One-liner#

Evaluate palpable lymph nodes by distinguishing benign reactive adenopathy (most common) from concerning causes requiring biopsy, using location, size, characteristics, and clinical context to guide workup and avoid both unnecessary biopsies and missed malignancies.

Quick nav#

• Red flags / send to ED
• Key history
• Focused exam
• Differential (quick pattern recognition)
• Workup
• Initial management
• Management by diagnosis
• Follow-up
• Patient instructions
• Smartphrase snippets

Red flags / send to ED#

• Airway compromise from massive cervical adenopathy → ED
• Superior vena cava syndrome (facial swelling, dyspnea, distended neck veins) → ED
• Severe systemic illness with lymphadenopathy (sepsis, hemodynamic instability) → ED

Urgent (expedited outpatient workup):

• Supraclavicular lymphadenopathy (high malignancy risk)
• Lymphadenopathy with B symptoms (fever, night sweats, weight loss >10%)
• Rapidly enlarging nodes
• Fixed, hard, matted nodes
• Lymphadenopathy >4 weeks without clear infectious cause
• Generalized lymphadenopathy
• Lymphadenopathy with hepatosplenomegaly
• Lymphadenopathy with cytopenias

Key history#

Characterize the lymphadenopathy:

• Location (localized vs generalized)
• Duration (acute <2 weeks, subacute 2-6 weeks, chronic >6 weeks)
• Rate of growth (rapid = concerning)
• Pain/tenderness (tender = usually reactive/infectious; painless = more concerning for malignancy)
• Associated symptoms

Definitions:

• Lymphadenopathy: Lymph node >1 cm (inguinal >1.5 cm; epitrochlear >0.5 cm)
• Localized: Single region involved
• Generalized: ≥2 non-contiguous regions involved

Location matters (drainage patterns):

• Cervical: Head, neck, oral cavity, upper respiratory tract
• Supraclavicular: Thorax, abdomen (left = Virchow’s node → GI malignancy)
• Axillary: Upper extremity, breast, chest wall
• Epitrochlear: Hand, forearm (often infectious; also lymphoma, sarcoidosis)
• Inguinal: Lower extremity, genitalia, perineum (reactive nodes very common)
• Generalized: Systemic process (infection, autoimmune, malignancy)

Associated symptoms:

• Fever, night sweats, weight loss (B symptoms → lymphoma, TB, HIV)
• Sore throat, URI symptoms (reactive)
• Skin lesions, wounds (regional infection)
• Joint pain, rash (autoimmune)
• Fatigue, malaise

Exposure history:

• Sick contacts
• Animal exposures (cat scratch, toxoplasmosis)
• Tick bites
• Sexual history (HIV, syphilis, HSV, LGV)
• Travel (TB, histoplasmosis, coccidioidomycosis)
• Occupational exposures

Risk factors for malignancy:

• Age >40 (malignancy risk increases significantly with age)
• Smoking history
• Prior malignancy
• Immunocompromised
• B symptoms
• Duration >4-6 weeks without improvement

Age and malignancy risk:

• Age <30: ~80% of unexplained LAD is benign
• Age 30-50: ~50% benign
• Age >50: Majority are malignant; low threshold for biopsy

Medication review:

• Phenytoin (can cause pseudolymphoma)
• Allopurinol
• Atenolol
• Carbamazepine
• Hydralazine
• Sulfonamides

Past medical history:

• Prior malignancy
• HIV status
• Autoimmune conditions
• Recent infections

Focused exam#

Lymph node characteristics (critical):

• Size: Measure in cm; >1 cm generally abnormal (>1.5 cm inguinal; >0.5 cm epitrochlear)
• Consistency: Soft/rubbery (reactive); firm/hard (malignancy); fluctuant (abscess)
• Tenderness: Tender (infection/inflammation); painless (malignancy, but not always)
• Mobility: Mobile (reactive); fixed/matted (malignancy, TB)
• Overlying skin: Erythema, warmth (infection); normal (malignancy)

Examine ALL lymph node regions:

• Cervical (anterior, posterior, submandibular, submental)
• Supraclavicular (examine with patient sitting, during Valsalva)
• Axillary
• Epitrochlear
• Inguinal
• Popliteal (rarely palpable)

Regional exam based on location:

Cervical adenopathy:

• Oropharynx (pharyngitis, dental infection, oral lesions)
• Ears (otitis)
• Scalp (infection, lesions)
• Thyroid
• Skin of head/neck

Axillary adenopathy:

• Breast exam
• Upper extremity (wounds, infection)
• Chest wall

Inguinal adenopathy:

• Lower extremity (wounds, cellulitis, tinea)
• Genital exam (STI, lesions)
• Perianal area

Systemic exam:

• Hepatomegaly, splenomegaly
• Other lymph node regions
• Skin (rashes, lesions)
• Joints
• Vital signs (fever)

Differential (quick pattern recognition)#

Common/likely (outpatient)#

Can’t-miss / urgent#

Workup#

Approach: Let clinical context guide testing—not every lymph node needs workup.

When NO workup needed (observe and reassess in 2-4 weeks):

• Localized LAD with clear infectious cause (URI, skin infection)
• Soft, tender, mobile nodes <1 cm
• Inguinal nodes <1.5 cm that are soft and mobile
• Duration <2 weeks with obvious trigger

When to pursue workup:

• Duration >4 weeks without improvement
• Supraclavicular location (always concerning)
• Size >2 cm
• Hard, fixed, or matted nodes
• B symptoms (fever, night sweats, weight loss)
• Generalized LAD
• Age >40 without clear cause
• Associated hepatosplenomegaly or cytopenias

Initial workup (when indicated):

Directed testing based on clinical suspicion:

When to biopsy:

Indications for lymph node biopsy:

• Supraclavicular node (any size)
• Node >2 cm persisting >4 weeks
• Hard, fixed, or matted nodes
• B symptoms with unexplained LAD
• Abnormal CBC or elevated LDH
• Generalized LAD without clear cause
• Increasing size despite observation
• Clinical suspicion for malignancy

Biopsy approach:

• Excisional biopsy preferred (preserves architecture; best for lymphoma diagnosis)
• Core needle biopsy acceptable if excisional not feasible
• FNA alone is inadequate for lymphoma diagnosis (cannot assess architecture)
• Choose the most abnormal, accessible node (avoid inguinal if possible—high false-negative rate)

Role of ultrasound:

• Can characterize node (size, shape, hilum, vascularity)
• Helpful to guide FNA or core biopsy
• Does NOT replace need for excisional biopsy if lymphoma suspected
• Benign features: Oval shape, echogenic hilum, hilar vascularity
• Concerning features: Round shape, absent hilum, peripheral/chaotic vascularity, necrosis

Initial management#

General approach:

1. Characterize the LAD (location, size, characteristics, duration)
2. Look for obvious cause (infection, inflammation)
3. If clear infectious cause: treat and observe
4. If concerning features: expedite workup and consider biopsy
5. If uncertain: observe 2-4 weeks, then reassess

Observation period:

• Appropriate for low-risk LAD (localized, <2 cm, soft, mobile, clear trigger)
• Reassess in 2-4 weeks
• If not resolving or enlarging, pursue workup

Management by diagnosis#

Reactive lymphadenopathy (viral)#

Education:

• Lymph nodes swell when fighting infection—this is normal
• Usually resolves in 2-4 weeks after infection clears
• No treatment needed for the nodes themselves

Management:

• Treat underlying infection if bacterial
• Supportive care for viral illness
• Reassurance

Follow-up: Return if nodes persist >4 weeks, enlarge, or new symptoms develop.

Infectious mononucleosis (EBV)#

Education:

• Viral infection causing prolonged fatigue, sore throat, swollen glands
• Contagious via saliva (“kissing disease”)
• Fatigue may last weeks to months
• Avoid contact sports for 4 weeks (spleen rupture risk)

Management:

• Supportive care (rest, fluids, antipyretics)
• Avoid contact sports until spleen not palpable (typically 4 weeks)
• Avoid amoxicillin/ampicillin (causes rash in EBV)
• Short course steroids only if airway compromise from tonsillar enlargement

Follow-up: 2-4 weeks; sooner if worsening or abdominal pain (splenic rupture).

Cat scratch disease (Bartonella henselae)#

Education:

• Bacterial infection from cat scratch or bite
• Causes regional lymph node swelling 1-3 weeks after exposure
• Usually self-limited; resolves in 2-4 months

Treatment:

• Mild disease: Observation (self-limited)
• Moderate-severe or immunocompromised:

Follow-up: 2-4 weeks; nodes may take months to fully resolve.

Lymphoma#

Recognition:

• Painless, firm, rubbery lymphadenopathy
• B symptoms (fever, night sweats, weight loss)
• May have hepatosplenomegaly
• Elevated LDH
• Hodgkin: Often cervical/mediastinal; contiguous spread
• Non-Hodgkin: More often generalized; extranodal involvement common

PCP role:

• Initial workup: CBC, CMP, LDH, HIV
• Imaging: CT chest/abdomen/pelvis
• Refer for excisional biopsy (do not delay)
• Refer to hematology/oncology

Do NOT:

• Delay referral for biopsy
• Rely on FNA alone (need excisional for architecture)
• Start steroids before biopsy (can obscure diagnosis)

Metastatic carcinoma#

Recognition:

• Hard, fixed, non-tender node
• Supraclavicular (especially left = Virchow’s node → abdominal malignancy)
• Age >40; smoking history
• Weight loss
• May have symptoms of primary tumor

PCP role:

• Urgent workup: CT to identify primary
• Biopsy of node
• Refer to oncology

Common primaries by location:

• Cervical: Head and neck, thyroid, lung
• Supraclavicular left: GI (stomach, pancreas, colon)
• Supraclavicular right: Lung, esophagus
• Axillary: Breast, lung, melanoma
• Inguinal: Genital, anal, melanoma (lower extremity)

HIV-associated lymphadenopathy#

Recognition:

• Generalized LAD (persistent generalized lymphadenopathy = PGL)
• Risk factors for HIV
• May have other HIV manifestations (oral thrush, rash, weight loss)

Management:

• Confirm HIV diagnosis (4th gen Ag/Ab test)
• Refer to HIV specialist for treatment initiation
• LAD often improves with antiretroviral therapy
• If LAD persists or is atypical after ART, consider other causes (lymphoma risk increased in HIV)

Tuberculosis (scrofula)#

Recognition:

• Cervical lymphadenopathy (most common extrapulmonary TB site)
• Risk factors: Immigration from endemic area, HIV, exposure
• Nodes may be matted, non-tender; may develop draining sinus
• Constitutional symptoms (fever, night sweats, weight loss)

PCP role:

• CXR
• TB testing (IGRA or PPD)
• Refer to ID or TB clinic
• Biopsy may be needed (shows caseating granulomas; AFB stain/culture)

Do NOT start empiric TB treatment without specialist guidance.

Sarcoidosis#

Recognition:

• Young to middle-aged adult; more common in African Americans
• Bilateral hilar lymphadenopathy on CXR (classic)
• May have peripheral LAD
• Other manifestations: Skin lesions, uveitis, pulmonary symptoms
• Elevated ACE level (not specific)

PCP role:

• CXR (bilateral hilar LAD)
• ACE level
• Calcium (may be elevated)
• Refer to pulmonology or rheumatology
• Biopsy shows non-caseating granulomas

Treatment: Many cases resolve spontaneously; steroids for symptomatic disease (specialist-directed).

Follow-up#

Observation (low-risk LAD):

• Reassess in 2-4 weeks
• Measure nodes; document size
• If resolving, no further workup
• If persistent or enlarging, pursue workup

After biopsy:

• Follow up for results (usually 1-2 weeks)
• Coordinate with specialists based on diagnosis

Return precautions:

• Node enlarging
• New nodes appearing
• Fever, night sweats, weight loss
• Fatigue, bleeding, bruising
• Difficulty breathing or swallowing

Patient instructions#

• Lymph nodes are part of your immune system and often swell when fighting infection. This is usually normal and temporary.
• Most swollen lymph nodes go away on their own within 2-4 weeks once the infection clears.
• You don’t need to do anything special for swollen glands from a cold or minor infection.
• Call us if: the lump is getting bigger, you develop fever/night sweats/weight loss, the lump is very hard or doesn’t move, or it’s been more than 4 weeks and it’s not going away.
• If we’ve scheduled a biopsy, this is to get a sample of the lymph node to look at under a microscope. It helps us figure out exactly what’s causing the swelling.
• Avoid squeezing or pressing on swollen lymph nodes repeatedly.

Smartphrase snippets#

.LADREACTIVE Lymphadenopathy evaluation. Patient presents with [location] lymphadenopathy, [size] cm, [tender/non-tender], [mobile/fixed], [soft/firm]. Duration [X days/weeks]. Associated with [URI symptoms/skin infection/other]. No B symptoms. Exam otherwise unremarkable. Most consistent with reactive lymphadenopathy in setting of [infection]. Plan: Observation with reassessment in 2-4 weeks. Return precautions reviewed: enlarging node, new nodes, fever/night sweats/weight loss.

.LADWORKUP Lymphadenopathy requiring workup. [Location] lymphadenopathy, [size] cm, present for [duration]. Concerning features: [>2 cm / supraclavicular / hard-fixed / B symptoms / age >40 / no clear cause]. Ordering: CBC, CMP, LDH, [HIV, CT, other]. Will reassess with results. If no clear diagnosis, will refer for [excisional biopsy / specialty evaluation].

.LADBIOPSY Lymphadenopathy referred for biopsy. [Location] node, [size] cm, [characteristics]. Duration [X weeks]. Workup to date: [labs, imaging]. Given [persistent LAD >4 weeks / concerning features / suspicion for malignancy], referring for excisional lymph node biopsy. Patient counseled on procedure and importance of tissue diagnosis. Will follow up with results.

.LADMALIGNANCY Concern for malignant lymphadenopathy. [Location] node, [size] cm, [hard/fixed/matted/painless]. B symptoms: [present/absent]. Labs: [LDH elevated / cytopenias / other]. CT shows [findings]. Referring urgently for excisional biopsy and hematology/oncology evaluation. Patient counseled on need for expedited workup.

Coding/billing notes#

• R59.0: Localized enlarged lymph nodes
• R59.1: Generalized enlarged lymph nodes
• R59.9: Enlarged lymph nodes, unspecified
• B27.90: Infectious mononucleosis, unspecified
• A28.1: Cat-scratch disease
• C85.90: Non-Hodgkin lymphoma, unspecified
• C81.90: Hodgkin lymphoma, unspecified
• C77.0: Secondary malignant neoplasm of lymph nodes of head, face, and neck
• B20: HIV disease
• A18.2: Tuberculous peripheral lymphadenopathy
• D86.1: Sarcoidosis of lymph nodes