9 Cervical Lymphadenopathy
Cervical lymphadenopathy is enlargement of, and implies disease involving, the cervical lymph nodes. The commonest causes are infection, inflammation and metastatic neoplasia. Patients with cervical lymphadenopathy present with a lump or several lumps in the neck. It is a common clinical problem and a favourite subject in examinations. Details regarding other neck lumps are found elsewhere (see Chapter 54, Neck Swellings). The remainder of the chapter is confined to cervical lymph node diseases and to the problem of neck node metastases. The causes of cervical lymphadenopathy are summarised as follows:
a. Acute (commonest): Viral or bacterial upper respiratory tract infection, acute oral and dental pathology, tonsillitis, infectious mononucleosis, Kawasaki’s disease in children.
b. Chronic: Tuberculosis, atypical mycobacterial infection, actinomycosis, toxoplasmosis, brucellosis, HIV, cat scratch disease, periodontal disease.
Sarcoidosis, systemic lupus erythematosus (SLE).
Lymphoma, metastases from head and neck primary, metastases from distant sites (e.g. lung, upper gastrointestinal tract, breast), skin cancer metastases.
9.1 Clinical Features
Most patients should present to secondary care via a rapid access referral to a dedicated Neck Lump Clinic. A thorough focused history and past medical history are extremely helpful. Most patients will have reactive lymphadenopathy. There may be a history of intermittent lymph node enlargement/regression which can occur in, not only reactive nodes, but also in lymphoma. Foreign travel and ethnicity may be suggestive. Systemic symptoms including loss of appetite and weight, and night sweats occur in lymphoma when there is a high volume of disease, but can also occur in inflammatory conditions and the menopause. In conjunction with the history a careful examination of the upper aerodigestive tract, ears, head and neck skin (don’t forget the scalp) will reveal the most likely diagnosis in most cases. The site, size and number of nodes should be recorded. The position of the nodes may point towards the eventual diagnosis. Enlarged upper neck nodes are usually from a head and neck source, parotid nodes are often enlarged in skin tumours, occipital nodes from scalp skin inflammation, supraclavicular nodes may be from gastric carcinoma (Troisier’s sign/Virchow’s node), and other sites below the clavicle (e.g. lung, breast, prostate). Generalised lymphadenopathy could suggest a lymphoma or an infection/inflammatory process.
Specific investigations will be dictated by the differential diagnosis.
• Fine-needle aspiration (FNA) biopsy is probably the single most useful diagnostic procedure. False-negative and, very rarely, false-positive results can occur with FNA cytology, so the information must always be used in conjunction with the clinical findings.
• An ultrasound scan may delineate impalpable nodes and confirm the ultrasonic characteristics of the node. Normal lymph nodes are a size less than 1 cm (or 1.5 cm for the jugulodigastric node), oval shaped, have well-defined borders and a well-preserved fatty hilum. Pathological nodes tend to be enlarged, with a round shape, indistinct borders, an infiltrated hilum and increased vascularity (see Chapter 40, Imaging in Head and Neck Surgery). Ultrasound (US) is also useful in directing FNA biopsy. It has been shown in several studies that US-guided FNA biopsy will give more accurate results than non-guided biopsies.
• Patients in whom there is clinical suspicion of an upper aerodigestive tract cancer should have a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the head and neck. A CT scan of the chest and upper abdomen to exclude metastases or a synchronous primary would also be mandatory in this event. Patients who have a lymphoma should have staging CT scans of the neck, chest, abdomen and pelvis. Patients who present with a primary of unknown origin should have an MRI of the head and neck and a positron emission tomography–computed tomography scan (PET-CT).
• Blood tests will be directed by the suspected cause. Antibody assays and serology are useful if HIV, cat scratch disease, toxoplasmosis or brucellosis are suspected.
Cervical lymphadenopathy is the most common head and neck manifestation of Mycobacterium tuberculosis infection. Most patients do not have a history of recent contact with the disease, but some may have visited epidemic areas. Half of them will have systemic symptoms. The nodes tend to be tender and the overlying skin may be inflamed with occasional sinus formation. US will often show multiple matted nodes. FNA cytology may reveal mycobacteria. A chest X-ray (CXR) and intra-cutaneous tuberculin test (Mantoux) complete the diagnosis. Incisional biopsy should be avoided as it may lead to a discharging sinus. Immediate anti-tuberculous chemotherapy with isoniazid, rifampicin and ethambutol is the usual regime. Neck dissection with excision of soft tissue and skin may be required.
9.3.2 Atypical Mycobacterial Infection
More commonly seen in children and caused by Mycobacterium avium complex and occasionally by Mycobacterium scrofulaceum and Mycobacterium haemophilum. The diagnosis is suggested by a negative tuberculin test. It usually manifests as lymphadenitis in the submandibular region. Suspicion of atypical mycobacterial aetiology of cervicofacial lymphadenitis should warrant surgical excision of all affected lymph nodes. Medical therapy with antibiotics is inferior to surgery. Incision and drainage should not be done as there is a high probability of recurrence and chronic sinus tract formation with discharge. Adjuvant antibiotics are not proven to improve outcome of this disease.
This is a parasitic infection with Toxoplasma gondii whose main reservoir is in cats, but transmission usually occurs from raw or under-cooked meat and unclean vegetables. Patients have cervical nodes with fever and malaise, and the diagnosis is confirmed by serology. Treatment is not usually indicated as it is self-limiting, but pyrimethamine or clindamycin have been used.
9.3.4 Cat Scratch Disease
This is an infection caused by Bartonella henselae acquired by exposure to an infected kitten or cat. Patients present with neck nodes and associated fever and arthralgia. A history of cat scratch should alert the possibility of the diagnosis. Diagnosis may be made from serological testing or from polymerase chain reaction (PCR) of a biopsy specimen. Serology consists of indirect fluorescence assay (IFA) and enzyme-linked immunoassay (ELISA) testing to detect serum antibodies to B. henselae, a titre above 1:64 suggesting recent infection. Paired acute and convalescent sera, taken 6 weeks apart, and showing a fourfold increase in titres, are confirmatory. PCR requires a biopsy specimen (which is rarely necessary), but it can differentiate Bartonella species, sub-species and strains. It is not readily available. Many infections resolve without intervention, but azithromycin and ciprofloxacin have been advocated.
Oral cavity anaerobes cause infection in the neck, usually following surgery or trauma to the mouth. It presents as a slow-growing anterior cervical triangle mass, or an abscess with sinus tracts to the skin. It can mimic tuberculosis (TB) or malignancy. The organisms form characteristic colonies known as sulphur granules, which may be apparent on FNA cytology. Treatment is with a 2-month course of penicillin and removal of any carious teeth.
There are many causes of inflammatory cervical lymphadenopathy including unusual conditions such as Kikuchi’s, Castleman’s and Rosai–Dorfman disease. However, two of the more common causes are detailed below.
This multi-system chronic inflammatory condition is characterised by the formation of non-caseating, epithelioid granulomata at various sites in the body. It largely affects patients in their 20s to 40s, but cases do appear infrequently in younger and older patients. Many patients will be asymptomatic, but some will present with fever, fatigue and lassitude. It has a predilection for the lungs, but also the skin (erythema nodosum), the eyes (uveitis), central nervous system (CNS) (Bell’s palsy), joints (arthritis) and often causes hypercalcemia. From an ENT perspective, it can cause sinonasal problems, salivary gland swelling (Heerfordt’s syndrome is bilateral parotid involvement, anterior uveitis, fever and facial palsy) and commonly, cervical lymphadenopathy. Diagnosis is usually reached by a CXR showing lung disease, a high calcium level, elevated angiotensin-converting enzyme (ACE) level, caseating granuloma on biopsy, and a negative tuberculin test. Treatment is with steroids and symptomatic.
9.4.2 Systemic Lupus Erythematosus
SLE is an autoimmune disease. Symptoms vary but include painful and swollen joints, fever, chest pain and hair loss. ENT manifestations include cervical lymphadenopathy, recurrent mouth ulceration, motility disorders of the oesophagus and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission when there are few symptoms. The cause is not entirely clear and it is diagnosed most commonly by anti-nuclear antibodies on serology. There is no cure for SLE. Treatments may include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, immunosuppressants, hydroxychloroquine and methotrexate.
9.5.1 Primary Lymphoma
The head and neck region is a common presenting site for lymphomatous lymphadenopathy. Lymphoma affects a wide age range. The nodes are often multiple, large and rubbery in consistency. Diagnosis may be suspected from FNA results, but confirmation requires a formal biopsy, either incisional or excisional, for formal tissue typing. Further management is usually undertaken by a haemato-oncologist and early liaison with them is essential. The patients are usually staged with an MRI or CT scan of the neck and CT of the chest, abdomen and pelvis or may undergo a PET-CT scan.
9.5.2 Metastatic Neck Nodes
• Squamous cell carcinoma (SCC) in a neck node may be metastatic from the upper aerodigestive tract (head and neck primary) or the skin.
• The salivary gland tumours which commonly metastasise are carcinoma ex pleomorphic salivary adenoma, high-grade mucoepidermoid and SCC.
• Papillary carcinoma of the thyroid also has a propensity to present with nodal disease.
• The carcinoma may also be from non–head and neck sites, usually the lung, upper gastrointestinal tract, breast or prostate.
A primary carcinoma arising in the upper aerodigestive tract may metastasise to the lymph nodes of the neck. Cervical node status is one of the most important prognostic factors in the head and neck cancer patient. In a patient with positive nodal disease, the usual expected survival rate for any specific primary tumour can be reduced by up to one-half. Therefore, control of regional metastatic disease constitutes a significant part of the management of head and neck cancer.
There are approximately 150 lymph nodes on each side of the neck and they are divided into superficial and deep groups. Most descriptions of cervical lymphadenopathy begin with which triangle of the neck the nodes are positioned. The anterior triangle is bounded by the mandible, anterior aspect of sternocleidomastoid, and the midline. The posterior triangle is bounded by the sternocleidomastoid, the trapezius muscle and the clavicle (Fig. 9.1). The lymph nodes are usually described within the seven levels of the neck (Fig. 9.2).
The following definitions are recommended for the boundaries of cervical lymph node groups:
• Level I (submental and submandibular nodes)
Consists of the submental (level IA) nodes—within the triangular boundary of anterior belly of digastric and the hyoid bone—and sub-mandibular lymph nodes (level IB)—within the triangle bounded by the anterior belly of the digastric, the hyoid bone, the posterior belly of digastric and the body of the mandible.
• Level II (upper jugular)
Consists of lymph nodes located around the upper third of the internal jugular vein and adjacent spinal accessory nerve extending from the skull base above to the level of the inferior border of the hyoid bone below. Sub-level IIA nodes are located anterior medial to the vertical plane defined by the accessory nerve and level IIB nodes are located posterior lateral to the accessory nerve.