Parapharyngeal involvement without T3 features Parapharyngeal involvement with T3 features Bone involvement below base of skull including \202oor of sphenoid sinus T3b T3c T3d N0 Involvement of base of skull Cranial nerve involvement Involvement of orbit, laryngopharynx, or infratemporal fossa No cervical lymph nodes palpable N1 Nodes wholly above the skin crease extending laterally and backwards from just below the th yroid notch N2 Nodes palpable between the skin crease and supraclavicular fossa N3 Nodes palpable in the supraclavicular fossa or skin involvement The groups can be condensed to \201ve stages: Stage I T1 N0 Stage II T2 and/or N1 Stage III T3 and/or N2 Stage IV N3 involvement irrespective of T stage Stage V Haematologous spread or nodal involvement below clavicles Table 24.2 UICC staging (1992) T1 Tumor limited to one subsite in the nasopharynx T2 Tumor involving more than one subsite T3 Tumor invades nasal cavity and/or nasopharynx T4 Tumor invades skull and/or cranial nerves N0 No regional lymph nodes N1 N2a N2b N2c N3 Single ipsilateral node <3 cm Single ipsilateral node >3 cm Multiple ipsilateral nodes >3 cm but <6 cm Bilateral or contralateral nodes all <6 cm Any node >6 cm OHO-24(443-468) 11/18/02 8:35 AM Page 453 CARCINOMA OF THE NASOPHARYNX 453 of overt and occult neck metastases. However, the radiation dose to the brain, eyes, and sp inal cord must be kept within tolerance. In order to reduce acute reactions as much normal mucosa as possible must be excluded from the irradiated volume. In general, doses of 65 \200\22370 Gy are given to the primary site in 6.5 \200\2237 weeks. Involved areas of the n eck are treated to 60 Gy with boosts of 70 Gy with electrons if necessary. Parapharyngeal m asses are also boosted. Brachytherapy may be used to increase the dose to the primary site. Local or regional recurrence developing two or more years after radiotherapy can be success fully treated by a second radical course of radiotherapy with a reported \201ve-year surv ival of 25 \200\22335% but with considerably increased morbidity. Chemotherapy (cid:2) Chemo-responsive tumor (cid:2) 20% complete response (cid:2) 70% overall response r ate in advanced disease (cid:2) 5FU, cisplatin, bleomycin (cid:2) May be advantage for chem otherapy before radiotherapy, especially in Stage IV Results The 10-year actuarial survival for 5037 patients treated in Hong Kong between 1976 and 1985 was 43%. Typical three-year survival \201gures, by stage, in Hong Kong are: (81%) I (63%) II III (54%) IV (36%) (cid:2) (cid:2) (cid:2) (cid:2) Future developments The following are under investigation: (cid:2) Development of an EBV va ccine (cid:2) Conformal radiotherapy to reduce dosage to normal tissue (cid:2) Accelerated hyperfractionated radiotherapy (cid:2) Combined radiation and chemotherapy OHO-24(443-468) 11/18/02 8:35 AM Page 454 HEAD AND NECK CANCER 454 Nasal cavity and paranasal sinuses Etiology Unlike the rest of the upper aerodigestive tract, smoking plays little if any role in malignant tumor development. However, for certain his- tology occupational factors are important. Adenocarcinoma of the ethmoids may develop from exposure to hard wood dust, wher eas soft wood dust may lead to the development of squamous cell carcinoma. The relative ris k of a wood worker developing adenocarcinoma is 70 times normal; adenocarcinoma has also be en associated with the manufacture of chrome pigment, isopropyl alcohol, textiles, clothing , leather, and shoes. Epidemiology Sinonasal malignancy is rare, constituting approximately 3% of head and neck c ancer. Global \201gures suggest an incidence of <1/100 000 people per year in most countr ies, though occupational factors pro- duce regional differences. The male to female ratio i s approximately 2:1 overall and, while the tumor may occur at any age, the majority present between 50 \200\22370 years. Pathology The sinonasal region offers a great histological diversity of tumors. Of these, s quamous cell carcinoma remains the commonest. Late pre- sentation may make it dif \201cult to de \201ne the exact site of origin. Generally, the maxillary sinus is regarded as the usual site, though lesions frequently arise in the lateral wall of the nasal cavity and eth - moids. The primary malignant tumors of the frontal and sphenoid sinuses are extremely rar e. The nasal cavity and sinuses are intimately related to the orbit and skull base (anterior a nd middle cranial fossae) \200\224areas into which the tumors may spread early and covertly . In addition, anterior spread into the soft tissues of the face, posterior involvement of the pterygoid region and nasopharynx, and inferior spread to the oral cavity may all be enc ountered, generally along the routes of least resistance. Distant lymphatic and haematogeno us spread are rare in the early stages of the disease and patients more often die of local disease before sec- ondary spread is apparent. OHO-24(443-468) 11/18/02 8:35 AM Page 455 NASAL CAVITY AND PARANASAL SINUSES 455 Table 24.3 Sinonasal malignancy Epithelial Malignancy Epidermoid/squamous Carcinoma (spindle cell, verrucous, transitional) Non-epidermoid Adenoid cycstic carcinoma Adenocarcinoma Mucoepidermoid carcinoma Acinic cell carcinoma Metastases Neuroectodermal Malignant melanoma Olfactory neuroblastoma Mesenchymal Vascular Angiosarcoma Kaposi \200\231s carcoma Haemangiopericytoma Muscular Leiomyosarcoma Rhabdomyosarcoma Cartilaginous Chondrosarcoma (mesenchymal) Osseous Osteogenic sarcoma Lymphoreticular Burkitt \200\231s lymphoma Non-Hodgkin \200\231s lymphoma Extra-medullary plasmacytoma Midline destructive lesions Miscellaneous Fibrosarcoma Liposarcoma Malignant \201brous histiocytoma Ewing \200\231s sarcoma Alveolar soft part sarcoma Presentation From the maxilla the tumor may spread into the nasal cavity pro- ducing nasal obstruction and discharge (often serosanguinous). Anterior spread along the infra-orbital c anal may produce pain and paresthesia. Orbital involvement produces displacement of the glo be with: (cid:2) Proptosis (cid:2) Diplopia (cid:2) Epiphora (cid:2) Chemosis (cid:2) Visua l loss OHO-24(443-468) 11/18/02 8:35 AM Page 456 HEAD AND NECK CANCER 456 Inferior involvement of the dental roots may lead to loosening of the teeth and/or a malign ant oro-antral \201stula or a mass in the hard palate. Posterior extension into the ptery goid and infra-temporal fossa produces pain and trismus. Spread from the ethmoid sinuses will involve the nasal cavity, con- tralateral ethmoid, and orbit with symptoms as described. Superior extension into the anterior cranial fossa is ge nerally asymptomatic. The middle cranial fossa may be involved by direct spread from the an terior cranial fossa or orbital apex, whence a cavernous sinus syn- drome may arise. Nasal cavity lesions, in addition to nasal symptoms, may spread posteriorly to obstruct the Eusta chian tube producing a unilateral serous otitis media or anteriorly to erode and displace t he nasal bones in the region of the glabella. Surgical principles The majority of tumors present late with involvement of import- ant adj acent structures. Even histologically \200\230benign \200\231 tumors may be associated wit h signi \201cant morbidity and/or mortality at this site. The principle of oncological res ection may be compromised by the proximity of vital structures. This, combined with the his to- logical diversity in this area, necessitates specialist management. Diagnosis and assessment of extent of disease relies upon expert imaging and histology. Ide ally, CT scanning (direct coronal and axial cuts with intravenous contrast enhancement) com bined with MRI should be undertaken. In addition, a chest X-ray and CT of the thorax, abdom en, and bone studies may be appropriate if occult pri- mary or systemic metastases are susp ected. Biopsy should ideally be performed under general anesthesia to obtain representative tissue . Tissue should also be removed via an endonasal endoscopic approach. Surgery alone, or in combination with radiotherapy, is required in the majority of cases. Surgical options inclu de craniofacial resection, maxillectomy, or occasionally total rhinectomy, with or without orbital exenteration. Prosthetic rehabilitation should be undertaken immediately when the p alate is sacri \201ced. Radiotherapy Radiotherapy may be given before or after surgery where appropriate. Care must be taken to shield the brain stem and orbit wherever possi- ble. Megavoltage photons are o ptimally used, in a dose of 60 \200\22366 Gy in 30 \200\22333 fractions given over 6 \200 \2236.5 weeks. The neck nodes do not require prophylactic treatment. Radiotherapy alone may be appro- priate for patients un \201t for radical surgery, but local control rates are i nferior to combined treatment. OHO-24(443-468) 11/18/02 8:35 AM Page 457 NASAL CAVITY AND PARANASAL SINUSES 457 Chemotherapy Although a number of agents (cisplatin, 5FU, methotrexate, bleomycin) have sig ni \201cant activity in recurrent or metastatic disease, with response rates reported of 3 0 \200\22370%, responses are often short- lived and the median survival in this setting is six months. Although response rates of 90% have been achieved with neo-adjuvant chemo- ther apy, no proven survival bene \201t has yet been shown. Concurrent chemo-irradiation is und er investigation. OHO-24(443-468) 11/18/02 8:35 AM Page 458 HEAD AND NECK CANCER 458 Eye and orbit Although primary intra-ocular and orbital tumors are rare, malig- nant involvement of the e ye is not unusual. Skin tumors often arise on the upper face and ocular involvement by meta static disease may not be appreciated or may be ignored due to spread to more critical orga ns. External eye \200\224skin, lids, lacrimal glands Basal cell carcinoma Basal cell carcinomas occur frequently on the face and particularly ar ound the eye. They have a predilection for the lower lid margin and adjacent inner canthus. It is unusual for the upper eyelid to be involved. Surgical excision, with either local tr ansposition or graft repair, is often appropriate. However, in more extensive lesions or wh ere surgery is contraindicated, radiotherapy can be given. Radiotherapy can be used as primary treatment, following excision when the surgical margins are positive or where a recurrence has occurred. Super \201cial X-rays (100 \200\223150 k V) are appropriate (e.g. 45 Gy in 10 daily fractions). It is easy to protect the eye using an internal eye shield and lead cut-outs. Margins around the lesion should be 5 mm, but inc reased if electrons are used rather than orthovoltage X-rays. If the nasolacrimal duct is involved by the tumor, epiphora will occur due to duct stenosis . Cannulation or stenting of the duct may be necessary later. However, carefully planned an d fractionated radio- therapy should not, of itself cause duct stenosis. Non-Hodgkin \200\231s lymphoma Lymphoma may involve the upper and lower lids/conjunctiva, m ajor lacrimal gland, or orbit. Most commonly it appears as a pink \202eshy lesion on the conjunctiva. Occasionally it presents with bilateral involvement but with no other evidence of more widespread disease. It is important to carry out staging procedures including CT s can through the orbits. Low-grade lymphoma with localized disease is treated with local radiotherapy; high-grade ly mphoma with localized disease, with chemotherapy followed by local radiotherapy. Other stag es are treated with chemotherapy. Radiotherapy technique and dose depend on the location, s tage, and grade of the disease. Squamous and adenocarcinoma Squamous carcinoma arising from the skin, lids, or, very rarely , con- junctiva contribute approximately 5% of tumors of the external eye. OHO-24(443-468) 11/18/02 8:35 AM Page 459 EYE AND ORBIT 459 They can be treated with radiotherapy as already discussed, although more generous margins should be given. Squamous carcinoma can affect the eye by direct spread from adjacent sites such as the maxillary antrum and paranasal sinuses. Sebaceous and lacrimal gland tumors ar e rare and not particularly radio-sensitive. Primary treatment should be surgery. Intra-ocular tumors Melanoma Melanoma can affect the uveal tract; its most frequent location is the choroid. Of ten the patient presents having attended the optician for a routine visit and a pigmented l esion has been noted. The patient may present with visual loss. Biopsies should not be perf ormed. Diagnosis should be made by an ophthalmologist with experience in this \201eld. Ma nagement should ideally be carried out in a combined ophthal- mic \200\223oncology clinic. Treatment may be observation, radioactive eye plaque (ruthenium or iodine), local resection , charged particles (proton beam), or enucle- ation. A small lesion may represent a naevus so it is important to doc- ument growth. This is carried out by three-monthly examinations with indirect ophthalmoscopy and serial photographs. An increase in size of 1 mm is signi \201cant. Treatment with Ruthenium 106 radioactive eye plaques causes less morbidity than iodine 125 plaques but can only treat tumors up to a maximum depth of 5 mm. Iodine plaques omit low-en ergy gamma- rays, so that tumors up to 8 mm depth can be treated. A dose of 80 \200\223100 Gy is given to the apex of the tumor, or 500 Gy to the base. Local resection and proton-bea m irradiation are used for larger tumors. Results after local resection have been shown to be better if a radioactive eye plaque is i nserted at the end of the operation to irradi- ate the tumor bed. Proton-beam irradiation s howed great promise but the treatment is expensive, time-consuming, and can be only used fo r very selected cases. The prognosis depends on the location of the tumor, tumor dimensions , and histology. Tumors with spindle B- cell elements do better than mixed epithelioid and spindle B tumors. Retinoblastoma This is a rare intra-ocular tumor arising in young children, usually in the \201rst two years of their life. In a large number of cases the disease is hereditary and often bilateral. As with melanoma, the diagnosis is made by clinical appearance of the les ions. Therefore patients should be managed in combined clinics by ophthalmologists experien ced in management of retinoblastoma. Biopsy should not be performed. Diagnosis may be made by routine screening in those with a family history, by parents notic ing their child had a squint or dif \201culty in