Lymph nodes: how they are examined and what they look for

Lymphadenopathy refers to a node's abnormal size, consistency, or morphology. It is a common finding in outpatient practice, but the range of causes is broad: from benign reactive changes associated with infections to hemato-oncological diseases and metastases. Early risk stratification based on clinical features helps reduce unnecessary testing and prevent the detection of malignant processes. [1]

Warning signs include age over 40, male gender, supraclavicular location, persistence of more than 2 weeks, and systemic symptoms such as unexplained weight loss, night sweats, and fever. These factors increase the pretest probability of a tumor cause and require more aggressive management. [2]

The nature of the spread is important. Localized lymphadenopathy is more often associated with processes in the regional drainage zone. Generalized lymphadenopathy, that is, the involvement of at least two non-adjacent zones, more often indicates systemic diseases such as viral infections, HIV, tuberculosis, sarcoidosis, drug reactions, and hematological diseases. [3]

Any rapidly increasing painful infiltration with hyperemia, bullae, areas of necrosis, severe pain “not in appearance” is considered a possible necrotizing soft tissue infection and requires immediate hospitalization. [4]

Anatomy in practice and normal sizes

Clinically significant nodes include those of the neck, supraclavicular, axillary, epitrocheal, inguinal, and popliteal origin. The assessment is conducted taking into account normal limits by region: for most zones, the upper limit is approximately 1 cm along the short axis, however, for jugular-digastric nodes, a size of up to 1.5 cm is acceptable, for inguinal nodes, values up to 1.5 cm are acceptable, and epitrocheal nodes greater than 5 mm are considered enlarged. Any supraclavicular nodes are clinically significant, regardless of size. [5]

The size criterion is always interpreted in the context of shape and structure. An oval shape with a preserved fatty hilum is typical of a reactive nodule, whereas a round shape, cortical thickening, loss of the hilum, and characteristic vascularization increase the likelihood of a malignant lesion. For cervical nodules, the short axis is used as a guideline, as it better correlates with risk. [6]

The degree of suspicion also depends on the draining areas. For example, supraclavicular nodes often reflect pathologies of the chest and abdominal organs, axillary nodes reflect pathologies of the mammary gland and upper limb, and inguinal nodes reflect pathologies of the lower limb, external genitalia, and the anterior abdominal wall below the umbilicus. These connections help to collect a targeted history and select examinations. [7]

Finally, in children, physically palpable small cervical and inguinal nodes are common and often benign. However, epitrocheal and supraclavicular nodes require careful evaluation at any age. [8]

Table 1. Normal size guidelines for anatomical regions in adults

Region	The "usually normal" benchmark	Comments
Cervical jugular-digastric	up to 1.5 cm	in other cervical ones, they are more often oriented at 1.0 cm along the short axis
Epitrocheal	up to 0.5 cm	more than 5 mm is considered an increase
Axillary	up to 1.0 cm	context of the mammary gland and skin of the upper limb
Inguinal	up to 1.5 cm	more often reactive in dermatitis and foot infections
Supraclavicular	any size is significant	high oncological alertness

[9]

History taking and red flags

The first set of questions clarifies the duration, dynamics, accompanying symptoms, and possible triggers. It is important to inquire about previous upper respiratory tract infections, skin infections in the drainage area, contact with cats, travel, risk of tuberculosis, sexual contact, medications, and vaccinations. Weight loss, night sweats, and persistent fever are assessed separately. [10]

Common situational causes include post-vaccination axillary lymphadenopathy on the injection site, which can persist for weeks or months and should not delay breast screening. Documenting the date and site of vaccination is recommended, and delayed follow-up is recommended unless the findings appear suspicious. [11]

Red flags include supraclavicular nodes, enlarged epitrocheal nodes, persistence for more than 2-4 weeks without a tendency to regress, progressive enlargement, a hard or "woody" consistency, attachment to surrounding tissue, and systemic symptoms. These signs should prompt imaging and a decision on biopsy. [12]

In cases of generalized lymphadenopathy, the initial screening includes testing for HIV and tuberculosis, as well as basic screening for herpes viruses and toxoplasmosis, depending on the clinical situation. Immunodeficiency factors and medications taken are clarified. [13]

Table 2. Red flags for lymphadenopathy

Sign	Why is it important?
Supraclavicular node of any size	high probability of malignancy
Epitrocheal node greater than 5 mm	often associated with systemic pathology
Duration more than 2-4 weeks without regression	increases oncological alertness
Solid, fixed, merger into a conglomerate	suspected metastases or lymphoma
Systemic symptoms and generalization	indicates systemic diseases

[14]

Palpation technique and sequential examination

The examination is performed under good lighting. First, an inspection for asymmetry and skin changes is performed, followed by systematic palpation with all fingertips using a gentle rolling motion. The size, shape, tenderness, consistency, mobility, cohesion, and temperature of the skin are assessed. Fixed, very dense nodules are a cause for concern; tenderness often accompanies acute inflammatory processes. [15]

For the neck, it is convenient to stand behind the patient, sequentially palpating the submental, submandibular, anterior and posterior cervical, supraclavicular, and infraclavicular regions. Axillary nodes are palpated deeply, slowly "rolling" the tissue over the ribs, moving the patient's elbow toward the torso to relax it. Inguinal nodes are palpated below the inguinal ligament along horizontal and vertical lines. Epitrocheal nodes are located above the medial epicondyle of the humerus. [16]

Characteristic descriptive terms aid communication. "Elastic" or "rubber-like" is more common in lymphoma, "stony" in metastases and granulomatous processes, and "fused" nodes are described as a conglomerate. The presence of fluctuation indicates abscess formation in bacterial lymphadenitis. [17]

To identify a potential source, drainage areas are always examined: the oropharynx, scalp and neck, mammary glands, skin and soft tissues of the upper or lower extremities, and external genitalia. This increases the diagnostic accuracy of the initial examination. [18]

Table 3.

Stage	Key actions	Tips
Inspection	asymmetry, redness, fistulas, scars	side-by-side comparison, side lighting
Cervical groups	sequence from chin to supraclavicular	more convenient from behind the patient's back
Axillary	deep palpation of the walls and apex	elbow closer to the body, the examiner's hand high in the armpit
Inguinal	horizontal and vertical lines	evaluate the skin of the feet and shins
Epitrocheal	above the medial epicondyle	fix the patient's hand with the hand of the same name

[19]

Differential diagnosis by pattern

Localized, unilateral, painful, reddened, and fluctuating lymphadenopathy suggests bacterial lymphadenitis. Localized, painless, and dense lymphadenopathy in adults, especially in the cervical-supraclavicular region, requires the exclusion of metastasis or lymphoma. Generalized lymphadenopathy with systemic symptoms is more often viral, drug-induced, or hematological in origin. [20]

Axillary lymphadenopathy following vaccination against the new coronavirus infection is usually benign and can persist for several months. If ultrasound findings are clearly benign, delayed follow-up is possible without immediate biopsy, but breast screening is not postponed. [21]

A chronic neck nodule with a tendency to fistula and pasty conglomerates suggests tuberculous lymphadenitis. Polymerase chain reaction and histology expedite verification. In regions with a high prevalence of tuberculosis, the threshold of suspicion is lower. [22]

Epitrocheal lymphadenopathy may accompany cat scratch infection, leprosy, leishmaniasis, filariasis, but also occurs with lymphoma and melanoma metastases of the upper extremity. Therefore, an enlargement in this area requires a thorough investigation of the cause. [23]

Table 4. Common clinical patterns and probable causes

Pattern	Possible causes	First steps
Acute painful localized with redness	bacterial lymphadenitis	complete blood count, C-reactive protein, ultrasound, antibiotics as indicated
Painless, dense pain in the cervical-supraclavicular region in an adult	metastases, lymphoma	CT scan of the neck with contrast, fine-needle aspiration or core biopsy
Generalized with systemic symptoms	viruses, HIV, hematology, drug reactions	HIV test, clinical serology, complete blood count with formula
Axillary after vaccination	benign reaction	document the side and date, delayed ultrasound monitoring for benign features
Chronic cervical with conglomerates and fistulas	tuberculous lymphadenitis	molecular tests, consultation with a phthisiatrician

[24]

Basic laboratory diagnostics

A basic diagnostic test for unexplained lymphadenopathy includes a complete blood count with differential, erythrocyte sedimentation rate, and C-reactive protein. These tests help differentiate inflammatory processes from hematological malignancies, although they are not specific. Absolute and relative cytopenias increase the suspicion of a hematological disorder. [25]

For generalized lymphadenopathy without a focal point, an HIV test is prescribed. Serology for Epstein-Barr virus, cytomegalovirus, toxoplasmosis, and syphilis may be added based on clinical findings. In high-risk areas, a test for latent tuberculosis and a chest X-ray are performed. [26]

Chronic, atypical, and recurrent nodules, especially those unresponsive to empirical therapy, warrant histological verification. The choice of biopsy method is determined by the location, accessibility, and suspected nature of the process. [27]

If tuberculosis is suspected, complete biopsy is preferred for molecular methods and staining. If lymphoma is suspected, excisional biopsy is advisable to assess the node architecture. [28]

Visualization: What, When, and Why

Ultrasound is the first-line method for superficial nodules. The shape, long-to-short axis ratio, cortical thickness, integrity of the fatty hilum, and Doppler blood flow patterns are assessed. Absence of a hilum, a rounded shape, diffuse cortical thickening, and peripheral or chaotic vascularization increase the likelihood of a malignant process. Elastography can improve accuracy in questionable cases. [29]

In adults with suspected malignant cervical masses, contrast-enhanced CT of the neck is recommended as the initial imaging modality, followed by image-guided fine-needle aspiration. Magnetic resonance imaging is preferred for suspected skull base and nasopharyngeal tumors. The choice is refined based on the clinical objective and level of suspicion. [30]

In pediatrics, imaging is chosen more conservatively. In a typical child with a viral infection and no "red flags," a wait-and-see approach is acceptable. If signs of bacterial lymphadenitis are present, ultrasound is helpful for detecting abscesses and monitoring response to therapy. [31]

A special case is post-vaccination axillary lymphadenopathy. Several studies have shown that the average time to resolution can reach three to four months or more, so delayed follow-up is advisable in cases of clearly benign symptoms and the absence of a history of tumor. Delaying breast screening is not recommended. [32]

Table 5. Ultrasound features of reactive and malignant nodes

Sign	Most likely a jet	Most likely malignant
Form	oval	rounded
Fat collar	saved	absent
Bark	thin, uniform	thickened, asymmetrical, nodular areas
Blood flow	portal-central	peripheral, mixed, chaotic
Elasticity	softer	denser

[33]

Table 6. Selection of visualization method according to the clinical situation

Situation	Preferred method	Target
Surface accessible node	ultrasound	nature of the node, navigation for puncture
Suspected neck tumor in an adult	computed tomography with contrast	staging, puncture planning
Suspected nasopharyngeal or basal tumor	magnetic resonance imaging	soft tissue assessment and spread
Searching for an abscess in a child with lymphadenitis	ultrasound	verification and control of treatment

[34]

Biopsy: When and Which One?

Indications for biopsy include persistence for more than 2-4 weeks without a tendency to regress, supraclavicular location, progressive enlargement, firm consistency and fixation, generalization with systemic symptoms, and an unclear diagnosis after the initial examination. The choice of technique depends on the clinical situation and the purpose. [35]

Ultrasound-guided fine-needle aspiration (FNA) allows for rapid collection of material for cytology and microbiology and is useful in metastatic lesions. A core biopsy yields a tissue core for histology. Excisional biopsy is preferred when lymphoma is suspected to assess the nodule's architecture. [36]

In case of suspected tuberculosis, material suitable for polymerase chain reaction and staining is preferred; in case of suspected atypical mycobacteria in children, excision of the entire node is recommended to avoid chronic fistulas. [37]

In controversial situations, the sequence “imaging - minimally invasive biopsy - extended biopsy if necessary” reduces the number of unnecessary operations and speeds up diagnosis. [38]

Table 7. Choice of biopsy method

Clinical task	Method	Note
Confirm metastasis	ultrasound-guided fine-needle aspiration	high availability, rapid cytology
Suspicion of lymphoma	excisional biopsy	preserving the node architecture
Chronic cervical with suspected tuberculosis	core biopsy or excision	material for polymerase chain reaction and histology
Childhood atypical mycobacteriosis	excision of the node	reduces the risk of chronic fistula

[39]

Special situations: children, immunodeficiency, post-vaccination reaction, tuberculosis

In children, the vast majority of cervical lymphadenopathy is benign and self-limited. In cases of typical viral manifestations, observation is indicated. In cases of unilateral, painful enlargement with fever and fluctuation, antibiotics are prescribed; if these are ineffective and an abscess is present, drainage is considered. [40]

Post-vaccination axillary lymphadenopathy is most often benign. Studies have shown that it can persist longer than initially expected. Screening tests do not need to be postponed. Information on the date and side of vaccination helps to correctly interpret the findings. [41]

Immunodeficiency dictates a lower threshold for imaging and biopsy, as well as expanded infectious screening, including atypical mycobacteria and deep fungal infections. The strategy is determined by the clinical context and severity of the condition. [42]

Tuberculous lymphadenitis remains the leading form of extrapulmonary tuberculosis. The cervical nodes are most frequently affected, and conglomerates and fistulas frequently form. Polymerase chain reaction improves the speed and accuracy of diagnosis compared to staining alone. [43]

Table 8. Pediatric tactics for cervical lymphadenopathy

Scenario	First-line actions	Criteria for deepening tactics
Typical viral picture, the child is in satisfactory condition	observation and control	increase for more than 2-4 weeks, increase in size, systemic symptoms
Bacterial lymphadenitis	antibiotics according to local protocol, ultrasound to exclude an abscess	no response, abscess formation, toxic appearance
Atypical mycobacteria	surgeon consultation, node excision	chronic course, fistulas
Unexplained, persistent lymphadenopathy	imaging and biopsy	"red flags", suspicion of a tumor

[44]

Primary Care Routing

In the case of a localized benign lesion without any "red flags," an examination with a repeat assessment in 2-4 weeks is acceptable. If the condition persists or progresses, a transition to visualization and morphological verification is recommended. This stepwise approach reduces the need for repeated examinations. [45]

Supraclavicular and epitrocheal nodes, as well as any persistent cervical mass in an adult with warning signs, require expedited imaging and consultation with an otolaryngologist or oncologist. Early access to CT scanning and biopsy improves diagnostic timeliness. [46]

In children, the diagnosis is based on clinical presentation and dynamics. Most cases do not require immediate imaging. If a bacterial cause is suspected, antibacterial therapy is initiated with early monitoring and ultrasound if necessary. [47]

Systemic symptoms, generalization, marked weight loss, night sweats, and persistent fever are indications for extensive laboratory testing and referral to a specialist. [48]

Table 9. Quick algorithm for a primary care physician

Step	Action	Continuation branch
1	History, inspection, search for "red flags"	if present, urgent visualization and consultation
2	Localized without warning signs	observation for 2-4 weeks or ultrasound as needed
3	Generalized	Basic tests and HIV testing, imaging as indicated
4	No regression, atypia	ultrasound and morphological verification
5	Confirmed cause	etiotropic treatment and monitoring

[49]