Oropharyngeal Carcinoma with comments on nasopharynx and hypopharynx

1. GROSS DESCRIPTION

Specimen

— fine needle aspirate/biopsy/tonsillectomy/adenoidectomy/pharyngec-tomy/pharyngooesophagectomy ± laryngectomy/neck dissection.

Depending on the anatomical site of the lesion, patients can present with dysphagia, hoarseness, deafness, cranial nerve palsy or cervical lym-phadenopathy. Investigation is by endoscopy with biopsy and cervical node FNA to obtain a diagnosis. CT and MRI scan are used to assess local tumour spread and metastasis to the neck and elsewhere. Chest X-ray can detect concurrent lung cancer. Extent of resection depends on tumour site, stage, lymph node spread, fitness of the patient and any concurrent tumour. Tonsil is submitted when there is asymmetrical enlargement or as a possible site of an occult primary in FNA-proven cervical node metastases. Carcinoma in the post nasal space is a not infrequent source.

Tumour

Site

Oropharynx: lies between the soft palate and tip of the epiglottis. Most tumours arise in the posterior third of tongue and the tonsil. Boundaries:

1. anterior wall posterior third tongue, vallecula

2. lateral wall tonsil, tonsillar fossa and pillars

3. posterior wall

4. superior wall inferior surface soft palate, uvula.

Nasopharynx (post nasal space): superiorly from the skull base and delineated inferiorly by the superior surface of the soft palate.

Hypopharynx: delineated anteriorly by the larynx and aryepiglottic folds, laterally the piriform sinus and superiorly the oropharynx at the level of the hyoid bone. It lies below the tip of the epiglottis down to the start of the oesophagus at the postcricoid area. The majority (75%) of tumours arise in the piriform fossa.

Keratinizing Squamous Cell Carcinoma

Size

— length x width x depth (cm) or maximum dimension (cm).

Appearance

— polypoid/sessile/ulcerated/fleshy.

Edge

— circumscribed/irregular.

2. HISTOLOGICAL TYPE

Squamous cell carcinoma

— 80% of cases and predominantly well-differentiated keratinizing.

— keratinizing/non-keratinizing.

variants:

— verrucous: elderly, tobacco usage, broad based exophytic and "church spire" hyperkeratosis with a pushing deep margin of cytologically bland bulbous processes. Locally invasive (75% 5-year survival) but may become aggressive after radiotherapy.

— papillary: >70% exophytic or papillary malignant epithelial fronds with focal invasion at the base (70% 5-year survival).

— spindle cell: polypoid and pleomorphic, cytokeratin (AE1/AE3—70%) positive, distinguish from sarcoma. A more obvious in-situ or invasive squamous component may be seen and nodal metastases can show a spectrum of epithelial and spindle cell changes. Prognosis (80% 5-year survival) relates to the depth of invasion.

— basaloid: poor prognosis, nests of palisaded basaloid cells with central comedonecrosis, hyalinised stroma.

— adenoid squamous: usual prognosis, acantholytic (pseudoglandular) pattern.

— adenosquamous: poor prognosis, mixed differentiation squamous carcinoma and adenocarcinoma (either obvious glands or solid with mucin positive cells).

— "transitional type": 10%. Features intermediate between squamous and "transitional cell" carcinoma with variable keratinization and differentiation.

Undifferentiated carcinoma

— absence of squamous or glandular differentiation.

— particularly nasopharynx where it is EBV related and associated with a prominent lymphocytic component (lymphoepithelioma).

Salivary gland tumours

— adenoid cystic carcinoma.

— acinic cell carcinoma.

— mucoepidermoid carcinoma.

— polymorphous low grade adenocarcinoma.

Malignant melanoma

— primary or secondary, poor prognosis.

Neuroendocrine carcinoma

— carcinoid/atypical carcinoid/small cell carcinoma.

Metastatic carcinoma

— renal cell carcinoma, breast, lung, gut.

3. DIFFERENTIATION

Well/moderate/poor/undifferentiated, or Grade 1/2/3/4.

— for squamous carcinoma based on cellular atypia, keratinization and intercellular bridges.

— undifferentiated carcinoma is grade 4.

— mainly well-differentiated keratinizing but varies according to tumour site, e.g. nasopharyngeal carcinoma is of undifferentiated type. Carcinoma of the tonsil and base of the tongue also tends to be poorly differentiated.

— most salivary gland tumours are graded according to type, e.g. acinic cell carcinoma and polymorphous low-grade adenocarcinoma are

Hypopharyngeal Cancer
Figure 12.2. Oropharyngeal carcinoma. |W

low-grade but salivary duct and undifferentiated carcinoma are high-grade.

4. EXTENT OF LOCAL TUMOUR SPREAD

Border: pushing/infiltrative.

Lymphocytic reaction: prominent/sparse.

The TNM classification applies only to carcinomas.

Oro-(hypopharynx)

pT1 tumour < 2 cm in greatest dimension (hypopharynx—and limited to one subsite)

pT2 2 cm < tumour < 4 cm in greatest dimension (hypopharynx—and more than one subsite or adjacent site, without fixation of hemilarynx)

pT3 tumour > 4 cm in greatest dimension (hypopharynx—or with fixation of hemilarynx*)

pT4 tumour invades any of oropharynx 4a: larynx, deep/extrinsic muscle of tonguef, medial pterygoid, hard palate, and mandible

*Fixation of hemilarynx is diagnosed endoscopically by immobility of the arytenoid or vocal cord.

invasion of deep muscle of tongue is usually associated with restriction of tongue mobility clinically.

pT4a

Oropharynx: tumour invades any of the following: larynx, deep/extrinsic muscle of tongue (genioglossus, hyoglossus, palatoglossus, and styloglossus), medial pterygoid, hard palate, and mandible

Figure 12.3. Oropharyngeal carcinoma. |W

Hypopharynx Tnm Staging
Figure 12.4. Nasopharyngeal carcinoma. ||W

4b: lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, skull base, or encases carotid artery.

hypopharynx 4a: thyroid/cricoid cartilage, hyoid bone, thyroid gland, oesophagus, central compartment soft tissue (including prelaryngeal strap muscles and subcutaneous fat) 4b: prevertebral fasia, encases carotid artery, or invades mediastinal structures.

Nasopharynx pT1 tumour confined to nasopharynx pT2 tumour into oropharynx and/or nasal fossa without/with (2a/2b) parapharyngeal extension pT3 tumour into bone and/or nasal sinuses pT4 intracranial extension and/or into cranial nerves, hypopharynx, orbit, infratemporal fossa, or masticator space.

Figure 12.3. Oropharyngeal carcinoma. |W

Space Cranial Nerve
Figure 12.5. Nasopharyngeal carcinoma. ||W

5. LYMPHOVASCULAR INVASION

Present/absent. Intra-/extratumoral.

6. LYMPH NODES

Site/number/size/number involved/limit node/extracapsular spread. Regional nodes: cervical

Level I: submental, submandibular

Level II: upper jugular

Level III: middle jugular

Level IV: lower jugular

Level V: posterior triangle

A selective neck dissection will ordinarily include a minimum of six lymph nodes, a (modified) radical dissection 10 lymph nodes.

Oro- and hypopharynx pN0 no regional lymph node metastasis pN1 metastasis in a single ipsilateral node < 3 cm pN2 metastasis in a. ipsilateral single node > 3 cm to 6 cm b. ipsilateral multiple nodes < 6 cm c. bilateral, contralateral nodes < 6 cm pN3 metastasis in a lymph node > 6 cm.

Nasopharynx pN1 unilateral nodal metastasis < 6 cm, above supraclavicular fossa pN2 bilateral nodal metastasis < 6 cm, above supraclavicular fossa pN3 metastasis in (a) nodes > 6 cm or (b) in supraclavicular fossa.

Presentation in up to 10% of cases is with upper cervical lymph node metastases mimicking malignant lymphoma. Cervical metastases of nasopharyngeal carcinoma may also show a necrotizing granulomatous nodal reaction. Carcinomas of the base of the tongue and oropharynx tend to metastasize to the retropharyngeal nodes and rarely (6%) the posterior triangle of neck.

7. EXCISION MARGINS

Distances (mm) to the nearest longitudinal and circumferential excision margins.

Due to anatomical limitations on resection, margins are usually only several millimetres.

8. OTHER PATHOLOGY

Concurrent carcinoma bronchus, oropharyngolaryngeal ring: 10-15%.

Primary treatment of oropharyngeal and hypopharyngeal carcinoma is surgical ± adjuvant radio-/chemotherapy, with the majority of lesions being well-differentiated keratinizing squamous cell carcinoma. In contrast, primary treatment of nasopharyngeal carcinoma is radio/chemotherapy. A majority of nasopharyngeal carcinomas are of undif-ferentiated type comprising a syncytial arrangement of enlarged tumour cells with a prominent nucleolus and an accompanying lymphoid stroma. The tumour is strongly associated with EBV infection, which can be shown by immunohistochemistry [EBV LMP (latent membrane protein)] or in-situ hybridization techniques. Serum EBV levels are also useful for monitoring the effects of treatment and detecting recurrence. Markers are helpful in distinguishing carcinoma (cytokeratins, EMA) from highgrade lymphoma (CD45) and malignant melanoma (S100, HMB-45, melan-A). Nasopharyngeal carcinoma has a biphasic age presentation (15-25 years, 60-90 years) with the keratinizing squamous cell variant (not EBV related) occurring in the older age group. Nasopharynx has separate pT and pN staging in the TNM system. Hypopharynx may also be submitted with a laryngectomy specimen due to spread from a laryngeal carcinoma.

Prognosis

Prognosis of oropharyngeal carcinoma relates to tumour site, stage and histological grade, with 20-40% 5-year survival rates for the posterior tongue, tonsil and palate. Undifferentiated carcinoma has a very poor prognosis. However, the chemo-/radiosensitivity of nasopharyngeal carcinoma results in complete remission in 80% of cases and 10-year survival rates of 40%. The keratinizing squamous cell variant in the older age group is of worse prognosis, as are cancers with lower cervical rather than upper cervical lymph node metastases.

9. OTHER MALIGNANCY

Leukaemia Lymphoma

— large B cell non-Hodgkin's lymphoma.

— mantle cell lymphoma: intermediate-grade and aggressive.

— MALToma with recurrence in other MALT sites, e.g. stomach, Waldeyer's ring.

— angiocentric T-cell lymphoma: aggressive.

Plasmacytoma/myeloma

K, % light chain restriction. Look for evidence of systemic disease, e.g. serum immune paresis and monoclonal gammopathy, Bence-Jones proteinuria, radiological lytic bone lesions.

Sarcoma

— children: embryonal rhabdomyosarcoma (subepithelial cellular cambium layer; deeper myxoid zone; desmin/myo Dl/myogenin positive).

— young adults: synovial sarcoma; pharynx, palate.

Nasopharyngeal chordoma (locally destructive), olfactory neuroblastoma, primitive neuroectodermal tumour

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