Rathke's pouch remnant and pharyngeal hypophysisThe pituitary gland begins its development as a pouch which forms in the roof of the pharynx (Rathke’s pouch). This tissue must migrate to the site of the developing hypothalamus. In humans, this migration does not always occur flawlessly. In some individuals, pituitary tissue remains in the roof of the pharynx as the pharyngeal hypophysis.

DOWN SYNDROMEDown syndrome is genetically defined by a nondisjunctionmutation that results in trisomy 21. The incidence is one in 700, which is more common than all other chromosomal anomalies. The midface hypoplasia contributes to the smaller volume of both the nasopharynx and the oropharynx.

CROUZON SYNDROMECrouzon syndrome is an autosomal dominant craniosynostosis.The syndrome is characterized by midface hypoplasia with relative mandibular prognathism with an anterior bite and class III occlusion. The orbits are shallow and eyes may appear proptosed. Frontal bossing is a marked feature. Airway obstruction because of the narrowed nasopharynx in the newborn period and severe obstructive sleep apnoea may necessitate a tracheostomy.

TREACHER COLLINS SYNDROMETreacher Collins syndrome, which was assigned the termmandibulofacial dysostosis by Franceschetti and Klein, is the most common of the genetic syndromes. It is an autosomal dominant condition. Typical features include downsloping palpebral fissures, coloboma of the outer one-third of the lower eyelid, with ciliary agenesis.Hypoplasia of the zygoma and short mandibular rami contribute to the typical appearance of a small face. There may be atresia of the external auditory canals and ossicular deformities. One-third of patients may have a cleft palate. Upper airway obstruction is usually due to the hypoplastic mandible but may be associated with anarrowed nasopharynx. A tracheostomy is often needed.

Juvenile angiofibromaJuvenile angiofibroma is an uncommon, benign and extremely vascular tumour that arises in the tissues within the sphenopalatine foramen. It accounts for less than 0.5% of head and neck neoplasms and is the most common benign tumor of the nasopharynx.Rarely, it is found at other sites in the nasal cavity and paranasal sinuses.

It develops almost exclusively in adolescent males. As it grows, the tumour extends into nasopharynx, paranasal sinuses, pterygopalatine and infratemporal fossa.

PATHOGENESISJuvenile angiofibromas present as well-defined, lobulated tumours that are covered by nasopharyngeal mucosa. The tumour consists of proliferating, irregular vascular channels within a fibrous stroma.

Tumour blood vessels typically lack smooth muscle and elastic fibres, this feature contributing to its reputation for sustained bleeding.

The stromal compartment is made up of plump cells that can be spindle or stellate in shape and give rise to varyingamounts of collagen. It is this that makes some tumoursvery hard or firm, while others may be relatively soft.

Sex-hormone receptors play some part in itsdevelopment that’s why more seen in adolescent boys. Recent immunocytochemical techniques have been used to show that androgen receptors are present in at least 75 percent of tumours, these receptors being present in both the vascular and stromal elements.

A much smaller proportion of tumours also have someprogesterone receptors. In contast, oestrogen receptors.have not been demonstrated.

The angiogenic growth factor (vascular endothelial growth factor (VEGF) has been found localized on both endothelial and stromal cells.

Overexpression of insulin-like growth factor II (IGFII) has also been found in a large number of juvenile angiofibromas. The IGFII gene is situated on the short arm of chromosome 11.

It is thought that overexpression of IGFII might be associated with a tendency to recurrence and poorer prognosis. Juvenile angiofibromas have also been reported todevelop 25 times more frequently in patients with familialadenomatous polyposis, a condition that is associatedwith mutations of the adenomatous polyposis coli (APC)gene.

PRESENTATIONRecurrent severe epistaxes accompanied by progressivenasal obstruction are the classical symptoms of JNA at the time of presentation. In most, there is a delay of at least six or seven months between the onset of symptoms and presentation.Other symptoms include swelling of the cheek, trismus, hearing loss secondary to Eustachian tube obstruction, anosmia and a nasal intonation or plummy quality to the voice. More extensive tumour growth with invasion of the orbit and cavernous sinus may cause proptosis, diplopia, visual loss, facial pain and headache.Anterior rhinoscopy is likely to confirm the presence of abundant mucopurulent secretions.The soft palate is often displaced inferiorly by the bulk of the tumour which can be seen clearly as a pink or reddish mass that fills the nasopharynx.

ASSESSMENTIn the past, the most suggestive finding was the antral or Holman-Miller sign: anterior bowing of the posterior wall of the maxillary sinus observed on a plain skull radiograph (Waters view). Nowadays, the diagnosis is based on the CT and MR appearances that are sometimes confirmed by angiography.

A trans-nasal biopsy is not necessary and can provoke brisk haemorrhage.The exact extent or stage of the tumour can only bedetermined by a combination of CT and MR imaging .

Several staging systems have been proposed but that of Fisch is the most robust and practical.

It defines clearly which tumours can be resected by endonasal techniques and those that would be better tackled by more open or infratemporal fossa/neurosurgical approaches.

Diagnostic angiography is undertaken to evaluate the source of blood supply and as a prelude to selective embolization.

Fisch staging system of juvenile angiofibromas.1 Tumour limited to the nasopharyngeal cavity; bone destruction negligible or limited to the sphenopalatine foramen.

2 Tumour invading the pterygopalatine fossa or the maxillary, ethmoid or sphenoid sinus with bone destruction.

3 Tumour invading the infratemporal fossa or orbital region: (a) without intracranial involvement (b) with intracranial extradural (parasellar) involvement.

4 Intracranial intradural tumour:(a) without infiltration of the cavernous sinus, pituitary fossa or optic chiasm(b) with infiltration of the cavernous sinus, pituitary fossa or optic chiasm.

SURGICAL RESECTION Until relatively recently, most small tumours wereresected either through a transpalatal approach, lateral rhinotomy or mid-facial degloving approach.

Open approaches can be used for tumours of all stages. Nowadays, stage Fisch I, 2 and some type 3 tumours are suitable for endoscopic resection using one or two surgeon techniques.

There is much to be gained by endonasal endoscopictechniques, for example, reduced intraoperative blood loss, fewer postoperative complications and a reduced length of hospital stay.

Nasopharyngeal carcinomaThis endemic disease has a close association with the EpsteinBarr virus (EBV) and is consistently (continually) of an undifferentiated or non-keratinizing carcinoma type. Early diagnosis is difficult, even in high prevalence areas where clinicians and the general public have an acute awareness of the disease WHY? Because of the location of the nasopharynx and the wide spectrum of presentations.In many ways, NPC differs from other head and neck cancers because of the wide spread of controversies.

EPIDEMIOLOGYIn endemic areas, the rate can be as much as 50 times higher than that in other countries.

The highest age-standardized incidence rate occurs in southern China in Guangdong Province that’s why NPC is frequently referred to as the 'Guangdong tumour'.

Other Southeast Asian races, including Malays, Indonesians, Thais, Vietnamese and Filipinos, as well as Eskimos (in Canada, Alaska and Greenland) are also noted for a high prevalence of NPC.

The disease is approximately three times as common in men as women this is generally true both in endemic and non endemic areas.

The tumour occurs at a much younger age than other cancers. Its incidence starts to rise after the second decade of life and slowly reaches a plateau, for both sexes, after the fifth decade then very gradually drops with increasing age. Below the age of 50, the incidence of NPC is higher than any other cancer.

M:F ratio 2-3:1

However, in certain low-risk populations, a bimodal age distribution with two maxima has been reported.

Nasopharyngeal carcinoma (WHO Classification)

Keratinizing squamous cell ca: type I Similar with that in rest of aerodigestive tract.

Non-keratinizing ca: type II and IIIDifferentiated non-keratinizing ca (type II)Undifferentiated ca (type III)

•Type I distinct from type II : Type II/III so called “NPC”

AETIOLOGY

The development of NPC is the result of a complex interplay of:• Genetic factors, •Early latent infection by EBV and its reactivation.•Exposure to environmental carcinogens. The lack of a single unique characteristic that defines a transformed NPC cell argues in favour of a multistep hypothesis.

Genetic factorsGenetically determined susceptibility plays role in the pathogenesis of NPC this is supported by the extremely high incidence amongst southern Chinese and retained high incidence in later generations of southern Chinese emigrants who settled in areas of low incidence. Low risk populations have a low incidence despite living in high incidence areas, for example, Indians in Singapore.The loci involved are the HLA-A, B and DR locus situated on the short arm of chromosome 6. Consistent deletion on the short arm of chromosomes 3 and 9 have been found on NPC biopsies, supporting the hypothesis of an NPC tumour suppressor gene locus at these sites.

EBV Raised antibodies to EBV in patients with NPC were confirmed first. Then the EBV genome was found in NPC cells. The discovery of EBV receptors on human pharyngeal epithelia.

To date, circumstantial evidence has indicated that the virus plays a critical role in the pathogenesis of NPC. Thus, although these undesirable consequences occur in only a tiny minority of cases infected, because the virus is so ubiquitous (being present everywhere) this minority is numerically very significant.

HPV: possible factor in WHO type I lesions

Environmental carcinogens•Inhalants are logically implicated as a carcinogen as they come into direct contact with the nasopharyngeal mucosa such as: dust, household smoke, industrial fumes and tobacco smoke. However, none of these factors has been conclusively implicated in high-risk populations. •Formaldehyde exposure: there was no association.• Ingestants: It’s observed that the fisherfolk of Hong Kong have a higher risk of NPC but less exposure to household smoke Salted fish. In Hong Kong and southern China, the highest incidence of NPC occurs in the fisherfolk, whose diet is high in salted fish and low in vitamin-rich fresh vegetables and fruits. • Volatile nitrosamines present in ungutted salted marine fish.Consumption of other salted preserved foods, such as vegetables and shrimp paste, was also found to be an independent risk factor. These dietary carcinogens perhaps only affect susceptible populations.

PATHOGENESISThe exact steps involved in the pathogenesis of NPC are far from clear. •Genetically determined susceptibility undoubtedly plays a fundamental role, which is supported by strong epidemiological evidence. •The part played by the EBV, although still unconfirmed, is likely to be critical. The EBV genome and latent gene products are consistently found in both differentiated and undifferentiated types of NPC. Within the tumour cells, the EBV DNA has the characteristic of being homogenous and is likely to be due to clonal cellular proliferation.A causal relationship between EBV and NPC can only be established when an anti-virus vaccine eradicates the cancer. Thus far, epidemiological evidence shows that an environmental carcinogen(s) has a definite role to play.

EBV infection is widespread in all parts of the world, infecting over 95 percent of the human population and earning it the nickname of 'Every Body's Virus'. Primary EBV infection usually occurs early in life and is largely asymptomatic. If primary EBV infection is delayed until adolescence, the clinical syndrome of infectious mononucleosis may result. The general cell-mediated immunity (CMI) of those in whom NPC eventually develops is more likely to be impaired. Although it is still unsure whether impaired CMI is the cause or effect of NPC, this impairment can be demonstrated by lymphocyte stimulation assay or by T-cell cytotoxicity. The degree of impairment of CMI may actually affect prognosis.

IMMUNOLOGY AND SEROLOGY

The anti-EBV serological response in NPC patients results in the production of a wide range of specific antibodies, particularly IgA class.

PATHOLOGYNasopharynge carcinoma may present itself in a variety ofways. However, a mass in the nasopharynx is a constant finding in almost all patients. However, nasopharyngeal carcinoma is by far the most common, irrespective of geography and race.

Nonetheless, the tumour is typically eccentric, being more bulky on one side. Morphologically, the tumour mass may present with:

1- more commonly as a lobulated mass of varying size with well-defined borders and it spreads earlier through lymphatics and is frequently accompanied by cervical lymphadenopathy.

2- Or , it appears to be more infiltrative with an indistinct border and is more likely to present with locally advanced disease with skull base erosion but without cervical lymphadenopathy.

When the disease is picked up at a very early stage the whole tumour may still be hidden within the fossa of Rosenmuller. In very rare cases, the tumour can be entirely submucosal without any observable mass in the nasopharynx.

WHO classification of tumours of the nasopharynx.I Epithelial tumoursA Benign1 Papil loma2 Pleomorphicadenoma3 Oncocytoma4 Basal cell adenoma5 Ectopic pituitary a denom a

B Malignant1 Nasopharyngeal carcinoma2 Adenocarcinoma3 Papillary adenocarcinoma4 Mucoepidermoid carcinoma5 Adenoid cystic carcinoma6 Polymorphous low-gra dea denocarcinoma

II Soft tissue tumoursA Benign1 Angiofibroma2 Haemangioma3 Haemangiopericytoma4 Neurilemmoma5 Neurofibroma6 Paraganglioma

B Malignant1 Fibrosarcoma2 Rhabdomyosarcoma3 Angiosarcoma4 Kaposi's sarcoma5 Malignant Haemangiopericytoma6 Malignant nerve sheath tumour7 Synovial sarcoma

III Tumours of bone and cartilage

IV Malignant lymphomas1 Non- Hodgkin's lym phoma2 Extramedullary plasmacytoma3 Midline malignant reticulosis4 Histocytic lymphoma5 Hodgkin's disease

V Miscellaneous tumoursA Benign1 Meningioma2 Craniopharyngioma3 Teratoma

B Malignant1 Malignant melanoma2 Chordoma3 Malignant germ cell tumours

VI Secondary tumoursVII Unclassified tumours

VIII Tumour-like lesions1 Cysts2 Meningocoele/meni ngoencephalocoele3 Granulomas4 Amyloid deposits5 Others

HISTOLOGICAL CLASSIFICATIONTo date, the WH0 classification is still the one most commonly used. It divides nasopharyngeal carcinoma into three histological subtypes on the basis of the light microscopic appearance:Type I Squamous cell carcinoma (keratinizing): - well differentiated; - moderately differentiated; - poorly differentiated.• Type II Nonkeratinizing carcinoma.• Type III Undifferentiated carcinoma. Now type II

only

The WHO (1978) classification grade 1 keratinizing squamous cell carcinoma and grade 2 nonkeratinizing squamous cell or undifferentiated carcinoma. In places where NPC is endemic, grade 2 tumours constitute more than 90 percent of all cases. These tumours are EBV-related as patients with this type of tumour typically have elevated serological titres of antiEBV antibodies. In fact, EBV-DNAs can be detectedwithin the tumour cells as well as in the peripheral circulations of these patients. In low incidence areas for NPC, 25 percent or more are grade 1 tumours. These tumours are not associated with EBV infection. In general, grade 1 tumours are less aggressive than grade 2 tumours, however, they are also less radiosensitive.Overall, the prognosis for patients with grade 1 tumours is less favourable when compared stage to stage with patients having grade 2 tumours.

CLINICAL FEATURES

The commonest complaint at presentation is thepresence of an upper neck swelling .Unilateral neck swelling is much more common althoughbilateral metastases are not infrequent. Cervical LAP is the presenting complaint in almost 50 % of patients. Overall, 75 % of all patients have palpable cervical LAP at diagnosis.30 % of patients present with nasal symptoms including bloodstained nasal discharge, nasal obstruction, post-nasal drip or even frank epistaxis.

Approximately 20 % of patients present with aural symptoms including deafness, tinnitus and otalgia.Retracted tympanic membrane or OME is a very common clinical finding.The cause of ET dysfunction may be due to the mechanical effect of the tumour or the tumour infiltrating the ET musculature. There is a good chance (approximately 50 percent chance from personal experience) of spontaneous resolution of effusion after radiotherapy.Headache is a common complaint occurring in almost 20 percent of patients. Headache alone may not necessarily imply locally advanced disease as it may be referred pain when distal branches of the trigeminal nasopharynx or nose. However, it can also be the result of bony erosion of the skull base.

Cranial nerve symptom(s) may be isolated or multiple. In either case, it occurs late in the disease from the spread of the tumour through the foramina of the base of the skull or with parapharyngeal involvement of the last four cranial nerves. Cranial nerves V and VI are the most commonly involved among all the cranial nerves.

Cranial nerves III-VI, when affected together, are indicative of cavernous sinus involvement.

Horner's syndrome is rare, but if present, is typically accompanied by paresis of one or more of the last cranial nerves.

Trismus, before radiotherapy, is rare and occurs only with direct infiltration of the pterygoid muscles.Ophthalmoplegia, when accompanied by proptosis, is indicative of direct tumour extension to the orbit. Orbital involvement was more frequently encountered in the pre-CT era.

Systemic metastasis at presentation is rare althougheventually most NPC patients die of distant failure. Thebones and lungs are the most common sites for secondarydeposits followed by the liver.

DIAGNOSISA good history, together with a thorough clinical examination including endoscopy of the nasopharynx, is the basis for making the diagnosis.

Oropharyngeal tumoursPATHOLOGYBenign tumoursBenign tumours occur more frequently in the oral cavity than in the oropharynx and include squamous papilloma, adenoma, fibroma, haemangioma, leiomyoma, lipoma, lymphangioma, schwannoma, neurofibroma and others.The lingual thyroid refers to a mass of ectopic thyroid tissue located in the base of the tongue in the midline. Affected individuals have no other thyroid tissue in 70-100 percent of cases. There is a marked female predominance. Most lingual thyroid glands contain histologically normal tissue, but there are rare reports of carcinoma arising within the lingual thyroid. The swelling can be treated with suppressive doses of thyroxine, with surgery reserved for large symptomatic masses or when the diagnosis is in doubt.

Desmoid tumours are rare, nonmalignant, slow growing neoplasms with the potential for locally aggressive growth invading surrounding structures. Desmoids are sometimes misclassified as low-grade fibrosarcomas because of their invasive growth patterns.

Histologically, they are of low cellularity, have a benign appearance lacking the nuclear and cytoplasmic features of malignancy and, clinically, they do not display any metastatic potential. Function-preserving surgery is the primary treatment to minimize morbidity.

Malignant tumoursMalignant tumours of the oropharynx may arise from anyof its constituent tissues but the vast majority of epithelialtumours are squamous cell carcinomas (70 percent). There is a higher concentration of lymphoid tissue in the oropharynx and the incidence of lymphomas (25 percent) is, therefore, considerably higher compared with other sites in the upper aerodigestive tract. There are also concentrations of minor salivary glands in the soft palate, uvula and base of tongue, whichmay present as a salivary malignancy 5 percent. Thereis the possibility of more uncommon tumours such assoft tissue sarcomas and metastases from distant sitespresenting in the oropharyngeal region.

Malignant Neoplasms of the Oropharynx• About 10% to 12% of all head and neck malignancies are oropharyngeal tumors,• On the basis of different diagnostic, therapeutic, and outcome characteristics, the oropharynx should be subdivided into soft palate, tonsillar fossae, base of tongue, and oropharyngeal wall.

SQUAMOUS CELL CARCINOMAEpidemiologyOropharyngeal squamous carcinoma is said to represent10-15 percent of all head and neck tumours, 0.3-0.5percent of all registered malignancies .The frequency distribution of the primary site carcinoma in the oropharynx is tonsil or faucial pillar 45 %,posterior tongue 40 % , soft palate 15 % andposterior pharyngeal wall 5 %. Thecondition is more common in men, with a sex ratio of4:1, and is usually associated with the sixth and seventhdecades of life. Patients aged less than 45 years are also susceptible to this disease, and the prevention of tobacco and alcohol abuse among younger patients is imperative.

Gross FindingsThe gross appearance of squamous lesions varies from subtle grayish-white thickening of the mucosa to large ulcerated, flat, or fungating masses with invasion of local structures. Depending on the degree of desmoplasia and tumor necrosis, the cut surface of invasivetumors ranges from solid and firm to cystic and friable.Microscopic FindingsDysplasia refers to neoplastic alterations of the surface epithelium prior to invasion of the submucosa.These changes include abnormal cellular organization, increased mitotic activity, and nuclear enlargement with pleomorphism. Although terminology varies, pleomorphismlimited to the lower third of the epithelium is generally referred to as mild dysplasia (Figure 9-4), pleomorphism limited to the lower two-thirds as moderate dysplasia (Figure 9-5), and pleomorphism involving the full thickness as severe dysplasia/carcinoma in situ(Figure 9-6). However, forms of severe dysplasia certainly can have less than full-thickness atypia.

Regardless of tumor grade, nests of infiltrating SCC tend to elicit a prominent host fibrotic stromal reaction (desmoplasia) (Figure 9-3).In contrast, HPV-related oropharyngeal SCC frequently adopts a “blue cell” morphology, characterized by scant cytoplasm and hyperchromatic nuclei, referred to as “nonkeratinizing” SCC.

This type usually lacks surface involvement and has large nests with smooth edges, little or no stromal reaction, and no (or limited) squamous maturation (Figure 9-7). Mitotic activity is brisk.

Lymphoepithelium-like oropharyngeal carcinoma and hybrid types having both keratinizing and nonkeratinizing features are also seen. Non-HPV-associated keratinizing SCC may also be seen in the oropharynx but are uncommon.

AetiologyThe main associated aetiological factors are: 1- Smoking and alcohol consumption, the effects of which are cumulative.2- Dietary deficiencies of vitamin A, 3- chronic irritants, poor dental hygiene, syphilis and marijuana smoking have also been identified as predisposing factors in upper aerodigestive tract cancers. 4- Enhanced expression of the human papilloma virus types 2, 11, and 16 has been observed,5- HIV may be implicated in the development or acceleration of squamous cell carcinoma.Patients who are HIV positive are prone to developing Kaposi's sarcoma, lymphoma or squamous cell carcinoma.

LYMPHOEPITHELIOMA

This type of malignant tumour is also know as anundifferentiated carcinoma of nasopharyngeal type and is a variant of squamous cell carcinoma.

It may be found in the tonsil and the base of tongue.

It is associated with a high incidence of nodal metastases and its clinical behaviour is similar to nasopharyngeal carcinoma.

LYMPHOMANon-Hodgkin's lymphoma accounts for approximately 8 percent of oropharyngeal cancers. The tonsil and the base of tongue are the most frequent sites. The vast majority are of the high grade B cell type (mostly large B cell type).

Men predominate 2:1 with the mean age at presentation being the mid-sixties.

These lesions present with similar symptoms to the more common squamous cell carcinoma but, predominantly, are usually not associated with fetor.

The majority of NHL of Waldeyer’s tonsillar tissues are B-cell lymphomas, including a wide spectrum of histologic types:• most common is a large cell B-cell lymphoma;• follicular low-grade lymphomas are uncommon.• Mucosa-associated lymphoid tissue (MALT) has been implicated as giving rise to a variety of extranodal malignant lymphomas, including head and neck sites (nasopharyngeal,tonsil, salivary glands, and others):• less than 4% of low-grade lymphomas of Waldeyer’s tonsillar ring are MALT lymphomas;

NON-HODGKIN’S LYMPHOMA (NHL) OF WALDEYER’S TONSILLAR RING (NASOPHARYNX, TONSILS, AND BASE OF TONGUE) Definition: Primary malignant lymphoid cell neoplasms with the bulk of tumor formed by a ring or group of extranodal lymphoid tissues about the upper end of the pharynx, including the palatine tonsils, pharyngeal tonsils (adenoids), base of tongue/lingual tonsils.Clinical• Accounts for:• approximately 20–25% of NHL in Asian countries;• approximately 16% of all head and neck NHL;• approximately 50% of all primary extranodal lymphomas in the head and neck.• Majority (approximately 80%) are primary to the site of involvement, with a minority representing secondary involvement toan NHL at another site.•

More common in men than women; occurs over a wide age range, but is most common in the sixth to eighth decades of life:• patients with underlying immunodeficiency condition usually are younger.• Most common sites of occurrence in descending order of frequency are:• tonsils > nasopharynx > base of tongue.• Most common symptoms include dysphagia, odynophagia, swelling or lump in throat, decreased hearing, pain, and sore throat:• majority of masses are unilateral (80–90% of cases);• cervical adenopathy is present in approximately 65% of patients;• systemic symptoms (e.g. fever, night sweats, other) not common;• multifocality may be present.

Etiology:• no known etiology in the majority of patients;• minority of patients have an underlying/associatedimmunodeficiency condition that may predispose to NHL,including:– post-transplantation, HIV infection/AIDS.• association of NHL, especially diffuse large B-cell lymphoma,with Epstein–Barr virus is considered weak.PathologyGross• Often a large exophytic submucosal mass with or withoutsurface ulceration.H

Histology• Although any type can occur, the most common NHL is diffuse large B-cell lymphoma (DLBCL), representing more than 50% of NHL of these sites.• Surface epithelium may be intact or ulcerated; crypt epithelium is usually intact.• Immunohistochemistry:• Waldeyer’s ring lymphomas are predominantly but not exclusively follicular center cell-derived, expressed by positive reactivity with B-cell markers and negative reactivity with T-cell markers (e.g. CD3, UCHL-1).Cytogenetics and molecular genetics:• clonal rearrangement of immunoglobulin heavy and light chain genes;Differential diagnosis• Reactive lymphoid (follicular) hyperplasia.• Infectious-related lymphoid enlargements:• infectious mononucleosis;• HIV-associated lymphoid lesions;• Nasopharyngeal non-keratinizing carcinoma, undifferentiated type.• Mucosal malignant melanoma.• Rhabdomyosarcoma.• Peripheral T-cell lymphomas:• represent less than 15% of Waldeyer’s ring NHL;• most show angiocentric features;• uncommonly, anaplastic large cell lymphoma (ALCL)

SALIVARY GLAND TUMOURS

Minor salivary gland tissue is located in the oropharynx and is concentrated in the soft palate, tonsil and the posterior tongue.

Of the malignant salivary tumours, more than 50 percent are adenoid cystic carcinoma but other malignancies include mucoepidermoid carcinoma, adenocarcinoma and malignant mixed salivary tumours.

METASTATIC DISEASE PRESENTING IN THE OROPHARYNXSeldom reported as a series and thus difficult toquantify metastatic disease presenting in the oropharynxare most likely to be primaries outside the head andneck area - breast, lung, stomach, prostate and kidney.Malignant melanoma should always be suspected if such a disease has been previously treated in the head and neck region.

DiagnosisDocumentation of a detected mass in the pharynx shouldinclude:• Multidimensional size of the tumour• Location in the different regions of the pharynx• Mobility of the lesion• Relationship to the prevertebral fascia• Relationship to the larynx and vocal cordsCT and MRI are useful in evaluating the deep extent ofthe tumour and the tumour’s relationship to surroundingstructures.Endoscopy in the operating room will add to the evaluationof the tumour and biopsies are made.

StagingOropharyngeal primary tumours are staged mainly bysize, while for hypopharyngeal tumours the location andthe relation to the larynx are also important.

Tongue Base TumoursTongue base tumours are particularly difficult to manage because of the important function of the tongue base. The tongue base is important to propel food over the larynx and provide sensation and bulk to protect the larynx.

The removal of the tongue base even without any removal of the supraglottis can therefore cause severe aspiration. If resection would require removal of large portions of the tongue base, a laryngectomy must be consideredto prevent aspiration. Owing to these concerns, attempts have been made to treat tongue base tumours primarily with chemoradiation.

Soft Palate and Pharyngeal WallsCancers of the soft palate or pharyngeal walls are treated analogously to tonsil and tongue base tumours.

Hypopharyngeal CarcinomaHypopharyneal squamous cell carcinomas are typicallyhighly infiltrative with significant submucosal spread.The majority of hypopharyngeal cancers occur in the pyriform sinus.

In hypopharyngeal cancer, the tumour’s relationshipto the oesophagus and larynx must be thoroughly evaluated. At the upper extent of the tumour, oropharyngeal involvement of the tonsil or tongue base may be detected.

HYPOPHARYNGEAL SQUAMOUS CELL CARCINOMA Definition: Hypopharyngeal carcinoma involves the pyriformsinus, posterior pharyngeal wall, and postcricoid area.

Pyriform sinus: inverted pyramid- or pear-shaped sinus composedof anterior, medial, and lateral walls converging inferiorlytoward an apex at the level of the inferior border of the cricoidcartilage:• superior border: at level of pharyngoepiglottic fold;• lateral wall: inner surface of thyroid cartilage and thyrohyoidmembrane;medial wall: posterior surface of the aryepiglottic fold and the arytenoids and cricoid cartilages.Posterior pharyngeal wall: three levels of the pharynx are recognized – the nasopharynx, oropharynx, and hypopharynx – with no specific anatomic barriers between them; tumors of the pharynx tend to be large at presentation and to involve more than one level.

Postcricoid area: is bounded laterally by the pyriform sinus and extends from the posterior surface of the arytenoid cartilage to the inferior surface of the cricoid cartilage.

Clinical• More common in men than in women; peak incidence in the sixth–seventh decades of life:• for postcricoid carcinomas there is an equal gender predilection or a greater occurrence in women.• In descending order of occurrence, hypopharyngeal carcinomas involve the pyriform sinus > posterior pharyngeal wall > postcricoid region:• pyriform sinus accounts for approximately 65–85% of carcinomas in this region;• posterior pharyngeal wall accounts for approximately 10–20% of carcinomas in this region;• postcricoid region accounts for approximately 5–15% of carcinomas in this region.• Symptoms include dysphagia, sore throat, sensation of a foreign body in the throat, hoarseness, referred otalgia, hemoptysis, or a neck mass.• Hypopharyngeal carcinomas tend to remain quiescent for longer periods and present with more advanced disease (i.e. T3 and T4).•

Etiology linked to:• tobacco smoking;• excessive alcohol use;• Plummer–Vinson syndrome, characterized by:– dysphagia due to webs, stenosis, or mucosal atrophy:

■ webs arise from anterior esophageal wall distal to thecricoid cartilage;

■ carcinomas develop immediately proximal to the websand not within them;

■ carcinomas may develop in other sites, including theoral cavity and esophagus;treatment with dietary supplements, particularly iron,may result in disappearance of the webs, therebydecreasing the incidence of carcinoma.– iron deficiency anemia;– glossitis;– cheilitis;– achlorhydria.

PathologyGross• Tumors of all hypopharyngeal sites tend to be large at presentation:• those of the posterior hypopharyngeal wall are often more than 5 cm in greatest dimension.Histology• Majority are moderately to poorly differentiated, with infiltrative margins.Spread• Pyriform sinus carcinomas:• medially to invade the lateral wall of the supraglottic larynx;• laterally, with erosion of the thyroid cartilage and invasionof the superior lobe of the thyroid gland;• superiorly into the base of the tongue;• across the postcricoid area, with involvement of theopposite pyriform sinus;• into the contiguous posterior pharyngeal wall.• The hypopharynx is rich in lymphatic spaces and manypatients (65–75%) present with clinically positive ipsilateralcervical lymph nodes; bilateral neck disease is uncommon.

• Posterior hypopharyngeal wall carcinomas:• may spread circumferentially to involve the larynx;• advanced carcinomas may extend superiorly, with involvement of the tonsillar pillars, soft palate, and nasopharynx;• advanced carcinomas may extend inferiorly, with involvement of the pyriform sinus or cervical esophagus.• Incidence of nodal metastasis is less than that for pyriform sinus carcinomas; however:• these tumors almost always cross the midline and bilateral cervical neck disease may occur;• lymphatic drainage is to the upper and middle jugular lymph nodes and to the retropharyngeal lymph nodes;• retropharyngeal nodal metastases occurs in over 50% of cases.

• Postcricoid carcinomas:• invasion of the cricoid cartilage and cricoarytenoid muscle;• circumferential growth may result in invasion through themuscular lateral walls, with direct invasion of the thyroidgland.• Nodal metastasis is common in hypopharyngeal carcinoma:• lymphatic draininage is to the middle and lower jugularchains, to the paratracheal nodes, and to the retropharyngeallymph nodes.