Laryngeal Cancer (Staging)

• Squamous cell carcinoma of the larynx is the most common head and neck cancer. The diagnosis is usually known before imaging referral 14
• Smoking, tobacco, and alcohol are the major risk factors 13
• Common presenting symptoms are hoarseness, difficulty in breathing, dysphagia, or odynophagia, foreign body sensation, earache, and advanced disease may lead to stridor or aspiration 13
• Carcinoma of the larynx arises in the supraglottic region (30%), glottis (65%), or subglottic region (5%) 13
• Lymphatic spread to cervical lymph nodes is very common in supraglottic cancers but glottic carcinomas do not have nodal spread commonly, being 0 -10% in early cancers and 10-35% in advanced cases, with distant metastasis even less common at 6.5-8.5% 2, 13
• Cross-sectional imaging is recommended for T2 lesions or above; lower stages may not be detectable on imaging but imaging may be indicated where clinical assessment is difficult or early disease is suspected 13, 14
• Thyroid and cricoid cartilage invasion are important features in the evaluation of laryngeal tumours as they can upstage tumours to critical points where decision-making for offered treatment is between chemoradiation and total laryngectomy 7
• Staging objectives are to identify:
  • Extent of local tumour and volume of paraglottic disease 13, 14
  • Extent and distribution of lymph node metastases 13, 14
  • Evidence of cartilage invasion 13, 14
• The staging of laryngeal cancer uses the TNM Staging System 2, 11
• CT is the modality of choice for initial evaluation due to its wide availability and fast acquisition 7, 11, 13, 14
• Ultrasound is useful for assessing neck nodes and to guide biopsy 13
• MRI is useful in indeterminate scenarios with dilemma of cartilage erosion versus tumour inflammation in borderline cases of T3 tumours 13
• FDG PET-CT is usually only considered in patients with advanced locoregional disease or for detecting metastases 13, 14. However, FDG PET-CT is increasingly used routinely for initial staging of laryngeal tumours, especially for identifying nodal disease 9.
• If imaging does not reveal an obvious primary cancer, FDG PET-CT should be ordered due to higher sensitivity than CT for assessing both nodal and distant metastasis  before examination under anaesthesia (EUA) or biopsies to help identify any primary sites before intervention continues 11
• Using the same imaging technique as for pre-treatment evaluation, imaging 3-4 months after radiotherapy completion is useful for documenting tumour response 13, 14

The staging of laryngeal cancer uses the TNM Staging System 2, 11

TUMOUR (T) STAGING

NODAL (N) STAGING

*Clinical extra-nodal extension is defined as the presence of skin involvement or soft tissue invasion with deep fixation to underlying muscle or adjacent or anatomical structures, or clinical signs of nerve involvement. Imaging is becoming a standard method of detecting unequivocal extranodal extension

DISTANT (M) STAGING

• M0: No distant metastasis
• M1: Distant metastasis

• Multidetector CT with contrast is generally preferred as the imaging technique given its ability to assess all tissues in the neck rapidly, its widespread availability, and its relatively cheaper cost compared with MRI 1, 7, 11, 13, 14
• CT is less prone to swallowing artefacts and provides better spatial resolution compared with MRI 13
• The examination time is short with less motion artefacts than an MRI scan. Thin slice, high resolution image acquisition allows high quality multiplanar reconstructions with superior evaluation of bony structures and calcifications. The study can be easily extended to the rest of the body for staging purposes. 1, 15
• CT may be complemented with MRI in cases with dilemma, especially related to cartilage involvement 1, 11, 13, 14
• CT of the neck should be obtained ideally in the venous phase, so that the contrast gets enough time to reach the normal and pathologic soft tissues. The scan is taken with the patient breathing quietly to allow better evaluation of anterior and posterior commissures when the vocal cords are abducted. The scan should be viewed in soft tissue and bone windows. Reformations are important. 13
• For optimal neck evaluation, the patient should be quietly breathing and not swallowing or holding their breath, both of which severely limit evaluation of the larynx 7. Additionally, during prolonged phonation of ‘e’, arytenoid mobility can be judged, and a better visualization of the laryngeal ventricles can be achieved; the slight distension of the lyriform sinuses may also allow better delineation of the aryepiglottic folds 1
• Slice thickness of 3 mm is generally optimal, while slice thickness >5 mm does not offer sufficient spatial resolution. Images should be reconstructed and viewed in both soft tissue and bone windows 4.

Recommended CT Protocol 13

• Multidetector CT (MDCT, 16 slice or above)
• Iodinated contrast agent (35-40g iodine) injected at a rate of 1-1.5ml/s, with subsequent saline injection at the same rate
• Scan should be started after the entire contrast volume injected, ideally in the venous phase with a 60-90s delay
• In supine position with the patient breathing quietly with patient instructed not to cough or swallow
• Axial images obtained from the skull base to the aortic arch; reconstruction parallel to the hyoid bone, to get images parallel to the true vocal cords
• Additional manoeuvres such as modified Valsalva or phonation for better visualization of the hypopharynx or laryngeal ventricle, respectively
• Sagittal and coronal plane reformats are important

• FDG PET-CT combines metabolic imaging using the glucose analog fluorodeoxyglucose (FDG) with CT anatomy to detect hypermetabolic tumours and nodal disease 13
• FDG PET-CT is superior to CT or MRI for detecting malignant lymph node disease
• FDG PET-CT is increasingly used routinely for initial staging of laryngeal tumours, especially for identifying nodal disease. It can reduce the chance of cervical nodal metastases going undetected in clinically N0 necks, as well as help identify which lymph nodes would be most suitable for percutaneous biopsy. It is also highly useful for restaging after treatment (assessing treatment response). 6, 9
• It is particularly useful for initial staging in patients with advanced locoregional laryngeal cancer because it improves the accuracy of nodal staging and detects more distant lesions than cross-sectional imaging alone 6, 13
• FDG PET-CT can also help detect synchronous tumours and locate occult or unknown primary malignancies 3, 13
• Some studies have shown FDG PET-CT to have a higher sensitivity (97%) than CT (86%) and MRI (88%) in detecting primary head and neck tumours. Despite this, it is unlikely to provide enough anatomic depth and surrounding structure detail necessary for surgical planning of tumour resection. For this reason, the inclusion of initial CT or MRI would still be necessary. 6, 9

• MRI, with contrast, unless contraindicated, is best for assessing pre-epiglottic space and tongue base invasion. MRI is also helpful for demonstrating cartilage involvement when CT is indeterminate. 11, 13, 14
• MRI offers excellent soft tissue contrast, multiplanar imaging, and evaluation of tumour extent without ionizing radiation or iodine-based contrast, making it valuable for staging and follow-up of laryngeal cancer 15
• MRI also adds information for bulky tumours and their relationship with prevertebral fascia as well as the carotid sheath in extralaryngeal spread 13
• MRI can demonstrate low T2 signal in scar tissue, helping to differentiate it from recurrent tumour, which typically shows higher T2 signal and contrast enhancement 1
• Diffusion-weighted MRI may help in differentiating carcinomas from benign lesions and metastatic from reactive neck nodes 1, 13
• Tumours extending beyond the external margin of the cartilage (extralaryngeal) is the most reliable feature of cartilage invasion. This finding can be difficult to define on CT; additionally, a variable degree of cartilage ossification makes it more challenging when looking for erosion, lysis, or transmural extension. 7
• Disadvantages of MRI are the presence of motion artefact due to deglutition and respiration, as well as artefact from air-mucosa interfaces. It is for these reasons, along with length of acquisition and cost, that MRI is not typically used as first-line imaging in suspected laryngeal malignancy 1

Recommended MRI Protocol 13, 10

• Multiplanar non-contrast T1-weighted with and without fat saturation, T2-weighted, T2-weighted fat-saturation images with post-contrast T1 fat-suppressed images. Diffusion-weighted imaging.
• Section thickness of 4 mm with an interslice gap of 0-1 mm
• A dedicated neck coil
• Instructions of not coughing and swallowing during the scan
• Scan from the skull base to the thoracic inlet, with scan orientation parallel to the true vocal cords
• Images in the axial and coronal planes are the most useful. The pre-epiglottic space is better seen in the sagittal plane, while the paraglottic space and the ventricle are better assessed in the coronal plane.

• In patients with head & neck cancers, subsequent new primary lung cancers may occur synchronously or metachronously, with new primary tumours in approximately 9% of patients 11
• Additionally, head & neck SCC are correlated with a prevalence of second primary lung cancer ranging from 5-19% 5
• LDCT of the chest is sufficient to screen for lung parenchymal metastases in high-risk patients but cannot reliably assess mediastinal or hilar lymphadenopathy 11
• More sensitive for small parenchymal nodules (<5 mm) compared to standard chest X-ray 5

• Ruling out of lymph node metastases should be conducted in advanced cases of laryngeal cancer with CT, with or without contrast, as clinically indicated, or MRI of the neck, whichever is suitable for primary site evaluation 11, 13
• For patients with multistation or lower neck nodal involvement or high-grade histology, consider CT of the chest to assess for mediastinal lymph node metastases or FDG PET-CT, which is associated with higher sensitivity for nodal and distant metastases 11
• CT evaluation of regional lymph nodes primarily relies upon size criteria and lymph node appearance to differentiate involved from uninvolved lymph nodes. CT is also highly sensitive for detection of extracapsular spread of the lymph nodes. 12
• Pathologic lymphadenopathy is usually defined radiologically as a node >10-11 mm in minimal axial diameter or one that contains central necrosis 8

• While US can detect the primary laryngeal tumour, it is not typically used for primary staging due to artefacts caused by thyroid cartilage calcification and by air within the laryngeal cavities 1, 13
• Rather than primary staging, US can be a useful adjunct to cross-sectional imaging. The most common use is in the assessment of cervical lymph nodes and to guide biopsy 1, 13
• Core biopsies are preferable to Fine-Needle Aspiration Cytology (FNAC) if technically possible and if local expertise is available. It preserves tissue architecture and samples can be sent for histopathology and additional testing including flow cytometry and genetics where indicated. 9
• In addition to nodal evaluation, US can be used to evaluate laryngeal anatomy for problem solving. It can also be used to evaluate extralaryngeal spread by identifying thyroid cartilage invasion, breach of cricothyroid membrane, or strap muscle involvement. 1

• For patients with locoregionally advanced cancer (T3-T4 primary or ≥N1 nodal staging), FDG PET-CT is preferred to evaluate distant disease and thoracic metastases 11, 9, 13
• If FDG PET-CT is not performed, CT of the chest should be performed to assess for presence of pulmonary metastases and mediastinal lymph node involvement 11
• Synchronous, second primary lesions – patients with a history of heavy alcohol or tobacco use are at increased risk of a synchronous, second primary malignancy 3, 13