Family Medicine Board Review · Case-Based · Difficult Level

Lymphadenopathy — Clinical Vignette MCQs

Board-style cases built from the lymphadenopathy summary — history red flags, exam texture traps, site-specific differentials, EBV pattern recognition, and evaluation/treatment pathways. Tap "Reveal Answer" on each, then read the pearl.

10 Questions ●●●● Difficult Single Best Answer

Q1History Risk Stratification●●●● Very Hard

A 52-year-old man presents with a persistent 2.5-cm left cervical lymph node first noticed 10 weeks ago. He reports unintentional weight loss of 6 kg over the past 4 months and drenching night sweats. He has no rash, arthralgias, or recent infections. Which combination of features in his history places him at increased risk for malignancy?

A. Duration of only 10 weeks alone
B. Male sex, age >40, persistent lymphadenopathy, and B symptoms (weight loss, night sweats)
C. Absence of rash and arthralgias
D. Node size of 2.5 cm alone, regardless of other features
E. Lack of recent infection alone

Reveal Answer

Correct answer: B

The classic high-risk combination is persistent lymphadenopathy + male sex + age >40 + B symptoms (fever, unintentional weight loss, night sweats). This patient meets all four criteria, substantially raising concern for malignancy and warranting prompt workup.

Why the others are wrong A — duration alone (10 weeks, i.e., >2 weeks but not >1 year without growth) doesn't by itself confer high risk; it's the combination of factors that matters. C — absence of rash/arthralgias lowers suspicion for autoimmune disease, but doesn't independently indicate malignancy risk. D — size alone is a general concerning feature but isn't the specific risk-stratifying combination tested here. E — absence of infection is not itself a validated risk factor in this framework.

Exam Pearl Memorize this exact combination: persistent + male + age >40 + B symptoms = the classic malignancy risk profile for lymphadenopathy. Weight loss >4.5 kg in 6–12 months, hemoptysis, fever, or night sweats should also raise concern for TB as an alternative diagnosis.

Q2Exam Texture Trap●●●●● Extreme

A 45-year-old woman has a firm, rubbery, freely mobile 3-cm axillary lymph node without overlying erythema or tenderness. A colleague states the node is "definitely benign" because it is mobile rather than fixed. What is the most accurate response to this statement?

A. Agree — mobile nodes are always benign
B. Disagree — mobility does not rule out malignancy; firm, rubbery nodes can represent lymphoma, and fixed (not mobile) nodes are the specific finding most associated with malignancy
C. Agree, but only because the node is nontender
D. Disagree — all axillary nodes greater than 2 cm are malignant by definition
E. Agree — mobility and firmness together confirm a benign reactive node

Reveal Answer

Correct answer: B

Mobile lymph nodes can represent both benign and malignant causes — mobility alone is not reassuring. In fact, firm, rubbery, mobile nodes are specifically described as potentially related to lymphoma. It is fixed nodes that are most specifically associated with malignancy (particularly metastatic disease), while stony-hard texture suggests metastasis.

Why the others are wrong A/C/E — all incorrectly treat mobility as a reassuring/benign finding; the summary explicitly states mobile nodes can be either benign or malignant. D — size alone doesn't make a diagnosis; a >2cm axillary node requires clinical correlation, not automatic malignancy classification.

Exam Pearl Texture cheat sheet: stony/hard → metastasis; firm, rubbery, mobile → possible lymphoma; fixed → malignancy in general; tender, fluctuant, not fixed → bacterial infection. "Mobile" is the trap answer choice boards use to test if you conflate it with "benign."

Q3Supraclavicular Node●●●●● Extreme

A 58-year-old man presents with a new, painless, firm left supraclavicular lymph node. He denies fever, recent vaccination, or travel. What is the most appropriate next step?

A. Reassure the patient and recheck in 6 months
B. Prompt evaluation for malignancy, particularly lung, breast, or retroperitoneal primary, given the high-risk location
C. Empiric antibiotics for presumed bacterial lymphadenitis
D. Reassure the patient since the node is painless
E. Order only a rapid strep test

Reveal Answer

Correct answer: B

Supraclavicular lymphadenopathy is highly suggestive of malignancy in all age groups — classically from breast, lung, or retroperitoneal primaries (left-sided supraclavicular node = "Virchow node," classically linked to abdominal malignancy). This location warrants prompt malignancy-focused evaluation even without other symptoms.

Why the others are wrong A/D — a painless supraclavicular node should never be simply observed; painlessness does not lower malignancy risk in this location — if anything, painless nodes are classically more concerning than tender ones. C — there's no clinical evidence (erythema, tenderness, size >2–3 cm with acute onset) supporting a bacterial cause; empiric antibiotics are not indicated here and would delay appropriate workup. E — a rapid strep test is irrelevant to this presentation and location.

Exam Pearl Supraclavicular = malignancy until proven otherwise, regardless of age. It can also be seen with vaccination, TB, or thyroid disease, but malignancy should be actively excluded first given the location's high predictive value.

Q4Epitrochlear Node●●●● Very Hard

A 39-year-old woman is found to have a firm, nontender right epitrochlear lymph node on routine exam. She denies any cat exposure, recent skin trauma, upper extremity infection, or rash. What is the most appropriate interpretation of this finding?

A. This is a normal exam finding requiring no further workup
B. This is most consistent with cat-scratch disease even without exposure history
C. Epitrochlear lymphadenopathy without an apparent infectious source is concerning for malignancy, such as lymphoma or melanoma, and warrants further evaluation
D. This finding is exclusively associated with tularemia
E. No workup is needed since epitrochlear nodes are never clinically significant

Reveal Answer

Correct answer: C

While epitrochlear lymphadenopathy can be benign (cat-scratch disease, tularemia, sporotrichosis via inoculation), the absence of an apparent infectious source in this location is specifically flagged as concerning for malignancy — lymphoma or melanoma — and should prompt further evaluation.

Why the others are wrong A/E — epitrochlear nodes are not a normal incidental finding and should not be dismissed, especially without an infectious explanation. B/D — both require a relevant exposure history (cat scratch or vector/tick exposure) that this patient specifically denies; without exposure, these become far less likely.

Exam Pearl Epitrochlear nodes: presence of a plausible inoculation source (cat scratch, skin lesion) points to benign causes; absence of one shifts concern toward lymphoma or melanoma. Always ask about exposure history before reassuring.

Q5EBV Pattern Recognition●●●●● Extreme

A 19-year-old college student presents with 10 days of fatigue, low-grade fever, and malaise. Exam reveals bilateral posterior cervical, axillary, and inguinal lymphadenopathy. She reports the lymph node swelling began within the first few days of her illness. What is the most likely diagnosis, and what should she be told about the expected course?

A. Streptococcal pharyngitis; lymphadenopathy should resolve within 48 hours of starting antibiotics
B. Epstein-Barr virus infection; lymphadenopathy typically appears within the first week of exposure and improves over 2–3 weeks
C. Cat-scratch disease; lymphadenopathy should resolve within 24 hours with azithromycin
D. Tuberculous lymphadenitis; lymphadenopathy typically resolves within 1 week without treatment
E. Drug-induced lymphadenopathy; resolution expected within 72 hours of stopping the offending agent

Reveal Answer

Correct answer: B

Bilateral posterior cervical, axillary, and inguinal lymphadenopathy with low-grade fever, fatigue, and prolonged malaise is the classic pattern of EBV infection. Lymphadenopathy characteristically appears within the first week of exposure and improves over 2–3 weeks — a timeline important for patient counseling and avoiding unnecessary repeat workup too early.

Why the others are wrong A — strep pharyngitis doesn't typically cause this generalized, multi-site nodal pattern, and lymphadenopathy doesn't resolve that quickly even with appropriate antibiotics. C — cat-scratch disease is a localized, not generalized, process tied to an inoculation site, and doesn't resolve within 24 hours. D — TB lymphadenitis is typically a more chronic, indolent process, not a 1-week self-limited course. E — no medication history is given, and drug-induced lymphadenopathy doesn't fit this specific generalized systemic pattern with fever/malaise.

Exam Pearl EBV lymphadenopathy pattern: bilateral posterior cervical + axillary + inguinal nodes, onset within the first week, resolution over 2–3 weeks, plus low-grade fever/fatigue/malaise. This exact distribution and timeline is a recurring board fact.

Q6Age-Based Imaging Selection●●●● Very Hard

Two patients present with concerning cervical lymphadenopathy warranting imaging: a 6-year-old child and a 55-year-old adult with risk factors for malignancy. What is the most appropriate first-line imaging modality for each, respectively?

A. Contrast CT for both patients
B. Ultrasound for the child; contrast CT or MRI of the neck for the adult
C. MRI for the child; ultrasound for the adult
D. Chest x-ray for both patients
E. PET/CT for both patients as the initial test

Reveal Answer

Correct answer: B

Ultrasound is the first-line imaging modality for peripheral lymphadenopathy in children ≤14 years (avoids radiation, well-tolerated). In adults with neck lymphadenopathy — especially those at higher risk for malignancy — contrast CT or MRI of the neck is first-line.

Why the others are wrong A — CT is not the pediatric first-line choice; ultrasound is preferred to avoid radiation exposure in children. C — this reverses the correct age-based recommendations. D — CXR is used for chronic localized/generalized lymphadenopathy to assess for mediastinal or hilar findings, not as the first-line modality for a concerning neck node in either group. E — PET/CT is not the initial imaging test; it's reserved for specific staging circumstances after a diagnosis is established.

Exam Pearl Age-based imaging split: ultrasound for children ≤14, contrast CT/MRI neck for adults (especially high malignancy risk). CXR is reserved for chronic lymphadenopathy to evaluate the mediastinum/hila, not as first-line for a focal neck node.

Q7Pathology Test Selection●●●●● Extreme

A 61-year-old man has a firm, fixed, 3.5-cm cervical lymph node with associated night sweats and 8% body weight loss over 3 months. Lymphoma is the leading clinical concern. Which initial pathology test is most appropriate?

A. Fine-needle aspiration, since it is the most minimally invasive option
B. Core needle biopsy, which is a better initial test than FNA when lymphoma is suspected
C. Skip tissue sampling and proceed directly to empiric chemotherapy
D. Repeat physical exam only in 3 months before any tissue sampling
E. Blood culture as the initial diagnostic test

Reveal Answer

Correct answer: B

While FNA is minimally invasive and useful in select situations, core needle biopsy is specifically a better initial test than FNA when lymphoma is the leading concern, as it better preserves architecture needed for accurate lymphoma subclassification.

Why the others are wrong A — FNA's minimal invasiveness doesn't make it the best choice specifically for suspected lymphoma; core biopsy is preferred here. C — treatment should never begin without tissue diagnosis. D — deferring biopsy for 3 months in a patient with concerning B symptoms and a fixed node risks delayed diagnosis of a potentially aggressive malignancy. E — blood culture doesn't address the diagnostic question of a solid lymph node mass.

Exam Pearl General pathology tools: FNA, core needle biopsy, and excisional biopsy can all diagnose lymphadenopathy causes — but when lymphoma is the specific concern, core needle biopsy beats FNA as the initial test. FNA is best reserved for when a small needle/less invasive sampling is specifically preferred.

Q8Antibiotic Selection●●●○ Hard

A 7-year-old boy presents with a tender, erythematous, fluctuant 3-cm cervical lymph node of 4 days' duration, without systemic symptoms. He has no known cat exposure. What is the most appropriate empiric antibiotic choice?

A. Azithromycin
B. Amoxicillin-clavulanate or cephalexin
C. No antibiotics are indicated; this should always be managed with observation alone
D. Vancomycin as first-line empiric therapy
E. Doxycycline

Reveal Answer

Correct answer: B

This presentation — unilateral, tender, erythematous node >2–3 cm — meets criteria for presumed bacterial lymphadenitis. The most common causative organisms are methicillin-susceptible S. aureus and group A Streptococcus, both appropriately covered by amoxicillin-clavulanate or cephalexin.

Why the others are wrong A — azithromycin is reserved specifically for suspected cat-scratch disease, which isn't supported here (no cat exposure). C — while antibiotics aren't used routinely for lymphadenopathy in general, this specific presentation (unilateral, erythematous, tender, >2–3 cm) does meet criteria for treatment. D — vancomycin is reserved for suspected MRSA or more severe/resistant infections, not first-line empiric therapy here. E — doxycycline isn't the standard first-line choice for this presentation.

Exam Pearl Treat with antibiotics only when the presentation fits: unilateral + erythematous + tender + >2–3 cm. Default coverage is amoxicillin-clavulanate or cephalexin (staph/strep); switch to azithromycin specifically when cat-scratch disease is suspected.

Q9Medication-Induced Lymphadenopathy●●●● Very Hard

A 63-year-old man with a history of gout on long-term allopurinol presents with new, mild, generalized lymphadenopathy. He denies fever, weight loss, or night sweats, and has no other new symptoms. What is the most appropriate initial approach?

A. Immediately order a PET/CT for staging
B. Consider medication-associated lymphadenopathy given his allopurinol use, and correlate clinically before pursuing invasive workup
C. Proceed directly to excisional biopsy regardless of history
D. Assume malignancy and refer urgently to oncology without further evaluation
E. Discontinue allopurinol permanently without further evaluation, and no follow-up is needed

Reveal Answer

Correct answer: B

Allopurinol is a recognized medication associated with lymphadenopathy. Given the absence of red-flag features (no B symptoms, no rapid growth, no concerning exam findings), it is reasonable to consider a medication-associated cause and correlate clinically — potentially with close follow-up — before proceeding to more invasive testing.

Why the others are wrong A — PET/CT is not indicated as an initial test without first considering more likely benign explanations. C — excisional biopsy is invasive and not the first step when a reasonable benign explanation (medication) exists and red flags are absent. D — this presentation lacks any high-risk features that would justify assuming malignancy and bypassing a stepwise evaluation. E — while considering stopping the medication is reasonable in select cases, doing so "without further evaluation and no follow-up" ignores the need to confirm resolution and rule out other causes.

Exam Pearl Always screen the medication list (and vaccine history) in new lymphadenopathy — agents like allopurinol, phenytoin, carbamazepine, gold, sulfonamides, and others, as well as vaccines like MMR, COVID-19, BCG, typhoid, can all cause reactive lymphadenopathy. This history can prevent an unnecessary invasive workup when red flags are absent.

Q10Integrative — Labs & Duration●●●●● Extreme

A 34-year-old woman has a 1-cm cervical lymph node that has been stable in size for 14 months, first noted incidentally. She is asymptomatic with no B symptoms, rash, arthralgias, or risk factors. What is the most appropriate management?

A. Order CBC, LDH, and CT neck given her age
B. No further workup needed; lymphadenopathy present without growth for more than 1 year is usually benign
C. Excisional biopsy given any persistent lymphadenopathy warrants tissue diagnosis
D. Empiric antibiotics for 2 weeks followed by reassessment
E. IGRA testing to rule out tuberculosis

Reveal Answer

Correct answer: B

Lymphadenopathy that has been present without growth for more than 1 year is usually benign in both children and adults. Combined with her lack of any risk factors (she's young, female, asymptomatic, no B symptoms, no autoimmune features), no further workup is indicated at this time — routine labs/imaging are not needed given this reassuring history.

Why the others are wrong A — labs are only indicated for suspected specific causes or lymphadenopathy persistent >1 month with concerning features; this reassuring, stable, long-duration node doesn't meet that threshold. C — biopsy is not warranted given the benign historical pattern and absence of risk factors; not all persistent nodes require tissue diagnosis. D — there's no indication of bacterial infection (no erythema, tenderness, or acute onset) to justify antibiotics. E — IGRA is reserved for suspected TB, which isn't supported by this clinical picture.

Exam Pearl Two reassuring historical patterns to memorize: lymphadenopathy present <2 weeks, OR present without growth for >1 year — both are usually benign and do not require aggressive workup absent other red flags.