Lymphatics of the Head and Neck

The lymphatic network of the head and neck area is located in two layers separated by the deep cervical fascia. The superficial lymphatics drain into suboccipital, preauricular and postauricular, prevascular facial, and external jugular lymph nodes. These lymph nodes eventually drain into the deep jugular lymph nodes. The major lymph node groups of the head and neck region are shown in Fig. 11.3 . The preauricular, periparotid, and intraparotid lymph nodes are the first-echelon lymph nodes for the anterior half of the scalp, the skin of the forehead, and the upper part of the face. The postauricular and suboccipital groups of lymph nodes provide drainage from the posterior half of the scalp and the posterior aspect of the external ear. Deep cervical lymph nodes in the lateral aspect of the neck primarily drain from the mucosa of the upper aerodigestive tract. These lymph nodes include the submental, prevascular facial, and submandibular group located in the submental and submandibular triangles of the neck. Deep jugular lymph nodes include the jugulodigastric, juguloomohyoid, and supraclavicular group of lymph nodes adjacent to the internal jugular vein. Lymph nodes in the posterior triangle of the neck include the accessory chain located along the spinal accessory nerve and the transverse cervical chain in the floor of the posterior triangle of the neck. Lymphatics of the pharynx also drain into the parapharyngeal and retropharyngeal lymph nodes.

The regional lymph nodes of the head and neck region.

(Courtesy Memorial Sloan Kettering Cancer Center.)

The central compartment of the neck includes the Delphian lymph node overlying the thyroid cartilage in the midline, which drains from the larynx and thyroid gland, and the perithyroid lymph nodes, as well as the pretracheal, paratracheal, and paraesophageal lymph nodes. Lymphatics of the thyroid gland, hypopharynx, subglottic larynx, and cervical esophagus drain into the paratracheal lymph nodes. Lymph nodes in the anterosuperior mediastinum provide drainage from the thyroid gland and the cervical esophagus and serve as a secondary lymphatic basin for central compartment viscera. Each previously described anatomic subgroup of lymph nodes serve as primary-echelon lymph nodes that drain from a specific site in the head and neck region. Thus the location of a palpable metastatic lymph node often may indicate the potential site of a primary tumor ( Fig. 11.4 ).

The regional lymph node groups draining a specific primary site as first-echelon lymph nodes.

(Courtesy Memorial Sloan Kettering Cancer Center.)

The conventional description of regional nodes is based on the leveling system first proposed from the Head and Neck Service at Memorial Sloan Kettering Cancer Center in New York nearly a century ago ( Fig. 11.5 ). This system divides the lymph nodes in the lateral aspect of the neck into five nodal groups or levels. In addition, lymph nodes in the central compartment of the neck are assigned level VI, and those in the anterosuperior mediastinum are assigned level VII.

The Memorial Sloan Kettering Cancer Center system of assigning levels to cervical lymph nodes. A , The lateral side of the neck. B , The central compartment and superior mediastinum.

(Courtesy Memorial Sloan Kettering Cancer Center.)

The American Academy of Otolaryngology-Head and Neck Surgery has modified the above system by subdividing levels I, II, and V into A and B categories for each of these levels ( Fig. 11.6 ).

The American Academy of Otolaryngology-Head and Neck Surgery modification of the system of assigning levels for cervical lymph nodes.

(Courtesy Memorial Sloan Kettering Cancer Center.)

Patterns of Neck Metastasis

Dissemination of metastatic cancer to regional lymph nodes from primary sites in the upper aerodigestive tract occurs in a predictable and sequential fashion. Thus only a select group of lymph nodes are at risk of initial metastases from a given primary site. Understanding the sequential patterns of neck metastasis greatly facilitates surgical management of regional lymph nodes in the clinically negative neck (N0), but if the lymph nodes are at risk of harboring micrometastasis.

For primary tumors in the oral cavity, the regional lymph nodes at highest risk for early dissemination by metastatic cancer are limited to levels I, II, and III ( Fig. 11.7 ). Anatomically, this translates into regional lymph node groups contained within the supraomohyoid triangle of the neck bounded superiorly by the lower border of the mandible, posteriorly by the posterior border of the sternocleidomastoid muscle, and anteriorly by the superior belly of the omohyoid muscle, and which includes the submental triangle. The following lymph node groups are contained in the supraomohyoid triangle: submental, submandibular, prevascular facial, jugulodigastric, upper deep jugular, superior spinal accessory chain of lymph nodes, and midjugular lymph nodes. Skip metastasis to levels IV and V in the absence of metastatic disease at levels I, II, or III is exceedingly rare. Therefore if findings of the neck are clinically negative, level IV and V lymph nodes generally are not at risk of harboring micrometastasis from primary squamous cell carcinomas of the oral cavity. Primary carcinomas of the lateral border of the tongue has a somewhat higher risk of involvement of lymph nodes at level IV, particularly if there is already metastatic disease present at levels II or III.

The first-echelon lymph nodes at highest risk for early dissemination by metastatic cancer from primary tumors in the oral cavity.

For tumors of the lateral aspect of oropharynx, hypopharynx, and larynx, the first-echelon lymph nodes at highest risk of harboring micrometastasis in the clinically negative neck are the deep jugular lymph nodes at levels II, III, and IV on the ipsilateral side ( Fig. 11.8 ). Contiguous lymph nodes lateral to the internal jugular vein overlying the cutaneous roots of the cervical plexus usually are considered a component of levels II, III, and IV. In patients with primary carcinomas of the oropharynx, hypopharynx, and larynx who have clinically negative neck, the risk of micrometastasis to levels I and V is exceedingly small. Skip metastasis to levels I and V in the absence of disease at levels II, III, or IV usually is not seen. Primary tumors that involve both sides of the midline in these primary sites have a potential risk of microscopic dissemination of metastatic disease to jugular lymph nodes on both sides of the neck. Similarly, tumors of the medial wall of the pyriform sinus are reported to have an increased risk of contralateral neck metastases.

The first-echelon lymph nodes at highest risk for micrometastasis in a neck with clinically negative findings from primary tumors of the hypopharynx and larynx.

Regional lymph node metastases from primary differentiated carcinomas of the thyroid gland occur in an occult manner in a high proportion of patients (approximately 50%), although clinically gross metastases at initial presentation are infrequent. The first-echelon lymph nodes at highest risk for metastases from a primary differentiated carcinoma of the thyroid gland are those adjacent to the thyroid gland, the so-called perithyroid lymph nodes, and those in the tracheoesophageal groove and superior mediastinum ( Fig. 11.9 ). Metastatic disease sequentially progresses from the central compartment lymph nodes to lower, middle, and upper jugular lymph nodes. Lymph nodes in the posterior triangle of the neck are involved infrequently unless there is gross metastatic disease at level IV, where contiguous metastatic spread to level VB is not uncommon. Metastatic disease from a primary carcinoma of the thyroid to level I is exceedingly rare.

The first-echelon lymph nodes at highest risk for micrometastasis in a neck with clinically negative findings from a primary carcinoma of the thyroid gland.

Regional lymph node metastasis develops in only 20% to 25% of patients with a carcinoma of the parotid gland. The lymph node groups at highest risk for metastases from a primary carcinoma of the parotid gland are those in the preauricular, periparotid, and intraparotid regions, as well as lymph nodes in the upper deep jugular chain and those in the upper spinal accessory chain in the posterior triangle of the neck ( Fig. 11.10 ). Initial dissemination of metastatic cancer from primary malignant tumors of the submandibular salivary gland occurs to lymph nodes in the supraomohyoid triangle ( Fig. 11.11 ).

The first-echelon lymph nodes at highest risk for dissemination of metastatic cancer from a carcinoma of the parotid gland are in the periparotid and upper cervical region.

The initial dissemination of metastatic cancer from primary malignant tumors of the submandibular and sublingual salivary glands occurs at lymph nodes in the supraomohyoid triangle.

Cutaneous malignant tumors of the scalp also spread to regional lymph nodes in a predictable fashion. A line joining the helix of one ear to the helix of the opposite ear in a coronal plane separates the watershed areas of the scalp. Tumors located anterior to this line in general metastasize to preauricular, periparotid, and anterior cervical lymph nodes (levels I to IV) and seldom metastasize to the posterior triangle of the neck. On the other hand, primary tumors of the scalp posterior to this line metastasize to the suboccipital and postauricular group of lymph nodes as well as those in the posterior triangle of the neck and the deep jugular chain (levels II to V).

Risk for Regional Metastasis

The risk for metastasis to regional lymphatics from primary squamous cell carcinomas of the upper aerodigestive tract depends on the primary site, T stage, and histomorphologic features of the primary tumor. In general, the risk of nodal metastasis increases from the anterior to posterior aspect of the upper aerodigestive tract, that is, the lips, oral cavity, oropharynx, and hypopharynx ( Fig. 11.12 ). For tumors of the larynx and pharynx, the risk of nodal metastasis increases with progression from the center of the upper aerodigestive tract (the vocal cords) to the periphery (the lateral pharyngeal wall). For example, the risk of regional lymph node metastasis from a carcinoma of the true vocal cords is exceedingly small. However, the risk increases with progression from the vocal cords to the false vocal cords, aryepiglottic fold, pyriform sinus, and pharyngeal wall. Nearly two-thirds of patients with primary carcinomas of the hypopharynx present with clinically palpable regional lymph node metastasis.

The risk of nodal metastasis increases in relation to the location of primary squamous cell carcinomas of the upper aerodigestive tract. FOM, Floor of mouth.

The T stage usually reflects tumor burden or invasiveness and is correlated with risk for nodal metastasis for any given primary site. Overall, the risk for metastasis is less than 15% for T1, 15% to 30% for T2, 30% to 50% for T3, and up to 75% for T4 head and neck primary squamous cell carcinomas. Certain histomorphologic features of the primary tumor also increase the risk of nodal metastasis. The risk of nodal metastases from HPV-positive oropharynx cancer is disproportionately high, even with a low T stage of the primary tumor. Endophytic tumors have a higher risk for metastasis compared with exophytic tumors. This is particularly true for primary carcinomas of the oral cavity (tongue and floor of mouth), where there is increasing risk of nodal metastases, with increasing depth of invasion (DOI). The AJCC and UICC have therefore revised the T staging of primary squamous cell carcinomas of the oral cavity, where each 5 mm increase in DOI will upstage the tumor by one T stage. Poorly differentiated carcinomas have a higher risk of nodal metastases compared with well-differentiated lesions. The pattern of invasion also has been shown to affect risk for metastasis. However, the influence of these parameters is not independent of T stage based on multivariate analysis. Only DOI has been shown to be an independent predictor of the risk for nodal metastases for cancers of the tongue and floor of the mouth. Metastatic spread from primary carcinomas of salivary origin is generally low (approximately 20%). The risk depends on the histology, grade, and stage of the primary tumor. Similarly, most head and neck sarcomas have a very low risk for regional metastasis with the exception of rhabdomyosarcoma, epithelioid sarcoma, synovial sarcoma, and angiosarcoma. Unlike other head and neck malignancies, even though the risk for dissemination to regional lymph nodes from differentiated carcinomas of the thyroid (papillary) is quite high (approximately 50% of occult metastases), elective dissection of regional lymph nodes is not recommended because it does not have an adverse impact on prognosis in a majority of patients who fall into the low-risk group stratification.

Risk of nodal metastases from cutaneous malignancies is relatively low. Basal cell carcinomas have a very low risk for metastasis (<1%), whereas the risk can be as high as 10% for cutaneous squamous cell carcinomas. Larger cutaneous squamous cell carcinomas (>2 cm) and those with adverse pathologic features (i.e., poor differentiation, DOI of >6 mm, and perineural invasion) have a higher risk for metastases. Once metastases develop from a cutaneous malignancy, the probability of survival decreases by up to 90%. On the other hand, cutaneous tumors of neuroendocrine origin (e.g., Merkel cell carcinoma and malignant melanoma) have a much higher risk for regional metastasis. For Merkel cell carcinomas larger than 1 cm, the risk of nodal metastases is 20% or more. The risk for nodal metastasis for cutaneous melanomas is related to tumor thickness and is higher for tumors thicker than 1 mm ( Fig. 11.13 ). Adnexal tumors of the skin rarely metastasize with the exception of sebaceous and eccrine gland carcinomas.

The risk of occult nodal metastasis in a cutaneous melanoma relative to the depth of the primary lesion.

Clinical Staging of Cervical Lymph Nodes (cN Staging)

The American Joint Committee on Cancer and the International Union Against Cancer have agreed upon a uniform staging system for cervical lymph nodes. The site, number, size, and extranodal extension (ENE) are the most important factors considered in nodal staging of most squamous cell carcinomas of the head and neck. The presence of clinical evidence of ENE has such an important negative prognostic impact that any lymph node with clinical or radiologic evidence of ENE gets upstaged to N3B category. ENE can be diagnosed clinically by the presence of a matted mass of nodes fixed to the overlying skin or adjacent soft tissue or clinical signs of cranial nerve invasion. Radiologic signs of ENE include amorphous, spiculated margins of a metastatic node and stranding of the perinodal soft tissue in previously untreated patients. The exact description of each clinical N stage of lymph node metastases from squamous cell carcinomas of the head and neck (oral cavity, HPV-negative oropharynx, hypopharynx, larynx, paranasal sinuses, salivary glands, and nonmelanoma skin cancers of the head and neck) is shown in Fig. 11.14 and Table 11.1 . Squamous cell carcinomas of the nasopharynx, HPV-positive cancers of the oropharynx (OPC), and well-differentiated thyroid carcinomas have a different biology, and cervical metastases from these tumors are assigned different staging systems. The natural history and response to treatment of cervical nodal metastases from nasopharynx and HPV-positive oropharynx primary sites are different in terms of their impact on prognosis, so they justify a different N classification scheme. For the nasopharynx, the size and location of the metastatic node(s) are important parameters ( Table 11.2 ). For HPV-positive OPC only the size of the metastatic nodes are considered in staging ( Table 11.3 ). Regional node metastases from well-differentiated thyroid cancer do not significantly affect the ultimate prognosis in a majority of patients (approximately 80%) who fall in the low-risk group category and therefore also justify a unique staging system. Staging for nodal metastases from differentiated thyroid carcinoma is largely based on the location of the metastases ( Table 11.4 ).

Clinical N staging (cN) of lymph node metastases from squamous cell carcinoma of the head and neck except for nasopharynx, human papillomavirus–positive oropharynx, and differentiated thyroid cancer.

(Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 8th edition, Springer Science and Business Media LLC, 2016. www.springer.com .)

Pathologic Staging of Cervical Lymph Nodes (pN Staging)

The American Joint Committee on Cancer and the International Union Against Cancer have developed a separate pathologic staging (pN) for those tumors primarily treated surgically, and where a pathologic specimen is available for accurate assessment of the extent of nodal metastases. For example even microscopic ENE (<2 mm) is considered as ENE(+), and thus entered into upstaging N category. This nodal staging is different than cN staging and offers more accurate information for overall pN staging of these cancers. Thus pN staging is often used for adjuvant treatment planning as well as for more accurate assessment of prognosis. The pN staging for oral cavity, HPV-negative oropharynx, hypopharynx, larynx, paranasal sinuses, salivary glands, and nonmelanoma skin cancers of the head and neck is shown in Table 11.5 . The pN staging for HPV-positive oropharynx cancers is shown in Table 11.6 . There is no pN staging developed for cancers of the nasopharynx and differentiated cancers of the thyroid gland.

Other Nodal Factors Affecting Prognosis

The pattern of the lymphatic drainage varies for different anatomic sites. However, the location of the lymph node metastases has prognostic significance in patients with squamous cell carcinoma of the head and neck. Survival is significantly worse when metastases involve lymph nodes beyond the first echelon of lymphatic drainage and, particularly, lymph nodes in the lower parts of the neck, i.e., level IV and level VB (supraclavicular region). Therefore the AJCC recommends that each N staging category be recorded on the staging forms to show whether the nodes involved are located in the upper (U) or lower (L) regions of the neck, depending on their location above or below the lower border of the cricoid cartilage.

When enlarged lymph nodes are detected, the actual size of the nodal mass(es) should be measured. It is recognized that most masses over 3 cm in diameter are not single nodes but are confluent nodes or tumor in soft tissues of the neck. Careful clinical examination; radiologic assessment; and, in surgically treated patients, detailed pathologic examination is necessary for documentation of tumor extent in terms of the location or level of the lymph node(s) involved, the number of nodes that contain metastases, and the presence or absence of ENE.

Involvement of lower cervical lymph nodes (levels IV and VB) by metastatic cancer usually is ominous. Lymph node density, which reflects tumor factors (number of positive lymph nodes), treatment factors (number of lymph nodes removed during neck dissection), and staging factors (completeness of the sampling procedure, including those related to the surgeon and pathologist) has been found to stratify risk of local regional recurrence and survival. Lymphovascular invasion (LVI) and perineural invasion (PNI) by a tumor, as well as the presence of tumor emboli in regional lymphatics, also has an adverse impact on prognosis. Therefore these factors must be considered when developing a treatment strategy for patients in whom regional lymph nodes are involved by metastatic disease, particularly for planning adjuvant therapy and in the assessment of prognosis.

Evaluation

Assessment and management of patients with head and neck primary tumors presenting with regional lymphatic metastasis can be divided into those with clinically detectable metastasis and those at risk of harboring occult metastasis. The approach to management of these two clinical scenarios is defined by patterns and risk of regional spread.

Clinically Evident Metastasis With a Known Primary Tumor

“A clinically palpable, firm, enlarged lymph node(s) in an adult should be considered metastatic until proven otherwise.” This was a statement made by Hayes Martin over six decades ago, and it still holds true. The clinically enlarged lymph node may be present at any of the previously described anatomic locations in the head and neck region. The location of a palpable lymph node may point to the potential site of a primary tumor ( Fig. 11.15 ). Important features to note during examination of the neck for cervical lymph nodes are the location, size, consistency, and number of palpable lymph nodes as well as clinical signs of ENE such as invasion of the overlying skin, fixation to deeper soft tissues, or paralysis of cranial nerves ( Fig. 11.16 ).

Clinically palpable 3-cm size mobile metastatic lymph node at level II with no clinical signs of extranodal extension (N1).

Conglomerate mass of multiple metastatic lymph nodes with reduced mobility and adherence of overlying skin, signifying extra nodal extension (ENE+ [N3b]).

A thorough clinical examination of the head and neck should be performed, including careful evaluation of the scalp, external auditory canals, and the skin. This examination is followed by careful clinical evaluation of the oral cavity, oropharynx, hypopharynx, and larynx, including digital palpation of the tonsillar fossae and the base of the tongue. After this evaluation, flexible fiberoptic nasolaryngoscopy is performed to assess the nasal cavity, nasopharynx, oropharynx, (particularly the base of the tongue) hypopharynx, and larynx for identification of the primary tumor. Erythema and mucosal hypervascularity should raise suspicion for a primary tumor. In the vast majority of cases, the primary tumor will be identified with a thorough clinical examination. Management of the neck in these patients is dictated by the site and stage of the primary tumor. However, approximately 10% of patients with a clinically palpable metastatic lymph node will not have a clinically obvious primary tumor. Many small primary tumors that may be missed on mirror examination are readily visible with the use of a fiber-optic nasolaryngoscope. If the primary tumor is identified, then further management is directed by the site and stage of the primary tumor.

Histologic diagnosis of metastatic carcinoma is usually established by fine-needle aspiration biopsy and cytologic examination of the smears. In addition to cytology, immunohistochemistry for p16 staining should be requested. An open biopsy is rarely indicated, usually only if the cytology is suspicious for lymphoma. If an open biopsy is planned, the incision should be made in such a location that it can be incorporated in the incision for a subsequent neck dissection if required.

Clinically Evident Metastasis With an Occult Primary Tumor

Approximately 10% of patients with metastatic squamous cell carcinoma to cervical lymph nodes do not have a clinically identifiable primary tumor. If a primary tumor is not evident after a thorough clinical examination, including fiberoptic nasolaryngoscopy, then the next step in the evaluation of the patient is the cytologic diagnosis of the neck mass by fine-needle aspiration biopsy. Further workup and management depend on the cytologic diagnosis. The algorithm for further management of cytologically confirmed metastatic carcinoma from an unknown primary source is shown in Fig. 11.17 . If the diagnosis of squamous cell carcinoma (SCC) or any of the variants of SCC is confirmed, then a p16 staining should be requested, to see if the cancer is HPV related. Further workup for the tumor requires imaging studies, including a contrast-enhanced computed tomography (CT) scan and a positron emission tomography (PET) scan to evaluate the head and neck region and also to rule out distant metastases. The PET scan may identify an occult primary tumor in a small percentage of patients. It is particularly important to perform the PET scan before any invasive intervention such as random biopsies in the search for a primary tumor. A contrast-enhanced CT scan, on the other hand, provides information about the size, extent, and number of lymph nodes as well as ENE from the metastatic lymph node. Cystic nodal metastases are seen commonly in patients with primary squamous cell carcinoma of the HPV-associated oropharynx cancer and papillary carcinoma of the thyroid gland. The presence of cystic metastasis in the upper neck often is confused with the diagnosis of a branchial cleft cyst. Although a branchiogenic carcinoma can occur, a primary carcinoma arising in a branchial cleft cyst is exceedingly rare.

Algorithm for workup and management of a patient with a metastatic neck node from an unknown primary source. CT, Computed tomography; FNAC, fine-needle aspiration cytology; MND, modified neck dissection; RND, radical neck dissection; RT, radiation therapy; PET, positron emission tomography; TGB, thyroglobulin.

At this juncture, further management of the patient requires examination and endoscopy under general anesthesia to search for the primary tumor. Evaluation under anesthesia allows palpation of areas that are not accessible during clinical examination in the office. These include the base of the tongue and tonsillar fossae, as well as the nasopharynx, which should be palpated from behind the soft palate. Suspicion of a primary tumor is raised by firm nodularity, submucosal induration, or surface bleeding upon palpation. Directed biopsy specimens are taken from areas that look suspicious for a primary site. The practice of performing multiple “random biopsies” is strongly discouraged, because it rarely identifies an occult primary tumor. If a primary tumor is not identified by routine evaluation, then bilateral tonsillectomies should be considered, particularly if the metastatic node is p16 positive, because a primary tumor can be hidden in the tonsillar crypts. Further management of the cervical lymph node metastases is deferred until after the final pathology report becomes available.

The vast majority of metastatic lymph nodes from an occult primary source are squamous cell or poorly differentiated or undifferentiated carcinomas, or basaloid squamous cell carcinomas, followed by adenocarcinoma, melanoma, and lymphoma. Metastatic adenocarcinoma in the upper neck usually originates from a primary tumor of salivary origin, whereas those in the lower neck represent systemic metastasis if thyroid carcinoma is ruled out. Immunohistochemical studies for thyroglobulin and calcitonin are helpful to rule out thyroid origin. A thorough examination of the skin of the entire body is required if the cytology of the neck node shows metastatic melanoma. Finally, a core or open biopsy of the neck node may be necessary for histologic diagnosis if cytologic examination raises suspicion for a lymphoma.

Management of the Post–Chemoradiation Therapy Neck

During the course of the past three decades, an increasing number of patients have received varying combinations of chemotherapy and radiation therapy for advanced stage squamous cell carcinomas of the pharynx and larynx. Initial neck dissection is seldom performed in these patients who have clinically evident neck metastases. However, a significant number of patients need surgical intervention for persistent or recurrent metastatic disease in the neck. To address this issue, planned dissection of the neck after chemoradiation therapy had been advocated in the past. However, a majority of patients undergoing planned neck dissection had histologically negative lymph nodes. Therefore planned neck dissection after chemoradiation therapy is no longer recommended. Neck dissection should be considered only in patients who have proven persistent viable disease or a high probability of residual metastatic cancer. Evaluation of the neck following chemoradiation therapy for persistence of metastatic disease is challenging. Grossly palpable or radiographically demonstrable metastatic lymph nodes are an obvious indication for salvage neck dissection. The use of PET/CT in the standard posttreatment clinical evaluation of response following chemoradiation has emerged as a very reliable indicator of viable tumor. However, the PET scan should not be performed earlier than 3 months after completion of treatment ( Fig. 11.18 ). In general, a period of at least 3 months is required for the PET scan to be accurate to show absence of any metabolic activity ( Fig. 11.19 ). A negative PET scan has allowed for the observation of initially N-positive necks who have achieved a complete clinical response. The algorithm for evaluation and management of the neck in patients treated with chemoradiation therapy is shown in Fig. 11.20 .

18F-fluorodeoxyglucose (FDG) PET scan 1 week following completion of concurrent chemoradiation therapy for carcinoma of the base of the tongue with right neck node metastases showing persistent FDG-avid nodal mass at level II.

18F-fluorodeoxyglucose (FDG) PET scan 3 months following completion of concurrent chemoradiation therapy for carcinoma of the base of the tongue with right neck node metastases showing a complete resolution of FDG activity in the nodal metastases at level II. Mild activity is noted at the base of the tongue due to postradiation ulceration at the primary site.

Algorithm for evaluation and management of the neck of a patient who has had chemoradiation therapy. CR, Complete response; CT, computed tomography; CTRT, chemotherapy and radiation therapy; MRI, magnetic resonance imaging; PET, positron emission tomography; PR, partial response; SUV, standardized uptake value; + ve, positive; − ve, negative.

Radiographic Evaluation

Identification of metastatic lymphadenopathy in the neck upon clinical examination obviously depends on the experience of the clinician, but factors such as the size of the node, the location in the neck, and the body habitus of the patient may render palpation of low-volume disease difficult. Other factors such as prior history of surgery or radiation to the neck may hamper the clinical detection of early metastatic disease. Therefore radiographic examination is of significant value in accurate assessment of the neck. Our ability to detect clinically occult metastasis has improved with the availability of anatomic imaging modalities such as US, contrast-enhanced CT, and MRI. Lymph nodes as small as 3 to 4 mm can be identified on CT or MRI. However, it is not easy to differentiate reactive from metastatic nodes. The role of 18F-fluorodeoxyglucose (FDG) PET for evaluation of a neck with cancer staged as cN0 is debatable, and the utility of this technique may be limited by its suboptimal resolution in detecting small metastases. However, PET scan may identify additional lymph nodes not clinically appreciated, as well as may show unsuspected distant metastatic sites, or occasionally a second primary tumor. In patients who do not have an obvious primary tumor identified on clinical examination or CT/MRI, PET scan may sometimes identify an occult primary tumor. While PET scan will show FDG avidity in metastatic tumor deposits, it is often negative in patients with cystic metastasis ( Fig. 11.21 ).

A contrast-enhanced computed tomography scan and an 18F-fluorodeoxyglucose (FDG) PET scan of a patient with partially cystic metastasis from squamous cell carcinoma of the tonsil. Note that the cystic component of the tumor shows no FDG activity, while the solid component shows intense FDG avidity.

In addition to the nodal size and shape, structural changes within the metastatic nodes should be studied for accurate imaging diagnosis of the metastatic cervical nodes. The radiographic features for diagnosis of a metastatic node are size, rim enhancement, central necrosis, and ENE ( Figs. 11.22 and 11.23 ). Even in patients who have clinically evident metastasis, radiographic evaluation is desirable to assess the extent of the nodal disease, such as number of nodes and location of nodes as well as extranodal extension and relationship of the nodes to the carotid artery, the skull base, and the parapharyngeal space on the ipsilateral side as well as to evaluate the clinically negative contralateral side of the neck. Several lymph node groups that are not accessible to clinical examination, such as those in the superior mediastinal, parapharyngeal, and retropharyngeal areas, are best assessed by a CT scan or an MRI scan.

The radiographic features for diagnosis of a partly cystic metastatic lymph node ( arrow ) on a computed tomography scan of the neck.

An axial view of the computed tomography scan of a patient with N3 metastasis showing extranodal extension with carotid artery invasion.

US-guided or CT scan–guided fine-needle aspiration biopsy is an excellent option for establishing accurate tissue diagnosis in a small lymph node that is detected radiographically but is not evident clinically. Although US-guided fine-needle aspiration biopsy is adequate for most cervical lymph nodes, a CT-guided biopsy becomes necessary in certain situations such as retropharyngeal and superior mediastinal lymph nodes.

Pathologic Evaluation

It is desirable to have a standard protocol for submission of neck dissection specimen to the pathology laboratory for routine analysis. To maintain anatomic accuracy following en bloc neck dissection, the surgical specimen is oriented on a card board with the levels of the dissected nodes identified, or each level is separated by the operating surgeon in the operating room and submitted separately in multiple containers designated by level and laterality. Upon gross evaluation and prosection of the neck dissection specimen performed by the pathologist, all lymph nodes must be submitted for histopathologic evaluation.

Evaluation of a sentinel node biopsy specimen for melanoma involves serial stepwise tests. Therefore generally the excised node is not sent for frozen section examination. Adequate assessment of the sentinel node requires subserial sections. If multiple hematoxylin and eosin serial sections are negative, immunohistochemistry is performed for a panel of melanoma markers. If this panel is negative, reverse transcriptase-polymerase chain reaction for tyrosinase messenger ribonucleic acid is performed. Similarly, examination of a sentinel node for squamous cell carcinoma may show isolated micrometastases (<2 mm) on hematoxylin and eosin serial sections, or isolated tumor cells may stain for cytokeratin. Although our ability to detect tumor cells has increased compared with the recent past, the precise implications of these findings in terms of selection of treatment and prognosis require continued investigation.

Treatment

Clearly the goal of treatment for cervical lymph node metastasis is improved survival and regional control of neck disease. Management of the neck must be considered on the basis of the plan for overall treatment of the primary tumor. The extent of the nodal metastasis also influences management.

Elective treatment of occult metastases in the neck with clinically negative findings intuitively would seem to offer improved survival, but prospective studies have failed to confirm this hypothesis. However, elective treatment of regional nodes has been shown to improve disease-free survival. Moreover, patients who are at risk of having micrometastasis do not progress to clinically or radiographically evident metastasis in a consistent and predictable manner ( Fig. 11.24 ). Most patients who are observed for a cancer in the neck that clinically is staged as N0 have nodal disease that is stage N2 or higher at the time of subsequent detection, even with close follow-up ( Figs. 11.25 and 11.26 ). Micrometastases are reported to show comparable control rates with elective neck dissection or radiation therapy. However, elective neck dissection has the advantage of assessing prognosis and identifies patients who may require adjuvant treatment. Patients whose primary tumors are treated with radiation therapy are best treated with elective irradiation of the neck. On the other hand, if the primary tumor is treated surgically, then elective neck dissection will provide information to select only those patients who need adjuvant radiation therapy and avoid unnecessary radiation in the remainder.

Not all patients with cancer staged as N0 in the neck who are at risk of having micrometastasis present for therapeutic neck dissection with N1 disease.

Clinical findings in a consecutive series of patients who had cancer staged as N0 in the neck were observed initially and subsequently underwent therapeutic neck dissection.

Pathologic findings in a consecutive series of patients who had cancer staged as N0 in the neck, were observed initially, and underwent subsequent therapeutic neck dissection.

Similarly, management of clinically evident nodal metastasis also is influenced by the treatment selected for the primary tumor. For example, patients with laryngopharyngeal carcinomas who are undergoing definitive chemoradiation therapy require neck dissection only for salvage of persistent or recurrent neck metastasis. For patients undergoing surgical management of the primary tumor (i.e., an oral cavity tumor), neck dissection is an integral part of the surgical plan. Following neck dissection, regional recurrence in the dissected neck is dependent on the volume and extent of neck metastasis at the time of neck dissection. Regional failure rates with surgical treatment alone are very high for patients with multiple positive lymph nodes in the neck. Other ominous findings that increase the risk for local recurrence include lymphovascular or perineural invasion by the tumor, tumor emboli in the lymphatics, and ENE of the tumor. Postoperative radiation therapy has been shown to significantly improve locoregional control in these settings. In addition, prospective clinical trials suggest that regional control may be further enhanced in selected patients, such as those with ENE when treated with postoperative chemoradiation, compared with patients treated with postoperative radiation alone.

In patients with clinically evident nodal metastasis and an occult primary site, treatment decisions are based on the location and extent of nodal disease in the neck. Patients with low-volume metastatic disease in the neck can be treated equally well with neck dissection or radiation therapy alone. The need for adjuvant radiation therapy in patients undergoing neck dissection depends on the location and extent of nodal metastases. Similarly, the need to include potential primary sites within the radiation portals is dependent on the location of the metastatic nodes in the neck. For example, metastatic lymph nodes confined to level VA would indicate a potential primary tumor in the nasopharynx that would be included in the radiation portal.

Surgical Treatment

The surgical treatment of regional lymph nodes for carcinoma of the head and neck region is based on the understanding of the anatomy of the regional lymphatics, the risk of nodal metastasis and the patterns of regional lymph node metastasis, depending on the characteristics of the primary tumor. When regional metastases are clinically palpable, comprehensive clearance of all regional lymph nodes at risk is recommended. The classic radical neck dissection traditionally has been the “gold standard” for the management of neck in patients with head and neck cancer. Although oncologically sound, the classic radical neck dissection is associated with significant cosmetic deformity and functional morbidity. Chronic pain resulting from shoulder disability secondary to accessory nerve sacrifice is common. In addition, atrophy of the trapezius muscle causing shoulder droop and winging of scapula is also a debilitating sequelae. Improved understanding of the biology of metastatic spread of head and neck cancer, and understanding of the patterns of neck metastases, has allowed modifications in the surgical management of cervical lymph nodes to reduce morbidity without compromising regional control or disease-specific survival. Preservation of the spinal accessory nerve significantly reduces the morbidity of neck dissection. Thus if the spinal accessory nerve is not involved by metastatic cancer, it should be routinely preserved even in patients with clinically evident metastatic lymph nodes. In spite of anatomic preservation of the accessory nerve, up to a third of the patients experience varying degrees of shoulder disability. This is due to ischemic injury to the nerve, which has been dissected circumferentially. Preservation of the sternocleidomastoid muscle or internal jugular vein in patients with gross cervical lymph node metastasis results in high regional failure rates but may be considered for low-volume disease.

When an elective neck dissection is undertaken to excise cervical lymph nodes at risk of harboring micrometastasis (occult metastasis), it is seldom necessary to perform a comprehensive neck dissection of all five neck nodal levels. The patterns of cervical lymph node metastasis from mucosal squamous cell carcinomas of the head and neck are predictable and occur in a predictable and sequential fashion. Thus an elective neck dissection can safely include the lymph node groups at highest risk of micrometastasis. Such a limited or “selective” dissection of lymph nodes is usually considered a “staging procedure.” The histologic information derived from the study of the excised lymph nodes facilitates selection of adjuvant therapy in patients who are at increased risk of neck failure and spares the need for a more comprehensive and morbid operation or adjuvant radiotherapy in others who are at reduced risk. Thus an elective operation for primary tumors of the oral cavity with a clinically N0 neck requires dissection of lymph nodes at levels I, II, and III and occasionally level IV (for lateral tongue lesions). For primary tumors of the pharynx and larynx, dissection of lymph nodes at levels II, III, and IV is recommended. If the primary tumor crosses the midline, bilateral clearance of levels II, III, and IV should be undertaken.