Nasopharyngeal Carcinoma - Causes, Symptoms, Spread

🎗️ Nasopharyngeal Carcinoma - Causes, Symptoms, Spread

🧾 Definition of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a malignant epithelial neoplasm of the nasopharynx (a non-lymphomatous squamous cell carcinoma of the nasopharyngeal mucosa).

It is a multifactorial disease with genetic, environmental and viral contributors.

📊 Epidemiology of Nasopharyngeal Carcinoma

• Age distribution: Bimodal — peak at 15–25 years (young adult peak) and a second peak at ~50–55 years. Overall common in 5th–7th decades as well.

• Sex: Male predominance (≈ 3 : 1).

• Geography: Very high incidence in southern China, Taiwan and Southeast Asia. Relatively uncommon in India (~0.4% of cancers).

• Familial clustering seen in ~10% → suggests genetic susceptibility.

🧬 Etiology of Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma arises from interplay between:

1 -Genetic factors

• Familial clustering and retained high incidence in migrant populations suggest genetic predisposition.

• Mechanism: certain HLA subtypes → impaired immune clearance of EBV → persistent latent infection → premalignant changes.

What are the HLA subtypes associated with increased risk of Nasopharyngeal Carcinoma?

What are the HLA subtypes associated with decreased risk of Nasopharyngeal Carcinoma?

2- Environmental factors

• Preserved / salted fish, nitrosamine rich diets (high nitrosamine exposure).

• Smoking - increases risk (notably in well-differentiated types).

• Burning incense / wood smoke - polycyclic hydrocarbons exposure.

• Vitamin C deficiency - less inhibition of nitrosation → higher risk.

3- Viral factor - Epstein–Barr Virus (EBV)

• Nearly all undifferentiated and many non-keratinizing NPCs show EBV association: elevated anti-EBV antibodies, EBV DNA sequences in tumor nuclei.

• EBV likely acts with genetic/environmental cofactors to transform mucosal epithelium.

🧪 Pathology & Classification of Nasopharyngeal Carcinoma

• Old WHO classification: Type I (keratinizing), Type II (non-keratinizing), Type III (undifferentiated).

• Modern classification: Keratinizing vs Non-keratinizing; non-keratinizing subdivided into differentiated and undifferentiated.

🔬 Macroscopic growth patterns of Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma may present in three macroscopic types with differing common sites & symptoms:

1- Ulcerative type

• Common origin: posterior wall or fossa of Rosenmüller.

• Often well differentiated, destructive to skull base → epistaxis is common.

2- Infiltrative (polypoidal) type

• Common origin: lateral wall / around Eustachian tube.

• Grape-like polypoidal mass; can invade anteriorly to pterygopalatine/infratemporal spaces, or superiorly toward orbit → trigeminal (V) involvement possible.

3- Exophytic type

• Common origin: roof of nasopharynx.

• Smooth, hemispherical pedunculated mass → early nasal obstruction symptoms.

What is Broder's grading?

🧭 Patterns of spread of Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma spreads locally, via lymphatics and rarely hematogenously.

A. Local (direct) spread

• Superior / intracranial: tumor can invade skull base (foramina) or extend through foramina → intracranial extension (via foramen lacerum commonly).

Intracranial spread → cranial nerve palsies (III, IV, V1/V2, VI), cavernous sinus involvement, optic apparatus in advanced disease.

• Lateral: through sinus of Morgagni → parapharyngeal space (retroparotid route). Parapharyngeal extension → infratemporal fossa, pterygoid muscles, parotid, skull base foramina (foramen ovale), and can cause trismus.

• Anterior: into nasal cavity, pterygopalatine fossa → infratemporal fossa.

• Inferior: into oropharynx, soft palate, and further into hypopharynx.

• Posterior: retro-pharyngeal/prevertebral spread (prevertebral muscles, C1 arch).

What is Linconi's highway?

B. Lymphatic spread

• Retropharyngeal (Node of Rouvière)

• Upper jugular (Level II, jugulodigastric)

• Nasopharyngeal Carcinoma often gives bilateral and extensive nodal disease (levels II, V commonly). Spread is typically orderly (superior → inferior); skip metastases are uncommon.

What is the first lymph node to be involved in Nasopharyngeal Carcinoma?

What is the first palpable lymph node in Nasopharyngeal Carcinoma?

C. Hematogenous spread (less common)

• Distant mets: bone (spine, pelvis, skull), liver, lungs.

• Bone spread commonly via paravertebral (Batson) venous plexus.

What is the most common site of origin of Nasopharyngeal Carcinoma?

🩺 Clinical Features of Nasopharyngeal Carcinoma

Nasopharyngeal Carcinoma has highly variable presentations -

1. Cervical lymphadenopathy (most common)

2. Otologic (Eustachian tube dysfunction / OME)

3. Nasal (obstruction, epistaxis)

4. Ophthalmic / orbital

5. Neurological / cranial nerve palsies

What is the most common clinical presentation of Nasopharyngeal Carcinoma?

1- Cervical lymphadenopathy

• Most commonly involved palpable nodes: Level II (upper jugular). Level V (spinal accessory chain) is also common.

• Presentation: painless, firm, often multiple/bilateral nodes. A neck node with unknown primary → always consider Nasopharyngeal Carcinoma.

• Pattern: orderly superior → inferior spread

What is Ho's triangle?

2- Nasal symptoms

• Epistaxis / blood-stained postnasal drip (common)

• Unilateral nasal obstruction → progressive → bilateral with growth

• Cacosmia (fetor/odor of blood) from bleeding tumor

Describe the endoscopic appearance of mass in Nasopharyngeal Carcinoma.

3- Otologic symptoms

• Eustachian tube obstruction → otitis media with effusion / conductive hearing loss (30–40%).

• Persistent/unresolved serous otitis media in an adult should prompt nasopharyngeal evaluation.

• Later: ear pain may occur with skull base invasion (referred trigeminal pain).

4- Ophthalmic symptoms

• Diplopia (III/IV/VI palsies), ptosis, proptosis, epiphora, reduced vision — occur with orbital or cavernous sinus involvement.

5- Neurological / cranial nerve palsies

• Signify advanced disease / skull base invasion.

• Most frequently affected: VI (abducent), IV, V (trigeminal divisions); lower cranial nerve palsies (IX–XI) from jugular foramen involvement.

• Presentations include facial pain / paresthesia (V2), palatal paralysis (IX/X), dysphagia, hoarseness. Headache localized to vertex/occiput common when skull base involved.

6- Constitutional & systemic

• Weight loss, anorexia, paraneoplastic phenomena (e.g., dermatomyositis occasionally associated).

🧠 Syndromes associated with Nasopharyngeal Carcinoma (Cranial nerve pattern syndromes)

• Gradenigo’s syndrome

• Trotter’s triad

• Jugular foramen (Vernet) syndrome: IX, X, XI palsy.

• Collet Sicard syndrome: IX–XII palsy.

• Garcin syndrome: unilateral paralysis of multiple cranial nerves (progressive).

• Horner syndrome / orbital apex syndromes may be seen depending on extension.

What is Trotter’s triad?

What is the triad seen in Gradenigo syndrome?