1 Clinical Assessment of Neck Lymphadenopathies Abstract Cervical lymphadenopathy is a common cause of clinic visits, which necessitates rapid and efficient diagnosis. The key requirement for this practice is the combination of the recognition of various risk factors in patients’ history with the understanding of neck anatomy and appropriate usage of diagnostic tools such as imaging and biopsies. This chapter aims to provide necessary information for clinicians in obtaining a thorough history and head and neck examination, as well as employing the correct imaging algorithm and the differential diagnosis in patients with cervical lymphadenopathy. Keywords: neck mass, lymphadenopathy, differential diagnosis, diagnostic imaging, pediatric lymphadenopathy, congenital lesions, neoplasms of the neck, carcinoma of unknown primary Neck is the bridge between the head and the trunk. Besides conveying spinal cord in a chamber made of vertebrae and muscles, neck contains important vasculature, nerves, fat and lymphatics, and elements of upper aerodigestive tract, as well as salivary, thyroid, and parathyroid glands. Seeing a lump or a swelling in the neck is a very common clinical finding in all age groups, which can be related to the structures in the neck or can be part of an infectious, inflammatory, or a neoplastic process. Therefore, diagnostic workup may pose a major challenge in the daily practice of any physician. The scope of this chapter is to provide a systematical approach for the evaluation of neck masses, specifically cervical lymphadenopathies, which entails obtaining a thorough history from the patient, performing a complete physical examination including endoscopy, utilizing relevant imaging modalities, and performing biopsies in the form of needle aspiration or excision as necessary. Many characteristics of the patient and the findings in the history are invaluable in presumptive diagnosis, and may help direct the subsequent physical examination and in selecting the appropriate laboratory and imaging studies. Detailed head and neck physical examination is the crucial step for proper diagnosis and management. Imaging should be directed for better delineation of pathology and/or involved nodal groups. A mass in the neck is a very common finding in patients of all age groups. Despite significant progress in clinical diagnostic and imaging modalities, history and physical examination of a patient with neck mass still remains the mainstay of diagnosis. A rapidly growing, tender mass in a child usually consists of reactive lymph nodes that are caused by inflammation after infections. On the other hand, a slow-growing, firm mass in a heavy drinker and smoker elderly male could be metastatic lymph node from a primary malignancy in the upper aerodigestive tract. More than 90% of all neck masses were estimated to be benign in pediatric age group, while—excluding thyroid masses—80% of adult neck masses are neoplastic and 80% of those are malignant.1 Therefore, every piece of information gathered from history of the patient and the present illness is not only important for obtaining a proper diagnosis, but may also save time by preventing unnecessary tests. History taking should be concentrated on the history of the present illness, onset and duration of the neck mass, and any associated symptoms such as pain, fever, anorexia, weight loss, night sweats, fatigue, otalgia, throat pain, dysphonia, dysphagia, odynophagia, hoarseness, and/or dyspnea. Past medical, surgical, social, and family histories are important parts of patient’s evaluation. Patient’s tobacco and/or alcohol consumption, its duration and intensity, and occupational exposures to environmental toxins, recent travels especially to exotic regions, exposure to animals and sexually transmitted diseases such as human papillomavirus (HPV), and any history of radiation to the head and neck should also be noted. After obtaining a detailed history, a careful head and neck physical examination should be carried out for evaluation of craniofacial skin, eyes, oral cavity, oropharynx, larynx, hypopharynx, ears, nasal cavity, and nasopharynx. Palpation of neck nodal basins, salivary glands, and thyroid, and bimanual palpation of tongue, tonsil, and floor of mouth should be part of the physical examination. A key adjunct to visual inspection is the fiberoptic endoscopy, which not only allows a thorough examination of the upper aerodigestive tract with illumination and magnification, but also provides a dynamic evaluation of swallowing and airway. Features of a palpable mass include mobility, tenderness, location in the neck, firmness, fluctuance, overlying erythema, pulsation, and palpable bruits.1 Several features may help in differentiating a benign reactive lymphadenopathy from a lymph node harboring malignancy. Cervical lymphadenopathy associated with viral infections is often soft, small, bilateral, mobile, nontender, and without overlying skin changes, although this general rule may not be true with some of the more subacute and chronic viral infections, such as Epstein–Barr virus (EBV) and cytomegalovirus.2,3 Cervical lymphadenopathy associated with bacterial infections is usually of acute onset and unilateral. Bacterial lymphadenitis develops more commonly in submandibular (50–60%) or upper cervical (25–30%) regions compared with other cervical lymph node subsites.3 Up to 25% of patients with acute bacterial lymphadenitis will demonstrate fluctuance on physical examination, and this is especially true with Staphylococcus aureus lymphadenitis.3 Concerning findings that may suggest malignancy include nodes that are rapidly enlarging, firm, nontender, and fixed-to-the-skin or underlying structures. Also, generalized lymphadenopathy, supraclavicular nodes regardless of size, lower cervical nodes, lymph nodes greater than 2 to 3 cm, and accompanying hepatosplenomegaly are associated with increased risk of malignancy.4 One should always keep in mind that a neck mass is maybe part of a systemic illness, especially in the absence of an obvious etiology within the head and neck.1 Although detailed surgical anatomy and patterns of nodal spread are given elsewhere in this book, it is crucial to review anatomy of the neck for proper documentation of the findings and differential diagnosis. Localization of cervical lymphadenopathy is closely associated with the origin of the pathology, and allows for a focused clinical examination with efficient use of diagnostic tools. It is also very important to organize physical examination findings in an order and understanding of the neck’s triangles and nodal levels. Therefore, relevant anatomy and nodal classification will be touched upon for these purposes. Most physicians find it helpful to define the neck in terms of triangles when communicating the location of physical findings.5 Each side of the neck is bordered by the inferior edge of the mandible superiorly, trapezius muscle posteriorly, clavicle inferiorly, and midline medially. The sternocleidomastoid muscle (SCM) divides the neck into a posterior and an anterior triangle. The posterior triangle is then subdivided by the inferi- or belly of omohyoid muscle into the supraclavicular triangle inferiorly and the occipital triangle superiorly. The anterior triangle is further divided into four smaller triangles, which are submandibular, submental, muscular, and carotid triangles. The submandibular triangle is formed by the two bellies of digastric muscle and the inferior border of the mandible. The submental triangle lies between the anterior bellies of digastric muscles and the hyoid bone. The muscular triangle is bordered by the SCM, superior belly of the omohyoid muscle, and the midline. The carotid triangle is the area between the anterior border of SCM, superior belly of the omohyoid, and posterior belly of the digastric muscles. Lymph nodes tend to be organized into groups or chains that drain discrete anatomic regions.6 Several classifications have been proposed to organize cervical lymph nodes into nodal regions that enable reliable localization of pathologic lymph nodes, effective communication among clinicians, and accurate cancer staging. The most widely used schemes historically have been those, such as that of Rouviere, describing nodal groups based on proximity to adjacent structures.7 This system was based on palpation and inspection of lymph nodes. With the development of cross-sectional imaging systems, a “level”-based classification was proposed8 and adopted by the American Joint Committee on Cancer for both radiologists and clinicians involved in the care of head and neck cancer patients in order to reliably communicate the location of pathologic lymph nodes and for cancer staging.6 Nodal basins of the neck will be discussed in detail in another chapter of this book. After acquiring a detailed history and necessary evidence from physical examination, it may be necessary to run additional diagnostic testing and/or imaging for accurate diagnosis. It is usually unnecessary and inefficient to run all imaging and diagnostic tests in every patient; the practitioner should have the knowledge on the indications, advantages, and pitfalls of each modality. Laboratory testing can usually be an adjunct to other findings in the differential diagnosis. Complete blood cell count can be useful to identify markers of infection, as elevated white blood cell count with neutrophil predominance. Elevated erythrocyte sedimentation rate and C-reactive protein (CRP) levels not only are useful in supporting the clinical suspicion of an infectious or an inflammatory mass, but also are used to monitor the response to treatment. Serologic testing can be necessary in the diagnosis or differential diagnosis of certain infectious diseases, such as tuberculosis, infectious mononucleosis, and brucellosis. Evaluation of a neck mass usually involves an imaging modality that confirms the presumed diagnosis or provides a differential diagnosis. The preferred imaging modality in the workup of a neck mass may differ mainly based on physical examination findings and associated conditions that may exclude utilization of certain modalities such as kidney failure that may exclude administration of iodine contrast in computed tomography (CT) or an implanted pacemaker that eliminates the option of performing a magnetic resonance imaging (MRI). Details of anatomic imaging and imaging criteria for characterization of metastatic lymph nodes are given elsewhere in this book. However, brief description of advantages and disadvantages of frequently used imaging modalities in differential diagnosis of neck masses are provided in this chapter ( Ultrasound (US) is typically the initial imaging performed for evaluation of a palpable neck mass as it utilizes no radiation, requires no sedation or intravenous contrast, is easily accessible, and is relatively low in cost. Advances in technology allowed clinicians to access more compact US devices with higher resolution at lower cost and helped popularizing clinician performed US examinations at office. US can provide information about the size and location of the lesion as well as its cystic or solid nature. Doppler feature can be utilized to identify vascularity of the mass.9 Certain findings in the US examination may provide clues in differentiating a normal or reactive lymph node from a malignant one, and also guide the examiner in performing needle biopsies for cytological evaluation. Normal lymph nodes are typically ovoid to kidney shaped in shape and are slightly hypoechoic when compared to the surrounding soft tissues with a hyperechoic region that represents the fatty hilum of the lymph node. On color Doppler examination, there is flow in normal lymph nodes, which is relatively increased near the hilum.9 Reactive lymph nodes are typically less than 1 to 1.5 cm in greatest diameter, and usually keep the fusiform shape with a short-to-long axis ratio of less than 0.5. Malignant lymph nodes are usually rounded in shape and increased in size, and have lost their characteristic architecture with lack of an echogenic fatty hilum, and distortion or displacement of normal vascularization.10 Despite being an excellent screening tool, US examination has several limitations and flaws in evaluation of neck masses. Penetration of high-frequency linear probe may be reduced at deep neck structures, especially at short and/or thick necks. Also, acoustic shadowing hinders evaluation of retrosternal, retropharyngeal lymph nodes, and parapharyngeal lesions. Proper US evaluation is also highly dependent on the skills and the proficiency of the examiner, especially in the pediatric age group. For the adult population, the diagnostic algorithm usually continues with a cross-sectional imaging modality such as CT and/or MRI. CT continues to be the most frequently utilized modality. Discrimination of fine anatomic characteristics of bone and of the soft tissues of the neck is particularly facilitated by the use of iodinated contrast studies ( MRI provides better soft-tissue delineation, with better appreciation of vascular and/or perineural invasion. MRI carries no risk of radiation; it can be safely used in pregnant or pediatric patients. On the other hand, MRI is less readily available and more expensive than the aforementioned studies. CT and MRI are not substitutes for each other, but are complementary to each other in the evaluation of malignant neck masses. Physician chooses one or both, depending on the suspected pathology. CT and MRI are usually ordered together in the evaluation of masses involving oral cavity, skull base, pharynx, and parapharyngeal space. Fig. 1.1 Discretization of cervical lymphadenopathies can be difficult in short and thick necks (a). Computed tomography with iodine contrast provides detailed information of lymph nodes regarding their size, location, and relationship to other structures (b). Positron emission tomography (PET) is another important imaging modality in evaluation of cervical lymphadenopathy, especially in the presence of a primary tumor in the head and neck. PET provides important information in head and neck oncology, especially in initial staging and in evaluation of the treatment response. Fine-needle aspiration biopsy (FNAB) has become an essential tool in the diagnosis of neck masses. Imaging can be highly suggestive in the diagnosis of certain neck masses with vascular, infectious, or congenital origin (i.e., thyroglossal duct cyst [TDC] or branchial cleft cyst), but cytopathological evaluation is usually necessary for most neck masses in adult patients. The procedure is quick and safe. Generally, a 22- to 25-gauge needle with 10-mL syringe is inserted into the mass, and multiple passes through the lesion are made with or without the suction of the syringe plunger. The aspirate is transferred on a microscope slide and dried on air, or inserted to a liquid medium and transferred to the laboratory depending on the practice of the institution. This can also allow staining of the tissue block obtained during the aspiration process. FNAB cytology is highly sensitive and specific in differentiating cystic masses from solid, benign masses from malignant, and epithelial metastases from lymphoid infiltration. Analysis of tissue architecture with immunohistochemistry and/or flow cytometry is usually required for the diagnosis of lymphoma and other pathologies of lymphoid origin. Therefore, core needle biopsy or open biopsy may be warranted for further identification of such lesions. Occasionally, CT- or MRI-guided FNAB may be necessary where US guidance is not adequate for targeting masses in locations with difficult access such as retropharyngeal space or the pterygopalatine fossa. The differential diagnosis of the neck masses can be listed under three main categories: • Infectious and inflammatory lesions. • Congenital lesions. • Neoplasms of the neck. Infectious and inflammatory lesions are the most frequently encountered neck masses in both adults and children. The neck has an extensive capillary lymphatic network that drains skin, upper aerodigestive tract, salivary glands, and thyroid gland. Approximately 40% of all the lymph nodes in the body are located in the head and neck.6 Thus, it is quite common to encounter enlarged submandibular masses as reactive lymphadenopathy in the neck, after a viral or bacterial upper respiratory tract infection or a dental infection. Often, these reactive nodes will manifest as palpable, mobile, and tender masses, and the patient may report fever, upper respiratory infection symptoms, tooth pain, or dysphagia.1 Occasionally, these lymph nodes will become necrotic in the course of a bacterial infection, and an abscess forms. US is usually the preferred imaging modality in such case, which will readily show the necrotic area in the lymph node, and enable aspiration of fluid for culture and cytology. CT scan with iodine contrast is best for delineating diffuse lymphadenopathy or an abscess formation in parapharyngeal, retropharyngeal, or masticatory spaces. Granulomatous diseases include a wide variety of pathologies, which may occasionally present as a neck mass. These include infectious or autoimmune diseases such as sarcoidosis, tuberculosis, atypical mycobacterial infections, cat-scratch disease, or Kawasaki’s disease. US-guided FNAB cytology may reveal important features of the disease or exclude a malignant process. Excisional or incisional biopsies are a last resort because of the concern for creation of a chronically draining wound.1 Infection or inflammation of the salivary or thyroid glands is not uncommon. Obstruction of Wharton’s or Stensen’s ducts by sialolithiasis or mucus plugs causes tender and swollen glands with warmth and hyperemia. The symptoms are usually unilateral and confined to one gland, and are usually exacerbated with ingestion of food or drinks. Infection may ensue behind the obstruction, and thus, examiner can see purulent discharge from the orifice of the salivary duct upon massage to the respective salivary gland. US shows signs of inflamed parenchyma and often dilated duct with calculi in it. CT scan may better show the place of calculi deposits, and often ordered if surgical treatment is anticipated. Inflammatory diseases of thyroid gland can be encountered in the differential diagnosis of anterior neck masses. Three broad categories of thyroiditis are defined: (1) acute suppurative thyroiditis, which is due to bacterial infection; (2) subacute thyroiditis, which results from a viral infection of the gland; and (3) chronic thyroiditis, which is usually autoimmune in nature. Acute thyroiditis is characterized with painful palpable thyroid gland with signs of infection. The pain worsens with extension of the neck. Subacute thyroiditis can also cause a tender and palpable thyroid gland, with systemic symptoms as fatigue, malaise, and low-grade fever. Chronic autoimmune thyroiditis has a slower course and results in a diffuse, nontender goiter. Diagnosis is usually done on clinical and laboratory findings. US is the preferred imaging modality for diagnosis and follow-up. Congenital lesions are an important cause of neck masses in childhood or early adulthood period. Detailed description of embryological development of the neck is beyond the scope of this chapter, but understanding certain features of congenital lesions is usually required for differential diagnosis and treatment. TDC is the most common congenital neck mass in children, which presents as a midline cystic mass. It represents 70% of all congenital neck masses.1 TDCs are formed due to a congenital defect in the closure of embryonic descent route of the thyroid gland. This route originates from foramen cecum, in the base of tongue, and courses in the anterior neck, close to the midline, usually deep to the hyoid bone and the strap muscles, to the isthmus of the thyroid gland. Remnants of the thyroglossal duct are actually found in approximately 7% of the population, but only a small number of these ever become symptomatic.11 TDCs usually become evident in childhood as a midline cystic neck mass that elevates in the neck with tongue protrusion or swallowing. Occasionally, cyst fluid gets infected, and presents as a painful and inflamed midline mass. Evaluation of thyroid function and US imaging is necessary to rule out lingual ectopic thyroid tissue. Acute infection of TDC is treated with aspiration of cyst contents and antibiotics. Complete removal of descent route by the Sistrunk procedure is recommended for definitive treatment. Branchial cleft anomalies are also common both in pediatric and in young adult populations. One-third of all congenital neck masses are the result of incompletely obliterated embryonic branchial tissue, which may be in the form of a cyst, sinus, or a fistula.1,11 Evaluation of their location and course requires understanding the branchial cleft embryonic development. First-arch anomalies represent about 1% of all branchial arch anomalies and are classified as type 1 or type 2. Type 1 anomalies are duplications of the external auditory canal, and they can have attachments to the skin of the external auditory canal. Type 2 anomalies are found within the parotid gland deep to the facial nerve. Their relation with the facial nerve makes the management difficult.1 Anomalies of the second arch are by far the most common (representing 95% of all branchial cleft anomalies) and typically manifest as a submandibular cystic mass, anterior to the SCM ( Third- and fourth-arch anomalies are extremely rare. Third-arch anomalies run deep to the internal carotid artery and open into the piriform sinus through the thyrohyoid membrane. They are superior to the superior laryngeal nerve. Fourth-arch anomalies are side dependent: on the right, they lie deep to the subclavian artery, whereas on the left they course under the aortic arch. Ultimately, they can enter the piriform sinus, inferior to the superior laryngeal nerve, and can be intimately associated with the thyroid gland.1 Evaluation of branchial cleft anomalies usually requires CT scan and US. US shows the cyst structure and enables aspiration and drainage, if required. CT scan with contrast shows the anatomic relations in the neck including the carotid artery.
1.1 Introduction
1.2 History and Physical Examination
1.3 Relevant Anatomy and Nodal Classification
1.3.1 Triangles of the Neck
1.3.2 Lymph Node Regions
1.4 Diagnostic Testing
1.5 Laboratory Testing
1.5.1 Imaging
Table 1.1).
Fig. 1.1). On the one hand, CT scans may provide excellent details about the head and neck mucosal sites, locate masses within or outside of glands or nodal chains, and give relation of the mass to lymph nodes, major blood vessels, airway, and bony structures such as the mandible and vertebral column.1 On the other hand, CT scans may expose the individual to radiation, which can be an important issue in pediatric cases or with repeated scans. Also, iodine contrast may cause allergic/anaphylactic reaction in susceptible individuals and may cause nephrotoxicity, particularly if utilized in a dehydrated patient.
1.5.2 Fine-Needle Aspiration Biopsy and Cytological Analysis
1.6 Differential Diagnosis of Neck Masses
1.6.1 Infectious and Inflammatory Lesions
1.6.2 Congenital Lesions
Thyroglossal Duct Cyst
Branchial Cleft Anomalies
Fig. 1.2). The course runs always lateral to the internal carotid artery. If it is in the form of sinus or fistula, it enters the pharynx at the tonsillar fossa. It may get infected during the course of an upper respiratory tract infection. Differential diagnosis may be required from cystic metastatic lymph nodes, especially in the young adults.
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