1. GROSS DESCRIPTION
— parotid/submandibular/sublingual/minor (oral).
— conservative superficial/radical parotidectomy, submandibulectomy, excision of oral tumour (sublingual glands, or minor salivary glands of mucosal origin), neck dissection.
— salivary gland tumours present as persistent unilateral enlargement the majority of which are in the parotid gland and are benign. There is a higher incidence of carcinoma arising in the submandibular glands, sublingual and minor glands of the oral cavity. Investigation is plain X-ray (for calculus), ultrasound scan (for cystic lesions), CT and MRI scan (for tumour stage). FNA is the method of choice in obtaining a likely tissue diagnosis for the purposes of planning operative management. Surgical treatment is by partial or total excision of the gland to include the tumour mass with a surround of either salivary gland tissue or soft tissues. Parotid tumours may also require excision of the skin and soft tissues of the side of the face and upper neck.
— salivary gland/nodal.
— parotid gland: superficial or deep lobe (subdivided by the plane of the facial nerve). Most arise in the superficial lobe.
— bilateral: Warthin's tumour, pleomorphic adenoma, acinic cell carcinoma.
— length x width x depth (cm) or maximum dimension (cm).
— circumscribed/irregular: presence of macroscopic extraglandular extension.
— intra-salivary lymph nodes/nerves. 2. HISTOLOGICAL TYPE Adenomas
— pleomorphic; 70% of salivary gland tumours, 80% in the parotid.
— Warthin's tumour (adenolymphoma).
— ductal papilloma (inverted/intra-ductal/sialadenoma papilliferum).
— cystadenoma (papillary/mucinous).
— mucoepidermoid: low-grade/well differentiated, high-grade/poorly differentiated.
— adenoid cystic: cribriform/tubular/solid.
— polymorphous low-grade.
— papillary cystadenocarcinoma.
— adenocarcinoma, not otherwise specified (NOS).
— carcinoma in pleomorphic adenoma (ex-PSA) usually adenocarci-noma, no special type.
— myoepithelial: spindle/clear cell types.
— extranodal lymphoma of salivary gland (MALToma).
— lymphoma of salivary gland nodes (nodal lymphoma).
— squamous cell carcinoma of head and neck region and upper aerodi-gestive tract, malignant melanoma from scalp or facial skin, renal cell carcinoma, lung and breast carcinoma, prostate, large bowel carcinomas. The metastasis is to adjacent or intrasalivary lymph nodes and the enlargement mimics a primary lesion. Note that secondary carcinoma of the submaxillary region is commoner than a primary neoplasm.
Well/moderate/poor/undifferentiated, or Gradel/2/3/4.
— grade is type dependent, e.g. acinic cell, basal cell and polymorphous low-grade adenocarcinomas are low grade but salivary duct, primary squamous cell and undifferentiated carcinomas are high grade. Adenocarcinoma, NOS is graded according to the percentage tumour gland formation, and adenoid cystic carcinoma is grade 2 (intermediate) unless it is solid pattern (grade 3, high grade). Mucoepidermoid carcinoma is assessed on the degree of cystic change, atypia, necrosis, perineural invasion and mitoses as low, intermediate or high grade. The latter tend to be solid and epidermoid in type with a scanty mucous component.
— a majority of salivary gland tumours are low grade but elderly patients not infrequently present with high-grade tumours.
4. EXTENT OF LOCAL TUMOUR SPREAD
— infiltrative margins are a useful diagnostic feature of malignancy in low-grade lesions, e.g. polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma.
Lymphocytic reaction: prominent/sparse.
Perineural space involvement particularly adenoid cystic carcinoma resulting in intractable facial pain. Skin, subcutis.
The TNM classification applies to major salivary glands: parotid, submandibular and sublingual. Minor salivary gland tumours (i.e. from the mucosa of the upper aerodigestive tract) are classified according to anatomical site, e.g. lip.
pTl tumour <2 cm, without extraparenchymal extension* pT2 tumour >2 to 4 cm, without extraparenchymal extension* pT3 tumour with extraparenchymal extension, and/or >4 cm pT4 tumour invades a. skin, mandible, ear canal, and/or facial nerve b. base of skull, and/or pterygoid plates and/or encases carotid artery.
5. LYMPHOVASCULAR INVASION
*Extraparenchymal extension is clinical or macroscopic evidence of invasion of skin, soft tissues, bone or nerve; microscopic evidence alone is not sufficient.
6. LYMPH NODES
Intra-/extraglandular: the parotid gland can contain up to 20-30 intraglandular 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.
pN0 no regional lymph node metastasis pN1 metastasis in single ipsilateral node <3cm pN2 metastasis in:
a. single ipsilateral node >3 cm but <6cm b. ipsilateral multiple nodes <6cm c. bilateral or contralateral nodes <6cm pN3 metastasis in lymph node >6 cm.
Regional nodes are the commonest site of metastasis followed by lungs and bone.
Distance (mm) to the nearest painted excision margin. Pleomorphic adenomas should not be surgically enucleated as the irregular margin can lead to residual tumour and local recurrence.
Fine needle aspiration cytology has an important role to play in the primary diagnosis of salivary gland enlargement and is capable of designating benignity and malignancy in a majority of cases. It can indicate non-neoplastic disorders such as simple cysts, abscess and fatty infiltration. The separation of benign from malignant salivary tumours results in more appropriate surgery (superficial conservative vs. radical parotidectomy) or the avoidance of it (lymphoma, secondary carcinoma). The experienced cytopathologist can in many cases obtain sufficient material to stipulate the tumour subtype. Some pitfalls are cystic lesions (simple cyst vs. cystic salivary tumour, e.g. mucoepidermoid carcinoma, acinic cell carcinoma or metastatic squamous carcinoma), clear cell lesions (primary epithelial or myoepithelial tumour vs. secondary renal, lung or thyroid carcinoma), metastases (primary squamous or mucoepi-dermoid carcinoma vs. secondary squamous carcinoma), the onset of low-grade lymphoma in lympho(myo-)epithelial sialadenitis and distinction from extranodal lymphoma and chronic sialadenitis. The technique is obviously reliant on representative sampling of the tumour and there can be a degree of cytological overlap between subtypes, e.g. pleomor-phic adenoma, adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma.
Necrotizing sialometaplasia of minor salivary glands in the mouth and palate can mimic carcinoma, e.g. mucoepidermoid carcinoma. It presents as an ulcerating lesion in middle-aged men.
There is a higher incidence of carcinoma in minor salivary glands (e.g. polymorphous low-grade adenocarcinoma of the palate or floor of mouth): palate 44%, submaxillary glands 38%, parotid 17% of salivary carcinomas.
Salivary tumours with clear cells tend to be malignant, and must also be distinguished from secondary renal cell carcinoma. A wide range of salivary tumours can show clear cell differentiation: acinic cell, mucoepi-dermoid, epithelial-myoepithelial, sebaceous, clear cell carcinomas and malignant myoepithelioma. Abdominal investigation may be necessary to distinguish metastatic renal cell carcinoma (vascular stroma, glyco-gen/fat-rich cells), S100, melan-A and HMB-45 (clear cell melanoma), and thyroglobulin/TTF-1 (clear cell thyroid carcinoma). Primary clear cell carcinoma of low grade arises in minor salivary glands, has uniform clear cells in a dense hyalinizing stroma and is locally infiltrative.
Acinic cell carcinomas occur in the parotid gland and have deceptively bland granular cells with a variably solid, papillary, clear cell, follicular or microcystic pattern but can still infiltrate and metastasize and more aggressive pleomorphic variants occur. Overall recurrence can be seen in 10-30% and death in about 6%. Peak incidence is in the third decade of life but, like mucoepidermoid carcinoma, acinic cell carcinomas are seen in childhood and teenage years. Gross invasion, cellular pleomorphism and incomplete primary excision are adverse indicators.
Mucoepidermoid carcinoma affects palate and parotid gland and is the commonest malignant salivary gland tumour (30% of cases). It shows a spectrum of epidermoid and mucous cells in varying proportions (mucin stains may be necessary). Well-differentiated lesions may be largely cystic with only mural tumour. Poorly differentiated (high-grade) lesions are more solid, squamoid and infiltrative. The mucin and keratin can be extruded into the interstitium causing an inflammatory reaction. Tumour grade dictates prognosis with multiple local recurrences dominating and nodal metastases late.
Adenoid cystic carcinoma forms 5% of salivary gland neoplasms but 20% of the carcinomas with equal distribution between the parotid and minor glands (palate). It shows biphasic cell differentiation (epithelial/myoep-ithelial: cytokeratin/S100, CK5/6 and smooth muscle actin positive) and biphasic histochemical staining of PAS positive luminal mucus and alcian blue positive matrix. It typically shows cribriform, hyaline and tubular patterns and indolent perineural spread with facial pain and late lymph node involvement. It is slow growing but highly malignant and locally recurrent. Prognosis relates adversely to a solid (basaloid) growth pattern, stage and incomplete primary excision, with radical surgery being the treatment of choice. Margins can be difficult to define, as there is often spread beyond the identifiable clinical edge.
Polymorphous low-grade adenocarcinoma is characterized by cellular uniformity and architectural diversity (solid/cribriform/single cell/cords/ tubular/ductal/papillary) with abundant stroma. Typically in the palate (second commonest after adenoid cystic carcinoma) with local recurrence in 21%, nodal metastases in 6.5% and distant metastases in 1.8%. An infiltrative margin and perineural invasion can be helpful in making the diagnosis. A somewhat more aggressive tumour is the related low-grade papillary adenocarcinoma.
Epithelial/myoepithelial carcinoma is a low-grade malignancy mainly of the parotid gland and recurs in one-third of cases, comprising ductal cells and outer clear myoepithelial cells in a biphasic pattern. Myoepithelial differentiation can be demonstrated by cytokeratin 5/6, S100 and smooth muscle actin. Although circumscribed, it has an infiltrative margin with perineural invasion. Death can occur in 7% and nuclear atypia in >20% of cells is an adverse prognostic factor. Occasionally one element dedif-ferentiates resulting in carcinomatous or sarcomatous overgrowth.
Myoepithelial carcinoma is a spindle cell lesion with mitotic activity, nuclear atypia, necrosis and invasion.
Ductal carcinoma resembles high-grade ductal carcinoma in situ of the breast. It shows aggressive behaviour with poor prognosis and 70% die within 3 years. Patients are >50 years of age and the male to female ratio is 3:1 with parotid being the main site. A low-grade variant also exists.
Primary squamous cell carcinomas (5-10%) occur mostly in the parotid gland and are aggressive with 5-year survival rates of 40%. Metastases to the parotid gland from other sites must be excluded, commonly upper aerodigestive tract or skin. Some primary lesions represent mucoepider-moid carcinoma or carcinoma within a mixed tumour.
Carcinoma in pleomorphic adenoma (3-4% of cases) is unusual and manifests itself as regrowth or facial pain in an existing lesion present for 15-30 years (9.5% risk after 15 years). In descending order of frequency the malignancy is carcinoma (adenocarcinoma of no specific type, poorly differentiated ductal and undifferentiated), malignant myoepithelioma, carcinosarcoma and metastasizing pleomorphic adenoma. Prognosis which is adverse relates strongly to the degree of extension of the malignancy beyond the capsule of the original benign tumour.
Basal cell carcinoma is the malignant counterpart of basal cell adenoma (solid nests surrounded by basal hyaline lamina material) except that it shows infiltration, perineural and vascular invasion. It occurs in the patient's parotid gland, 50-60 years of age.
Carcinosarcoma, small cell carcinoma and undifferentiated carcinoma (some of which are lymphoepitheliomatous in character and EBV related similar to nasopharyngeal carcinoma) have poor prognosis.
Most low-grade carcinomas of mucoepidermoid or acinic cell type can be treated by superficial parotidectomy, whereas more radical surgery with sacrifice of the facial nerve is needed for large (>4cm), higher-grade or advanced carcinomas. Submandibular and sublingual tumours are treated by total removal of the gland with a margin of normal tissue.
Prognosis relates to tumour stage, anatomical location and histological type and grade.
— minor salivary gland tumours have a higher incidence of recurrence and metastases than equivalent parotid lesions.
— examples of 5-year survival rates: low-grade mucoepidermoid, 90-95%; high-grade mucoepidermoid, 50-60%; squamous cell carcinoma, 40%.
— histological type:
better prognosis: low-grade mucoepidermoid/acinic cell carcinomas worse prognosis: high-grade mucoepidermoid/acinic cell carcinomas; adenoid cystic carcinoma, malignant mixed tumour, salivary duct carcinoma, squamous carcinoma.
9. OTHER MALIGNANCY
— children. Desmin/myo Dl/myogenin positive. Note that mucoepider-moid and acinic cell carcinomas can also typically occur in childhood and young adults.
Malignant fibrous histiocytoma, fibrosarcoma, malignant peripheral nerve sheath tumour
— 2-5% of salivary gland neoplasms.
— 20% have Sjogren's syndrome or LESA (lymphoepithelial or myoepithelial sialadenitis).
— one-third are diffuse large B-cell lymphoma, of nodal or parenchymal origin.
— one-third are follicular lymphoma, usually of nodal origin.
— one-third are MALToma. LESA has a x40 increased risk of developing low-grade lymphoma and 15-20% do so over a variable period of 5-20 years. MALToma is characterized by lymphoepithelial lesions surrounded by broad haloes or sheets of centrocyte-like (marginal zone/monocytoid) B cells. Other features include monotypic plasma cells and follicular colonization. High-grade transformation to large cell lymphoma can occur. Polymerase chain reaction demonstration of clonality does not always reliably predict those lymphoid lesions that will progress to clinical lymphoma.
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