Brett A. Miles, DDS, MD
Since the description of the radical neck dissection reported by Crile in 1906 there has been an enormous amount of literature regarding the neck dissection for head and neck squamous cell carcinoma.1 Over the last 100 years, the continued evolution of the neck dissection has resulted in less aggressive operations with preservation of non-lymphatic structures, such as the spinal accessory nerve and internal jugular vein, which lead to the development of the modified radical neck dissection.2, 3 Ultimately as metastatic patterns were described and the outcomes following neck dissection were evaluated, selective neck dissection was introduced.4, 5 This allowed surgeons to tailor surgical therapy to the cervical node levels at greatest risk for metastatic disease, thereby sparing the patient from unnecessarily aggressive surgery. Further work continues to define the role of neck dissection and alternative techniques such as sentinel node biopsy are currently being evaluated for oral cavity squamous cell carcinoma.
As noted previously, the presence of metastatic cervical lymph nodes is the most important factor in outcomes with head and neck squamous cell carcinoma. Therefore the treatment of the neck is critical in patients with advanced stage oral cavity malignancy. Current imaging modalities offer approximately 70-80% accuracy for the detection of cervical metastatic disease and it has been observed that neck dissection offers substantially more accurate information for staging, treatment planning and surveillance.6-8
Historical Background Despite continued debate in the literature regarding the appropriate therapy for the NO neck it is generally accepted that routine surgical dissection of the N neck is required for advanced stage oral cavity SCC.9, 10 11, 12 13 This recommendation is in light of the fact that oral cavity SCC has an extremely high rate (60-80%) of clinically evident and occult cervical lymph node metastasis to levels I-III, with a moderate risk of level IV involvement.14-19
Traditionally, surgical management of the ipsilateral neck in advanced oral cavity SCC consists of the modified radical neck dissection including levels I,II,III and IV with preservation of the spinal accessory nerve, internal jugular vein and sternocleidomastoid muscle.14, 20, 21 T3 or T4 lesions, lesions located in the floor of mouth, or lesions approaching the midline require bilateral modified radical neck dissection due to the risk of contralateral lymph node metastasis.14, 20-23 The risk of level V cervical lymph node metastasis in oral cavity SCC is extremely low and therefore the utility of level V dissection may is questionable for many these lesions.24-26 It should also be noted that the utility of dissection in the submuscular recess (level IIb), namely the cervical nodes superior to the spinal accessory nerve, has also been questioned for oral cavity SCC as the risk of metastatic disease to this area is extremely low in the clinically negative neck. Involvement of this compartment is increased if there is N2 cervical disease however and in this case dissection of level IIb should routinely be performed.2, 27
Recently, many investigators have reported employing a selective neck dissection, including levels I,II, and III, with similar results in terms of locoregional control and overall survival20, 21, 28-30. Despite the interest in selective neck dissection, many investigators recommend more aggressive cervical lymphadenectomy with advanced stage disease.3, 14, 16, 20, 23, 26, 31-40 Further work in this area may reveal more clear indications for the type of neck dissection but at the current time the selective neck dissection (Levels I-III) is the minimum surgical therapy for advanced primary lesions, with most authors recommending modified radical neck dissection (I-IV) the operation of choice for advanced stage oral cavity SCC. Additional adjunctive radiotherapy is warranted for increased regional control of disease in the presence of cervical metastasis.21, 41
Anatomy of the Cervical Lymphatics Rouviere is credited with the classic anatomic description of the lymphatic drainage of the head and neck. His description is exhaustive and has been further elaborated by others.42, 43 The lymphatic vascular system arises from endothelial buds which coalesce to form the lymphatic vessels. These vessels act to return interstitial fluids, plasma, and cells to the blood stream. Interstitial pressure and lymphatic vessel contraction allow for the flow of the lymph and cell migration. In the classic model, lymph flows from the capillaries through afferent vessels and into the marginal sinus in the cortex of the first echelon lymph node. The lymph flows via hilar efferent channels into the lymphatic trunks, joining lymph from neighboring nodal basins. These lymphatic trunks then drain into three terminal collecting ducts: the thoracic, subclavian, and right lymphatic ducts. Lymph is then returned to the venous system at the junctions of the internal jugular and subclavian veins. It should be noted that the flow of lymph does not always follow this classic pattern and lymph flow may completely bypass any intercurrent lymph node via pericapsular channels that have been demonstrated to connect the afferent and efferent lymphatics. Processes such as tumor cell infiltration, reactive hyperplasia, and post surgical or radiation sequelae may increase the hydrostatic pressure in the intervening lymph node will increase the flow through the path of least resistance, notably the aforementioned pericapsular channels. This explains the clinically observed fact that lymphatic drainage does not always follow the classic pattern and may be somewhat unpredictable when dealing with cervical metastasis.
In general however, the classic model holds true for lymphatic drainage of the cervical region.42, 43 Therefore for the sake of clinical utility the cervical lymph nodes (roughly 300 lymph nodes, 150 per side) are generally broken down into groups or levels.This system of lymph node levels was originally proposed by the Head and Neck Service at Memorial Sloan-Kettering Cancer Center and is classified as follows: submental and submandibular (level I), upper jugular (level II), middle jugular(level III), lower jugular (level IV), spinal accessory and transverse cervical nerve (posterior triangle) (level V), and anterior compartment (level VI) lymph nodes. There are several other clinically important lymph node groups, which are not included in this system, such as the facial nodes(mandibular, buccinator, infraorbital, malar, and retrozygomatic), the retropharyngeal nodes of Rouviere, the tracheoesophageal and paratracheal nodes, the periparotid and intraparotid nodes, the postauricular node, the superficial occipital node, and the upper mediastinal lymph nodes.44 45
Level I Lymph Nodes Level I includes the contents of the submandibular and submental spaces. The submandibular space is bound anteriorly by the anterior belly of the digastric muscle, posteriorly by the posterior belly of the digastric muscle, laterally by the mandible, and superiorly by the mylohyoid and hyoglossus muscles.
45, 46 These nodes are generally located around the submandibular gland, surrounding fibrofatty tissue and perivascular to the facial vessels. Additionally, intracapsular or intraglandular nodes are located within the parenchyma of the submandibular gland. The submental lymph nodes receive their efferent lymphatics from the skin of the chin, the midlower lip, the tip of the tongue, and much of the mucosa of the anterior floor of mouth. Also of note are the mandibular periosteal lymphatics which drain to the submandibular or upper deep cervical nodes.
Level II Lymph Nodes Level II contains the upper jugular lymph nodes located around the upper one third of the internal jugular vein and adjacent spinal accessory nerve and is bound anteriorly by the lateral border of the sternohyoid muscle, posteriorly by the posterior border of the sternocleidomastoid muscle, and superiorly by the skull base. The inferior border is defined surgically by the carotid bifurcation and radiographically by the hyoid bone. There are several nodes within Level II however the highest node lying in contact with the posterior belly of the digastric-referred to as the jugulodigastric node (principle node of Kuttner). The level II group receives efferent lymphatics from the facial, pre- and postauricular parotid, and submandibular, submental, and retropharyngeal nodal groups. Level II also directly receives the collecting lymphatics from the nasal cavity, pharynx, larynx, external auditory canal, middle ear, tongue, hard and soft palate, tonsils, and sublingual and submandibular glands.
Level III Lymph Nodes Level III contains the middle jugular lymph nodes located around the middle one third of the internal jugular vein. Level III is bound anteriorly by the lateral border of the sternohyoid muscle, posteriorly by the posterior border of the sternocleidomastoid muscle, and superiorly by the inferior border of level II (carotid bifurcation or hyoid bone). The inferior border is defined surgically by the junction of the omohyoid muscle and the internal jugular vein (radiographically by the cricoid cartilage).
These nodes are described as deep to the sternocleidomastoid muscle posterior to the internal jugular vein. These nodes lie superior, and deep to the spinal accessory nerve below the posterior belly of the digastric muscle and before it enters the sternocleidomastoid muscle. Level III contains a highly variable number of nodes and receives efferent lymphatics from level II and level V, some efferent lymphatics from the retropharyngeal, pretracheal, and recurrent laryngeal nodes and collecting lymphatics from the tongue base, tonsil, larynx, hypopharynx, and thyroid gland. 47
Level IV Lymph Nodes Level IV contains the lower jugular lymph nodes located around the lower one third of the internal jugular vein. It is bound anteriorly by the posterior border of the sternohyoid muscle, posteriorly by the posterior border of the sternocleidomastoid muscle, superiorly by the inferior border of level III (omohyoid-IJV junction or cricoid cartilage), and inferiorly by the clavicle. Level IV contains a variable number of nodes and receives efferent lymphatic drainage from level III and level V, as well as from the retropharyngeal, pretracheal, and recurrent laryngeal nodes and collecting lymphatics from the hypopharynx, larynx, and thyroid gland.
Level V Lymph Nodes Level V contains all the lymph nodes in the posterior triangle of the neck. It is bound anteriorly by the posterior border of the sternocleidomastoid muscle, posteriorly by the anterior border of the trapezius muscle, superiorly by the mastoid process and inferiorly by the clavicle. Level V receives efferent lymphatics from the occipital and postauricular nodes as well as collectively lymphatics from the occipital and parietal scalp, the skin of the lateral and posterior neck and shoulder, tonsils, tongue base, and nasopharynx.
Level VI Lymph Nodes Level VI, which is also referred to as the anterior compartment nodal basin, contains the lymph nodes in the visceral space and receives efferent lymphatics from the thyroid gland, larynx, hypopharynx (notably the subglottis), and cervical esophagus. It is bound laterally by the medial borders of the carotid sheaths, superiorly by the hyoid bone, and inferiorly by the suprasternal notch.
Diagnostic considerations of the N0 Neck
The current American Joint Committee on Cancer head and neck cancer staging system, is a clinical tumor-node-metastasis (TNM) staging system. The TNM system is based on clinical examination of the primary lesion and the status of the regional lymph nodes.48 It is generally augmented by computed tomographhy (CT) or magnetic resonance imaging (MRI), and confirmed by biopsy.44, 48 The traditional classification of the N0 neck is the clinical absence of cervical metastatis when palpating the neck. Although the appropriate treatment of the N0 neck is controversial within the literature, it should be noted that there exists significant disparity among authors when establishing criteria for defining the N0 neck as well. Additional controversy regarding appropriate diagnostic imaging exists and recent advances in imaging technology have added fuel to this controversy. The diagnostic evaluation of the patient with head and neck malignancy continues to evolve and it is likely that there will be significant changes in the future regarding the definition of the N0 neck.
Clinical Examination
As stated above, the traditional definition of the N0 neck was based on clinical examination. The utility of this system both in clinical practice and for investigational research has been questioned due to the fact that clinical evaluation is notoriously inaccurate and may be inaccurate in as many as 60% of cases.4, 49-51Therefore the employment of imaging technology is currently utilized when evaluating the cervical lymphatics of patients with head and neck malignancy.
Imaging Studies Computerized Tomography
As noted previously, CT and MRI improve clinical staging and are routinely used in many centers involved in the treatment of head and neck malignancy. CT and MRI are valuable adjuncts to clinical examination when evaluating inaccessible sites such as retropharyngeal, deep cervical, and upper mediastinal nodes or evaluating positive nodes for extracapsular extension. Malignancy criteria for CT (and MRI) have been defined by a number of authors and continue to evolve as newer-generation imaging technology emerges.6, 9, 51-58 Current malignancy criteria include:
- Nodes >15 mm for Level II and >10 mm for nodes located in Levels III-VI
- Three or more borderline nodes (1 to 2 mm smaller)
- Evidence of central necrosis
- Loss of tissue planes (fat planes).
- Loss of ovoid nodal shape with a more rounded appearance
Of the criteria listed above, size is the least reliable criteria and tumor necrosis is generally accepted as the most reliable criteria. Size criteria are notoriously inaccurate for detecting occult metastasis in the level I group and >80% of lymph nodes smaller than 10 mm may harbor metastatic carcinoma depending on the primary lesion. Unfortunately approximately 40-70% of malignant cervical lymph nodes will be missed by CT, confirmed by histologic evaluation of whole neck specimens. 6, 9, 51-58
While limitations exist, computed tomography remains the imaging modality of choice when evaluating the neck for cervical metastatic disease in the patient with HNSCC. In the absence of palpable adenopathy, obesity, or previously radiated neck CT scanning is useful to assess the status of the cervical lymph nodes. When a large node is palpable in the neck CT scanning is useful to clarify its relationship to the anatomic structures of the neck such as the carotid artery, internal jugular vein, paraspinal muscles and the cervical spine. Cervical CT findings may alter the staging of head and neck squamous cell carcinoma in nearly 30% of patients who have a clinically N0 neck.56CT scanning allows for relatively accurate staging for advanced nodal disease (area 45mm2) with accuracy approaching 80% with histologic confirmation.9 However, as noted previously, CT does not possess the accuracy to evaluate nodal metastatic disease at the histologic level and it is generally accepted that the accuracy of CT in staging for cervical metastasis ranges from 60-80%6, 59, 60.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) has been utilized in the evaluation of head and neck malignancy and it is accepted that MRI offers superior soft tissue resolution when compared to computerized tomography. Increased diagnostic accuracy in extension of soft tissue primary lesion as well as improved accuracy for cervical lymph node staging has prompted some authors to recommend routine MRI scanning for head and neck malignancy.6, 61, 62MRI offers an excellent imaging modality, with accuracy superior to conventional CT scanning, when evaluation of the extent of invasion of the primary tumor is required. It has been shown that Gadolinium DTPA enhanced accurately depict central lymph node necrosis which is the most specific criterion for lymph node metastasis. 63 Despite this increased accuracy, as in the case of CT, MRI offers insufficient accuracy to detect micrometastatic disease. Additionally, MRI may be overly sensitive to detect recurrent SCC as its superior resolution often leads to erroneous investigations of abnormalities located within the post therapy tissues.62
Ultrasound / Ultrasound Fine Needle Aspiration
While ultrasound (US) has been proposed and evaluated as an imaging modality for the detection of metastatic cervical lymphadenopathy there is little debate that US is inadequate for this purpose due to lack of accuracy. The overall accuracy of ultrasound examinations in the detection of cervical metastasis rarely exceeds 70-80%. Therefore, US alone does not adequately evaluate the neck for cervical metastatic disease. 6, 53, 64
Ultrasound guided fine needle aspiration with cytology (US-FNA) has shown promise however and continues to be investigated for the detection of metastatic disease. Accuracy of this technique has been reported to be approximately 80-90% and may offer an appropriate evaluation of the clinically N0 neck superior to CT and MRI. 6, 53, 54, 64-66 In addition, US-FNA enables early detection of cervical metastatic disease when observation of the N0 neck is planned.50, 54. The use of US-FNA in the detection of metastatic cervical disease may be revolutionized by newer molecular techniques which increase the accuracy, reported at 97-100%.6 The clinical utility of these techniques remains to be investigated.
Positron Emission Tomography
Positron emission tomography (PET) is perhaps the most dynamic field of imaging currently applied to head and neck oncology. PET is a functional imaging technique which utilizes a radio-labeled tracer, most commonly 18-FDG (18-fluoro-2-deoxyglucose) which is utilized by metabolically active cells, as is the case with active malignancy. Radiolabelled tracer is transported across the cellular membrane of metabolically active cells. Once inside the cell, tyrosine kinase phosphorylates 18-FDG which does not allow this molecule to be further metabolized or to be transported back through the cell membrane. The radioactivity of 18-FDG collides with gamma rays in an annihilation reaction which produces positrons. This form of radioactivity is detected by the PET scanner.6 PET scanning has been shown to increase accuracy (true positives) for the detection of head and neck malignancy and is currently utilized in the detection of unknown primary tumors, post-therapy tumor surveillance, and evaluation for cervical/distant metastatic disease.10, 59, 60, 67-69 PET has also been utilized to determine which patients require elective neck dissection after primary radiotherapy for head and neck malignancy.70
While the gold standard of panendoscopy with directed biopsies remains, an emerging role of PET in the evaluation of HNSCC is the detection of the unknown primary lesion. Additionally PET offers promise for the detection of metastatic and recurrent disease. With a known primary lesion in the advanced stage, PET offers little advantage over CT/MRI in the evaluation of the primary tumor or cervical region. PET offers inferior resolution for evaluating the extent of the primary lesion and should be combined with CT to improve diagnostic accuracy. Small primaries or primaries in areas demonstrating physiologically increased FDG uptake may be missed with PET, with current technology offering a resolution of approximately 5mm.69While PET offers significant promise in the evaluation of the N0 neck in early stage disease, in patients with advanced primary lesions the status of the neck is only of prognostic significance. These patients generally benefit from formal therapy of the neck, either radiation or surgery. Furthermore, the literature regarding PET has shown shortcomings similar to CT/MRI for the detection of micrometastatic disease. Therefore, because of the sensitivity limitations of PET, in patients with advanced stage HNSCC most authors recommend a more aggressive evaluation of the neck including staging neck dissection and/or possibly (see section below), sentinel node biopsy.57, 67, 69, 71-74 Recent reports indicate that multimodality imaging combining PET with high-end CT scanning increases the diagnostic accuracy. The clinical value of PET-CT in initial staging of neck lymph nodes has shown some promise however the accuracy of the technique remains in question.70, 74, 75
Lymphoscintigraphy/Sentinel Node Biospy
Recently, much interest and research has been reported regarding sentinel node biopsy(SLB) for squamous cell carcinoma of the head and neck, especially of the oral cavity. While the interpretation of results is somewhat less straightforward when compared to cutaneous melanoma results, the technique has some promise for head and neck squamous cell carcinoma. The primary advantage of the sentinel node technique is the potential to decrease the number of neck dissections performed in clinically negative necks (N0), thus reducing the associated surgical morbidity in this group of patients. The technique has been shown to be feasible and relatively accurate for the N0 neck.68, 71, 76-78
A recent international conference on the subject of sentinel lymph node biopsy for mucosal head and neck cancer evaluated the literature and reported on the results of twenty institutions which performed SLB in over 370 patients with N0. The consensus panel reported an encouraging 96% negative predictive value for SLB in the clinically negative neck. Minimal requirements for the technique included the use of a radiotracer, lymphoscintigraphy, and a handheld gamma probe for lymphatic mapping. The use of hematoxylin and eosin staining with immunohistochemistry for cytokeratin was determined to be a mandatory component of this technique. Step-sectioning of the entire node at intervals of 150 micrometers was recommended as well.77 The consensus conference concluded that SNB for early stage (N0) oral and oropharyngeal cancer should be considered sufficiently validated although work continues to define the role of SNB in squamous cell carcinoma of the head and neck. 79
Several newer innovations such as newly designed contrast agents and the use of radiolabelled monoclonal antibodies for immunoimaging and US-FNA/SNB are currently being investigated for the detection of occult metastases 6, 57, 58
Rationale for Elective Neck Therapy
In light of current limitations regarding current diagnostic techniques in the detection of cervical metastasis, many authors recommend elective treatment of the neck when there is an increased risk of cervical metastasis determined by tumor subsite or stage.10 70, 74 This therapy may be surgical or non-surgical however surgical therapy has the benefit of staging the neck when treating the N0 neck. Pathologic data gained from neck dissection can alter decisions regarding additional treatment such as postoperative radiotherapy.80 In general, treatment of the primary tumor, whether with radiotherapy or surgery, determines the treatment planning of the N0 neck. If the primary tumor is to be treated with radiation alone, and indications exist for elective treatment of the neck, it is generally reasonable to irradiate the neck. If the primary tumor is excised surgically, and involves an approach through the neck, then an elective neck dissection is usually performed when indicated.
Nevertheless the rationale for elective treatment of the NO neck depends on several considerations which are outlined below.
Factors affecting risk of metastasis
The histopathological evaluation of tissue is invaluable in the treatment planning of head and neck malignancy. Histopathological grading may influence treatment decision making when deciding on appropriate elective therapy of the neck. Despite the fact that poorly differentiated squamous cell carcinomas are predictably worse in terms of prognosis when compared to well differentiated counterparts, there are several distinctive histopathological findings that deserve attention. Cellular histopathologic grading features such as nuclear atypia, mitosis, etc. have been implicated in higher rates of cervical metastasis in several reports. Perineural invasion has been associated with poorer outcomes as well. 81-83 Numerous molecular markers involved in tumor invasion, angiogenesis, and metastasis are currently being investigated with the goal of eventual identification of patients with a high risk of cervical metastasis. 24, 82, 84, 85 A discussion of the molecular biology related to cervical metastasis is beyond the scope of this article.
The affect of tumor thickness related to prognosis has been examined by multiple investigators. In general, increased tumor size and thickness is significantly predictive of decreased survival and increases the rate of locoregional recurrence.86-88Several authors feel that patients with tumor diameter greater than 1.5cm or greater than 5mm of tumor thickness may then be considered for more aggressive adjuvant therapy and elective neck dissection regardless of stage due to increased risk for cervical lymph node metastasis.84, 88-92 Although tumor thickness reliably predicts regional nodal metastasis and decreased survival, specific treatment strategies based on tumor thickness have yet to be evaluated due to the wide range of factors related to prognosis among patients with oral cavity SCC.84, 91, 93
Primary Tumor Location
The location of the primary tumor subsite is of critical importance regarding the elective therapy of the N0 neck. The risk of cervical metastasis varies depending on the location of the primary tumor and therefore affects treatment planning. As a rule of thumb most authors advocate electively treating the neck if the risk of occult metastatic disease is greater than 15-20%. In the sections below specific primary tumor subsites will be discussed regarding the risk of occult cervical metastatic disease and the necessity of elective neck therapy.
Oral cavity
The anatomic boundaries of the oral cavity are vermilion border of the lips extending posteriorly to the junction of the hard and soft palates superiorly and the circumvallate papillae inferiorly. Clinically, this includes the anterior two thirds of the tongue, floor of mouth, maxillary and mandibular alveolar ridges, retromolar trigone, buccal mucosa, hard palate, and upper and lower lips. Interestingly, in 1980 Van den Brekel et al, addressed the issue of elective neck dissection in a prospective, randomized trial of 75 patients with T1-T3 oral tongue and floor of mouth lesions. Although a trend for neck failure was indicated the study design prohibits meaningful conclusions due to the fact that the primary site therapy was interstitial iridium-192 and the overall survival was equivalent.94 In 1994 Kligerman et al, conducted a randomized prospective study of 67 patients with previously untreated T1-T2 squamous cell carcinomas of the oral cavity, limited to oral tongue and floor of mouth. The patients were stratified to receive resection alone or resection plus elective supraomohyoid neck dissection. Nodal recurrence rates were significantly higher (35%) when neck dissection was not performed compared to 13% in the supraomohyoid neck dissection group. In addition, tumor thickness of greater than 4 mm, when treated with resection and neck dissection, had a significant benefit on disease-free survival (P = 0.05). 95
Several investigations have shown that for oral cavity squamous cell carcinoma the risk of occult cervical metastatic disease is high with the exception of very early or superficial lesions of the oral cavity, on the order of 25-50% depending on stage. Given the high rates of occult cervical metastatic disease and poor salvage rates, observation of the N0 neck with oral cavity primary is ill advised.4, 95-97 Therefore elective radiotherapy or the appropriate neck dissection is recommended when treating patients with oral cavity SCCA depending on the institution and the patients desires. Most authors agree that surgery and radiotherapy offer equal rates of local control with primary T1-2 oral cavity carcinomas. While complications of surgery are well known and often sited, it should be kept in mind that up to 40% of patients treated with irradiation suffer a complication that involves bone. Nevertheless, radiotherapy may offer superior functional results for deeply infiltrating tongue lesions and therefore may be appropriate for the elective neck therapy. 4, 95-98 Bilateral elective neck therapy should be provided for patients with anterior or midline/near midline lesions due to the propensity of oral cavity primary lesions to exhibit lymphatic crossover. 97In the event multiple nodal metastases are discovered or extracapsular invasion is present, postoperative radiation decreases recurrence rates, and should be administered. 96, 98
Oral tongue
Primary oral tongue lesions may have a different biologic behavior and may exhibit more frequent level II/III/IV cervical metastasis with rates as high as 60% depending on stage.90, 99, 100 For anterior primary tongue squamous cell carcinomas 5mm thick or posterior lesions, elective neck therapy is recommended due to high rates of cervical failure when the neck is observed.89, 101, 102 Most authors recommend an extended (including level II-IV) selective neck dissection is the most appropriate type of neck dissection when surgical therapy of the neck is selected for oral tongue primary tumors.5, 40, 47, 80, 96, 102-104It should be noted that occult metastasis to the level V nodes is extremely rare, even with clinically obvious cervical metastases in other levels.4, 5, 40, 80, 96, 99, 104
Oropharynx
The oropharynx is bound anteriorly by the junction of the hard and soft palate, the circumvallate papillae, and the anterior tonsillar pillars. The superior boundary is determined by a horizontal line through the soft palate to the posterior pharyngeal wall. The inferior boundary is the vallecula. The subsites include the base of tongue, the tonsils, soft palate, and posterior pharyngeal wall, although these tumors frequently involve more than one subsite. When including all stages, up to 75% of patients will have clinically positive cervical nodes at presentation. The risk for occult cervical metastasis from oropharyngeal primary tumors is from 21% to 45% and therefore elective therapy of the neck is warranted for all patients with oropharyngeal squamous cell carcinoma. In contrast to the oral cavity Level V is often involved and the posterior triangle is also at significant risk of cervical metastatic disease. There is also a high incidence of bilateral cervical occult metastasis due to the lymphatic drainage pattern of the oropharynx. Therefore most authors recommend bilateral elective neck therapy, whether surgery or radiotherapy when dealing with oropharyngeal SCCA.104, 105 Often radiotherapy or chemoradiotherapy is the preferred method of elective neck therapy as this will often be the preferred primary modality of therapy for squamous cell carcinoma of the oropharynx. It should be noted that Level I is somewhat less frequently involved (approx 10%) and therefore if the decision is made to treat the necks surgically, it may not be necessary to include Level I for oropharyngeal primary lesions.21, 29
Hypopharynx
The hypopharynx is bounded superiorly by the hyoid bone and inferiorly by the cricoid cartilage. Subsites included within the hypopharynx are the pyriform sinuses and the post-cricoid The hypopharynx is richly supplied with lymphatics with extensive efferent drainage leading to high rates of cervical metastasis. It should be noted that the size of the primary tumor is not often correlated with cervical metastasis in hypopharyngeal lesions. The most commonly involved cervical regions of lymph node metastasis are Levels II-IV although additional regions include the retropharyngeal, the paraesophageal, the paratracheal, and level VI nodes, although somewhat less frequently. The risk of cervical metastasis from hypopharyngeal lesions ranges from 20-60% and is frequently bilateral in up to 25% of cases.21, 29, 105-108 For this reason elective therapy of the neck (surgical or radiotherapy) is mandatory for hypopharyngeal squamous cell carcinoma. The retropharyngeal nodes are also commonly involved and should be routinely dissected. The issue of bilateral elective neck therapy has been evaluated by Johnson et al. who reviewed 169 patients with carcinoma of the hypopharynx and separated the patients into medial pyriform and lateral pyriform lesions. Patients with medial pyriform carcinomas and N0 necks treated with ipsilateral were found to have 14% failure rate in the contralateral neck compared to 5% failure in patients with LP carcinomas. Therefore it may not be necessary to treat bilateral cervical regions in all cases of hypopharyngeal malignancy.106
Supraglottis
The anatomic limits of the supraglottis extend from the vallecula to the apex of the laryngeal ventricle. Anatomic structures within the supraglottis include the epiglottis, aryepiglottic folds, arytenoids, false vocal cords, and the laryngeal ventricle to its apex. It has long been recognized that the risk of cervical metastatic disease is far greater in the supraglottic region when compared to the glottis. In fact the majority of failure after therapy for supraglottic squamous cell carcinoma is due to cervical lymph node metastasis rather than locoregional recurrence.109 The risk of occult cervical metastatic disease has been reported to range from 23.5-38.5% depending on stage.29, 110-112 113, 114 Therefore elective treatment of the neck is generally recommended for squamous cell carcinomas of the supraglottic region. Some authors have recommended closely observing the neck with early T1 lesions, especially of the epiglottis.113, 114 The advent of transoral laser resection of these lesions may allow for observation of the neck although cervical metastatic rates are still somewhat high (>15-20%)and close follow-up is mandatory. 115-117When considering the risk of cervical metastasis the supraglottis is considered a midline structure and the risk for contralateral cervical metastases is similar regardless of whether the lesion is in the midline or laterally located.29, 110-113
Glottis/Larynx
The anatomic boundaries which define the glottis are the apex of the laryngeal ventricle superiorly to approximately 5mm inferior to the margin of the true vocal cord. Patients with laryngeal squamous cell carcinoma present earlier than other anatomic subsites owing to early symptoms such as hoarseness and therapy for early laryngeal tumors is extremely effective. The incidence of cervical metastasis for these early lesions is extremely low and ranges from 2-10%.7, 21, 105, 118 Therefore clinical observation of the neck is the standard of care for these early stage lesions.
The management of patients with T3-T4 N0 laryngeal carcinomas is somewhat less clear. The reported rate of cervical metastatic disease in this group of patients is 16-18% which is at the threshold at which most surgeons would electively treat the neck. Therefore controversy exists regarding the appropriate therapy for these patients with some authors recommending observation, some recommending elective neck therapy, and some basing the decision on stage and histopathologic features. 118-124 For advanced stage disease however it has been pointed out that elective neck dissection offers excellent pathologic information to guide management and reduces cervical nodal recurrence which is associated with poor survival outcomes. Therefore for advanced T3 and T4 lesions, elective therapy of the neck should be considered.118, 121, 122 It should be noted that the risk of metastic disease to Level IIB and perhaps Level IV is extremely low and dissection in these regions is often unnecessary for glottic squamous cell carcinoma. 125
Subglottis
The subglottis is somewhat arbitrary and extends from the axial plane 5mm below the margin of the true vocal cord which defines the inferior aspect of the glottis, to the inferior border of the cricoid cartilage. This is an area of about 1.5cm below the glottis. Subglottic involvement with advanced stage glottic squamous cell carcinoma is a common finding but isolated subglottic squamous cell carcinoma is relatively rare . The subglottic region drains into Level IV, V and lateral paratracheal nodes, which are continuous with the upper mediastinal nodes Unfortunately there is little data regarding cervical lymph node metastasis in the setting of subglottic squamous cell carcinoma. The incidence of cervical lymph node metastasis has been reported to range from 10- %. Unfortunately there is insufficient data to make strong recommendations for the management of the N0 neck
Lederman reported a 10% incidence of positive cervical nodes in patients with subglottic carcinoma. Shaha and Shah reported no clinically positive nodes in 12 patients with T1-T2 lesions, but two of four patients with T4 lesions had positive nodes. They reported a 77% cure rate (at 5 years) with total laryngectomy.126 Ward et al. reported a 70% rate of local control and 61% cure rate with radiation alone.127 In the absence of good data on nodal recurrence and control, it is difficult to make recommendations on the treatment of the N0 neck in subglottic carcinoma.
Nasopharynx
The nasopharynx is defined by the base of the skull superiorly to the axial plane of the hard palate inferiorly. It has often been pointed out that patients with nasopharyngeal carcinoma generally present with a neck mass and therefore N0 status is rare. Also in contrast to other subsites within the head and neck, there is no significant difference in survival in patients with disease limited to the nasopharynx compared with patients with upper cervical metastasis.56, 56, 128, 128, 129 There is a significant decrease (approximately 50%) in survival in the presence of lower cervical metastasis as defined by the level of the thyroid notch. 56, 128
The standard treatment for nasopharyngeal carcinoma is radiotherapy which generally includes the upper echelon of cervical nodes. Elective therapy of the lower cervical nodes is generally unnecessary.56, 128
CONCLUSION
The management of the N0 neck continues to evolve with emerging imaging and metastatic detection techniques. A sound knowledge of the lymphatic drainage patterns within the head and neck coupled with an accurate assessment of the primary tumor as well as the utilization of current imaging technology with an understanding of its limitations, will allow appropriate therapy to be administered to patients afflicted with head and neck squamous cell carcinoma.
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