Cancer of the Larynx

Epidemiology

Etiology and Risk Factors

• Tobacco smoking - the dominant risk factor; risk is proportional to exposure. Prior to malignant transformation, epithelial changes can regress after smoking cessation.
• Alcohol - synergizes with tobacco to substantially increase risk.
• Asbestos exposure.
• HPV infection (especially types 16 and 18) - found in about 15% of tumors; these tend to have a better prognosis.
• Irradiation, nutritional factors.
• Robbins Pathologic Basis of Disease, p. 693; Basic Pathology, p. 494

Histopathology

• ~95% are squamous cell carcinomas (SCC); adenocarcinomas are rare.
• Gross appearance: pearly gray, wrinkled mucosal plaques progressing to ulcerated, fungating masses.
• Adjacent mucosa commonly shows squamous hyperplasia, dysplasia, or carcinoma in situ - reflecting the Hyperplasia-Dysplasia-Carcinoma sequence.
  • Mild dysplasia: 1-2% risk of malignant transformation over 5-10 years.
  • Severe dysplasia: 5-10% risk.
• Histologically well- to moderately-differentiated keratinizing SCC in most glottic tumors. - Robbins Pathologic Basis of Disease

Anatomical Classification (Sites)

Clinical Features

• Glottic tumors: Early hoarseness (dysphonia) - most common presenting symptom. Because they interfere with vocal cord mobility early and lymphatics are sparse, they present at an early stage.
• Supraglottic tumors: "Hot potato voice," dysphagia, referred otalgia, neck mass. Symptoms appear late, so nodal metastases are common at presentation.
• Subglottic tumors: Vocal cord paralysis and/or airway compromise. Very few early symptoms.
• General features: progressive voice change, dysphagia, weight loss, referred otalgia, stridor (late).
• Vocal cord fixation results from paraglottic space invasion, cricoarytenoid joint involvement, or recurrent laryngeal nerve (RLN) invasion. - Schwartz's Principles of Surgery

Workup and Staging

• Direct laryngoscopy - assesses local tumor extent, vallecula, base of tongue involvement, subglottic extension. Also allows biopsy and planning of surgical entry if laryngectomy is needed.
• Esophagoscopy + bronchoscopy - assess for synchronous second primary tumors.
• CT scan with contrast (preoperative) - evaluates cervical lymphadenopathy, thyroid/cricoid cartilage invasion, preepiglottic and paraglottic space extension.
• MRI - superior for soft tissue and skull base assessment.
• PET-CT - complete staging, radiation field planning.

Lymphatic Drainage (for staging)

• Supraglottis: drains via neurovascular bundle through thyrohyoid membrane to upper/lateral cervical nodes (levels II-IV).
• Glottis/Subglottis: drains through cricothyroid membrane to Delphian (prelaryngeal) nodes, paratracheal nodes, and lower cervical nodes (levels IV and VI).
• Schwartz's Principles of Surgery

TNM Staging (AJCC)

Management

Principles

• Early-stage (T1-T2): Single-modality treatment - surgery OR radiotherapy.
• Advanced-stage (T3-T4): Combined modality - surgery + radiotherapy ± chemotherapy, OR concurrent chemoradiotherapy for organ preservation.
• Larynx-preservation is a key goal; the VA Laryngeal Cancer Study showed concurrent chemoradiation is effective for laryngeal preservation in advanced disease.

Glottic Carcinoma

• T1/T2 glottic - managed with single modality: radiotherapy OR transoral laser microsurgery (TLM) / conservation laryngeal surgery (partial laryngectomy). Both give equivalent oncologic results with high cure rates.
• T3/T4 glottic - concurrent chemoradiation (cisplatin-based) for laryngeal preservation; total laryngectomy if preservation fails or primary functions are compromised.

Supraglottic Carcinoma

• Typically treated with primary concurrent chemoradiotherapy for organ preservation.
• Surgery (supraglottic laryngectomy or total laryngectomy) if chemoradiation fails or primary laryngeal functions are irrecoverably lost.
• Bilateral neck dissection is commonly required due to bilateral lymphatic drainage.

Subglottic Carcinoma

• No difference in survival between surgery-first vs. chemoradiation-first approaches.
• Concurrent chemoradiotherapy is the modality of choice for laryngeal preservation.
• Surgical salvage has lower cure rates and increased wound complications.
• Rare early T1 lesions without adenopathy may be treated with primary radiotherapy alone.

Total Laryngectomy

• Indications: T4 disease with cartilage invasion, failure of organ-preservation therapy, poor laryngeal function after organ-preservation attempts.
• Involves removal of larynx from epiglottis to inferior cricoid border, total thyroidectomy, and bilateral neck dissection (levels II-IV + level VI).
• Creates a permanent tracheostoma.
• Reconstruction with pedicled pectoralis major flap or free flaps (radial forearm, anterolateral thigh) when pharyngeal reconstruction is needed.
• Schwartz's Principles of Surgery, p. 668-669

Prognosis

Summary Key Points

1. 95% SCC - linked to tobacco and alcohol in chronic smokers, typically males >40 years.
2. Glottic tumors most common (60-75%) and have the best prognosis due to early hoarseness and sparse lymphatics.
3. Supraglottic tumors - rich lymphatics, ~30% have nodal mets at diagnosis.
4. Subglottic tumors - rarest, worst prognosis, presents late.
5. Workup: direct laryngoscopy + biopsy, CT neck, PET-CT for staging.
6. Early disease: single modality (surgery or RT). Advanced disease: concurrent chemoradiation ± surgery.
7. Laryngeal preservation is the primary goal for advanced disease using chemoradiation (VA Laryngeal Study protocol).

🔷 CANCER OF LARYNX — Diagrammatic Notes

                        CANCER OF LARYNX
                               |
              ┌────────────────┼────────────────┐
         SUPRAGLOTTIS        GLOTTIS        SUBGLOTTIS
         (25-40%)           (60-75%)          (<5%)
              |                 |                |
         Late symptoms    EARLY hoarseness   Late airway
         Dysphagia         (earliest sx)     compromise
         Neck mass                           Cord fixation
              |                 |                |
         Rich lymphatics   SPARSE lymphatics  Rich lymphatics
         ~30% LN mets      1-4% LN mets      Bilateral mets
              |                 |                |
         WORST at staging  BEST prognosis    WORST prognosis

🔷 ETIOLOGY (Risk Factors)

        ┌─────────────────────────────────┐
        │     LARYNGEAL CARCINOMA         │
        └────────────┬────────────────────┘
                     │
     ┌───────────────┼───────────────────┐
     ▼               ▼                   ▼
  TOBACCO          ALCOHOL           HPV (16,18)
(Main factor)   (Synergistic)      ~15% of tumors
Risk ∝ dose                        Better prognosis
     ▼               ▼                   ▼
  ASBESTOS       RADIATION          NUTRITIONAL
  exposure        exposure            deficiency

🔷 PATHOLOGY

HYPERPLASIA → DYSPLASIA → CIS → INVASIVE CARCINOMA
     |              |
  No risk      Mild dysplasia → 1-2% risk (5-10 yrs)
               Severe dysplasia → 5-10% risk

95% = SQUAMOUS CELL CARCINOMA
  ↓
Pearly gray → Ulcerated → Fungating mass

🔷 CLINICAL FEATURES

GLOTTIC              SUPRAGLOTTIC            SUBGLOTTIC
   |                      |                      |
Hoarseness           Hot potato voice        Stridor
(EARLIEST)           Dysphagia               Airway obstruction
                     Referred otalgia        Cord fixation/paralysis
                     Neck mass (30%)

🔷 WORKUP / INVESTIGATIONS

SUSPECTED LARYNGEAL CA
        |
        ▼
Direct Laryngoscopy + BIOPSY  ← Gold standard
        |
        ├──► CT Neck (contrast) — cartilage invasion, LN, paraglottic space
        ├──► MRI — soft tissue detail
        ├──► PET-CT — distant mets, staging
        └──► Panendoscopy — rule out second primary
             (laryngoscopy + esophagoscopy + bronchoscopy)

🔷 TNM STAGING (Glottis)

🔷 MANAGEMENT FLOWCHART

         LARYNGEAL CANCER
                |
    ┌───────────┴────────────┐
  EARLY (T1-T2)           ADVANCED (T3-T4)
       |                        |
  Single modality        Combined modality
       |                        |
 ┌─────┴──────┐       ┌─────────┴──────────┐
SURGERY      RT    Chemo + RT         Surgery + RT
(TLM/partial       (Larynx             (if preservation
laryngectomy)       preservation)       not possible)
                        |
                 TOTAL LARYNGECTOMY
                 (if functions lost /
                  RT fails)
                        |
              Permanent tracheostoma
              + Neck dissection (II-VI)
              + Reconstruction (pec major
                flap / free flap)

🔷 PROGNOSIS SUMMARY

BEST ──────────────────────────────── WORST
  |                                     |
GLOTTIC          SUPRAGLOTTIC      SUBGLOTTIC
T1/T2             T3-T4             All stages
90% confined     30% LN mets       Late presentation
at diagnosis     at presentation   Bilateral nodes

🔷 HIGH-YIELD EXAM POINTS