The formation in the neck: examination of the patient and differential diagnosis
Dr. Vilija Rupšienė
Republican Šiauliai Hospital
Introduction
Neck mass is a common problem that prompts patients to seek medical attention (1). Patients usually discover the mass incidentally or it is pointed out by others (1). Often, the patient has no other complaints (1). The first step when a patient presents with a neck mass is a thorough collection of medical history and examination (2). Subsequently, it is usually possible to preliminarily assess to which of the three categories the existing pathology can be attributed: a) congenital pathology, b) inflammatory process in the neck, c) neoplasm (3). Congenital pathology usually manifests in childhood (3). In inflammation (both infectious and non-infectious), there is an enlargement of regional lymph nodes and local as well as systemic signs of inflammation (1). Suspecting that the mass is neither due to congenital pathology nor inflammation, the first priority is to assess whether the mass is malignant; only after confirming that the mass is benign, the diagnosis of a malignant mass is ruled out (2, 4). An assessment of the anatomical location sometimes also helps to orient towards the possible etiology of the neck mass (3).
Patient Examination for Observed Neck Mass
Medical History
Thorough collection of medical history usually narrows down the list of possible diagnoses (1). It is very important to assess the patient's age:
• up to 16 years old – masses are usually of inflammatory origin or due to congenital pathology;
• 16–40 years old – inflammatory and congenital masses still predominate, but the likelihood of malignant masses increases;
• >40 years old – it is reasonable to consider that a neck mass is a neoplasm and possibly malignant until proven otherwise (1, 5).
The rate of mass growth is also evaluated - how long the mass has been observed, how it is growing, whether there is pain or not:
• masses that have been observed for several years and remain unchanged over time are more likely benign (e.g., benign salivary gland tumors, paragangliomas);
• rapidly growing masses raise suspicion of an infectious process or rapidly growing lymphomas;
• masses that change in size due to viral diseases or upper respiratory tract infections are usually congenital cysts (1, 5).
Pain is usually proportional to the rate and spread of mass growth, and can also be due to direct involvement of nerve structures in the malignant process (1). For example, a fixed and painful parotid gland mass is likely to be malignant (1).
Symptoms such as voice changes, hoarseness, dysphagia, ear pain suggest that the mass is a metastatic lymph node due to oncological diseases of the upper respiratory tract or upper digestive tract (1). It is important to ask the patient about fever, night sweats, weight loss - symptoms typical of lymphomas (1). However, a very high, rapidly rising temperature is more characteristic of infectious diseases (1).
Assessing social factors is also important: smoking, alcohol consumption, drug use, human immunodeficiency virus (HIV) infection, it is important to know what risk factors the person faces in the workplace, whether there is contact with animals, or recent travel history (1). Oral cavity and throat cancer are associated with smoking and alcohol consumption, but in recent years, there has been an increase in cases of squamous cell carcinoma in this location related to human papillomavirus (6). Squamous cell carcinoma associated with human papillomavirus is most commonly diagnosed in white, non-smoking men up to 65 years of age, without other serious illnesses, with a higher social and economic status, and with risk factors for human papillomavirus infection (7). Most concerning is that about two-thirds of cases present as asymptomatic neck masses - delaying the diagnosis of the disease (8).
Physical Examination of the Patient
First, the head and neck area is carefully evaluated, but often a more comprehensive assessment is necessary due to possible systemic pathology - infections, inflammatory and oncological diseases (1).
Assessment of the location of the neck mass helps to evaluate its possible origin:
• area in front of the ear and angle of the mandible - characteristic of parotid gland or lymphatic tissue pathology in the parotid region;
• central neck area - characteristic of thyroid pathology, malignant mass, or cyst;
• upper anterior area from the sternocleidomastoid muscle - in adults, enlarged lymph nodes are most commonly observed (enlargement is also possible due to a malignant process), in children (less frequently in adults), congenital pathologies are more often seen, for example, branchial cleft cysts;
• posterior triangle of the neck - high risk of a malignant process when a mass is observed in this area;
• supraclavicular areas (especially on the left side) - possible metastasis due to lung, gynecological, or gastrointestinal oncological diseases (1, 9).
When palpating the mass, attention is paid to its location, size, shape, consistency, tenderness, mobility, and color:
• so-called reactive lymph nodes are usually palpable as solitary, mobile, firm or rubbery (but not as hard as a stone) and are slightly painful;
• Solid, non-tender, painless formations raise suspicion of a malignant process;
• Infected lymph nodes usually present with isolation, asymmetry, characteristic tenderness, warmth, and redness at the site of the formation, fluctuation may be felt;
• A soft, fluctuant, movable formation is usually a congenital cyst, but it should be noted that in adult patients, a cystic formation in the neck is also characteristic of metastatic human papillomavirus-related squamous cell carcinoma;
• A firm formation on the side of the neck, with mobility to the sides but not vertically, may be due to the involvement of the carotid sheath in the pathological process - due to a carotid body tumor or vagus nerve schwannoma;
• Pulsation or audible bruit is characteristic of vascular origin formations;
• A non-tender, but elevating when swallowing saliva formation along the midline of the neck is characteristic of thyroid pathology and thyroglossal duct cysts (1).
General patient examination. A thorough examination of the oral cavity and oropharynx is advisable, assessing possible mucosal lesions, bimanual examination of the floor of the mouth, tongue, and neck (1). During ear examination, unilateral serous exudate in the middle ear may be associated with nasopharyngeal carcinoma (1). In the absence of changes in the oral cavity and oropharynx, a targeted examination of the nasal cavity and throat is performed using mirrors or a flexible fiberoptic endoscope (1). A visual inspection of the scalp and neck skin is recommended for possible squamous cell skin carcinoma or melanoma (1). Evaluation of cranial nerves can help assess possible nerve tumors or contact nerve damage (1). Generalized skin rash suggests a systemic viral infection, while localized skin lesions may indicate more specific infections (e.g., cat scratch disease, tularemia) (1). Abdominal palpation should assess for possible liver or spleen enlargement, or non-palpable unclear formations (1).
Instrumental examinations
Imaging studies allow evaluation of the anatomical location, consistency, involvement of adjacent structures, blood flow, and suspected primary focus of oncological disease in the neck (1). Valuable methods include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), combined positron emission tomography (PET) with CT scans (1, 10).
Ultrasound examination is the least invasive, providing real-time evaluation of the formation and its position in relation to other neck structures (11). Ultrasound-guided fine-needle aspiration can be conveniently performed during the ultrasound examination (1). Ultrasound is excellent for initial assessment of a formation, especially when the likelihood of oncological disease is low, for example, when evaluating thyroid nodules (1). Ultrasound is useful to avoid ionizing radiation, for instance, in pediatric patients or when frequent imaging follow-up is needed (1). Ultrasound examination is relatively inexpensive (1). However, its main drawback is the subjective interpretation of results, highly dependent on the examiner's experience, equipment used, and challenges in image storage (as it is a real-time examination) (1).
CT scan is well-tolerated by patients and is performed relatively quickly (1). It is excellent for evaluating bony structures, making it suitable when a formation originates from bone tissue or is closely related to bone (1). CT is a valuable tool when there is a high suspicion of oncological disease or when deeper neck structures are suspected to be affected, particularly areas that are difficult to visualize with ultrasound, such as the parapharyngeal or masticator muscle regions (1). During CT scans, ionizing radiation is used, with an average radiation dose of 4 mSv for a head and neck examination (12).
MRI is useful for assessing soft neck tissues, such as infiltrating soft tissue masses, suspected perineural spread of malignant disease, or lesions of central nervous system origin (1). Drawbacks of MRI include its cost, lengthy scan duration, and potential discomfort for claustrophobic patients (1).
PET combined with CT imaging is beneficial in oncological diseases (1). PET/CT scans are more useful for evaluating treatment response, residual disease, and less useful for primary neck formation assessment (1). A patient undergoing this examination receives a relatively high radiation dose of about 32 mSv (13).
Invasive examinations
Fine-needle aspiration (FNA) is the primary choice of examination when a neck formation is present (1). It is performed using a 25 G or 27 G needle with a 20 ml syringe (1, 14). The aspirated material for cytological examination can be prepared on glass slides - the accuracy of the test is limited by blood, various slide thicknesses, and a small amount of cells (1). A more accurate examination is performed when cell blocks are prepared along with the slide - the aspirated material is placed in a special solution, then centrifuged, and the mentioned cell blocks are prepared (1). The aspirated material can also be tested using biochemical tests - suspecting metastasis of papillary or follicular thyroid carcinoma, a thyroglobulin concentration test is performed, suspecting parathyroid adenoma, parathormone concentration is examined, suspecting medullary carcinoma metastasis, a calcitonin test is performed (15). The aspirate can also be tested using the polymerase chain reaction (PCR) method - it is important to determine human papillomavirus expression in cases of oropharyngeal squamous cell carcinoma (1).
Differential Diagnosis
Congenital Pathology
The formation in the neck, if it is a congenital pathology, is usually detected after birth, but can occur in people of any age (3). In children, non-infectious neck formations are usually congenital (3). In the adult patient group, a neck formation that is always present at the beginning should be evaluated as malignant until it is determined to be benign (4). Cystic structure is characteristic of congenital formations. Therefore, when a cystic structure is detected in an adult's neck, it is not appropriate to assume that the formation is congenital and benign until it is proven that the formation is non-malignant (3). Tonsil, tongue base, and thyroid carcinomas can also have a cystic structure (3).
Branchial arch cysts account for about 20% of all neck formations in children (16). They are most commonly diagnosed in late childhood or early adulthood when an undiagnosed cyst becomes infected (3). The characteristic localization of cysts is in front of the sternocleidomastoid muscle (3). In cases of recurrent infections of branchial arch cysts, a fistula with the skin may form (3).
Thyroglossal duct cysts. The characteristic localization is along the midline of the neck (3). They are usually asymptomatic until they become infected - often after a respiratory tract infection (3).
Vascular anomalies are classified into vascular tumors and vascular malformations (3). Vascular tumors are neoplasms of endothelial origin (3). Hemangioma is the most common, but there can be rarer variants (hemangiopericytoma, hemangioendothelioma, angiosarcoma) (3). Hemangiomas most commonly occur in newborns and are characterized by rapid growth followed by slow regression (3). Typically, this condition is indicated by changes in the skin above the formation (palpable compressible, soft, red or bluish structure), and a bruit may be heard on auscultation (3). Vascular anomalies develop due to incorrect embryo and fetal development (3). Vascular anomalies can be arterial, venous, lymphatic, or mixed in origin (3). Neck formations usually develop due to lymphatic malformations (3). Upon examination, a soft, painless, compressible structure is usually palpable, the skin above the formation is unchanged, and the formation may transilluminate (3).
Laryngocele - a dilatation of the laryngeal saccule (3). The dilatation can be limited to the laryngeal area - internal laryngocele (3). However, it can also extend through the thyrohyoid membrane - external or mixed laryngocele (3). External laryngocele presents as an air-filled cyst in the anterior neck (3). Patients usually seek medical attention due to choking, coughing, and a sensation of a foreign body (3).
Ranula - a pseudocyst that develops due to obstruction of the sublingual glands in the floor of the mouth (3). They are usually painless, grow slowly, and are typically located below the tongue (3).
Teratoma - usually arises from pluripotent cells and consists of structures from all three germinal layers (3). They are usually large, have a capsule, and have a cystic component (3).
Dermoid cysts - develop due to epithelial blockage in deeper layers during development or after trauma (3). Congenital lesions are usually along the midline, below the tongue, painless, and mobile (3).
Submaxillary gland cyst - develops due to the migration of submaxillary gland tissue along the embryonic tract during embryogenesis (3). It is usually localized along the midline, but can be anywhere from the angle of the mandible to the midline of the neck (3).
Inflammatory Neck Formations
Infectious neck formations are rare, but they should be quickly diagnosed and treated with antibiotics (1). The etiology of an infectious neck formation is suspected based on the course of the disease - the neck formation develops within a few days or weeks after respiratory, dental infections, trauma, travel, or contact with certain animals (1). Typical clinical signs:
- skin over the formation is warm, red, painful to touch, swelling around the formation;
- fever, tachycardia, or other symptoms typical of systemic infection;
- rhinorrhea, odynophagia, otalgia, toothache, or other symptoms typical of head/neck infections (1).
Lymphadenopathy is usually observed in the case of an infectious neck formation (3). However, lymphadenopathy can occur in both infectious and non-infectious inflammation (3). The most common causes of lymphadenopathy are listed in Table 1 (3).
Neoplasm
A mass in the neck may be either benign or malignant neoplasm (3). When evaluating an adult patient with a neck mass, it is recommended to consider the mass as malignant until proven otherwise (1, 4).
Suspicion of malignancy during patient evaluation is raised by:
• lack of signs of infection;
• duration of mass development ≥2 weeks or unknown;
• size >1.5 cm;
• firm consistency on palpation;
• fixed or limited mobility of the mass;
• skin ulceration overlying the mass (1).
Less suspicious but significant signs include:
• patient age >40 years;
• history of tobacco or alcohol use;
• history of head and neck tumor;
• history of scalp, facial, or neck skin tumor;
• immune system deficiency;
• hoarseness or sudden change in voice;
• ear pain or sudden onset of ear fullness on the side of the mass;
• nasal congestion or nosebleeds, especially if bleeding is from the same side nostril as the mass;
• skin ulceration in the oral cavity or oropharynx;
• odynophagia or dysphagia;
• pharyngitis or throat pain;
• coughing up blood or blood in saliva;
• dyspnea;
• unexplained weight loss;
• painless neck mass;
• asymmetric tonsils;
• skin ulcerations in the scalp, face, or neck (1).
Metastatic head and neck carcinoma most commonly metastasizes to the neck lymph nodes from squamous cell carcinomas of the respiratory and upper digestive tracts (17). This diagnosis should be one of the first in the differential diagnosis list (3). Metastatic lymph nodes often do not cause any symptoms, with clinical symptoms more characteristic of the primary oncological focus (3). To confirm the diagnosis, the first-choice test is fine-needle aspiration (3). If metastasis is detected, a search for the primary oncological focus is performed using imaging tests (3). The location of the mass can provide some clues about the localization of the primary focus: metastases are most commonly found in the posterior triangle of the neck due to nasopharyngeal carcinoma; lymph nodes affected near the superior jugular vein are usually due to oral cavity, oropharyngeal, or laryngeal pathology; isolated lymph node changes in the supraclavicular area are typical for tracheal and bronchial, distal esophageal, and gastric carcinomas (18). Additionally, head and neck skin tumors can metastasize to the neck lymph nodes: melanoma, aggressive squamous cell carcinoma, and Merkel cell carcinoma (rarely) (3). The drainage of specific head and neck areas into the neck lymph nodes is presented in Table 2 (3).
Thyroid tumor – typically presents as a mass in the front of the neck (3). The majority of thyroid masses are benign nodules or cysts, but a malignant tumor is also possible (3). Evaluation of the mass with ultrasound is recommended, and fine-needle aspiration is performed when indicated (19). A history of voice changes and previous radiation therapy in the neck area increase suspicion of thyroid oncological disease (19).
Salivary gland neoplasms – about 80% of salivary gland neoplasms are found in the parotid glands (20). About 80% of parotid gland tumors are benign, with pleomorphic adenoma being the most common (20). Malignant tumors occur in about 50% of submandibular gland neoplasms (3). Common benign salivary gland tumors include pleomorphic adenoma (comprising about 80–85% of all benign tumors), Warthin tumor, lymphoepithelioma, oncocytoma, and monomorphic adenoma (3). Common malignant tumors include mucoepidermoid carcinoma, adenoid cystic carcinoma, variants of adenocarcinoma, salivary duct carcinoma, squamous cell carcinoma, carcinoma ex pleomorphic adenoma (3). Benign tumors typically present as enlarging masses without other symptoms (3). If there is pain, clinical signs of cranial nerve involvement, skin involvement overlying the mass, a diagnosis of malignancy is more likely (3).
Paragangliomas. Carotid body and jugulotympanic paragangliomas (also known as glomus jugulare and glomus tympanicus) are highly vascularized, usually benign tumors (3). Carotid body paragangliomas typically have lateral mobility but are non-compressible vertically (3). Approximately one-third of paragangliomas are hereditary as part of a genetic syndrome, so genetic testing is recommended for patients (3).
Schwannoma - develops due to neoplastic Schwann cells (neuronal sheath cells) proliferation (3). Schwannomas are closely related to peripheral nerves, but are relatively separate from the nerves (3). Schwannomas can develop in any peripheral nerve; most commonly, vagus nerve or upper cervical sympathetic chain schwannomas develop in the neck (3). Schwannomas usually develop unnoticed, grow slowly, and may present with neurological symptoms (3). Vagus nerve schwannoma, when localized below the skull base, can cause voice hoarseness or aspiration (3). Upper cervical sympathetic chain schwannomas often present with Horner's syndrome (3). When suspecting a schwannoma, imaging studies are recommended (3). CT imaging does not always distinguish schwannoma from carotid body paraganglioma, but with contrast-enhanced imaging and absence of vascularity, it is likely that the neck mass is a schwannoma (3). MRI is a more precise study (3).
Lymphoma can manifest in the head and neck region (3). In children with Hodgkin's lymphoma, about 80% of cases involve the disease localized in the neck lymph nodes (3). Suspicion of Hodgkin's lymphoma increases when the patient is young, complains of recurrent fever, night sweats, chills, and presents with widespread lymphadenopathy (3).
Lipoma and benign skin cysts. Lipoma is a benign neoplasm of fatty tissue (3). Lipomas are usually asymptomatic (3). They grow slowly and can develop in any location in the neck (3). Lipomas are soft to the touch, with unclear borders (3). Pain, rapid growth raises suspicion of liposarcoma (malignant tumor) (3). Benign skin cysts (epidermoid cysts, dermoid cysts, pilomatrixomas) can also manifest as neck masses (3).
Summary
Most neck masses are benign. When evaluating an adult patient, one should always consider the possibility of a malignant neck mass. Only after establishing that the mass is benign, can the diagnosis of a malignant disease be ruled out. A detailed medical history, physical examination of the patient, imaging studies (if suspicion of malignancy is low, the first-choice study is ultrasound; if suspicion of malignancy is high, that the mass is malignant - CT using contrast material). Fine-needle aspiration - the first-choice invasive test.
Table 1. Possible causes of neck lymphadenopathy (3)
| Possible causes of neck lymphadenopathy | Examples |
|
Infections: Bacterial: |
|
| Localized | Streptococcal pharyngitis, skin infections, tularemia, plague, cat-scratch disease, diphtheria, chancroid, rat-bite fever |
| Generalized | Brucellosis, leptospirosis, venereal lymphogranuloma, typhoid fever |
| Viral | Human immunodeficiency virus, Epstein-Barr virus, Herpes simplex virus, cytomegalovirus, mumps, measles, rubella, hepatitis B, dengue fever |
| Mycobacterial | Tuberculosis, atypical mycobacterial infection |
| Fungal | Histoplasmosis, coccidioidomycosis, cryptococcosis |
| Protozoal | Toxoplasmosis, leishmaniasis |
| Spirochetal | Secondary syphilis, Lyme disease |
| Oncologic diseases | Head and neck squamous cell carcinoma, metastases to neck lymph nodes, lymphoma, leukemia |
| Lymphoproliferative diseases | Angioimmunoblastic lymphadenopathy with dysproteinemia, autoimmune lymphoproliferative diseases, Rosai-Dorfman disease, hemophagocytic lymphohistiocytosis |
| Immune disorders | Serum disease, drug reactions, IgG4-related disease |
| Endocrine disorders | Addison's disease |
| Various causes | Sarcoidosis, lipoidosis, amyloidosis, histiocytosis, chronic granulomatous diseases, Castleman's disease, Kikuchi disease, Kawasaki disease, inflammatory pseudotumor, systemic lupus erythematosus, rheumatoid arthritis, Still's disease, dermatomyositis, Churg-Strauss syndrome |
Table 2. Drainage of anatomical head and neck regions to regional lymph nodes (3)
| Lymph node group | Related anatomical area |
| Occipital | Posterior scalp |
| Postauricular | Lateral and parietal scalp |
| Preauricular | Anterior and lateral scalp, midface, nose, auricle, lateral conjunctiva |
| Parotid | Cheek, lateral scalp, midface, nose, external ear lobule, middle ear, gums, parotid salivary gland |
| Submandibular | Cheeks, nose, lips, front part of the tongue, sublingual salivary gland, buccal mucosa |
| Submandibular | Central part of the lower lip, floor of the mouth, tongue |
| Superficial neck | Skin, lower part of the throat, subauricular canal, submandibular salivary gland |
| Superficial deep neck | Tonsils, adenoids, posterior scalp and neck areas, tongue, larynx, lower part of the pharynx, thyroid gland, palate, nose, esophagus, preauricular glands, nasopharynx, other neck lymph nodes |
| Deep deep neck | Posterior scalp and neck areas, nasopharynx, superficial thoracic upper limb region, upper deep neck lymph nodes |
Publication "Internistas" No. 9 2019
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