creation date: 2025-09-11 16:22
tags: Workups
Lymphadenopathy
Background
Lymphadenopathy or adenopathy is an abnormal finding described by an abnormality in the size, consistency, or morphology of one or more lymph nodes. This can be localized (eg. involving one lymph node or one region) or generalized (involving two or more noncontiguous regions).
A lymph node is considered abnormal if:
- Size is >1 cm in diameter
- Have abnormal consistency (hard, fixed, or matted)
- Located in regions that are more suggestive of malignancy (eg. supraclavicular area)
In the majority of cases, lymphadenopathy are benign and self-limited but persistent, unexplained, or high-risk presentations should warrant investigation.
Pathophysiology
Lymph nodes function as an antigen filter for the body. One consists of multi-layered sinus that exposes B-cells, T-cells, and macrophages to extracellular fluid allowing for recognition of foreign proteins. When an immune response is mounted, the cell lines multiply and thus the lymph node enlarges.
In cases of lymphoma, the enlargement occurs due to the proliferation of the cells of the node.
Differential Diagnosis
A number of etiologies can result in lymphadenopathy.
Infectious disease
- Viral (eg. HIV, mononucleosis from EBV or CMV, roseola, HSV, varicella, adenovirus)
- Bacterial (eg. Staphylococcus, Streptococcus, Salmonella, Syphilis, Yersinia)
- Mycobacterial (eg. tuberculosis, Mycobacterium avium intracellular)
- Fungal (eg. coccidioidomycosis, histoplasmosis, Candida)
- Parasitic (eg. toxoplasmosis, Chagas, ectoparasites)
Neoplasm
Primary malignancies and metastatic malignancies: - Acute lymphoblastic leukemia
- Hodgkin lymphoma
- Non-Hodgkin lymphoma
- Neuroblastoma
- Pediatric acute myelocytic leukemia
- Rhabdomyosarcoma
- Metastatic carcinoma of the lungs
- Metastatic carcinoma of the viscera of the GI tract
- Metastatic breast cancer
- Metastatic thyroid cancer
- Metastatic renal cancer
Autoimmune disease - Sarcoidosis
- Juvenile rheumatoid arthritis
- Serum sickness
- Systemic lupus erythematosus
Inborn metabolic storage disorder - Niemann-Pick disease
- Gaucher disease
Exposure to toxic/medication - Allopurinol
- Atenolol
- Captopril
- Carbamazepine
- Cephalosporins
- Gold
- Hydralazine
- Penicillin
- Phenytoin
- Primidone
- Para methylamine
- Quinidine
- Sulfonamides
- Sulindac
Initial Evaluation
History
History should aim to elucidate relevant symptoms. This consist of:
- Prodromal illness
- Fever
- Chills
- Night sweats
- Weight loss
- Localizing symptoms
- Possible exposures to infectious disease, toxins, medications
- Habits that may be risk factors (eg. smoking, alcohol consumption, high-risk sexual behaviour)
Five important components to gather information on are:
- Chronicity - observed for >3 weeks but <1 year suggests ominous cause
- Localization - generalized vs localized
- Physical characteristics of the node
- Concomitant symptoms (see above)
- Epidemiology (exposures; see above)
Physical Exam
A thorough lymph node exam should be performed to assess the pattern, distribution, and quality of the lymphadenopathy.
Certain lymph nodes drain specific areas:
- Submandibular - tongue, lips, mouth, conjunctiva
- Submental - lower lip portion of oropharynx and cheek
- Jugular - tongue, tonsils, pinna, paratid
- Posterior cervical - scalp, neck, skin of arm, legs
- Suboccipital - scalp
- Perauricular - eyelids, conjunctiva, pinna
- Postauricular - scalp in external auditory meatus
- Right supraclavicular - mediastinum of lungs in esophagus
- Axillary - arm at thoracic wall, breast
- Inguinal - penis, scrotum, vulva, vagina, perineum, gluteal region, lower abdominal wall, portions of lower anal canal
Localized lymphadenopathy involving one area are often due to infection or malignancies related to the drainage area:
- Cervical - URTI, Epstein-Barr virus, head/neck malignancies
- Axillary - local skin infections, cat scratch, breast cancer
- Inguinal - STIs, lower extremity infections, malignancies such as lymphoma or metastatic carcinoma
- Supraclavicular - highly suspicious for malignancy (lymphoma, metastatic cancers from thoracic or abdominal organs)
- Left supraclavicular (Virchow’s node) - malignancy of abdomen/pelvis
- If this is location of lymphadenopathy, must do head-to-toe lymph node exam due to supraclavicular drainage.
Generalized lymphadenopathy suggests systemic diseases such as infection or hematologic malignancy.
Node morphology can be characterized as:
- Tenderness (pain may arise from inflammation, perforation, hemorrhage)
- Firm/rubbery nodes - suggests lymphoma
- Soft - infection/inflammation
- Hard, stonelike - suggests metastatic cancer
- “Shotty” (small scattered) - children with viral illness
- Matting (seemingly conjoined nodes) - suggests malignancy
Investigations
Laboratory tests
- CBC with differential - for infectious and hematological causes
- Complete metabolic panel:
- BMP: sodium, potassium, chloride, bicarbonate, creatinine, eGFR
- LFT: ALT, AST, ALP, albumin, bilirubin
- Calcium, glucose
- CRP - measure of inflammation (ESR not great due to false positive, esp. with chronic disease)
- Testing for specific causes:
- EBV serology - for Epstein Barr
- Cytomegalovirus titers
- HIV serology
- Bartonella henselae serology
- FTA/RPR (syphilis)
- Herpes simplex serology
- Toxoplasmosis serology
- Hepatitis B serology
- ANA (lupus)
Radiological
- CXR - can reveal tuberculosis, pulmonary sarcoidosis, pulmonary neoplasm
- Chest CT - hilar adenopathy
- Abdo pelvis CT - neoplasms and other causes
- Ultrasonography - assessment of node characteristics
- MRI - evaluation of masses if available
Purified protein derivative (PPD) - Assessment of tuberculosis (TB skin test)