Lymphadenopathy Workup

• Greater than 1 cm is the usual working threshold, but applying it everywhere is wrong in both directions.
• An epitrochlear node above about 0.5 cm is always abnormal and warrants explanation -it is a small, specific finding that is easy to skip on examination.
• Inguinal nodes up to about 1.5 to 2 cm are commonly normal in adults, particularly in people who go barefoot or have recurrent lower limb minor trauma, so this is the site most likely to be over-investigated.
• Any supraclavicular node is abnormal, whatever its size.

• Localized means a single region, and prompts you to examine the territory that node drains for the cause -scalp and dentition for cervical nodes, the arm and hand for axillary, the genitals, perineum and lower limb for inguinal.
• Generalized means two or more non-contiguous regions, and shifts the thinking toward systemic causes: infection (EBV, CMV, HIV, toxoplasmosis, tuberculosis, syphilis), autoimmune disease (lupus, rheumatoid arthritis, Still disease), malignancy (lymphoma, leukemia), sarcoidosis, and drugs.
• ⚠ Do not forget medications. Phenytoin, carbamazepine, lamotrigine, allopurinol and sulfonamides among others can cause lymphadenopathy, sometimes as part of a drug reaction with eosinophilia and systemic symptoms. A drug history costs nothing and occasionally ends the workup.

• Exposures: cat scratch or bite (Bartonella), undercooked meat and cat litter (toxoplasmosis), tuberculosis contact and country of origin, tick bites, farm and animal contact, travel.
• Sexual history -acute HIV presents as a mononucleosis-like illness with generalized lymphadenopathy, and syphilis is a classic mimic; both are missed by not asking.
• Occupational and hobby exposures, including silica and beryllium.
• Full medication review as above, and any recent vaccination.
• Prior malignancy, which reframes any new node as possible recurrence until proven otherwise.

• Examine ALL nodal regions, not just the one the patient noticed -cervical, supraclavicular, axillary, epitrochlear, inguinal- because finding a second non-contiguous region converts this to generalized lymphadenopathy and changes the workup entirely.
• Record size, consistency, mobility, tenderness and whether nodes are matted, since these are the features that will be compared at follow-up. "Enlarged node" documented without measurement makes the next visit uninterpretable.
• Examine the drainage territory and the liver and spleen. Inspect skin, scalp and oral cavity in cervical presentations, and breasts in axillary ones.
• Feel for a supraclavicular node deliberately, with the patient performing a Valsalva, which can bring an otherwise impalpable node up into reach.

• Complete blood count with differential and film -atypical lymphocytes point at a viral cause; cytopenias or blasts point at marrow involvement and change the urgency completely.
• LDH, elevated with high cell turnover in lymphoma, and ESR or CRP as non-specific supports.
• Targeted serology and testing based on the history: HIV (test broadly, not selectively), EBV and CMV, toxoplasma, Bartonella, syphilis, and tuberculosis testing where the exposure history or presentation fits.
• Chest radiograph to look for mediastinal or hilar adenopathy, which can be the finding that reframes the whole picture toward lymphoma, sarcoidosis or tuberculosis.
• Ultrasound is the useful first imaging test for accessible nodes, describing size, shape and internal architecture. CT for deep or mediastinal disease, and to map extent once malignancy is suspected.

• ⚠ Do not give empiric corticosteroids before a diagnosis is established. Steroids are lympholytic and can shrink a lymphoma temporarily, which is falsely reassuring, and they can obscure the histology enough to make the eventual biopsy uninterpretable. If a node is worrying enough to want to treat it, it is worrying enough to biopsy first.
• Do not run repeated courses of empiric antibiotics for a persistent node. A short course is reasonable when there is a plausible bacterial source; a second and third course in the absence of one is simply time passing while a diagnosis waits.
• If the biopsy is non-diagnostic but suspicion remains, repeat it. A "reactive" result from a node that is still enlarging has not answered the question.

• Which nodal site carries the highest malignancy risk? Supraclavicular -roughly 90% over age 40 and about 25% under 40. Investigate at any size, regardless of tenderness or duration.
• What does a LEFT supraclavicular node suggest, and why? Virchow node -abdominal or gastrointestinal malignancy, because that region drains via the thoracic duct. The right side points more toward mediastinum, lung or esophagus.
• Why excisional biopsy rather than FNA for suspected lymphoma? Classification requires tissue architecture plus immunophenotyping. FNA gives cells without architecture, so it is frequently non-diagnostic, and a "reactive" result does not exclude lymphoma.
• Which node should be excised? The largest and most abnormal, not the most accessible, and avoid inguinal nodes where possible because they so often show non-specific reactive change.
• Why must you avoid steroids before biopsy? They are lympholytic, can transiently shrink lymphoma and falsely reassure, and can obscure the histology enough to make the biopsy uninterpretable.
• Define generalized lymphadenopathy. Two or more non-contiguous nodal regions, which shifts thinking to systemic infection, autoimmune disease, malignancy, sarcoidosis or drugs.
• What size is abnormal? Generally over 1 cm, but site-specific: epitrochlear over about 0.5 cm is always abnormal, inguinal up to 1.5 to 2 cm is often normal, and any supraclavicular node is abnormal.
• Name drugs that cause lymphadenopathy. Phenytoin, carbamazepine, lamotrigine, allopurinol and sulfonamides among others, sometimes as part of DRESS.
• What are the B symptoms? Fever, drenching night sweats and unintentional weight loss, classically more than 10% of body weight over 6 months.
• How long may you observe, and in whom? About 3 to 4 weeks, in a patient under 40 with a small localized node, no red flags and a plausible reactive cause -with explicit return criteria and a booked follow-up.

"Mr. P is a 58-year-old man with a 6-week history of a painless left supraclavicular node, now about 2 cm, hard and fixed. He has lost around 7 kg over 4 months and describes drenching night sweats, so he has B symptoms. This is the highest-risk presentation in lymphadenopathy: a supraclavicular node at his age carries roughly a 90% malignancy risk, and being on the left it raises abdominal or gastrointestinal primaries via thoracic duct drainage, so I have examined the abdomen carefully and will image it. On full nodal examination I found no second non-contiguous region, and there is no hepatosplenomegaly. I have sent a CBC with differential and film, LDH, ESR, HIV and a chest radiograph, and requested CT of chest, abdomen and pelvis. The key management point is that this needs an excisional biopsy, not an FNA: if this is lymphoma, classification requires architecture as well as immunophenotyping, and a reactive FNA result would not exclude it. I have discussed with surgery and alerted pathology so the specimen goes fresh for flow cytometry. I have specifically not started steroids or empiric antibiotics, because steroids could shrink a lymphoma transiently and render the histology uninterpretable."

• Is it supraclavicular? If yes, investigate now regardless of size or symptoms.
• All nodal regions examined, plus liver and spleen, and the drainage territory of the affected node.
• Size and character documented in numbers, so follow-up is interpretable.
• B symptoms asked about explicitly -fever, night sweats, weight loss.
• Drug list and exposure history reviewed, including sexual history and tuberculosis risk.
• If observing: 3 to 4 weeks, explicit return criteria given, follow-up booked rather than left open.
• If biopsying: excisional, largest and most abnormal node, avoid inguinal, and warn the laboratory so tissue arrives fresh.

• Supraclavicular is never "let's watch it." Location beats size, tenderness and duration as a risk signal.
• Excise, do not aspirate, when lymphoma is on the list. A reactive FNA answers nothing.
• No steroids before tissue. Treating the node you have not diagnosed can destroy the diagnosis.