Laryngeal Carcinoma

1. GROSS DESCRIPTION

Specimen

— biopsy/hemi-/partial or total laryngectomy/neck dissection.

Typically presenting with hoarseness, investigation is by indirect laryn-goscopy with biopsy. Chest X-ray and endoscopy of the upper aerodi-gestive tract are done to exclude a concurrent cancer elsewhere. CT and MRI are used to stage the tumour and cervical lymph node enlargement necessitates FNA to establish if there are metastases. Tumour stage and fitness of the patient determine the appropriate choice of treatment, i.e. radiotherapy, laryngectomy, neck dissection. Laryngectomy may also accompany a pharyngectomy for cancer of the hypopharynx.

Tumour

Site supraglottic 20% glottic 70%

infraglottic 5% transglottic 5%

Supraglottis: from the tip of the epiglottis to the true cords including the aryepiglottic folds, false vocal cords and ventricles.

Glottis: true cords and anterior commissure.

Subglottis: from the lower border of the true cords to the first tracheal cartilage.

Anterior/posterior/lateral(right, left)/commissural/ ventricles/false cords. Anterior glottis is the commonest site.

Size

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

— polypoid/verrucous/plaque/ulcerated/multifocal.

Edge

— circumscribed/irregular.

2. HISTOLOGICAL TYPE

Squamous cell carcinoma

— keratinizing/non-keratinizing.

variants:

— verrucous: broad based exophytic and "church-spire" hyperkeratosis with a pushing deep margin of cytologically bland bulbous processes arising in the glottis. Locally invasive, rarely metastatic, radiation may result in anaplastic change. 70% 5-year survival.

— papillary: >70% papillary or exophytic fronds, covered by malignant type epithelium with focal invasion at the base. Better prognosis (70% 5-year survival).

— spindle cell: polypoid, glottic, elderly, ±history of irradiation for previous carcinoma. A minor squamous element is present (in-situ or invasive) with a major variably pleomorphic fibrosarcoma-like component. Diffuse or focal cytokeratin (70% - AE1/AE3) positivity suggests that it is a metaplastic form of carcinoma. Prognosis is better if polypoid and superficial than infiltrative, when the outlook is poor. Distinguish from sarcoma and bizarre post-irradiation granulation tissue.

— basaloid: poor prognosis, nests of basaloid cells with peripheral palisading and central comedonecrosis, hyalinised stroma.

Supraglottis

Glottis

Subglottis

— 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).

Undifferentiated carcinoma

— absence of squamous or glandular differentiation.

— includes lymphoepithelioma type.

Neuroendocrine carcinomas

— chromogranin/CD56/synaptophysin ± CAM5.2 positive.

— well differentiated: carcinoid tumour.

— moderately differentiated: atypical carcinoid tumour.

— poorly differentiated: small cell/large cell carcinoma.

Atypical carcinoid and large cell neuroendocrine carcinoma are commoner in the larynx than carcinoid tumour and are aggressive lesions with 50% mortality.

Adenocarcinoma

— salivary type, e.g. adenoid cystic, mucoepidermoid carcinomas of mucosal gland origin.

— adenocarcinoma of no specific type.

Metastatic carcinoma

— direct spread: thyroid, oesophagus.

— distant spread: malignant melanoma, kidney, breast, pancreas, colon, ovary, prostate.

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 shows no squamous or glandular differentiation (grade 4).

4. EXTENT OF LOCAL TUMOUR SPREAD

Border: pushing/infiltrative. Lymphocytic reaction: prominent/sparse.

A glottic tumour is best sliced horizontally to demonstrate its anatomical relationships, a supraglottic tumour sagitally.

Anterior

— mucous membrane, cricothyroid membrane, thyroid cartilage, thyroid gland, strap muscles, jugular vein.

Superior

— base of epiglottis, vestibular folds, pyriform fossa and limits.

Inferior

The TNM classification applies only to carcinomas. pTis carcinoma in situ.

Supraglottis pT1 one subsite, normal mobility pT2 mucosa of more than one adjacent subsite of supraglottis or glottis or adjacent region outside the supraglottis; without fixation pT3 cord fixation or invades post cricoid area, pre-epiglottic tissues, paraglottic space, thyroid cartilage erosion pT4a through thyroid cartilage and/or into trachea, soft tissues of neck: deep/extrinsic muscle of tongue, strap muscles, thyroid, oesophagus pT4b prevertebral space, mediastinal structures, carotid artery. Glottis pT1 limited to vocal cord (s), normal mobility

(b) both cords pT2 into supraglottis and/or subglottis and/or impaired cord mobility pT3 cord fixation and/or into paraglottic space and/or thyroid cartilage erosion pT4a through thyroid cartilage or into trachea, soft tissues of neck: deep/extrinsic muscle of tongue, strap muscles, thyroid, oesophagus pT4b prevertebral space, mediastinal structures, carotid artery. Subglottis pT1 limited to subglottis pT2 extends to vocal cord(s) with normal/impaired mobility pT3 cord fixation pT4a through cricoid or thyroid cartilage and/or into trachea, deep/

extrinsic muscle of tongue, strap muscles, thyroid, oesophagus pT4b prevertebral space, mediastinal structures, carotid artery.

5. LYMPHOVASCULAR INVASION

Present/absent. Intra-/extratumoral.

6. LYMPH NODES

The incidence of nodal metastases at presentation varies according to the site of the primary tumour from glottic (<10%) to supra-/infraglottic (30-50%). Well-differentiated carcinomas are less likely to metastasize than poorly differentiated cancers.

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

Epiglottis

Epiglottis

One Both

Tumour confined to the vocal cord(s) with normal mobility pT2

Tumour confined to supra-/subglottis and/or impaired cord mobility

Figure 14.2. Laryngeal carcinoma: glottic. [Q§|

Tumour extension to the larynx but with vocal cord fixation and/or into paraglottic space and/or minor thyroid cartilage pT4

Tumour invades through thyroid cartilage and/or into other extra-laryngeal tissues,e.g.trachea, thyroid, pharynx, strap muscles,tongue, prevertebral space, mediastinum, or encases carotid artery

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 < 3 cm pN2 metastasis in:

a. single ipsilateral node > 3 cm but <6cm b. ipsilateral multiple nodes < 6 cm c. bilateral, contralateral nodes < 6 cm pN3 metastasis in lymph node > 6 cm.

7. EXCISION MARGINS

Distances (mm) to the tracheal limit, aryepiglottic fold and pre-laryngeal anterior fascia of infiltrating carcinoma and any mucosal dysplasia or carcinoma in situ.

8. OTHER PATHOLOGY

Laryngeal carcinoma is predominantly (>95%) in males who smoke and are 50-60 years of age. Smokers and heavy voice users can develop keratosis with hoarseness and thickened white cords on laryngoscopy. A proportion may be associated with dysplasia and progression to carcinoma in situ and eventually over a period of years squamous carcinoma. These premalignant changes can be treated by local excision, laser or irradiation. Carcinoma in situ may be leukoplakic, erythroplakic or inapparent and biopsy is necessary.

Radionecrosis

— post-radiotherapy confluent necrosis which may lead to local airway obstruction and necessitate laryngectomy.

Concurrent carcinoma bronchus/oropharynx

Verrucous squamous cell carcinoma has to be distinguished from benign squamous epithelial papilloma and hyperplasia by its pushing deep margin. It can also co-exist with squamous carcinoma of usual type. Beware granular cell tumour with overlying pseudoepitheliomatous hyperplasia—the granular cells (Schwann cell origin) are S100 protein positive.

Juvenile laryngeal papillomatosis (multiple squamous papillomas of the upper respiratory tract) is a rare cause of squamous cell carcinoma, usually after radiotherapy.

Prognosis

Prognosis relates to tumour site, stage and histological grade. Early (pT1, pT2) glottic and supraglottic carcinoma may be treated by local excision, laser or radiotherapy. Partial laryngectomy (supraglottic or vertical hemi-laryngectomy) may be carried out for small volume T2 or T3 cancers. Advanced carcinoma, infraglottic and transglottic tumours and cancers refractory to radiotherapy usually necessitate laryngectomy supplemented by radiotherapy. Site-related 5-year survival:

glottic 80%

supraglottic 65%

transglottic 50%

subglottic 40%.

Stage-related 5-year survival:

glottic I 90%

III 60%

Most glottic carcinomas are well to moderately differentiated, while non-glottic carcinomas are more frequently moderately to poorly differentiated.

9. OTHER MALIGNANCY

Lymphoma/leukaemia

— primary MALToma or secondary to nodal/systemic disease.

— sinonasal (angiocentric) T/NK cell lymphoma.

Plasmacytoma/myeloma

— initially localized but generally becomes part of disseminated myeloma. Look for K, % light chain restriction and evidence of systemic disease (elevated ESR, serum immune paresis and monoclonal gammopathy, Bence-Jones proteinuria, radiological lytic bone lesions).

Sarcoma, particularly low-grade chondrosarcoma and rhabdomyosarcoma (embryonal—childhood), occasionally angiosarcoma, liposarcoma, fibrosarcoma

Malignant melanoma

— primary or secondary (commoner). S100, HMB-45, melan-A positive.

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