Lymphadenopathy & Splenomegaly Evaluation
Which node to watch, which to excise, and what a big spleen is telling you
Which nodes are worrisome
Normal versus enlarged. Most palpable nodes are reactive. Nodes above about 1 cm are generally enlarged, although inguinal nodes up to 1.5 cm are common in healthy adults and any epitrochlear node above 0.5 cm is abnormal. Generalized lymphadenopathy means two or more noncontiguous regions and implies a systemic process.
Red flags. Cancer becomes more likely with age over 40, size over 2 cm, persistence beyond 4–6 weeks, and hard, fixed, or matted consistency (stony-hard suggests carcinoma, rubbery suggests lymphoma). B symptoms (fever above 38 °C, drenching night sweats, loss of more than 10% of body weight in 6 months) and generalized nodes with hepatosplenomegaly point toward lymphoma or leukemia. Tender, soft, mobile nodes beside an obvious infection favor a reactive cause.
Supraclavicular nodes. A palpable supraclavicular node is never normal. The right side drains the mediastinum, lungs, and esophagus; the left (Virchow) node receives the thoracic duct and signals abdominal or pelvic cancer, classically gastric or pancreatic adenocarcinoma (a palpable Virchow node is the Troisier sign).
| Node group | Drainage field | Classic causes |
|---|---|---|
| Cervical | Pharynx, teeth, scalp | Pharyngitis, dental infection, EBV (posterior cervical), head and neck cancer |
| Axillary | Arm, chest wall, breast | Arm infection, cat-scratch disease (Bartonella), breast cancer |
| Epitrochlear | Hand, forearm | Hand infection, secondary syphilis, lymphoma, CLL |
| Inguinal | Leg, genitals, perineum | Leg wounds; STIs (syphilis, LGV, chancroid, HSV) |
Stepwise evaluation
- History and examinationAge, duration, size, consistency, location, B symptoms, exposures, and drugs; examine every node group, the liver, and the spleen.
- Benign-appearing localized node with a clear causeTreat a bacterial infection if present and re-examine in 3–4 weeks.
- Persistent, generalized, or red-flag nodesCBC with smear, HIV testing, EBV and CMV serologies, RPR or treponemal test, IGRA or PPD, ANA, and chest imaging or CT.
- Tissue diagnosisExcisional biopsy of the largest, most abnormal node when the cause remains unclear.
Never give empiric corticosteroids to an undiagnosed node: they shrink lymphoma and leukemia infiltrates and can leave the eventual biopsy nondiagnostic.
Choosing the biopsy. Excisional biopsy preserves nodal architecture and supplies tissue for flow cytometry, immunohistochemistry, and cytogenetics, all needed to diagnose and subclassify lymphoma. Fine-needle aspiration shows cells without architecture and is adequate mainly for metastatic carcinoma; core needle biopsy is the fallback when excision is impractical, and LDH or protein electrophoresis cannot make the diagnosis. Cervical or supraclavicular nodes are preferred over inguinal nodes, which often show only nonspecific reactive change.
Causes of generalized lymphadenopathy
| Category | Cause | Clues |
|---|---|---|
| Infection | EBV mononucleosis | Fever, exudative pharyngitis, posterior cervical nodes, splenomegaly, atypical lymphocytes, positive heterophile test |
| Infection | CMV, toxoplasmosis, acute HIV | Heterophile-negative mono-like illness; HIV adds rash and mucocutaneous ulcers |
| Infection | Secondary syphilis, TB | Palm-sole rash with epitrochlear nodes; matted cervical nodes (scrofula) |
| Autoimmune | SLE, sarcoidosis | Positive ANA; bilateral hilar nodes with noncaseating granulomas |
| Drug | Phenytoin, DRESS | Pseudolymphoma; fever, rash, facial edema, eosinophilia, hepatitis |
| Neoplastic | Lymphoma, CLL, metastases | B symptoms, lymphocytosis, rubbery or hard nodes |
Infection pearls. Ampicillin or amoxicillin often provokes a diffuse maculopapular rash in EBV mononucleosis, and corticosteroids are reserved for complications such as impending airway obstruction. In a heterophile-negative illness with rash and oral ulcers, test for acute HIV with HIV RNA plus an antigen/antibody assay, because RNA turns positive before antibodies.
Drug reactions. DRESS follows aromatic anticonvulsants, allopurinol, or sulfonamides by 2–8 weeks. Stopping the culprit resolves drug-induced adenopathy; severe DRESS also needs systemic corticosteroids.
Uncommon nodal diseases. IgG4-related disease forms tumefactive pancreatic, salivary, and nodal lesions with IgG4-rich plasma cells and storiform fibrosis and responds to steroids. Castleman disease is unicentric (cured by excision) or multicentric with IL-6–driven fevers and cytopenias, driven by HHV-8 in HIV. Kikuchi–Fujimoto disease affects young women with fever, leukopenia, and tender cervical nodes; biopsy shows necrotizing histiocytic lymphadenitis without neutrophils, unlike the neutrophilic stellate microabscesses of cat-scratch disease or the caseating granulomas of TB. It is self-limited, but SLE can coexist, so ANA is checked.
Splenomegaly
| Mechanism | Examples |
|---|---|
| Congestive | Cirrhotic portal hypertension, right heart failure, portal or splenic vein thrombosis |
| Infectious | EBV, malaria, subacute endocarditis, visceral leishmaniasis |
| Hematologic | Hemolysis (spherocytosis, thalassemia), MPNs, lymphomas, leukemias |
| Infiltrative | Gaucher disease, amyloidosis, sarcoidosis |
Massive splenomegaly. A spleen reaching the pelvis or crossing the midline suggests CML, primary myelofibrosis, hairy cell leukemia, lymphoma (such as splenic marginal zone lymphoma), chronic malaria, visceral leishmaniasis (kala-azar), or Gaucher disease; β-thalassemia major can also do it. Portal hypertension, EBV, and spherocytosis usually cause only mild-to-moderate enlargement.
Pancreatitis can thrombose the adjacent splenic vein, causing left-sided portal hypertension: splenomegaly and isolated gastric varices with a normal liver. Splenectomy cures the variceal bleeding.
Hypersplenism and splenic complications
Hypersplenism. An enlarged spleen pools and destroys blood cells, causing cytopenias, most prominently thrombocytopenia, despite a cellular marrow. A normal spleen holds about one-third of circulating platelets; an enlarged one can hold most of them. Compression of the stomach adds early satiety and left upper quadrant fullness.
Infarction and rupture. Massive spleens can outgrow their blood supply and infarct, causing sudden pleuritic left upper quadrant pain and a friction rub. Rupture causes left upper quadrant pain referred to the left shoulder and hypotension; in mononucleosis the risk peaks in the first weeks, so contact sports are avoided for at least 3–4 weeks.