Synoptic Overview Of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a type of cancer that originates in the nasopharynx, which is the upper part of the pharynx behind the nose.

Epidemiology

1. Geographic variation:

NPC is more common in certain regions, such as Southeast Asia and North Africa.
2. Age and sex:

NPC can occur at any age, but it has a bimodal distribution.It is more common in men and between the ages 50-60 year old.

Two Peaks:

First peak: A smaller peak in late adolescence to early adulthood ( 15-24years ).

Second Peak: A larger peak in middle age to older adulthood ( 50-60years).

The bimodal age distribution is more pronounced in certain populations, such as in SouthEast Asia, where NPC is more common.

Pathophysiology

1. Genetic and environmental factors:

NPC development involves a complex interplay between genetic and environmental factors.
2. Epstein-Barr virus (EBV):

EBV infection is strongly associated with NPC, particularly in endemic regions.

Aetiological Factors

1. EBV infection:

EBV is a major risk factor for NPC.
2. Genetic predisposition:

Certain genetic mutations can increase the risk of NPC.
3. Environmental factors:

Consuming salted fish and other preserved foods, as well as exposure to certain chemicals, may increase the risk.

Role of Epstein-Barr Virus (EBV) and Evidence

1. Association with NPC:

EBV is detected in tumor cells of most NPC patients, particularly those with undifferentiated carcinoma.
2. Serological evidence:

Elevated EBV antibody titers are often found in NPC patients.

Histological Types

1. Keratinizing squamous cell carcinoma (Type I):

A type of NPC that resembles other squamous cell carcinomas.
2. Non-keratinizing carcinoma:

Further divided into differentiated (Type II) and undifferentiated(Type III) subtypes, with the latter being more common in endemic regions.

Sites Of Origin Of NPC

1. Fossa of Rosenmuller:

A common site for NPCs to arise.
2. Lateral wall of the nasopharynx:

Tumours can originate from the epithelial cells lining the lateral wall of the nasopharynx
3. Nasopharyngeal mucosa :

NPCs can arise from the mucosal lining of the nasopharynx.

These sites are critical areas to consider during diagnosis and treatment of nasopharyngeal carcinomas.

Symptoms and Signs

Symptoms

1. Nasal symptoms: Nasal obstruction, epistaxis, and discharge.
2. Otologic symptoms: Hearing loss, tinnitus, and ear fullness.
3. Cervical lymphadenopathy : Enlarged lymph nodes in the neck.
4. Headache : May result from spread into the paranasal sinuses, irritation of the dura etc

Signs

1. Nasopharyngeal mass: Visible on endoscopy or imaging studies.

2. Cervical lymph node metastasis: Enlarged lymph nodes in the neck.

Investigations

1. Endoscopic biopsy: Biopsy of the nasopharyngeal mass.
2. Imaging studies: MRI, CT, and PET scans to assess the extent of disease.
2. Serological test: EBV antibody titers.
4. Audiometry:

Pure tone audiometry may show air-bone gap suggestive of conductive hearing loss.
Tympanometry may show either Type A (normal ), type C (eustachian tube dysfunction) or type B (serous otitis media or glue ear).

NOTE: Any adult with unilateral glue ear must have NPC ruled out.

Test for EBV on Biopsy Sample

1. TEBV-encoded RNA (EBER) in situ hybridization: A test to detect EBV in tumor cells.

TNM Classification of NPC

The current TNM classification for nasopharyngeal carcinoma (NPC) is based on the 8th edition of the AJCC/UICC staging system. However, recent studies suggest refinements to this system, particularly for EBV-related NPC.

T Category:

T1: Tumor confined to nasopharynx or extends to oropharynx and/or nasal cavity without parapharyngeal extension

T2: Tumor with parapharyngeal extension or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, and/or prevertebral muscles)

T3: Tumor invades bony structures beyond the skull base or involves the skull base

T4: Tumor invades intracranial structures, cranial nerves, or orbit.

Proposed revision: Down-classify T3 with early skull-base invasion (T3_ESBI-only) to T2

N Category:

N0: No regional lymph node metastasis
N1: Unilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa
N2: Bilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa
N3: Metastasis in a lymph node greater than 6 cm and/or in the supraclavicular fossa

Proposed revision: Up-classify N1/N2 with grade 3 image-identified extranodal extension (G3_iENE) to N3.

M Category:

M0: No distant metastasis
M1: Distant metastasis

Proposed revision: Subdivide M1 into M1a (1-3 lesions, none in liver) and M1b (>3 lesions or liver metastasis).

EBV Positive vs. EBV Negative NPC:

Proposed Revisions

These proposed revisions aim to improve the accuracy and prognostic value of the TNM staging system for NPC, particularly for EBV-related cases.

Stage Grouping

The stage grouping is based on the T, N, and M classifications. The 8th edition of the AJCC/UICC staging system has undergone significant changes, including the reclassification of medial and lateral pterygoid muscle involvement from T4 to T2 and the addition of prevertebral muscle involvement as T2.

The 8th edition staging system has been shown to have superior prognostic value compared to the 7th edition, particularly in the IMRT era. However, further refinements to the staging system may be necessary to improve its accuracy and clinical utility.

Staging Of NPC Associated With EBV

The current staging system for nasopharyngeal carcinoma (NPC) incorporates Epstein-Barr virus (EBV) DNA status to refine prognosis and treatment planning.

Here’s an overview of the staging system:

Recursive Partitioning Analysis (RPA) Staging System

This system has shown improved prognostic performance compared to the traditional TNM staging system.

EBV DNA Status

EBV DNA-positive patients:

Tend to have worse survival outcomes and higher risk of distant metastasis
EBV DNA-negative patients:

May have better survival outcomes and lower risk of distant metastasis

EBV DNA status is an independent prognostic factor for patients with stage III-IVB NPC.

Neoadjuvant chemotherapy plus concurrent chemoradiotherapy may be a better treatment regimen for EBV-positive patients, while concurrent chemoradiotherapy may be sufficient for EBV-negative patients .

Prognostic Factors

1. Overall stage:

Remains the most* important prognostic factor in patients with stage III-IVB NPC.
2. EBV status:

Independent prognostic factor for disease-free survival, overall survival, and distant metastasis-free survival

It’s essential to note that the staging system may vary depending on the specific patient population and treatment context. Further research is needed to validate the RPA staging system in different populations and to refine treatment strategies based on EBV DNA status.

Management

1. Radiotherapy:

The primary treatment for NPC, often used in combination with chemotherapy.
2. Chemotherapy:

Used in combination with radiotherapy for advanced disease.
3. Surgery:

May be used for residual or recurrent disease.

Complications

Complications of Radiotherapy and Management

1. Xerostomia: Dry mouth, managed with saliva substitutes and stimulants.
2. Mucositis: Oral mucosal inflammation, managed with pain relief and oral care.
3. Radiation-induced ototoxicity: Hearing loss, managed with hearing aids and monitoring.

Complications of Chemotherapy and Management

1. Nausea and vomiting: Managed with antiemetics.
2. Myelosuppression: Managed with blood transfusions and growth factors.
3. Nephrotoxicity: Managed with hydration and monitoring.

Prognostic Factors

1. Stage at diagnosis:

Early-stage disease has a better prognosis.
2. Histological type:

Undifferentiated carcinoma tends to have a better response to treatment.
3. EBV status:

Independent prognostic factor for disease-free survival, overall survival, and distant metastasis-free survival.
4. EBV DNA levels:

Elevated EBV DNA levels may indicate a poorer prognosis

Management of Recurrence

1. Re-irradiation:

May be considered for localized recurrences.
2. Chemotherapy:

Used for systemic recurrences or metastatic disease.
3. Palliative care:

Focuses on symptom management and quality of life.

In conclusion, nasopharyngeal carcinoma is a complex disease that requires a multidisciplinary approach to management. Understanding the role of EBV and the different treatment options can help improve patient outcomes.

Get in Touch

Read doctor-produced health and medical information written for you to make informed decisions about your health concerns.

Address

Adenta

Email

info@grovehealth.net

Working Hours

Mon - Friday @ 8am - 5 pm