Nodules in the Neck: Evaluating Potential Causes

The appearance of tumors in the neck is common. These are abnormal lesions that are located under the jaw, above the clavicle and deep in the skin. They may be visible, palpable, or seen on imaging studies. The underlying pathology of these nodules is usually not easy to identify.

Nodules in the neck can develop from infectious, inflammatory, congenital, traumatic, benign or malignant processes.

Unlike children in whom the most common cause of neck nodules is infection, in adults, the most common cause is malignancy. In fact, there is abundant literature suggesting that the persistence of a tumor in the neck of an adult should be considered malignant until proven otherwise.

As such, in adults, further investigation is essential because it may be the only manifestation of a head and neck malignancy. The location of the mass, imaging findings, and history are important in the differential diagnosis.  

A complete examination of the head and neck can provide additional details about the cause. Key components include

>  Characteristics of the tumor

-Size

-Location

-Quality (soft, fluctuating, rubbery, firm)

-Mobility (mobile, hypomobile or immobile)

-Sensitivity

>  Skin changes: skin erythema, fixed to the skin

>  Head and neck examination

• ​ Skin : evaluate the face and scalp for lesions, ulcerations, erythema

•​ Oral cavity and oropharynx : examine the tonsil, palate, posterior pharynx, tongue, tongue mobility, buccal mucosa and gum (remove dentures or other prostheses). Take into account erythema, ulcerations, decreased movements or asymmetries. Palpation of these structures may reveal occult lesions.

• ​ Nose : examine the external part of the nose, the nasal mucosa, the septum and the turbinates. Assess sinus sensitivity

• ​ Ear : evaluate the presence of hearing loss and effusions through otoscopic examination

• ​ Larynx : Palpation during swallowing and evaluation of laryngeal crepitation may reveal underlying pathology.

• Cranial nerves

Order imaging studies for patients with a neck mass who are considered to be at higher risk for malignancy. The two main imaging modalities recommended are contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI):

• CT : It is the most commonly used imaging modality for the craniocervical region and is the initial diagnostic test of choice for patients with a persistent tumor in the neck. CT has several advantages, including its wide availability, rapid acquisition, and low cost. It is an excellent initial imaging test because of its ability to characterize the mass in relation to other structures in the head and neck, and evaluate involvement of deep neck spaces. Although CT uses ionizing radiation, it is considered acceptable in the adult population.
   
• MRI : Like CT, it allows precise localization of the mass and can accurately characterize tumors and inflammation. Although both studies are effective for oncologic evaluation, MRI provides superior visualization of soft tissues and possible perineural extension. Its advantages include lack of radiation exposure, and image quality, which is preserved in patients with dental work such as crowns, caps or implants. However, MRI is more expensive, difficult for patients with claustrophobia, takes longer (approximately 30 minutes), and is contraindicated in patients with certain implantable medical devices such as pacemakers.

Regardless of the imaging modality selected, the use of contrast substance is essential unless there is a contraindication, such as contrast allergy or renal failure. There is rarely any additional benefit to ordering a non-contrast scan and therefore it should be avoided. Contrast improves nodule characterization, maps edges, and may better identify the relationship of the neck nodule to major vessels.

The other commonly used imaging modality is ultrasound , which is the least invasive imaging technique and can provide real-time evaluation of the mass and image-guided sampling. Ultrasound can adequately characterize benign, vascular, inflammatory, and malignant lesions, and is the gold standard for evaluating the thyroid. However, there are several disadvantages to using this tool.

One limitation is the evaluation of deep neck spaces, and is highly operator dependent. Therefore, it is not recommended as a first option. The few exceptions to this are delay in obtaining CT/MRI, contraindication to the use of contrast, or its need as an adjunct to accelerate a fine-needle aspiration (FNA) biopsy.

In cases of uncertain diagnosis, a biopsy is indicated. FNA represents the gold standard and should be the initial test for histological evaluation. It is a procedure using a small gauge needle (25 or 27) that is inserted into the mass to obtain a small sample.

FNAB does not expose patients to the risks of anesthesia. It can be done with and without image guidance using ultrasound or CT. It is highly accurate, safe, cost-effective, and provides a timely diagnosis with lower morbidity compared to an open biopsy.

Although FAP of neck nodules is very accurate, some results may not provide a definitive answer; which may occur because there is not enough lesional material for the pathologist to make a diagnosis, which is usually described as inadequate specimen. The other reason this can occur is when there is enough sample but the cells obtained from it do not provide a specific diagnosis. In both cases, if the patient presents with worrying signs and symptoms of malignancy or has a persistent nodule in the neck, a repeat FNA should be attempted before resorting to an open biopsy.

If FNA results are inadequate or indeterminate to provide a diagnosis, a core or core biopsy may be considered . This biopsy is generally performed under local anesthesia, using a larger gauge needle compared to FNA(14-18) for tissue removal. Core needle biopsies can also be chosen when lymphoma is suspected, as it allows for greater appreciation of the tissue architecture. However, core needle biopsies increase the possibility of trauma due to their larger caliber, in addition to increasing the risk of tumor seeding, the latter being the reason why it is contraindicated in patients with suspected squamous cell carcinoma (SCC). .

On the other hand, the most definitive way to obtain a diagnosis is an open biopsy. It consists of making an incision in the neck and removing all or part of the tumor; which is done under local anesthesia and often in an operating room. Because it is more invasive than FNA, it should be reserved for those cases where FNA has failed to provide a diagnosis or the pathologist requires more tissue.

Certain laboratory tests may be useful and are ordered based on clinical suspicion of a specific disease.

In adults, common causes of neck nodules can be classified into 6 main categories:

• Congenital

• Thyroglossal duct cysts : They are the most common congenital anomaly of the head and neck region, and although they are more commonly seen in children, they can be present in 7% of the adult population. These malformations can develop anywhere between the base of the tongue to the native position of the thyroid in the neck. Most commonly, they present as midline cysts near the hyoid bone that rise with tongue protrusion or swallowing. These cysts can be observed in their evolution or surgically removed using the Sistrunk procedure, which involves removing the cyst along with a portion of the hyoid bone.

• Branchial cleft cysts : are a congenital anomaly that can arise from the first to the fourth pharyngeal cleft. Similar to thyroglossal duct cysts, they are usually present at birth but become evident or symptomatic in childhood. Rarely, these cysts can persist into adulthood and are often discovered when they become tender, larger, or inflamed after an upper respiratory infection. They can also become infected and cause purulent drainage into the skin or pharynx. Treatment consists of surgical excision.

• Venolymphatic malformations

 - Cystic hygroma (lymphangioma): is a benign congenital anomaly of the lymphatic system that occurs most commonly in children. It rarely occurs de novo in adult patients. These lymphatic malformations can occur anywhere in the head and neck region, with mild, fluctuating pain and enlargement of the neck tumor. The cause is unknown, but it is likely due to acquired processes such as infection, surgical manipulation, or lymphatic obstruction. These tumors can be observed or treated with sclerotherapy or surgery.

• Venous malformations : arise from abnormal and ectatic venous channels and often occur in the head and neck region. Similar to hemangiomas, venous malformations may be present at birth; However, they tend to grow as the patient ages, without spontaneous resolution. Depending on their size, architecture, location, and flow rate, they may be asymptomatic or cause significant morbidity (pain, discomfort, life-threatening bleeding, or respiratory compromise). Current therapeutic strategies are: surgery, laser therapy or sclerotherapy.

-  Pseudoaneurysms or arteriovenous fistulas: can occur as a result of sharp or penetrating trauma to the neck. They present with mild, throbbing pain. The tumor has a thrill or murmur. These masses are potentially lethal and require prompt treatment to prevent rupture or neurological dysfunction. In the past, the standard treatment was surgical repair and ligation of the carotid artery, but now, endovascular techniques with stenting have evolved as effective options.

• Infectious 

-  Viral infection : various viruses can cause lymphadenopathy. The most common ones that cause upper respiratory tract infections are: rhinovirus, coronavirus and influenza. The resulting lymphadenopathy usually resolves within 3 to 6 weeks after symptomatic resolution.

• Bartonella henselae : is the etiologic agent of cat scratch disease, and classically, these patients present after a bite/scratch from an infected cat. Patients may develop a bulbous or vesicular lesion at the inoculation site, followed by ipsilateral lymphadenopathy in the cervical, inguinal, or axillary region. The usual treatment is a 5-day course of azithromycin.

-  Tuberculous cervical lymphadenitis : tuberculosis of the lymph nodes is one of the most frequent extrapulmonary manifestations of the disease. It may be caused by tuberculous or nontuberculous mycobacteria and may be observed in immunocompromised patients or those who have recently traveled to endemic regions. It usually presents as a chronic, painless cervical tumor without apparent signs of infection such as heat or edema. This finding may be accompanied by other constitutional signs of tuberculosis, such as night sweats, chills, and involuntary weight loss.

• Benign tumor

-  Lipomas : they are benign subcutaneous nodules of mesenchymal origin that can occur in the head and neck region. They are usually smooth and mobile and asymptomatic. They may remain under observation or be surgically removed.

-  Thyroid nodules : they are common and can be seen in 65% of the population. Most are benign and are usually found incidentally. The gold standard for evaluating a thyroid nodule is ultrasound. Results are reported based on the TI-RADS (Thyroid Imaging Reporting & Data System) score. Management of thyroid nodule depends on the size of the nodule combined with the TI-RADS score, which may be observation or indication for FNA of the nodule. FNAC results are typically reported using the Bethesda Classification.

• Malignant neoplasm:

-   Malignant neoplasm of the upper aerodigestive tract. Malignant neoplasms in the oral cavity, nasopharynx, oropharynx, sinonasal cavity, hypopharynx and larynx can metastasize to the neck, with a nodular appearance. The most common malignancy is SCC, which is usually caused by alcohol, smoking, and also the human papillomavirus. The presentation of SCC on the head and neck caused by smoking and alcohol is quite different from that of SCC caused by papillomavirus. SCC caused by smoking and alcohol presents with painful tumors in the neck and upper aerodigestive tract along with other symptoms such as dysphagia, odynophagia, voice changes or otalgia. On the other hand, patients with SCC caused by papillomavirus present only with a painless tumor in the neck, and most of them have no other symptoms, and are often mistakenly diagnosed as a branchial cleft cyst. Management of cancers of the upper aerodigestive tract depends on the location and stage of the cancer.

-  Thyroid cancer : the most common type of thyroid cancer is papillary. Other cancers of the thyroid gland include follicular, medullary, and anaplastic cancers. In general, it has a very good prognosis, with the exception of anaplastic carcinoma. Treatment typically involves a thyroidectomy and may include adjuvant radioactive iodine based on the pathology.

-   Salivary gland cancer : these cancers can originate in the major (parotid, submandibular and sublingual) or minor salivary glands (located throughout the upper digestive tract). Management typically involves surgery followed by adjuvant therapy depending on the pathology.

-   Lymphoma : Cervical lymphadenopathy is one of the most common manifestations of lymphoma. Lymphoma is usually classified as Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma usually involves lymph nodes in the neck, while non-Hodgkin lymphoma can spread to extranodal sites, including the major salivary glands, paranasal sinuses, and Waldeyer’s ring. The signs in the images do not allow us to differentiate these 2 forms. Management generally involves chemotherapy and sometimes the addition of radiation therapy.

-  Metastasis of thoracoabdominal malignant tumors : occasionally, malignancies of the abdomen and thorax can metastasize to a supraclavicular lymph node, known as Virchow’s node. The management of these cancers is based on malignancy.

• Systemic diseases:

-  Sjogren’s syndrome : this is an autoimmune disease that commonly occurs in older women. Patients typically present with dry eyes and mouth. Many show persistent enlargement of the submandibular or parotid glands. Patients may have elevated levels of antineutrophil antibodies and rheumatoid factor, as well as anti-Ro/SS-A or anti-La/SSB antibodies. However, these antibodies are not specific for the syndrome. Treatment is intended to control symptoms, including topical tear replacement for xerophthalmia, and oral hygiene to increase the flow rate of salivation.

-  Sarcoidosis : This inflammatory syndrome is characterized by the development of granulomas, leading to permanent scarring or thickening of the organ tissue. Signs and symptoms depend on the location of the granulomas, and up to 10%-15% of patients may have head and neck manifestations. In many cases, sarcoidosis will resolve on its own; But there are several therapies including steroids, immunosuppressants and antimalarial medications, which can control symptoms and prevent further destruction.

-  Other autoimmune diseases : Several conditions including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and vasculitis may have manifestations in the head and neck region and may be the only presenting feature. Laboratory tests are needed to classify the specific type of autoimmune disease while management depends on the type of disease.

Management of a neck lump depends on the underlying cause. Because the most common cause of a neck lump is infection, it is reasonable to prescribe an antibiotic and reevaluate in 2 weeks. Additional evaluation is warranted in patients who do not respond appropriately or have a recurrence of the neck mass.

There are several causes of neck lumps, and it can be very difficult to discern a precise cause. Using a systematic approach will usually result in an accurate diagnosis and guide appropriate treatment. A careful history and physical examination can provide important clues regarding the diagnosis and dictate the need for follow-up and evaluation with imaging, tissue biopsies, and referrals to specialists. The most important cause that must be ruled out is malignancy.

In cases where a diagnosis is not obtained, patients should be monitored closely. If the mass does not resolve or recurs, repeat testing and/or referral to the appropriate specialist should be considered.