Overview of head and neck soft-tissue and bony tumors

History

Advanced age is not associated with increased surgical complications but, because the elderly population generally has more comorbidities and less physiological reserve, they are at higher risk of perioperative complications, namely cardiovascular and pulmonary events. Presenting symptoms generally reflect the site and depth of the involved tissues. It follows then that lip and oral cavity SCC present earlier with painful or bleeding non-healing ulcers. In other sites of the upper aerodigestive tract small volume disease is commonly occult, and presentation delayed until the disease is locoregionally advanced causing symptoms such as hemoptysis, dysphagia, odynophagia, ear pain (oropharynx), hoarseness (hypopharynx), or nasal obstruction and motor/sensory changes relating to cranial nerve involvement (nasopharynx). A painless neck lump may be the only presenting complaint with HPV-positive oropharyngeal and EBV-positive nasopharyngeal SCC ( Fig. 8.3 ). The latter should be suspected in any Southeast Asian patient presenting with a neck lump. A history of rapidly progressive symptoms suggests a more aggressive disease process which should be particularly concerning in the immunocompromised patient. Previous head and neck surgeries and radiotherapy complicate management and salvage surgeries are associated with increased surgical morbidity. The history should also screen for risk factors, aim to identify comorbidities, establish the patient’s nutritional and functional status as well as social circumstances, all of which will guide treatment options and planning besides having prognostic implications.

Physical examination

After the skin, the oral cavity is the most easily accessible area of the head and neck region to examine. With a headlight and tongue depressor each of the anatomical subsites of the oral cavity should be carefully inspected and any irregularity/tumor examined with particular attention paid to the appearance, site, size, depth and functional impairment. Palpation can reveal more about the extent of the tumor than inspection and is essential in the assessment of oral cavity SCC as depth of invasion (DOI) affects T classification. While inside the mouth dental assessment should be performed routinely, as tooth decay and periodontal disease are common in this patient demographic. Preoperative orthopantomogram (OPG) is complementary and should help guide decisions about prophylactic removal of teeth at the time of surgical ablation to avoid subsequent dental disease complicating treatment (e.g., osteoradionecrosis) ( Fig. 8.4 ). Systematic examination of the cranial nerves, parotid gland, and cervical lymph nodes follows. The latter is performed standing, and from behind the patient with their neck slightly flexed to relax the strap muscles, the purpose being to identify the site, size, number of any malignant cervical lymph nodes, and whether any underlying structures, such as accessory nerve, are involved. Compared with imaging studies clinical examination of the cervical lymph nodes is in general inferior but remains important to surgical planning. For suspect lymph nodes fine-needle aspiration cytology (FNAC) is the investigation of choice. It has been shown to be reliable, particularly if performed under ultrasound guidance, and accurate with a high sensitivity (89.6%) and specificity (96.5%). The examination of the head and neck region is not complete without fiberoptic endoscopy to inspect the nasal cavity, pharynx, base of tongue and larynx for synchronous tumors. Specific manoeuvres to improve visualisation include asking the patient to exhale against a closed mouth causing the cheeks to blow outwards (piriform fossa) and say ‘eee’ (vocal cord symmetry and mobility). Finally, the cardiovascular, respiratory and gastrointestinal systems are examined to screen patients for distant metastases and medical issues which might affect their fitness for surgery. Head and neck cancer patients are often cachectic owing to a combination of disease-related impairments of mastication and swallowing as well as poor lifestyle choices (i.e., smoking, alcohol, and an inadequate diet). Malnutrition compromises wound healing and predisposes to infection so formal nutritional assessment should be considered along with preoperative supplementation if it is identified. Patients who might be expected to have a delayed return to swallowing post-treatment, such as following laryngectomy, may require a percutaneous enteral gastrostomy (PEG). In patients at risk of upper airway obstruction or aspiration, particularly if they have poor pulmonary reserve preoperatively, a tracheostomy should be planned.

Radiological examination

Imaging is central to the staging and planning of treatment of head and neck cancer. Physical examination combined with contrast-enhanced computed tomography (CT) of the head, neck, and chest is sufficient in most instances for diagnostic and staging purposes. The superior soft tissue resolution available with magnetic resonance imaging (MRI) is desirable for further delineating disease extent in the parotid, oropharynx, larynx, and base of skull, as well as identifying perineural invasion and dural involvement. However, it is generally a less available resource, and with long scanning times making it susceptible to motion artefact, may be less effective in head and neck cancer patients who have breathing and swallowing issues when lying supine. In contrast, despite concerns about radiation exposure and its susceptibility to metallic artefact (e.g., dental fillings and metal implants), CT is fast, easily obtained, and provides superior evidence of bone (and cartilage) invasion with adequate soft-tissue definition (with 2 mm slices) in most circumstances. It is also a reliable and accurate tool for diagnosing cervical lymph node metastases, based on size (>10 mm in minimum axial dimension) and appearance (central necrosis) criteria, as well as the presence of extracapsular spread. Furthermore, when integrated with the physiological data obtained with positron-emitting tomography (PET), PET/CT provides a superior tool than either CT or MRI to identify cervical or distant metastases, with a meta-analysis showing 91% sensitivity and 87% specificity for synchronous primaries and unknown primaries ( Fig. 8.5 ). False-negatives with PET/CT can occur with superficial mucosal lesions (making panendoscopy critical), occult cervical metastases <5 mm (therefore it does not replace neck dissection when indicated), and unknown primaries near the pharyngeal lymphoid tissues with high background physiologic activity. As already mentioned, OPG completes the radiological work-up.

Endoscopy

Examination under anesthesia (EUA), using a rigid endoscope, may be necessary in the workup of a head and neck cancer patient as it provides the surgeon with the opportunity to carefully assess tumors not detectable on physical examination and make a surgical plan whilst affording the opportunity to obtain a tissue biopsy for histologic diagnosis (see Fig. 8.5 ). Routine panendoscopy (laryngoscopy, bronchoscopy, esophagoscopy, or “triple endoscopy”) used to be performed for all head and neck cancer to exclude synchronous tumors, however this remains controversial. Those opposed to it argue it is resource-intensive and unnecessary with advanced imaging techniques guided by patient symptoms being equally effective. Instead, they suggest panendoscopy only in high-risk patients (i.e., heavy smoker or drinker) with tumors strongly associated with synchronous tumors (i.e., oropharynx), or suspicious lesions identified on imaging. For unknown primary tumors, panendoscopy remains an essential component of the workup as sites at high risk of occult disease (i.e., nasopharynx, tonsil, tongue base, piriform fossa) need to be closely inspected for subtle lesions, and blind biopsies performed. More than 90% of tumors of unknown primary are HPV- or EBV-positive oropharyngeal or nasopharyngeal tumors.

Biopsy and histology

Histological confirmation of the diagnosis is essential prior to the commencement of any cancer treatment. A representative sample(s) of tumor must be obtained to enable the pathologist to provide not only a diagnosis but also any additional information needed to accurately stage the tumor, including depth of invasion (DOI), perineural invasion, lymphovascular invasion and p16 status. Practical tips for achieving this include using a 3–4 mm punch biopsy and avoiding the center of the tumor which may be necrotic, and the peripheries which may show dysplasia only. All imaging should be acquired prior to biopsy as the associated edema may inaccurately upstage the tumor.

Histologically , HPV-negative SCC tends to be moderately-to-well differentiated resembling the normal stratified epithelium of the aerodigestive tract with mature cells with occasional keratinization irregularities (“keratin pearls”) while HPV-positive SCC tend to be poorly differentiated. H&E is usually adequate, however IHC using pancytokeratin antibodies (e.g., cytokeratin 5, 6, p63) may be required. Testing of HPV status is indicated for all oropharyngeal tumors, or those with an unknown primary. Most commonly this is done with IHC stain for the cell cycle protein p16INK4A, other techniques include the detection of E6 and E7 mRNA and HPV DNA.

Staging

Head and neck cancers are commonly staged using the tumor, node, metastases (TNM) staging system, developed in 2002 by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC), which serves to standardize the assessment of tumor burden, prognostication, and management. Clinical information gathered from the physical examination, radiology, pathology, and intraoperative findings is used to establish a patient’s TNM classification which then translates into early , Stage I–II, or advanced , Stage III–IV, disease ( Table 8.1 ). Almost universally, nodal or distant metastases are associated with advanced disease with the exception of nasopharyngeal and thyroid tumors and HPV-positive oropharyngeal SCC, which have their relatively better prognoses reflected by downstaging under AJCC 8th edition. A notable shortcoming of the TNM staging system is that it does not distinguish between a locally advanced primary tumor without metastases and a small primary tumor with metastases, both of which may have very different prognoses. Finally, pathological staging, unlike clinical staging, is only achievable after surgical ablation.

T– relates to the site, size, depth of the primary tumor, and involvement of surrounding structures with the definition for T1–4 varying according to the anatomical subsite of the tumor; N– relates to the site, size, number, and extent of cervical node involvement; and M– relates to the presence or otherwise of distant metastases; Tx indicates the tumor cannot be assessed; T0 indicates no known primary tumor; Tis refers to in situ carcinoma.

Key updates to the head and neck section in the 8th edition AJCC Staging Manual included the addition of DOI to the T status of oral cavity SCC, a separate section for HPV-positive oropharyngeal SCC to better reflect its improved prognosis, changes to the T and N status of nasopharyngeal SCC, and the addition of extranodal extension to the N status.

The oral cavity

Anatomically, the boundaries of the oral cavity extend anterior to posterior from the lip vermilion to the hard–soft palate junction above, the line of circumvallate papillae below, and the anterior tonsillar pillars and glossotonsillar folds laterally. For prognostication purposes the oral cavity is further subdivided into seven subsites under AJCC staging – lip, floor of mouth (FOM), oral tongue, buccal space, hard palate, gingiva, and retromolar trigone (see Fig. 8.1 ). Critical functions of these oral cavity structures include oral continence, speech, mastication, deglutination, and oral hygiene.

The most common cancer of the oral cavity is SCC (>90%), less commonly salivary gland tumors and sarcoma are encountered. The lower lip followed by the lateral oral tongue are the most common subsites involved, while the lip (88%) and FOM (54%) are associated with the best and worst overall prognoses, respectively. Uniquely, buccal SCC is the most common subsite of oral cavity SCC in Southeast Asia owing to widespread Areca nut chewing but rare in Western populations. Although oral cavity SCC is relatively more likely to present early than other head and neck cancers, presentation is still more commonly with locally invasive T3–4 disease (involving buccinator, parotid duct, VII, cheek skin, mandibular ramus, pterygoids, maxillary alveolus) or lymphatic metastasis (40%).

Staging is the most important determinant of prognosis, with overall 5-year survival dependent on the presence of small volume, localized disease (84%), lymph node metastasis (65%), and distant metastasis (39%). (Refer to T-staging of oral cavity SCC per AJCC Staging Manual, 8th edition).

Surgery is the preferred primary treatment modality for tumors of the lip and oral cavity as it provides comparable oncological outcomes with the least morbidity compared to the alternatives ( Figs 8.6 & 8.7 and Algorithm 8.1 ). For early stage (I–II) disease, primary radiotherapy may provide equivalent oncological outcomes but is generally reserved for those unfit for surgery due to the risk of early and late toxicities (e.g., mucositis, xerostoma radionecrosis). More commonly, radiotherapy is used adjunctly in instances where either the primary tumor (T3–4, perineural invasion, lymphovascular invasion) or neck disease (>N1) is considered at risk of locoregional failure. For those at particularly high risk of locoregional failure (i.e., incomplete/close [<5 mm] resection margins or ENE) adjuvant chemoradiation is recommended, provided the patient is fit enough to tolerate the increased toxicity of combined therapy.

Algorithm 8.1

Management of lip defects.

Unlike the oropharynx, hypopharynx, and larynx, “organ preserving” treatment for oral cavity SCC with primary chemoradiation has been shown to be inferior in terms of overall survival and morbidity compared to surgery. Whether novel treatment regimens using neoadjuvant chemotherapy, or immunotherapy, prior to surgical resection can be used to reduce morbidity without compromising oncological outcomes are currently under investigation.

While historically debated, today elective neck dissection for the clinically N0 (cN0) oral cavity SCC is supported by level 1 evidence, demonstrating improved pathological staging of disease and a 12.5% improvement in overall survival compared to observation at 3 years follow-up. Subgroup analysis showed that this benefit was restricted to primary tumors with DOI >3 mm. T1 tumors may therefore be alternatively kept under close observation, which puts the emphasis on the quality of preoperative assessment and in particular the clinical examination (to distinguish between exophytic, ulcerative, infiltrative lesions) and baseline radiology of the cervical nodal field. American Society of Clinical Oncology (ASCO) guidelines suggest that an adequate elective neck dissection should include ipsilateral levels I–III, including at least 18 lymph nodes, and should be bilateral if the lesion is midline or a T3/4 oral tongue or FOM SCC. The perifacial lymph nodes should be carefully included in the 1b dissection as their involvement is estimated to be between 7% and 35% in oral cavity primaries. Notably, D’Cruz et al . documented 6.5% adverse events complicating elective neck dissection. Whether SLNB can offer a less morbid alternative in cN0 disease awaits the results of randomized control trials.

Surgical technique and considerations

Technically, resection of oral cancers can be challenging. Because the resection is performed with restricted vision through limited access, in three planes and in an anatomically dense and complex region, there can be a delicate balance between acquiring inadequate margins and causing additional morbidity through unnecessarily wide surgical margins. Practically a 1 cm clinical margin is planned with the aim being to avoid a close (<5 mm) pathological margin. A partial glossectomy is illustrative. There are limited planes within the substance of the muscular tongue to use as anatomical guides, with the exception of the midline raphe which facilitates a compartmented hemiglossectomy resection. As a result, the resection technique involves marking a 1 cm margin around the tumor with loupe magnification and optimal lighting, a fine-tip diathermy is then used on the outer side of a palpating fingertip which always remains in contact with the margins of the cancer ( Fig. 8.8 ). Most oral cavity cancers can be accessed transorally. More invasive incisions such as lower and upper (Weber–Ferguson) lip-splitting incisions or degloving visor or facial maneuvers, which are associated with increasing morbidity, should be carefully considered, and adequately justified.

The FOM, gingival, and retromolar trigone SCCs are uncommon but SCCs of these subsites are aggressive. Uniquely in these locations the mucosa is thin and tightly adherent to the underlying periosteum which provides a limited barrier against bone invasion and T4 (stage IV) disease. From an oncologic perspective the periosteum is considered a barrier to invasion, but in the elderly and edentulous atrophic mandible this physiological barrier is impaired. Careful preoperative clinical assessment and imaging determines the extent of bony involvement and the resection required. Thin slice/high resolution CT can identify cortical erosion of the mandible with a sensitivity and specificity of 97–100% and 88%, respectively. In equivocal cases a complementary SPECT scan may be used to exclude bone involvement as it has a specificity of 100%. In general, SCC that is close to, but does not abut bone, may be removed with a 1–2 cm radial margin using the periosteum alone as the deep margin. For SCCs of the mandible that abut but do not invade the bone, or only superficially invade bone that is thick enough to permit a “scalloped” cortical resection leaving an intact mandible with a minimum height of 1 cm for stability, a marginal resection is permissible. This is contraindicated in a previously irradiated mandible which is prone to pathological fracture and osteoradionecrosis. Otherwise, a segmental resection is indicated. Planning for the resection should consider the potential local spread of disease into the adjacent masticator space from the retromolar trigone (to involve the pterygoid muscles, mandibular nerve [V3], soft palate musculature) or into the sublingual space from the FOM (to invade genioglossus, geniohyoid) ( Fig. 8.9 ). Extended access incisions are generally required when bone is resected. Composite resections including segments of maxilla or mandible create complex defects with connection between the oral cavity and the nose or neck. Bone and alveolar defects limit the restoration of speech, swallow, and dental rehabilitation (i.e., prosthesis, implants) as well as disrupting the height and width of the middle and lower thirds of the face. Such defects are best reconstructed with free tissue transfer.