Eduovisual
Blood & Lymphoreticular
Lymphadenopathy: outpatient workup
— Epitrochlear >0.5 cm is abnormal
— Inguinal up to 1.5 cm can be normal in adults
— Any palpable supraclavicular node is pathologic until proven otherwise
— ~75% of patients presenting with peripheral lymphadenopathy have localized disease
— Of those, the vast majority are benign/reactive (viral URI, dental, skin)
— Only ~1% of unselected primary care lymphadenopathy represents malignancy, but risk rises sharply with age >40, B symptoms, and supraclavicular location
— Age >40 years
— Node >2 cm, hard, fixed, matted, or rubbery
— Duration >4–6 weeks without resolution
— Supraclavicular, scalene, or epitrochlear location
— Generalized (≥2 noncontiguous regions) lymphadenopathy
— Constitutional "B symptoms": fevers >38°C, drenching night sweats, weight loss >10% over 6 months
— Hepatosplenomegaly, unexplained cytopenias, or LDH elevation
— Step 1: Localized vs generalized
— Step 2: Acute (<2 weeks), subacute (2–6 weeks), or persistent (>6 weeks)
— Step 3: Identify red flags warranting expedited workup vs observation
— Step 4: Targeted labs/imaging → biopsy if criteria met
Board pearl: A 55-year-old smoker with a 1.5 cm left supraclavicular node ("Virchow node") needs urgent evaluation for intra-abdominal or thoracic malignancy—do not "watch and wait." Right supraclavicular nodes drain mediastinum, lungs, and esophagus.
Step 3 management: In ambulatory practice, the highest-yield initial decision is whether the node meets "watchful waiting" criteria (young, localized, soft, mobile, <2 cm, identifiable source, <4 weeks) or "expedited workup" criteria. Document size, consistency, mobility, tenderness, and overlying skin at every visit.
— Usually infectious; track the drainage basin
— Cervical → pharyngitis, dental, otitis, scalp
— Axillary → arm/hand infection, cat scratch, breast
— Inguinal → lower extremity, perineal, STI
— Consider TB, atypical mycobacteria, toxoplasmosis, EBV, CMV, HIV acute retroviral syndrome, syphilis, Bartonella, sarcoidosis
— Malignancy (lymphoma, metastatic carcinoma, leukemia), autoimmune (SLE, RA, Sjögren), HIV, sarcoidosis, Castleman, IgG4-related disease
— Duration, growth rate, prior similar episodes
— B symptoms (fever, drenching night sweats, weight loss)
— Pruritus (Hodgkin), alcohol-induced node pain (classic Hodgkin pearl)
— Sore throat, dental pain, skin lesions, animal scratches (Bartonella)
— Travel: TB-endemic areas, histoplasmosis (Ohio/Mississippi valley), tularemia, plague
— Occupational/recreational: hunters, gardeners, cat owners, raw milk
— Sexual history (HIV, syphilis, HSV, chancroid, LGV)
— Medications: phenytoin, allopurinol, carbamazepine, hydralazine, atenolol, sulfa drugs can cause drug-induced pseudolymphoma/lymphadenopathy
— Tobacco, alcohol (head/neck cancer)
— Vaccinations (recent immunization can produce ipsilateral regional adenopathy, especially post-COVID/post-HPV)
— Family history of lymphoma, leukemia, breast/ovarian, head/neck cancer
— Tick exposures (Lyme, tularemia)
Key distinction: "Painful, rapidly enlarging" nodes favor infection or hemorrhage into a node; "painless, slowly progressive, rubbery" nodes favor lymphoma; "stony hard, fixed" nodes favor metastatic carcinoma.
Board pearl: Alcohol-induced lymph node pain, though rare, is highly specific for Hodgkin lymphoma. Pruritus without rash plus cervical adenopathy in a young adult should also prompt Hodgkin workup.
Step 3 management: Always ask about new medications within the prior 1–8 weeks—stopping the offending agent often resolves drug-induced lymphadenopathy and avoids unnecessary biopsy.
— Size (measure in two dimensions with a ruler—document, don't estimate)
— Consistency: soft (reactive), rubbery (lymphoma), stony hard (metastatic carcinoma), fluctuant (suppurative)
— Mobility: mobile vs fixed/matted (concerning)
— Tenderness: painful = often infectious/inflammatory; painless ≠ benign
— Overlying skin: erythema, warmth, fistula (scrofula), ulceration
— Number: single vs multiple; contiguous vs noncontiguous regions
— Submental/submandibular → mouth floor, lower lip, anterior tongue
— Anterior cervical → pharynx, tonsils, larynx
— Posterior cervical → scalp, EBV classically
— Preauricular → conjunctiva, lateral eyelid, parotid (Parinaud oculoglandular: cat scratch, tularemia)
— Occipital → posterior scalp; rubella in children
— Supraclavicular → R: mediastinum/lung; L (Virchow): abdominal (gastric, pancreatic, ovarian, testicular, renal)
— Axillary → arm, breast, upper chest wall
— Epitrochlear → ulnar forearm/hand; bilateral in syphilis, sarcoidosis, HIV
— Inguinal → lower extremity, external genitalia, perineum, anus (below dentate line)
— Full skin exam (melanoma, primary skin cancers)
— Breast exam for axillary nodes
— Genital and rectal exam for inguinal nodes
— Thyroid and oral cavity for cervical nodes
— Hepatosplenomegaly—suggests systemic process (lymphoma, mono, leukemia, sarcoid)
— Vitals + weight trend
Board pearl: Generalized lymphadenopathy + splenomegaly + atypical lymphocytes in a young adult → EBV mononucleosis; avoid amoxicillin (causes rash) and contact sports for ≥3 weeks (splenic rupture risk).
Step 3 management: A node that is >2 cm, hard, fixed, supraclavicular, or persistent >4–6 weeks crosses the threshold for expedited imaging and biopsy referral—skip prolonged "watchful waiting."
— CBC with differential — atypical lymphocytes (EBV/CMV), blasts (acute leukemia), lymphocytosis (CLL in older adults), neutrophilia (bacterial), cytopenias (marrow infiltration)
— Peripheral blood smear if abnormal CBC
— CMP including LDH (elevated in lymphoma, infection, hemolysis)
— ESR and CRP — nonspecific but trend useful
— HIV 4th-generation Ag/Ab (must be offered in all unexplained lymphadenopathy)
— Heterophile (Monospot) ± EBV VCA IgM in young adults with pharyngitis
— RPR/treponemal test if risk factors or generalized adenopathy
— TSH in cervical adenopathy (rule out thyroid pathology adjacent)
— CMV IgM/IgG — heterophile-negative mono
— Toxoplasma IgM/IgG — posterior cervical, cat exposure
— Bartonella henselae — cat scratch, regional lymphadenitis
— Tularemia, brucellosis — animal/occupational exposure
— Histoplasma/Coccidioides — endemic travel
— ANA — generalized adenopathy with arthralgias
— PPD or IGRA (QuantiFERON) — TB risk factors, scrofula
— ACE level — sarcoidosis suspicion (poor sensitivity, supportive only)
— Chest X-ray in nearly all persistent or generalized cases — looks for hilar/mediastinal adenopathy (sarcoid, lymphoma, TB, fungal, metastatic) and parenchymal disease
— Neck ultrasound for cervical nodes — distinguishes reactive (hilum preserved, oval, vascular hilum) from suspicious (round, loss of hilum, peripheral vascularity, microcalcifications)
Board pearl: Bilateral hilar lymphadenopathy in an asymptomatic young Black or Scandinavian patient with erythema nodosum = Löfgren syndrome (sarcoidosis); often self-limited, no biopsy needed.
Step 3 management: Avoid "shotgun" serology. Order tests driven by drainage basin, exposures, and red flags. Reflexively ordering a full panel on every reactive cervical node wastes resources and triggers false positives.
— CT neck/chest/abdomen/pelvis with contrast — indicated when malignancy suspected, generalized adenopathy, supraclavicular node, abnormal CXR, or before biopsy planning
— PET-CT — staging once lymphoma diagnosed; not a first-line diagnostic test in primary care
— MRI neck — head/neck cancer staging or when CT contrast contraindicated
— Ultrasound-guided FNA — first-line tissue sampling for many head/neck and superficial nodes; high sensitivity for carcinoma metastases
— Node persisting >4–6 weeks without diagnosis
— Size >2 cm with concerning features
— Supraclavicular node at any size
— Hard, fixed, matted, or progressively enlarging
— Constitutional B symptoms + adenopathy
— Abnormal CBC/smear suggesting hematologic malignancy
— Failure to regress after empiric treatment of presumed cause
— Excisional biopsy is the gold standard for suspected lymphoma — preserves nodal architecture for classification, flow cytometry, immunohistochemistry, cytogenetics
— Core needle biopsy acceptable when excision not feasible
— FNA alone is inadequate for lymphoma diagnosis but acceptable for confirming metastatic carcinoma or recurrent disease
— Select the largest, most abnormal, most accessible node; avoid inguinal nodes if possible (often chronically inflamed, lower yield)
— Hematology-oncology for suspected lymphoma/leukemia
— ENT/head & neck surgery for cervical nodes with suspected head/neck primary
— Surgical oncology for supraclavicular, axillary unknown primary
— Infectious disease for atypical TB, persistent unexplained infection
Key distinction: FNA = carcinoma; Excisional = lymphoma. Sending a suspected lymphoma to FNA only often delays diagnosis by weeks.
Step 3 management: Do not biopsy a node within 2 weeks of an obvious URI in a young patient with a soft, tender, <2 cm node. Reassess at 4 weeks; biopsy if unchanged or growing.
— Age <40 years
— Localized cervical, axillary, or inguinal node
— Soft, mobile, tender, <2 cm
— Identifiable triggering source (URI, dental, skin infection, recent immunization)
— No B symptoms, no hepatosplenomegaly, no cytopenias
— Duration <4 weeks
— Plan: reassess in 2–4 weeks; treat underlying source; counsel patient on return precautions
— Subacute duration 2–6 weeks
— Mild constitutional symptoms
— Multiple nodes in one region
— Plan: CBC, smear, LDH, HIV, RPR, EBV/CMV, CXR; reassess in 2 weeks
— Age >40 with any persistent node
— Supraclavicular at any age
— Hard, fixed, matted, or >2 cm
— Generalized adenopathy
— B symptoms, hepatosplenomegaly, cytopenias, elevated LDH
— Plan: CT with contrast, urgent specialist referral, prepare for excisional biopsy
— Reserved for clear bacterial lymphadenitis (warm, fluctuant, overlying cellulitis) — cephalexin or clindamycin, cover MRSA if risk factors
— Do NOT use empiric antibiotics as a "diagnostic trial" for ambiguous adenopathy—it delays cancer diagnosis and is a documented cause of malpractice claims
Board pearl: The "50-50-50 rule": in patients >50 years old with a hard cervical node >1 cm, there is a >50% chance of malignancy.
Step 3 management: Document the specific reassessment plan at every visit—"return in 3 weeks for size recheck, return sooner for B symptoms or growth." Unscheduled, undocumented "watchful waiting" is a high-liability pattern in transition-of-care and outpatient settings.
— Supportive care only — NSAIDs/acetaminophen for tenderness
— No antibiotics; no steroids (can mask lymphoma and complicate biopsy interpretation)
— Cephalexin 500 mg PO QID × 10 days, or dicloxacillin
— MRSA coverage: clindamycin 300–450 mg PO QID, or TMP-SMX DS BID, or doxycycline 100 mg BID
— Incision and drainage if fluctuant abscess; send cultures
— Reassess at 48–72 hours
— Usually self-limited
— Azithromycin 500 mg day 1, then 250 mg daily × 4 days — shortens course in larger nodes
— Avoid I&D (risk of chronic draining sinus)
— RIPE therapy: rifampin, isoniazid, pyrazinamide, ethambutol × 2 months, then RH × 4 months
— Confirm with biopsy + AFB stain + culture + NAAT
— DOT (directly observed therapy) per public health
— Immunocompetent: usually self-limited, no treatment needed
— Symptomatic or severe: pyrimethamine + sulfadiazine + leucovorin
— Benzathine penicillin G 2.4 million units IM × 1 (primary/secondary/early latent); 3 doses weekly for late latent
— Initiate ART promptly per current DHHS guidelines; persistent generalized lymphadenopathy often improves with viral suppression
— Discontinue offending agent; nodes typically regress in 2–6 weeks
— Common culprits: phenytoin, carbamazepine, allopurinol, hydralazine
Board pearl: Empiric steroids before biopsy can temporarily shrink lymphoma, delaying diagnosis by months. Defer steroids until tissue diagnosis is secured.
Step 3 management: When prescribing antibiotics for presumed bacterial lymphadenitis, schedule a 1–2 week follow-up; if no improvement, escalate to imaging and biopsy rather than a second antibiotic course.
— Indicated for fluctuant suppurative lymphadenitis with abscess
— Send pus for Gram stain, aerobic + anaerobic culture, AFB, fungal culture if indolent
— Avoid I&D for cat scratch and mycobacterial nodes — risk of chronic sinus tract
— Office-based or US-guided
— Best for: suspected metastatic carcinoma, recurrent malignancy, infectious workup (cytology + cultures)
— Limitations: inadequate for primary lymphoma diagnosis (cannot assess architecture)
— Send aspirate for: cytology, flow cytometry (if lymphoma considered), cultures, AFB
— Acceptable for deep/inaccessible nodes (mediastinal, retroperitoneal) via IR
— Provides limited architectural information; multiple cores improve yield
— Gold standard for lymphoma
— Performed by general surgery, surgical oncology, or ENT
— Choose the largest, most abnormal, most accessible non-inguinal node
— Send fresh tissue (not just in formalin) to enable flow cytometry, cytogenetics, FISH
— Document size, capsular status, and adjacent structures
— Bone marrow biopsy if cytopenias, suspected leukemia/lymphoma staging
— Endobronchial ultrasound (EBUS) for mediastinal/hilar nodes (sarcoid, lung cancer staging, lymphoma)
— Mediastinoscopy when EBUS nondiagnostic
— Same-week ENT or surgery referral for high-risk neck masses
— Heme-onc consultation triggered by abnormal smear, B symptoms, or biopsy showing lymphoma
— Multidisciplinary tumor board for head/neck unknown primaries
CCS pearl: If the simulated case involves a 60-year-old with a 3-cm fixed cervical node, your CCS orders should include CBC, CMP, LDH, HIV, CT neck/chest/abdomen/pelvis with contrast, and ENT referral for excisional biopsy—not a trial of antibiotics. Advance the clock with these orders queued.
Board pearl: Always specify excisional biopsy with fresh tissue to pathology and flow cytometry when lymphoma is on the differential.
— Pretest probability of malignancy is substantially higher; lower threshold for biopsy
— Common etiologies: NHL, CLL, metastatic carcinoma (lung, breast, GI, prostate, head/neck), myelodysplasia
— Reactive adenopathy is less likely the older the patient
— Consider monoclonal B-cell lymphocytosis (MBL) and CLL with isolated lymphocytosis + small mobile nodes—flow cytometry on peripheral blood often diagnostic without biopsy
— Polypharmacy review: phenytoin, allopurinol commonly used in this group
— Frailty assessment before biopsy/anesthesia; consider performance status (ECOG)
— Contrast-enhanced CT: assess eGFR; hold metformin if eGFR <30; use iso-osmolar contrast and IV hydration if eGFR 30–60
— MRI gadolinium contraindicated if eGFR <30 (nephrogenic systemic fibrosis risk with older agents)
— Adjust antimicrobials: cephalexin, TMP-SMX, clindamycin all need renal dose review
— Watch for hyperkalemia with TMP-SMX in CKD + ACEi/ARB combinations
— Avoid hepatotoxic antibiotics where possible (isoniazid, rifampin, pyrazinamide require careful LFT monitoring in TB)
— Consider portal/celiac lymphadenopathy as reactive in cirrhosis—often benign but warrants follow-up imaging
— Increased baseline risk of hepatocellular carcinoma metastasizing to porta hepatis nodes
— Expanded differential: PTLD (post-transplant lymphoproliferative disorder, EBV-driven), atypical mycobacteria, CMV, Kaposi sarcoma, lymphoma
— Lower threshold for biopsy and EBV viral load testing in transplant patients
Board pearl: A solid organ transplant recipient with new lymphadenopathy + elevated EBV viral load should be evaluated for PTLD; initial management includes reducing immunosuppression and obtaining tissue diagnosis.
Step 3 management: In CKD patients needing CT, document eGFR, hold nephrotoxic agents, and arrange IV hydration; coordinate with radiology rather than canceling the study outright.
— Palpable cervical, axillary, inguinal nodes <2 cm are common and usually benign in children, especially <12 years
— Most common cause: viral URI, reactive cervical adenitis
— Bacterial lymphadenitis: Staph aureus, Group A Strep — cephalexin or clindamycin
— Atypical mycobacteria (M. avium, M. scrofulaceum) — unilateral subacute cervical node, violaceous overlying skin in a 1–5 year old; surgical excision is treatment of choice (not antibiotics alone)
— Kawasaki disease: unilateral cervical node >1.5 cm + fever ≥5 days + 4 of 5 criteria (conjunctivitis, rash, mucositis, extremity changes); urgent IVIG + aspirin
— Pediatric red flags for biopsy: supraclavicular, >2 cm, fixed, hard, persistent >4 weeks, B symptoms, abnormal CXR, cytopenias
— Most common pediatric lymphoid malignancies: ALL, Hodgkin (adolescents), Burkitt (abdominal)
— EBV mononucleosis peak incidence; avoid contact sports ≥3 weeks; avoid amoxicillin (morbilliform rash)
— Hodgkin lymphoma classic age peaks: 15–35 and >55
— Physiologic mild reactive adenopathy can occur
— Imaging: ultrasound first-line; MRI without gadolinium acceptable; avoid CT with contrast when feasible
— Biopsy is safe during pregnancy under local anesthesia
— Hodgkin lymphoma in pregnancy: ABVD generally safe in 2nd/3rd trimester; coordinate with maternal-fetal medicine and oncology
— Toxoplasmosis in pregnancy: spiramycin to prevent vertical transmission; pyrimethamine/sulfadiazine only after 1st trimester if fetal infection confirmed
— Syphilis: penicillin remains standard; desensitize if allergic—no acceptable substitute in pregnancy
Board pearl: A unilateral, subacute, violet-colored cervical node in a toddler with minimal systemic symptoms = nontuberculous mycobacterial lymphadenitis; surgical excision is curative; antibiotics alone often fail.
Step 3 management: In a pregnant patient with persistent lymphadenopathy, start with US + targeted labs; if biopsy needed, proceed under local anesthesia without delay—diagnostic workup should not be deferred until postpartum.
— Missed lymphoma → upstaging, worse prognosis, more intensive therapy required
— Missed head/neck squamous cell carcinoma → progression from curable early-stage to advanced disease
— Missed metastatic disease (gastric, lung, breast) presenting as Virchow node — delay in palliative or curative-intent therapy
— Empiric antibiotic trials >4 weeks are a leading cause of cancer diagnostic delay
— Excisional biopsy: bleeding, infection, scarring
— Cervical biopsy: spinal accessory nerve injury (winged scapula, shoulder weakness)—major posterior triangle risk
— Axillary biopsy: long thoracic nerve injury (winged scapula), intercostobrachial nerve injury (sensory loss), lymphedema
— Inguinal biopsy: chronic lymphedema, wound dehiscence, infection
— FNA: bleeding, nondiagnostic samples, tract seeding (rare)
— EBV: splenic rupture (avoid contact sports ≥3 weeks), airway obstruction from tonsillar hypertrophy, hemolytic anemia
— Suppurative lymphadenitis: abscess, bacteremia, jugular vein septic thrombophlebitis (Lemierre syndrome with Fusobacterium)
— TB lymphadenitis: sinus tract formation, scrofula scarring, dissemination
— Lymphoma: tumor lysis syndrome at chemo initiation, SVC syndrome (mediastinal mass), spinal cord compression
— Sarcoidosis: hypercalcemia, pulmonary fibrosis, cardiac/neuro involvement
— Incidental nodes on imaging trigger cascades of testing
— Counsel proactively about benign vs concerning features
Board pearl: A young adult with sore throat, high fever, neck swelling, and septic pulmonary emboli on CT chest = Lemierre syndrome (Fusobacterium necrophorum jugular thrombophlebitis); treat with prolonged IV beta-lactam + metronidazole; anticoagulation controversial.
Step 3 management: Before any neck biopsy, counsel patients about spinal accessory nerve risk and document informed consent specifically addressing nerve injury, scarring, and possibility of nondiagnostic results requiring repeat procedures.
— Airway compromise from a neck mass (stridor, dysphagia, drooling)
— Suspected SVC syndrome — facial/upper extremity edema, dilated chest wall veins, dyspnea; often anterior mediastinal lymphoma or lung cancer
— Tumor lysis syndrome — bulky lymphoma with hyperuricemia, hyperkalemia, hyperphosphatemia, AKI
— Severe B symptoms with hemodynamic instability or new cytopenias suggesting acute leukemia
— Suspected spinal cord compression from lymphoma — back pain, weakness, sensory level, urinary retention
— Lemierre syndrome, septic shock from suppurative adenitis
— Suspected Kawasaki disease in a child — IVIG within 10 days of fever onset
— Supraclavicular node in adult — ENT or surgical oncology within days
— Pancytopenia or circulating blasts on smear — heme-onc emergent
— Suspected acute HIV with seroconversion adenopathy — ID
— Active TB lymphadenitis — public health notification + ID
— Hematology-oncology: suspected lymphoma/leukemia, abnormal flow cytometry, cytopenias with adenopathy
— ENT/head & neck surgery: persistent neck mass, suspected mucosal primary
— Surgical oncology: axillary mass, unknown primary
— Infectious disease: persistent fever of unknown origin, TB, atypical mycobacteria, HIV
— Rheumatology: generalized adenopathy with autoimmune features
— Dermatology: skin lesions, suspected cutaneous T-cell lymphoma (mycosis fungoides)
CCS pearl: If a CCS case presents a young adult with anterior mediastinal mass and facial swelling, elevate the head of bed, obtain CT chest with contrast, type & screen, urgent oncology consult, and avoid sedatives that compromise airway. Do not put the patient supine for imaging without anesthesia backup.
Step 3 management: "Right care, right place, right time"—stratify mass-related neck masses by airway risk, cytopenia severity, and mediastinal involvement; supraclavicular adenopathy never warrants pure observation.
— Viral: EBV, CMV, HIV (acute), HSV, rubella, measles, COVID-19 (regional post-vaccine)
— Bacterial: Staph aureus, Group A Strep, Bartonella (cat scratch), Francisella (tularemia), Yersinia pestis, Brucella, Treponema pallidum
— Mycobacterial: M. tuberculosis (scrofula), atypical mycobacteria (children)
— Fungal: Histoplasma, Coccidioides, Cryptococcus (immunocompromised)
— Parasitic: Toxoplasma, Leishmania (visceral)
— Hodgkin lymphoma — bimodal age, contiguous nodal spread, Reed-Sternberg cells, mediastinal mass, pruritus, alcohol-induced pain
— Non-Hodgkin lymphoma — DLBCL (most common aggressive), follicular (most common indolent), Burkitt (highly aggressive, "starry sky"), MALT, mantle cell
— CLL/SLL — elderly, lymphocytosis, smudge cells, often asymptomatic; diagnosed by peripheral flow cytometry
— Acute leukemias (ALL, AML) — blasts on smear, cytopenias, often without dramatic adenopathy except ALL
— Hairy cell leukemia — splenomegaly > adenopathy, pancytopenia
— Castleman disease — unicentric (curable with excision) or multicentric (HHV-8 associated, often HIV+)
— Multiple myeloma: rarely causes adenopathy directly; consider extramedullary plasmacytomas
— Rosai-Dorfman (sinus histiocytosis with massive lymphadenopathy) — young adults, massive painless cervical nodes
— Kikuchi-Fujimoto — young Asian women, painful cervical adenopathy + fever, self-limited
— Langerhans cell histiocytosis — children, lytic bone lesions + adenopathy
Key distinction: Hodgkin spreads contiguously between adjacent nodal groups; NHL often presents with noncontiguous, extranodal disease (GI, CNS, skin, bone).
Board pearl: A young Asian woman with painful cervical adenopathy, fever, and self-limited course with negative infectious workup = Kikuchi-Fujimoto disease; biopsy shows necrotizing lymphadenitis without neutrophils; supportive care, watch for later SLE development.
— Head/neck SCC → cervical chain
— Lung → supraclavicular, mediastinal
— Breast → axillary, supraclavicular
— GI (gastric, pancreatic, colorectal) → left supraclavicular (Virchow), periumbilical (Sister Mary Joseph nodule), perirectal
— GU (renal, testicular, prostate) → retroperitoneal, supraclavicular
— Melanoma → regional drainage basin; sentinel node biopsy
— Thyroid → cervical (central and lateral compartments)
— SLE — generalized soft adenopathy, often with serositis, cytopenias, ANA+
— Rheumatoid arthritis — axillary, cervical reactive nodes; Felty syndrome (RA + splenomegaly + neutropenia)
— Sjögren — parotid + cervical; increased lifetime MALT lymphoma risk
— Adult-onset Still disease — quotidian fevers, salmon rash, arthritis, ferritin >>
— IgG4-related disease — multi-organ infiltration, elevated IgG4
— Sarcoidosis — bilateral hilar adenopathy ± peripheral nodes; noncaseating granulomas
— Phenytoin, carbamazepine, lamotrigine, allopurinol, hydralazine, atenolol, captopril, sulfa drugs
— DRESS syndrome — drug rash, eosinophilia, lymphadenopathy, systemic symptoms; high mortality
— Thyroid nodules, thyroglossal duct cysts, branchial cleft cysts — congenital neck masses mimicking nodes
— Submandibular salivary gland enlargement
— Lipomas, sebaceous cysts, lymphangiomas
— Gaucher disease, amyloidosis
— Reactive hyperplasia from chronic dermatitis (dermatopathic lymphadenopathy)
— Silicone-induced lymphadenopathy (breast implants → axillary nodes)
Board pearl: Bilateral hilar adenopathy + uveitis + parotid enlargement + facial nerve palsy = Heerfordt syndrome (uveoparotid fever), a sarcoidosis variant.
Key distinction: A neck mass in a midline submental location in a young patient that moves with tongue protrusion = thyroglossal duct cyst, not a lymph node—imaging and surgical excision (Sistrunk procedure).
— Document baseline node size in chart for future comparison
— Counsel patient on return precautions: growth, new B symptoms, new nodes elsewhere
— Routine age-appropriate cancer screening per USPSTF (cervical, breast, colorectal, lung if eligible)
— Address modifiable risk factors: tobacco cessation, HPV vaccination (up to age 45), HIV prevention (PrEP if indicated)
— EBV: avoid contact sports ≥3 weeks; counsel on prolonged fatigue
— TB: complete DOT regimen, contact tracing, screen household
— HIV: link to care, ART initiation, opportunistic infection prophylaxis if CD4 low, partner notification
— Syphilis: treponemal titers at 6 and 12 months; partner treatment; coinfection screening (HIV, hepatitis B/C, gonorrhea, chlamydia)
— Bartonella: usually no follow-up needed once resolved
— Care plan coordinated with oncology
— Survivorship plan: surveillance imaging, late effects monitoring, secondary malignancy screening
— Hodgkin survivors: increased risk of breast cancer (early MRI screening), thyroid cancer, cardiovascular disease from prior chest radiation
— Lymphoma chemotherapy survivors: cardiotoxicity (anthracyclines—baseline and surveillance echo), infertility counseling, hepatitis B reactivation screening before rituximab
— Vaccination: avoid live vaccines during active immunosuppression; inactivated influenza, pneumococcal, COVID, recombinant zoster appropriate
— Document the offending agent prominently in allergy/intolerance list
— Avoid re-exposure; communicate with all prescribers
— Ensure biopsy results are reviewed and communicated within 1 week
— Patient portal messaging + phone confirmation for abnormal results
— Closed-loop referral tracking for specialist visits
Board pearl: Hodgkin lymphoma survivors treated with mantle-field radiation in adolescence need annual breast MRI starting 8–10 years post-treatment or age 25 (whichever later)—well before standard screening age.
Step 3 management: Build a structured post-diagnosis follow-up template including labs, imaging cadence, vaccinations, screening, and patient-reported outcomes; ambulatory continuity is the Step 3 differentiator.
— Low-risk reactive node: recheck at 2–4 weeks; if smaller or resolved, no further workup
— Persistent unchanged node at 4 weeks: targeted labs + imaging; biopsy by 6 weeks if unresolved
— Post-biopsy benign result: follow-up at 3 months; if growing again, repeat biopsy
— Post-treatment infectious: follow-up at 2 weeks; node may take weeks to fully resolve
— HIV: viral load, CD4 every 3–6 months until stable
— TB: monthly LFTs during RIPE; sputum/clinical reassessment
— Syphilis: RPR titers at 6, 12, 24 months (4-fold decline = treatment success)
— Lymphoma in surveillance: CBC, CMP, LDH every 3 months × 2 years, then less frequently; imaging per NCCN
— CLL Rai/Binet stage progression: CBC every 3–6 months
— Clear explanation of differential and reasoning
— Specific return precautions in writing: new B symptoms, rapid growth, new nodes, bleeding, fatigue, dyspnea
— Realistic timelines—reactive nodes can take 4–6 weeks to resolve fully
— Avoid manual manipulation/squeezing of nodes (does not help and increases anxiety)
— Address health literacy: use teach-back
— Post-axillary surgery: lymphedema precautions, physical therapy
— Post-cervical surgery: shoulder ROM exercises to prevent stiffness
— Cancer survivors: structured exercise programs reduce fatigue and recurrence in several lymphomas
— Watchful waiting vs immediate biopsy discussions documented with patient preferences
Board pearl: A 4-fold drop in RPR titer at 6–12 months indicates adequate syphilis treatment response; failure of titers to decline warrants HIV testing, LP, and retreatment evaluation.
Step 3 management: Always close the loop—reviewing the biopsy result with the patient is your responsibility, not just the consultant's. Missed result communication is one of the most common ambulatory malpractice scenarios.
— Discuss risks: bleeding, infection, scarring, nerve injury (spinal accessory in neck, long thoracic in axilla), nondiagnostic result, possibility of malignancy diagnosis
— Document specifically in cervical biopsies: spinal accessory nerve injury risk and resultant shoulder dysfunction
— Verify decision-making capacity, especially in elderly with mild cognitive impairment
— Active tuberculosis — reportable to public health in all states; initiate contact tracing
— Syphilis, HIV, gonorrhea, chlamydia — STD reporting per state law; partner notification services
— Suspected child abuse when adenopathy accompanies unexplained injuries — mandatory reporter obligations
— Certain rare infections (plague, tularemia, brucellosis) — public health notifiable
— Closed-loop tracking of biopsy results — never assume "no news is good news"
— Direct communication of malignant or unexpected results within 24–72 hours
— Warm handoff to oncology with documented appointment date
— Medication reconciliation when discontinuing causative drugs (e.g., phenytoin in drug-induced adenopathy)—coordinate with neurology to avoid breakthrough seizures
— Avoid anchoring bias ("it's just reactive")—reassess at scheduled intervals
— Document differential reasoning at each visit
— Empiric antibiotic trials >2–4 weeks without reassessment = high-liability pattern
— Track no-show rates for follow-up appointments; outreach for missed visits
— HIV-related adenopathy results — heightened confidentiality protections under state laws
— Adolescent care: many states allow minors to consent to STI/HIV testing without parental notification
— Access to imaging and specialty referral varies; document barriers and arrange social work support when needed
— Language-concordant counseling using qualified medical interpreters (not family members) for biopsy consent
Board pearl: Discovering occupational TB lymphadenitis in a healthcare worker triggers both public health reporting and occupational health notification—dual reporting obligations.
Step 3 management: When biopsy returns malignant, call the patient personally, schedule an in-person visit within 1 week, and document the conversation; abnormal results communicated only via portal messages are a recognized safety failure.
— Virchow node (left supraclavicular) → abdominal malignancy (gastric, pancreatic, ovarian)
— Sister Mary Joseph nodule (periumbilical) → intra-abdominal malignancy
— Delphian node (midline pretracheal) → thyroid or laryngeal cancer
— Cloquet node (deep inguinal) → pelvic/lower extremity
— Rotter nodes (interpectoral) → breast cancer staging
— Irish node (left axillary) → gastric cancer
— Hodgkin: contiguous spread, Reed-Sternberg "owl eyes," alcohol-induced pain, pruritus
— Burkitt: "starry sky" pattern, jaw mass (endemic African), abdominal mass (sporadic), EBV-associated
— Cat scratch: Parinaud oculoglandular syndrome (preauricular node + conjunctivitis)
— Toxoplasmosis: posterior cervical, cat exposure, pregnancy concern
— Tularemia: ulceroglandular (skin ulcer + regional node), rabbit/tick exposure
— Sarcoidosis: bilateral hilar adenopathy, noncaseating granulomas, elevated ACE
— Kikuchi-Fujimoto: young Asian women, painful cervical, self-limited
— Castleman: hyaline-vascular (unicentric) vs plasma cell (multicentric, HHV-8)
— Rosai-Dorfman: massive painless cervical adenopathy, emperipolesis on biopsy
— Smudge cells on smear → CLL
— Atypical lymphocytes >10% + heterophile+ → EBV mono
— LDH elevation in lymphoma correlates with tumor burden
— Bilateral hilar adenopathy: sarcoid, lymphoma, TB, fungal, metastatic, silicosis, berylliosis
— Eggshell calcification of hilar nodes → silicosis, sarcoidosis
— "Popcorn" calcifications → granulomatous (TB, histo)
— Mnemonic: "PHACAS" — Phenytoin, Hydralazine, Allopurinol, Carbamazepine, Atenolol, Sulfa
Board pearl: A young man with right-sided hilar adenopathy, fever, and erythema nodosum on the shins likely has Löfgren syndrome — supportive care with NSAIDs; corticosteroids only for severe disease; excellent prognosis with spontaneous remission >80%.
— 62-year-old smoker with weight loss, early satiety, and a 2 cm hard, fixed left supraclavicular node
— Next best step: CT abdomen/pelvis with contrast (looking for gastric/pancreatic primary); avoid trap answer of "antibiotics" or "observe 4 weeks"
— 19-year-old college student with sore throat, posterior cervical adenopathy, splenomegaly, atypical lymphocytes
— Best initial test: heterophile antibody (Monospot); avoid amoxicillin; counsel on contact sports avoidance × 3 weeks
— 24-year-old with painless cervical adenopathy, night sweats, pruritus, mediastinal mass on CXR, alcohol-induced node pain
— Diagnostic step: excisional lymph node biopsy (not FNA); subsequent PET-CT for staging
— 70-year-old with asymptomatic lymphocytosis (WBC 25k, lymphs 80%), small mobile cervical nodes, smudge cells on smear
— Next step: peripheral blood flow cytometry (CD5+, CD19+, CD23+); biopsy often unnecessary
— 45-year-old with epilepsy on phenytoin × 6 weeks, new generalized adenopathy, rash, eosinophilia, fever, transaminitis
— Diagnosis: DRESS syndrome; discontinue phenytoin immediately; coordinate alternative AED with neurology; supportive care, possibly systemic steroids
— 8-year-old with right axillary adenopathy 2 weeks after kitten scratch on the arm; low-grade fever
— Diagnosis: Bartonella henselae; azithromycin if large node; avoid I&D
— 3-year-old with unilateral subacute cervical node, violaceous overlying skin, afebrile, no systemic symptoms, PPD weakly positive
— Treatment: surgical excision (antibiotics alone often fail)
— 28-year-old Scandinavian woman with bilateral hilar adenopathy, erythema nodosum, ankle arthralgias
— Management: NSAIDs, observation; biopsy not always required given high specificity of the triad
Board pearl: When the stem mentions "painless, rubbery, supraclavicular," plus B symptoms or mediastinal widening, the answer pathway is almost always excisional biopsy → flow cytometry/IHC → staging PET-CT.
Step 3 management: Recognize that stems describing >4 weeks of empiric antibiotics without reassessment are signaling diagnostic delay—the correct answer is escalation, not another antibiotic course.
Lymphadenopathy in the outpatient setting is a clinical triage problem: stratify by location, duration, size, consistency, and constitutional symptoms to separate benign reactive nodes from those requiring expedited imaging and excisional biopsy.
Board pearl: When in doubt on a board stem—supraclavicular node, B symptoms, or >4 weeks unresolved—the answer is almost never another antibiotic course; it is imaging plus excisional biopsy.
Step 3 management: Master the ambulatory choreography: stratify, target labs by drainage basin, image when red flags appear, biopsy decisively, communicate results personally, and coordinate longitudinal follow-up with documentation that withstands both clinical and medicolegal scrutiny.