Lip and Oral Cavity Carcinoma

1. GROSS DESCRIPTION

Specimen

— fine needle aspirate/diagnostic or (wedge) excision biopsy/resection, e.g. glossectomy/neck dissection.

— pathological lesions present either as a lump, ulcer, red or white mucosal patch and require biopsy to determine their nature.

— preoperative investigation of a mass will include plain X-ray, MRI and CT scan to assess local spread, bone destruction and/or cervical nodal metastases. Local wedge excision (± shave excision of adjacent mucosa) is used for small tumours of the lip and tip/lateral border of tongue, hemiglossectomy for deeply infiltrative cancers and (sub)total glossectomy for large tumours crossing the midline or involving the posterior one-third. Sublingual gland is submitted with anterior floor of mouth lesions and superficial gingival tumours require mucosal excision only. Periosteum acts as a barrier to bone spread but where it is demonstrated radiologically rim or hemimandibulectomy may be required. Previous irradiation can disrupt the periosteum increasing bone spread. Adequate demonstration will require decalcification with the overlying soft tissues in place. Where there is proven or likely nodal metastases an en bloc neck dissection is performed.

Tumour

Site

external lower. commissures.

When the skin is involved if >50% of the tumour is within the vermillion border the tumour is designated as lip in origin.

buccal mucosa—lips/cheek/retromolar areas/bucco-alveolar sulci. upper alveolus and gingiva (upper gum). lower alveolus and gingiva (lower gum).

hard palate.

tongue—dorsal surface and lateral borders (anterior two-thirds); inferior (ventral) surface. floor of mouth.

The commonest sites are, in order of decreasing frequency, lip (90% lower), lateral borders of tongue (35%), anterior floor of mouth (20%) and the soft palate complex (soft palate, anterior pillar of fauces and retromolar areas).

Multifocal lesions are not uncommon (10%), both synchronous and metachronous.

Size

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

— verrucous/warty/nodular/sessile/plaque/ulcerated. Edge

— circumscribed/irregular. 2. HISTOLOGICAL TYPE

Squamous cell carcinoma

— 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).

Salivary gland tumours

— there is a higher frequency in the oral cavity (particularly palate) of carcinoma of minor salivary gland origin, e.g. polymorphous low-

grade adenocarcinoma (cytological uniformity with architectural diversity), adenoid cystic carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, carcinoma ex pleomorphic adenoma.

Small cell carcinoma

— aggressive: pure or with a squamous component. Chromogranin/ synaptophysin/CD56/paranuclear dot CAM5.2 positive.

Malignant melanoma

— Japanese/Africans, palate and gingiva, ± adjacent junctional activity. Prognosis is poor with nodal and distant metastases common.

— lip: desmoplastic melanoma. Show S100 positivity to distinguish from fibrous tissue; ± neurotropism. Can be negative for HMB-45 and melan-A.

Metastatic carcinoma

— lung, breast, kidney, gut, malignant melanoma or direct spread from nasal cavity/maxillary sinus.

3. DIFFERENTIATION

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

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

— usually moderately differentiated, whereas carcinomas at the base of the tongue can be poorly differentiated/undifferentiated and immuno-histochemistry for cytokeratins is needed to distinguish from malignant lymphoma.

— undifferentiated carcinoma is grade 4.

— most salivary gland tumours are graded according to type, e.g. acinic cell carcinoma and polymorphous low-grade adenocarcinoma are 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 to carcinomas of the lip and oral cavity including those of minor glands.

pTis carcinoma in situ pT1 tumour < 2 cm in greatest dimension pT2 tumour > 2 cm but < 4 cm in greatest dimension pT3 tumour > 4 cm in greatest dimension pT4a Lip: tumour invades adjacent structures, e.g. through cortical bone, inferior alveolar nerve, floor of mouth, skin (chin or nose) Oral cavity: tumour invades adjacent structures, e.g. through cortical bone, into deep (extrinsic) muscle of tongue, maxillary sinus, skin of face pT4b Lip and oral cavity: tumour invades masticator space, pterygoid plates, or skull base, or encases internal carotid artery.

Cancers of the lip and lateral borders of the tongue may remain localized for considerable periods of time prior to invasion of local adjacent structures.

Tongue Cancer Extrinsic Muscle
Tumour > 4 cm in greatest dimension
Clear Cell Carcinoma Oral Cavity
Figure 11.3. Lip and oral cavity carcinoma. j[W

pT4a

pT4a

Figure 11.4. Lip and oral cavity carcinoma.

Figure 11.4. Lip and oral cavity carcinoma.

Lip Carcinoma

Distinguish tumour extending to or overlying bone from gross erosion or radiographic destruction of bone.

5. LYMPHOVASCULAR INVASION

Present/absent. Intra-/extratumoral.

Perineural spread: predictor of local recurrence.

6. LYMPH NODES

Metastases are mainly lymphatic with the more anterior the tumour the lower the position of the cervical nodes involved. Nodal metastases may also undergo cystic degeneration with central straw-coloured fluid and viable cells at the tumour margin only. Residual paucicellular masses of keratin with a foreign body reaction may result from radiation therapy. These features should be borne in mind on FNA of cervical nodes and a careful search made for malignant cells, which may be very well differentiated. A common differential diagnosis is branchial cyst.

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 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.

Extracapsular extension: present/absent. Increases the risk of local recurrence and distant spread. Metastasis is usually to ipsilateral nodes but lesions of the tip of the tongue, those that cross the midline or the posterior one-third can cause contralateral node involvement.

7. EXCISION MARGINS

Distances (mm) of tumour to the nearest painted excision margins. Epithelial dysplasia/carcinoma in situ present at excision margins. An ideal therapeutic margin is 10 mm but often resections afford only 2-3 mm which is compounded by a peritumoral zone of dysplastic or hypertrophic mucosa.

8. OTHER PATHOLOGY: PREDISPOSING FACTORS

Gender (M:F 2: 1), smoking and alcohol are the main risk factors.

Clinical leukoplakia erythroplakia thin, smooth thick, fissured granular, verruciform erythroleukoplakia 25-33% risk 50% cancer risk.

cancer risk rises

Histological: dysplasia

— mild/moderate/severe. Most clinical examples of leukoplakia do not show histological dysplasia, although if present it indicates a greater predisposition to carcinoma. Note that carcinoma can also arise from lesions with no dysplasia.

Others

— smokeless tobacco keratosis.

— chronic hyperplastic candidosis. This may also mimic squamous carcinoma histologically and treatment of infection is advised prior to any designation of malignancy.

human papilloma virus (HPV 16, 18): aetiological factor contributing to verrucous and squamous carcinoma.

— smoking, alcohol, post-transplant immunosuppression.

Squamous carcinoma is positive for a range of cytokeratins (excluding

CK 20 and CAM5.2) and this is of use in the distinction of spindle cell carcinoma from sarcoma.

Prognosis

Prognosis relates to tumour site, stage and histological grade.

lip anterior tongue posterior tongue, floor of mouth

90% 5-year survival 60% 5-year survival (20 % with large tumours and positive nodes) 40% 5-year survival.

Treatment is by surgery and/or radiotherapy supplemented by chemotherapy depending on the site and stage of disease.

9. OTHER MALIGNANCY

Lymphoma

— Waldeyer's ring is the commonest site of oropharyngeal non-Hodgkin's lymphoma but it can arise in gingiva, buccal mucosa and palate. Most are B cell and diffuse, although others, e.g. T-cell non-Hodgkin's lymphoma (NHL) and anaplastic large cell lymphoma, do occur. Some are MALT derived and associated with extranodal lymphomas elsewhere, e.g. stomach, whereas others are of nodal type, e.g. mantle cell. Prognosis relates to histological type and grade and stage of disease. There is an increasing incidence with AIDS.

Leukaemia

— direct infiltration or ulceration with opportunistic infection, e.g. herpes simplex virus, cytomegalovirus. Gingival involvement is seen in 4% of acute myeloid leukaemia. Rarely granulocytic sarcoma (CD68/chloroacetate esterase/myeloperoxidase positive) is the first presentation of disease.

Plasmacytoma/myeloma

K, % light chain restriction. Look for evidence of systemic disease, e.g.

serum immune paresis and monoclonal gammopathy, Bence-Jones pro-

teinuria, radiological lytic bone lesions.

Odontogenic/osseous cancers by direct spread

Sarcoma

— leiomyosarcoma: cheek.

— rhabdomyosarcoma: embryonal—children soft palate, desmin/myo D1/myogenin positive.

— synovial sarcoma: young adults, cheek, tongue, palate.

Granular cell tumour

— a benign nerve sheath tumour composed of S100 positive granular cells. Commonly, overlying pseudoepitheliomatous hyperplasia can mimic squamous cell carcinoma and a careful search for granular cells in the biopsy subepithelial connective tissues must be made.

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