Causes of Hoarseness of Voice & Carcinoma Larynx

PART I: CAUSES OF HOARSENESS OF VOICE

A. Inflammatory / Infective

B. Benign Laryngeal Lesions

• Vocal cord polyps
• Vocal cord nodules (singer's nodules, screamer's nodules)
• Contact ulcers / granulomas
• Reinke's edema (polypoid corditis)
• Papillomatosis (HPV-related, recurrent respiratory papillomatosis)
• Retention cysts

C. Malignant Lesions

• Carcinoma of the larynx (glottic > supraglottic > subglottic)
• Carcinoma of thyroid / hypopharynx - external compression
• Mediastinal malignancy compressing recurrent laryngeal nerve (RLN)
• Lymphoma

D. Neurological / Neuromuscular

• Recurrent laryngeal nerve (RLN) palsy:
  • Left RLN: lung carcinoma (Pancoast), aortic arch aneurysm, mediastinal lymphadenopathy, cardiac surgery
  • Right RLN: right lung apex tumors, thyroid surgery
  • Bilateral: thyroid surgery, esophageal carcinoma
• Superior laryngeal nerve palsy
• Vagal nerve lesions - skull base tumors
• Neurological diseases: motor neuron disease, multiple sclerosis, Parkinson's disease, myasthenia gravis

E. Trauma / Iatrogenic

• Post-intubation trauma (arytenoid dislocation, granuloma)
• Post-thyroid or parathyroid surgery (RLN injury)
• Post-radiotherapy to the neck

F. Systemic / Endocrine / Metabolic

• Hypothyroidism - myxedematous change of vocal folds
• Acromegaly - laryngeal cartilage enlargement
• Rheumatoid arthritis - cricoarytenoid joint fixation
• Systemic lupus erythematosus - laryngeal edema/paralysis
• Amyloidosis

G. Functional / Psychogenic

• Mutational dysphonia (puberphonia)
• Psychogenic / conversion dysphonia
• Muscle tension dysphonia

H. Miscellaneous

• Angioedema of the larynx
• Foreign body impaction
• Voice overuse/misuse (professional voice users)
• Presbylarynx (age-related vocal fold atrophy)

PART II: CARCINOMA LARYNX

Epidemiology & Etiology

• Tobacco - primary risk factor; proportional to dose and duration
• Alcohol - independent risk factor; synergistic with tobacco
• HPV (especially types 16, 18) - detected in ~22% of laryngeal SCC by DNA; a more relevant causative fraction is ~8.6%
• Laryngopharyngeal reflux (LPR) - controversial but possible contributor
• Occupational carcinogens: asbestos, diesel exhaust, sulfuric acid, mustard gas, wood/stone/metal dust
• Genetic susceptibility

Pathology

• 95% are squamous cell carcinomas (SCC); rarely adenocarcinoma
• Macroscopic: pearly gray, wrinkled plaque that may ulcerate and fungate
• Microscopically: keratinizing, well-to-moderately differentiated SCC; adjacent mucosa may show hyperplasia, dysplasia, or carcinoma-in-situ

Clinical Features

• Persistent hoarseness - the cardinal early symptom (because even small tumors interfere with vocal fold vibration and mobility)
• Hoarseness that persists >3 weeks in a smoker warrants urgent laryngoscopy
• Dysphagia and airway obstruction occur late
• Cervical lymphadenopathy rare initially (sparse glottic lymphatics)

• Dysphagia and odynophagia (early symptoms)
• Feeling of something in the throat / referred otalgia (via Arnold's nerve - auricular branch of vagus)
• Hoarseness is a late feature (when tumor spreads to true cords)
• Early cervical lymphadenopathy (bilateral in ~1/3 of cases due to rich lymphatics)

• Airway obstruction and stridor (often first presentation)
• Hoarseness (late)
• Paratracheal and mediastinal lymph node involvement common

• Stridor and dyspnoea (airway compromise)
• Dysphagia
• Haemoptysis
• Weight loss, cachexia
• Cervical lymphadenopathy
• Fixed, immobile neck mass
• Referred otalgia

Diagnosis & Staging

1. Flexible/indirect laryngoscopy - assesses vocal fold mobility, extent of lesion, anterior commissure involvement
2. Microlaryngoscopy under GA + biopsy - histological confirmation (mandatory before treatment)
3. CT neck with contrast - preferred for imaging; assesses cartilage invasion, paraglottic space, preepiglottic space, nodal disease
4. MRI - better for soft tissue detail, diffusion-weighted imaging for cartilage invasion
5. PET-CT - for advanced disease, distant metastases, synchronous primaries
6. Chest X-ray / CT chest - exclude pulmonary metastases or second primary
7. Videostroboscopy - documents mucosal wave for small glottic lesions

• T1 - limited to subsite, normal cord mobility
• T2 - extends to adjacent subsite or impaired mobility
• T3 - vocal cord fixation or invasion of paraglottic/preepiglottic space, inner cortex of thyroid cartilage
• T4a - through thyroid cartilage, trachea, cricoid, soft tissue of neck
• T4b - prevertebral space, mediastinum, carotid encasement

Management

Early Stage Disease (T1, T2)

• Transoral laser microsurgery (TLM) - CO₂ laser; 5-year local control rates 85-94% for T1; laryngeal preservation >93%
• Radiotherapy (RT) - equal oncological outcomes to surgery for T1; preferred when voice quality is paramount; 5-year local control ~85-95% for T1a
• RT preferred for T1 tumors involving anterior commissure in some centers

• TLM or open supraglottic partial laryngectomy (voice-preserving)
• Bilateral selective neck dissection (Levels II-IV) given high occult nodal metastasis rates
• RT with or without elective neck irradiation

Advanced Disease (T3, T4)

• Concurrent chemoradiotherapy (CRT) - cisplatin-based; landmark VA Laryngeal Cancer Study and RTOG 91-11 trial established larynx preservation without survival compromise for many T3 tumors
• Response to induction chemotherapy predicts suitability for organ preservation
• Return of vocal cord mobility after RT is a positive prognostic sign

• Supracricoid partial laryngectomy - selected T3 tumors; preserves speech and swallowing
• Total laryngectomy - standard for T4a disease, or failed organ preservation
  • Creates permanent tracheostome
  • Voice rehabilitation: tracheoesophageal puncture (TEP) with voice prosthesis (primary or secondary), electrolarynx, esophageal speech
• Near-total laryngectomy (Pearson) - selected cases; preserves voice shunt

• Supraglottic SCC: bilateral selective neck dissection (N0 and N1); comprehensive neck dissection for N2/N3
• Glottic SCC: elective neck treatment for T3/T4 (risk of occult metastasis: 18-32%)
• Subglottic SCC: paratracheal (Level VI) nodes at highest risk

• Salvage surgery after RT failure: total laryngectomy is usually required
• Systemic therapy: cetuximab (anti-EGFR), pembrolizumab/nivolumab (checkpoint inhibitors) for recurrent/metastatic disease

Prognosis

• Cummings Otolaryngology Head and Neck Surgery, Chapter 105 (Squamous Cell Carcinoma of the Larynx)
• Robbins & Kumar Basic Pathology, p. 494-495 (Carcinoma of the Larynx)
• Robbins, Cotran & Kumar Pathologic Basis of Disease, Block 8