Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma T3N I

Epstein Barr Virus may lead to the following:

• Infectious mononucleosis
•  EBV associated tumors

Ref: Harrison’s Principles of Internal Medicine, 16th Edition, Pages 1046, 47

Role of smoking and development of nasopharyngeal carcinoma is still not clear.

T2 N0 M0 Glottic Cancer is an early stage glottis tumor extending to supraglottis and /or subglottis and /or with impaired vocal cord mobility, with no lymph node involvement or distant metastasis.

Radiotherapy alone is the standard treatment for early glottis cancer.

Concurrent chemoradiotherapy is indicated in locally advanced disease.

In ulcerative form of nasopharyngeal carcinoma, epistaxis is the common symptom. Proliferative type causes obstructive nasal symptoms. Growth infiltrates submucosally in infiltrative type of carcinoma.

Ref: Diseases of Ear, Nose and Throat By PL Dhingra, 4th Edition, Page 232, 233.

Nasopharyngeal cancer can cause conductive deafness (Eustachian tube blockage), ipsilateral (not contralateral) temporoparietal neuralgia (involvement of cranial nerve V) and palatal paralysis (CN X)- collectively called Trotter’s triad.

Over 95% of endemic nasopharyngeal carcinomas (NPC) are classified as WHO type 3 and associated with EBV.

NPC tends to occur in younger persons and is not associated with tobacco usage.

NPC is an aggressive neoplasm with cervical lymph node metastases present in 60 to 90% of patients at diagnosis.

Because of unique anatomic, biological, and clinical characteristics, therapy for NPC is distinctive.

Radiotherapy is the mainstay of local therapy. NPCs are highly chemoradiosensitive.

Intensity-modulated radiation therapy (IMRT) allows for greater conformality of the high-dose regions with relative sparing of adjacent normal tissues compared to traditional radiation techniques.

Nasopharyngeal carcinoma is most common in China particularly in southern states and Taiwan.

Ans. is ‘d’ i.e., Epidermodysplasia 

Epstein – Barr Virus (EBV)

.    Belongs to Herpes viruses family.

.   Infection is most common in early childhood, with a second peak during late adolescence.

.   Infectious mononucleosis (IM) is usually a disease of young adults.

.   EBV is transmitted by saliva (oral secretions) of infected person.

.   Intimate oral contact, as in kissing is the predominant mode of transmission         causes kissing disease.

.   The virus enter the pharyngeal epithelial cells and B cells through (CR 2 / or CD21) receptors.

.     Memory B Cells are the reservoir of EBV:

Clinical Manifestations  :Most primary infections are asymptomatic

.     Causes an acute self limited illness          —>          Infectious mononucleosis (Glandular fever)

.     Incubation period                                                         4-8 weeks

.    Age groups                                                                     young adults

.    Most common symptom of IMN is sore throat

.   Most common sign is lymphadenopathy

.   Most common complication —> meningitis/encephalitis

Ans. is ‘d’ i.e., Carcinoma Cervix

Ans. is ‘d’ i.e., Multiple myeloma

Ans. is ‘c’ i.e., Carcinoma nasopharynx

Ans is ‘b’ i.e., Infects epithelial cells of oropharynx 

.   Main target for EBV is B- cell.

A i.e. Nasopharyngeal Carcinoma T3N1

Radiotherapy is the standard treatment of nasopharyngeal carcinomaQ, as surgery is not fesibleQ. Patient with advanced disease also receive concurrent chemotherapy.

Radical Radiotherapy is preferred treatment for early supraglottic carcinomas (i.e. small (< 6m1) tumor mass and absence of cartilage invasion). In unfavourable conditions voice preserving supraglottic laryngectomy (surgery) is preferred. Tumors involving the true vocal cords or cartilage are treated with supracricoid laryngectomy & for advanced tumors total laryngectomy is required. Cord fixation is an indirect evidence of cricoarytenoid joint involvement. It upstages the tumor to T3 and precludes voice preserving surgery in all laryngeal cancers. Radiotherapy is preferred modality for definitive treatment of early glottic carcinoma (T2 NO) as it allows voice preservation. Hemilaryngectomy is the usual surgical procedure in early glottic cancers and supracricoid laryngectomy is performed if there is imaging evidence of invasion of anterior or posterior commissure, contra lateral true vocal cord, false vocal cord or parglottic fat invasion.

Ans. is ‘c’ i.e., Ca. Nasopharynx 

Ans. is ‘b’ i.e., Nasopharyngeal carcinoma 

Ans is “b” i.e. Nasopharyngeal carcinoma 

Note: Glottic carcinoma never metastasizes to lymph nodes and carcinoma lip metastasizes rarely and very late

Ans is B i.e. T2 NO MO Glottic Cancer 

Concomitant chemoradiation means- chemotherapy and radiation therapy are given simultaneously rather than vii sequentially.

“Principles of Combining Anticancer Agents with Radiation Therapy‑

Combining chemotherapy with radiation therapy has produced important improvements in treatment outcome. Randomized clinical trials clinical trials show improved local control and survival through the use of concurrent chemotherapy and radiation therapy for patients with high-grade gliomas and locally advanced cancers of the head and neck, lung, esophagus, stomach, rectum, and anus. There are least two proposed reasons why chemoradiotherapy might be successful. The first is radiosensitization. The underlying concept is that the observed effect of using chemotherapy and radiation concurrently is greater than simply adding the two together. A second proposed reason to combine radiation and chemotherapy is to realize the benefit of improved local control radiation along with the systemic effect of chemotherapy; a concept called spatial additivity.” [Devita, Hellman & Rosenberg’s Cancer: Principles & Practice of Oncology, 8th EditionChapter 211

Now coming to the given options:

• Anal cancer: Concomitant chemoradiotherapy is the treatment of choice. Chemoradiotherapy achieves survival rates similar to those of radical surgical excision without loss of continence.
• Cervical cancer: Treatment of cervical cancer is based on stage of disease. In general, early stage disease (I—IIa) can be treated with either radical surgery or radiation therapy. Advanced stage disease (III —IV)is best treated with chemoradiation. [Novaks gynaecology 14/e p1403]
• Head and Neck Cancer: [Harrison I7/e p550]
• Patients with head and neck cancer can be categorized into three clinical groups: those with localized disease, those with locally or regionally advanced disease, and those with recurrent and/or metastatic disease.
• Localized Disease- that is, TI or T2 (stage I or stage II) lesions without detectable lymph node involvement or distant metastases. These lesions are treated with curative intent by surgery or radiation therapy. The choice of modality differs according to anatomic location and institutional expertise. Radiation therapy is often preferred for laryngeal cancer to preserve voice function, and surgery is preferred for small lesions in the oral cavity to avoid the long-term complications of radiation, such as xerostomia and dental decay. Overall 5-year survival is 60-90%.
• Locally or Regionally Advanced Disease- i.e.disease with a large primary tumor and/or lymph node metastases. Such patients can also be treated with curative intent, but not with surgery or radiation therapy alone. Combined modality therapy including surgery, radiation therapy, and chemotherapy is most successful. Concomitant chemotherapy and radiation therapy appears to be the most effective approach. It can be administered either as a primary treatment for patients with unresectable disease, to pursue an organ preserving approach, or in the postoperative setting for intermediate-stage resectable tumors.

• Recurrent and/or Metastatic Disease- Patients with recurrent and/or metastatic disease are, with few exceptions, treated with palliative intent. Some patients may require local or regional radiation therapy for pain control, but most are given chemotherapy.
• Option D – T1 N2 MO Nasopharyngeal cancer is stage III ds. (Locoregional advanced ds.) and hence would need concurrent chemoradiation.
• Option C – T2 NO MO Glottic cancer is stage II ds. (Localized ds.) and therefore would not need chemoradiation. 

Ans is None > Ca Nasopharynx

All the given options are mentioned by Harrison:

• Harrison 17/e p2737 writes- “Tobacco smoking causes cancer of the lung, oral cavity, naso-, oro-, and hypopharynx, nasal cavity and paranasal sinuses, larynx, esophagus, stomach, pancreas, liver, kidney (body and pelvis), ureter, urinary bladder, and uterine cervix and also causes myeloid leukemia. There is evidence suggesting that cigarette smoking may play a role in increasing the risk of colorectal and possibly premenopausal breast cancer, but there is no association with postmenopausal breast cancer. There does not appear to be a causal link between cigarette smoking and cancer of the endometrium, and there is a lower risk of uterine cancer among postmenopausal women who smoke.”
• Thus the answer should be none, however Nasopharyngeal carcinoma is found to be least associated with smoking. Head & Neck Cancers by Enslow Jacobs 2003e p492 writes-“Association between smoking and nasopharyngeal carcinoma has been shown only by a few studies. If the association of tobacco and NPC is real, the possible mechanism of tumor induction would be the nitrosamines and its precursors in tobacco.”

Ans. is ‘b’ i.e. Nasopharyngeal carcinoma 

Nasopharyngeal carcinoma most commonly arises from fossa of rosenmuller in lateral wall of nasopharynx.

Nasopharyngeal cancer arises from fossa of Rosenmuller in the lateral wall of nasopharynx and can spread to various sites.

Etiology of Nasopharyngeal Carcinoma

• Genetic: It is most common in China.
• Viral: Epstein-Barr virus is closely associated with nasopharyngeal cancer. Epstein-Barr virus has identified in tumor epithelial cells (not lymphocytes) of most undifferentiated and nonkeratinizing squamous cell carcinoma.
• Environmental: Burning of incense or wood (polycyclic hydrocarbon); smoking of tobacco and opium; air pollution; nitrosamines from dry salted fish along with vitamin C deficient diet have been linked to the etiology of nasopharyngeal cancer.

The most common complain at presentation is the presence of an upper neck swelling. Unilateral neck swelling is much more common although bilateral metastasis also occur.

Nasopharyngeal carcinoma spreads to Eustachian tube, blocks it and causes Serous Otitis Media which in turn causes Conductive hearing loss.

 Nasopharyngeal carcinoma can cause Horner’s syndrome due to involvement of cervical sympathetic chain. –Mohan Bonsai

In nasopharyngeal carcinoma, radiotherapy is the mainstay of treatment.

Radical neck dissection is required for persistent nodes when primary has been controlled.

TOC for persistent nasopharyngeal fibroma – Radiation + Surgery

TOC for advanced carcinoma – Chemotherapy + Radiation

Cervical lymphadenopathy is the M/C presentation of nasopharyngeal carcinoma. It may be the only manifestation in some cases.

Ans. D i.e. Kaposi sarcoma

Human Herpes Virus type 8 is associated with 3 conditions, i.e. Kaposi’s disease, B-cell lymphoma and Castleman’s disease

Ans. D i.e. All of the above

Epstein-Barr virus (EBV)/ Human herpesvirus 4 (HHV-4)

• It is a virus of the herpes family, and is one of the most common viruses in humans.
• It is best known as the cause of infectious mononucleosis (glandular fever).
• It is also associated with particular forms of cancer, such as Hodgkin’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma, and conditions associated with human immunodeficiency virus (HIV) such as hairy leukoplakia and central nervous system lymphomas.
• There is evidence that infection with the virus is associated with a higher risk of certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s syndrome, and multiple sclerosis.
• Infection with EBV occurs by the oral transfer of saliva and genital secretions.

Ans. C: Pancreatic carcinoma

The virus infects more than 90% of the average population and persists lifelong in peripheral B-lymphocytes. The virus is produced in the parotid gland and spread via the oral route.

Serology suggests that the Epstein-Barr virus might be involved in the causation of two neoplastic diseases of humans: African Burkitt’s lymphoma and nasopharyngeal carcinoma. Whereas the development of the lymphoma has an even better linkage with chromosomal rearrangements, nasopharyngeal carcinoma shows a unique association with Epstein-Barr virus

It is also associated with causation of glandular fever and lymphoma

Treatment of nasopharyngeal carcinoma

• Radiation therapy is the mainstay of treatment, with chemotherapy used in advanced cases.
• Concurrent cisplatin, 5-fluorouracil, and radiotherapy have been shown to improve survival.
• Sequential chemoradiotherapy with gemcitabine and cisplatin has been shown to improve survival in locoregionally advanced nasopharyngeal carcinoma.
• Many pediatric studies have used neoadjuvant chemotherapy followed by radiation therapy with improvement in local control or progression-free survival rates over radiotherapy alone.

Ans. B: Nasopharyngeal carcinoma with metastasis

Causes of Homer’s syndrome:

First-order neuron lesions

– Arnold-Chiari malformation

– Basal meningitis (e.g., syphilis)

– Basal skull tumors

– Cerebral vascular accident (CVA)/ Wallenberg syndrome (lateral medullary syndrome) disease (e.g., multiple sclerosis)

– Intrapontine hemorrhage

Neck trauma (e.g., traumatic dislocation of cervical vertebrae, traumatic dissection of the vertebral artery)

– Pituitary tumor

– Syringomyelia

Second-order neuron lesions

– Pancoast tumor (tumor in the apex of the lung – most commonly squamous cell carcinoma)

– Birth trauma with injury to lower brachial plexus

– Cervical rib Aneurysm/dissection of aorta

– Nasopharyngeal carcinoma (involvement of cervical sympathetic chain)

– Central venous catheterization

Trauma/surgical injury (e.g., radical neck dissection, thyroidectomy, carotid angiography, coronary artery bypass graft)

– Lymphadenopathy (e.g., Hodgkin disease, leukemia, tuberculosis, mediastinal tumors)

– Neuroblastoma

Third-order neuron lesions

– Internal carotid artery dissection (associated with sudden ipsilateral face and/or neck pain)

– Raeder syndrome (paratrigeminal syndrome) – Oculosympathetic paresis and ipsilateral facial pain with variable involvement of the trigeminal and oculomotor nerves

– Carotid cavernous fistula

Cluster/ migraine headaches

– Herpes zoster

• Drugs (may cause symptoms similar to Horner syndrome and may affect any region)

– Acetophenazine

– Bupivacaine

– Chloroprocaine

– Chlorpromazine

Ans. is ‘a’ i.e., EBV

Nasopharyngeal Carcinoma

• Nasopharyngeal carcinoma is a rare tumor arising from epithelium of the nasopharynx. Nasopharyngeal cancer is uncommon in India except in North East region where people are predominantly of Mongoloid origin. People in Southern china, Taiwan and Indonesia are more prone to this cancer. The maximum age incidence is in the fifth decade and the male : female ratio is 2 : 1. Squamous cell carcinoma in various grades of its differentiation or its variants as transitional cell carcinoma and lymphoepithelioma, is the most common (85%).

Etiology

Nasopharyngeal carcinoma is multifactorial in origin, the three risk factors are :‑

1. Genetic : Chinese have a higher genetic susceptibility to nasopharyngeal cancer. Even after migration to other countries they continue to have higher incidence.
2. Viral : Epstein- Bar virus is closely associated with nasopharyngeal cancer. Specific viral markers are being developed to screen people in high incidence areas.
3. Environmental: Air pollution, smoking of tobacco and opium, nitrosamines from dry salted fish, smoke from burning of incense and wood have all been incriminated.

Origin and spread

The commonest site of origin of nasopharyngeal carcinoma is fossa of Rosenmuller in the lateral wall of nasopharynx.

Ans. is ‘d’ i.e., Sensineuronal hearing loss

Ans. is ‘d’ i.e., CMV-Nasopharyngeal carcinoma

Ans. is ‘a’ i.e., Type I