wood dust, mustard gas, nickel exposure (occupational).
• Radiation exposure, vitamin A deficiency.

Premalignant lesions: leukoplakia, erythroplakia, chronic hyperplastic laryngitis, keratosis with dysplasia. Verrucous carcinoma is a well-differentiated, locally invasive but rarely metastasising variant (Ackerman tumour) — classically does NOT metastasise.

High-yield: Smoking + alcohol act synergistically (multiplicative, not additive) to raise risk. Supraglottic cancer correlates strongly with alcohol; glottic cancer correlates with smoking.

Pathophysiology & spread

The anterior commissure and pre-epiglottic / paraglottic spaces govern spread:

• The anterior commissure tendon (Broyles ligament) lacks perichondrium, allowing tumour to reach the thyroid cartilage and spread between cords.
• The pre-epiglottic space (of Boyer) and paraglottic space are fat-filled potential conduits that allow occult deep spread, upstaging supraglottic tumours and necessitating their inclusion in resection.

Transglottic carcinoma = tumour crossing the ventricle to involve both supraglottis and glottis; has a high incidence of cartilage invasion and nodal metastasis → contraindicates conservation surgery.

Clinical features

The presenting symptom depends entirely on subsite:

1. Glottic → Progressive hoarseness of voice is the earliest and often only symptom. Any hoarseness persisting >3 weeks in an adult (especially a smoker) demands laryngoscopy to exclude malignancy.
2. Supraglottic → Throat discomfort, referred otalgia (via Arnold's nerve / CN X & glossopharyngeal), foreign-body sensation, dysphagia, a neck node may be the first sign, "hot-potato" voice, halitosis.
3. Subglottic → Stridor and dyspnoea (airway narrowing), late hoarseness.

Late/advanced disease (any site): stridor, dysphagia, haemoptysis, weight loss, fixed vocal cord, cervical lymphadenopathy, aspiration.

High-yield: Hoarseness > 3 weeks in an adult = laryngeal cancer until proven otherwise → indirect laryngoscopy is the FIRST investigation. Referred otalgia is a sinister sign in supraglottic cancer (vagus → Arnold's nerve).

Mnemonic for warning symptoms — "HEARS": Hoarseness, Earache (referred otalgia), Airway obstruction/stridor, Regurgitation/dysphagia, Swelling in neck (node).

Diagnosis & investigations

Stepwise approach:

Indirect/flexible laryngoscopy (visualise + assess cord mobility) → Contrast CT/MRI neck (cartilage & deep spread, nodes) → Direct laryngoscopy under GA with BIOPSY (confirm + map) → Stage (TNM)

• Indirect laryngoscopy / flexible fibreoptic laryngoscopy — first-line OPD examination; note the lesion and, critically, vocal cord mobility (mobility = T1/T2; fixation = T3).
• Direct laryngoscopy with biopsy under general anaesthesia — the investigation of choice for tissue diagnosis and accurate mapping of tumour extent.
• Contrast-enhanced CT neck — best for thyroid cartilage invasion, paraglottic/pre-epiglottic space, and nodal staging. MRI is superior for soft-tissue and cartilage marrow assessment.
• CT chest / PET-CT — for distant metastases and second primaries (field cancerisation — lung & oesophagus).
• Stroboscopy for subtle early mucosal/cord-vibration changes.

High-yield: Direct laryngoscopy with biopsy = investigation of choice (gold standard) for diagnosis. CT/MRI is best to assess cartilage invasion and stage. Cord fixation (immobility) automatically makes it T3.

TNM (glottic) — the most tested staging

T stage (Glottis)	Definition
T1a	Tumour limited to one vocal cord, normal mobility
T1b	Both vocal cords involved, normal mobility
T2	Extends to supraglottis/subglottis and/or impaired cord mobility
T3	Vocal cord fixation, and/or paraglottic space / inner thyroid cartilage
T4a	Through thyroid cartilage / invades beyond larynx (trachea, soft tissues of neck, thyroid, oesophagus)
T4b	Prevertebral space, mediastinum, encases carotid (unresectable)

High-yield exam triggers: T1a = one cord, mobile. Impaired mobility = T2. Fixation = T3. Cartilage destruction through = T4a.

Management

Treatment is individualised by stage and subsite, balancing oncological cure with voice/airway preservation. Modalities: surgery, radiotherapy (RT), chemotherapy (chemoradiation), or combinations.

Early disease (T1–T2)

• Transoral laser microsurgery (laser cordectomy) OR radiotherapy — both give comparable ~90–95% cure for early glottic cancer.
• Radiotherapy is often preferred for early glottic cancer because of superior voice preservation; surgery (laser) reserves RT for recurrence and is cheaper/quicker.

Advanced disease (T3–T4)

• Organ-preservation protocol: concurrent chemoradiotherapy (cisplatin + RT) to preserve the larynx (based on the VA Larynx and RTOG 91-11 trials).
• Total laryngectomy — reserved for T4a with cartilage invasion, extensive disease, failed organ preservation, or chondroradionecrosis. A permanent end tracheostome results.
• Partial / conservation laryngectomy (vertical hemilaryngectomy, supraglottic/horizontal laryngectomy, supracricoid laryngectomy) — selected cases to preserve some voice.
• Neck dissection for clinically positive nodes; elective neck irradiation/dissection for supraglottic & subglottic cancers because of occult nodal risk (high lymphatics).

High-yield: Early glottic cancer → RT or laser cordectomy (excellent prognosis, voice preserved). Advanced (T3–T4) larynx-preservation → concurrent chemoradiation (cisplatin). T4a with cartilage invasion → total laryngectomy.

Drug of choice

Cisplatin is the chemotherapeutic agent of choice, given concurrently with radiotherapy. Cetuximab (anti-EGFR) is an alternative radiosensitiser when cisplatin is contraindicated.

Airway emergency

Stridor from an obstructing tumour is managed by securing the airway — tracheostomy (emergency) before definitive treatment.

Voice rehabilitation after total laryngectomy

After total laryngectomy the airway and food passage are permanently separated (permanent tracheostome), so the patient cannot aspirate but loses normal voice. Three rehabilitation methods:

Method	Mechanism	Notes
Tracheo-oesophageal puncture (TEP) + voice prosthesis (e.g., Blom-Singer)	One-way valve shunts pulmonary air into oesophagus to vibrate the pharyngo-oesophageal segment	Best/most preferred — fluent, near-normal voice
Oesophageal speech	Patient swallows/injects air into oesophagus and eructates it to phonate	No device; needs training; slower, lower volume
Electrolarynx (artificial larynx)	External vibrating device held to neck	Robotic monotone voice; easiest to learn

High-yield: TEP with Blom-Singer prosthesis gives the best quality of voice after total laryngectomy. After total laryngectomy a patient breathes through a permanent tracheostome and CANNOT aspirate (airway and GI tract are separated).

Complications

• Tumour-related: airway obstruction/stridor, aspiration pneumonia, dysphagia, haemorrhage, cervical and distant metastases (lung), cachexia.
• Surgery-related: pharyngocutaneous fistula (commonest after total laryngectomy, more so post-RT), wound infection, hypoparathyroidism/hypothyroidism (if thyroid removed), carotid blowout, stomal stenosis/recurrence, permanent loss of natural voice, loss of smell.
• Radiotherapy-related: mucositis, xerostomia, laryngeal oedema, chondroradionecrosis (perichondritis/cartilage necrosis — a dreaded complication mimicking recurrence), hypothyroidism, second malignancy.

High-yield: Pharyngocutaneous fistula is the commonest complication after total laryngectomy (risk rises with prior radiotherapy). Chondroradionecrosis is the feared late complication of laryngeal RT and can mimic tumour recurrence.

Key differential diagnoses

Condition	Distinguishing feature
Vocal cord nodule/polyp	Benign, bilateral (nodule) or unilateral (polyp), voice abuse history, no cord fixation
Laryngeal papillomatosis	HPV 6/11, recurrent, multiple wart-like lesions, children & adults
Tuberculosis of larynx	Posterior larynx (interarytenoid), painful, secondary to pulmonary TB; "mouse-nibbled" ulcers
Laryngeal amyloidosis	Submucosal, smooth, slow-growing
Contact ulcer/granuloma	Posterior third, reflux/intubation related
Vocal cord palsy	Cord immobile but mucosa normal — look for left RLN (mediastinal/lung) cause
Reinke's oedema	Diffuse polypoid cord swelling, smokers, deep hoarse voice
Verrucous carcinoma	Warty, well-differentiated SCC variant; locally aggressive, rarely metastasises

Recently asked / exam angle

• Commonest site of laryngeal carcinoma = glottis; commonest type = SCC. Repeatedly tested.
• Glottic cancer presents EARLIEST (hoarseness) and has the BEST prognosis because cords have poor lymphatics; supraglottic presents late with nodes, worst prognosis.
• Cord fixation = T3; impaired mobility = T2 — classic single-best-answer trap.
• Investigation of choice = direct laryngoscopy + biopsy; CT/MRI for cartilage invasion & staging.
• Best voice rehabilitation after total laryngectomy = tracheo-oesophageal puncture with Blom-Singer prosthesis.
• After total laryngectomy the patient has a permanent tracheostome and cannot aspirate (favourite "true statement" question).
• Early glottic cancer → radiotherapy or laser cordectomy; advanced → chemoradiation (cisplatin) for organ preservation; T4a cartilage invasion → total laryngectomy.
• Broyles ligament at the anterior commissure — lacks perichondrium → route of cartilage spread.
• Pre-epiglottic space (of Boyer) involvement upstages supraglottic tumours.
• Verrucous carcinoma — well-differentiated, rarely metastasises (Ackerman tumour).
• Chondroradionecrosis mimics recurrence; pharyngocutaneous fistula is the commonest post-laryngectomy complication.
• RTOG 91-11 / VA Larynx trial basis for chemoradiation organ-preservation strategy.

Rapid revision

1. SCC is >90% of laryngeal cancers; glottis is the commonest subsite.
2. Hoarseness > 3 weeks in an adult smoker = laryngeal cancer until excluded → laryngoscopy.
3. Glottis = poor lymphatics → early presentation, best prognosis; supraglottis = rich bilateral lymphatics → late nodes, worst prognosis.
4. Cord fixation = T3; impaired mobility = T2; one mobile cord = T1a.
5. Direct laryngoscopy + biopsy = investigation/gold standard of choice for diagnosis.
6. CT/MRI best assesses thyroid cartilage invasion and staging; PET-CT for mets/second primary.
7. Early glottic cancer → RT or transoral laser cordectomy (RT preferred for voice).
8. Advanced larynx → concurrent chemoradiation with cisplatin (organ preservation); cetuximab if cisplatin contraindicated.
9. T4a with cartilage invasion → total laryngectomy + permanent tracheostome.
10. TEP with Blom-Singer voice prosthesis = best voice rehabilitation; oesophageal speech and electrolarynx are alternatives.
11. After total laryngectomy: cannot aspirate (airway separated from GI tract); commonest complication = pharyngocutaneous fistula.
12. Broyles ligament (anterior commissure, no perichondrium) and pre-epiglottic space (of Boyer) are key spread routes; chondroradionecrosis is the dreaded RT complication mimicking recurrence.