Family Medicine Board Review · Part 2 · Case-Based

Lymphoma — Very Difficult Clinical Vignettes

Integrative, multi-step cases pulled from the combined lymphoma module — epidemiology, infections, staging, emergencies, treatment complications, and survivorship. Tap "Reveal Answer" on each to check yourself, then read the pearl.

10 Questions ●●●● Very Hard Single Best Answer

Q1Staging Nuance●●●● Very Hard

A 29-year-old woman is diagnosed with classic Hodgkin lymphoma. PET/CT shows a 12-cm anterior mediastinal mass and right cervical lymphadenopathy, both above the diaphragm. She denies fever, night sweats, or weight loss. Which staging designation is most accurate, and how does it affect management?

A. Stage IV-A; requires systemic chemotherapy for extralymphatic disease
B. Stage II-A, bulky; may be treated as limited or advanced based on additional prognostic factors
C. Stage III-A; splenic involvement must be excluded before treatment
D. Stage II-B; the mass size alone qualifies as a B symptom
E. Stage I-A; only one true nodal region (mediastinum) is involved

Reveal Answer

Correct answer: B

Two nodal groups (mediastinal + cervical), same side of the diaphragm = Stage II. No B symptoms reported = A. A mass >10 cm is classified as bulky disease, which is a modifier — not an automatic upstage to III/IV — and directs whether she's treated along a limited or advanced-disease protocol based on other prognostic factors (e.g., ESR, number of nodal sites).

Why the others are wrong Both nodal sites are supradiaphragmatic — no extralymphatic or contralateral involvement, ruling out IV and III. Bulky size is not itself a B symptom (B requires fever >38.5°C, drenching night sweats, or ≥10% body weight loss over 6 months) — she has neither. Two involved regions excludes Stage I.

Exam Pearl Bulky disease (>10 cm) is a separate modifier layered onto Lugano staging — don't confuse "bulky" with upstaging. It changes prognosis and treatment intensity, not the stage number itself.

Q2Infection Link●●●● Very Hard

A 48-year-old man who emigrated from southwestern Japan presents with diffuse lymphadenopathy, hepatosplenomegaly, hypercalcemia, and lytic bone lesions on imaging. Peripheral smear shows atypical lymphocytes with multilobulated, "flower-shaped" nuclei. Which underlying infection best explains this presentation?

A. Epstein-Barr virus
B. Human T-lymphotropic virus type 1 (HTLV-1)
C. Helicobacter pylori
D. Hepatitis C virus
E. HIV

Reveal Answer

Correct answer: B

HTLV-1 causes adult T-cell leukemia/lymphoma via direct lymphocyte transformation. Endemic areas include southwestern Japan, the Caribbean, and parts of Africa. Hypercalcemia, lytic bone lesions, and "flower cells" on smear are classic exam clues for ATLL.

Why the others are wrong EBV → Burkitt, Hodgkin, and other NHL, but not this smear finding or endemic pattern. H. pylori → gastric MALT, presents with GI symptoms, not this systemic picture. Hepatitis C → splenic marginal zone lymphoma. HIV → immunosuppression-driven Hodgkin/non-Hodgkin lymphoma, but doesn't produce this specific smear finding.

Exam Pearl Match the mechanism, not just the organism: direct transformation (EBV, HTLV-1) vs. immunosuppression (HIV) vs. chronic antigenic stimulation (H. pylori, Campylobacter, Borrelia, hepatitis C). Boards love testing the mechanism category.

Q3Infection Link●●●○ Hard

A 52-year-old man with a remote history of untreated erythema migrans (never treated for Lyme disease) presents with a slowly enlarging, violaceous cutaneous plaque on the trunk. Biopsy is consistent with primary cutaneous B-cell lymphoma. Which organism is most strongly associated with this presentation?

A. Chlamydia psittaci
B. Borrelia burgdorferi
C. Campylobacter jejuni
D. Hepatitis C virus
E. Human papillomavirus

Reveal Answer

Correct answer: B

Borrelia burgdorferi, the causative organism of Lyme disease, is linked to cutaneous MALT lymphoma through chronic antigenic stimulation of skin-associated lymphoid tissue.

Why the others are wrong C. psittaci is linked to ocular adnexal (orbital) MALT lymphoma, not cutaneous. C. jejuni is linked to immunoproliferative small intestinal disease. Hepatitis C → splenic marginal zone lymphoma. HPV is not a recognized lymphoma-associated organism in this framework.

Exam Pearl Each chronic-antigenic-stimulation organism has a site-specific MALT association: H. pylori → stomach, C. psittaci → eye/orbit, Borrelia → skin, Campylobacter → small intestine. Location in the vignette is the clue.

Q4Oncologic Emergency●●●●● Extreme

A 34-year-old man with known bulky mediastinal Hodgkin lymphoma is brought to the emergency department with stridor, facial and upper-extremity swelling, and new confusion. Exam shows engorged neck veins and facial plethora. CT confirms severe SVC compression with cerebral edema. Tissue diagnosis was established at the time of initial workup two weeks ago. What is the most appropriate immediate step?

A. Withhold steroids and wait for outpatient oncology follow-up since diagnosis is already confirmed
B. Begin urgent corticosteroids and emergent definitive therapy (radiotherapy/chemotherapy or stenting) given airway compromise and cerebral edema
C. Repeat lymph node biopsy before any treatment is given
D. Start therapeutic anticoagulation with heparin
E. Discharge home with close outpatient follow-up in 1 week

Reveal Answer

Correct answer: B

This is now a true oncologic emergency — airway compromise plus cerebral edema. Unlike the stable SVC syndrome case where biopsy precedes treatment, here the tissue diagnosis is already confirmed, so there is no reason to delay: give urgent steroids and pursue emergent definitive therapy (radiotherapy, chemotherapy, and/or SVC stenting) to relieve obstruction and swelling.

Why the others are wrong A — withholding treatment risks airway loss and neurologic injury; the concern about steroids obscuring biopsy no longer applies since diagnosis is confirmed. C — unnecessary and dangerous delay; tissue diagnosis already exists. D — no evidence of thrombus; this is extrinsic compression, not a clotting emergency. E — this patient requires immediate inpatient emergent management, not discharge.

Exam Pearl The "don't give steroids before biopsy" rule only applies before tissue diagnosis is obtained. Once diagnosis is confirmed, or if the patient develops airway compromise/cerebral edema, steroids and emergent therapy should not be delayed. Boards test this exact flip between the stable and unstable versions of the same disease.

Q5Late Cardiac Complication●●●●● Extreme

A 46-year-old woman, 16 years out from mediastinal radiation for Hodgkin lymphoma, presents with progressive exertional dyspnea, lower extremity edema, and elevated jugular venous pressure that rises with inspiration. On exam, there is a pericardial knock. Echocardiogram shows a thickened pericardium with normal ejection fraction and septal bounce. What is the most likely diagnosis?

A. Anthracycline-induced dilated cardiomyopathy
B. Radiation-induced constrictive pericarditis
C. Acute pericarditis from lymphoma recurrence
D. Restrictive cardiomyopathy from amyloidosis
E. Cardiac tamponade

Reveal Answer

Correct answer: B

Kussmaul sign (JVP rising with inspiration), pericardial knock, and echo findings of a thickened, non-compliant pericardium with preserved EF and septal bounce are classic for constrictive pericarditis — a recognized late complication of mediastinal radiation, occurring years to decades after treatment.

Why the others are wrong Anthracycline cardiomyopathy presents with reduced EF and a dilated, poorly contractile ventricle — not a thickened pericardium or knock. Acute pericarditis would show pleuritic chest pain, friction rub, and diffuse ST elevations, an acute presentation, not this chronic pattern. Amyloid restrictive cardiomyopathy shows myocardial (not pericardial) thickening with low-voltage ECG, not a knock. Tamponade presents with pulsus paradoxus and hypotension acutely, not this indolent course.

Exam Pearl Radiation-induced cardiac disease is latent — it can present 10–20+ years after chest RT. Cardiac surveillance (stress test/echo every 10 years per guideline) exists specifically to catch this before it becomes symptomatic.

Q6Survivorship Screening●●●● Very Hard

A 38-year-old woman received chest radiation for Hodgkin lymphoma at age 33 (not between ages 10–30). She is now 5 years post-treatment and asks about breast cancer screening. Which recommendation is most appropriate?

A. No screening needed since she was irradiated after age 30
B. Begin annual mammography now (8 years post-radiation would be age 41, but average-risk screening starts at 40); annual breast MRI is not specifically indicated based on her age at radiation
C. Begin annual mammography and breast MRI now, since any chest radiation triggers both
D. Delay all breast screening until age 50
E. Order genetic testing before determining a screening plan

Reveal Answer

Correct answer: B

The "8 years post-RT or age 40, whichever comes first" rule for mammography applies to any history of chest/axilla radiation, regardless of age at exposure — here that's age 41 (8 years after 33), so average-risk screening starting at 40 actually comes first. However, the added breast MRI recommendation specifically applies to radiation received between ages 10–30; she was irradiated at 33, outside that window, so MRI isn't specifically indicated on this basis alone.

Why the others are wrong A — radiation after age 30 doesn't eliminate screening; standard age-40 mammography still applies, and the 8-year rule is still compared against it. C — MRI add-on is tied to the 10–30 age-at-exposure window, not to any chest radiation. D — delaying to 50 ignores both her radiation history and average-risk guidelines. E — this is treatment-related risk, not a hereditary syndrome indication.

Exam Pearl Two separate rules, don't conflate them: (1) mammogram timing = 8 yrs post-RT or age 40, whichever is first — applies to any chest/axilla RT; (2) added annual MRI = specifically tied to RT received at age 10–30. Boards test the boundary case where a patient is irradiated outside that window.

Q7Immunization Sequencing●●●○ Hard

A 50-year-old Hodgkin lymphoma survivor, 2 years post-chemotherapy completion, is being updated on his immunizations. He has never received a pneumococcal vaccine. Which sequence is correct?

A. PPSV23 now, then PCV13 eight weeks later
B. PCV13 now, followed by PPSV23 at least 8 weeks later, then PPSV23 repeated at 5 years
C. PPSV23 annually indefinitely
D. PCV13 alone, no further doses needed
E. Both vaccines given simultaneously at the same visit

Reveal Answer

Correct answer: B

Correct sequence: PCV13 first, then PPSV23 at least 8 weeks later, with a repeat dose of PPSV23 at least 5 years after the first PPSV23 dose.

Why the others are wrong A — reverses the correct order; PCV13 should precede PPSV23. C — pneumococcal vaccination is not annual. D — PCV13 alone is insufficient; PPSV23 follow-up is required for broader serotype coverage. E — the two vaccines require spacing, not simultaneous administration.

Exam Pearl Remember the order alphabetically-reversed trick: "13 before 23." Give the conjugate (PCV13) first, then the polysaccharide (PPSV23) — this order maximizes immune response in immunocompromised/asplenic-equivalent hosts.

Q8Diagnostic Pitfall●●●● Very Hard

A 26-year-old man has a firm, painless, enlarging cervical lymph node. A fine-needle aspiration (FNA) is performed and shows "atypical lymphoid cells," but the pathologist notes the sample is non-diagnostic for subclassification. What is the most appropriate next step?

A. Repeat FNA of the same node
B. Proceed to open (excisional) lymph node biopsy
C. Start empiric antibiotics and reassess in 4 weeks
D. Order a PET/CT and treat empirically for lymphoma based on imaging alone
E. Obtain a core needle biopsy and consider that definitive regardless of results

Reveal Answer

Correct answer: B

Lymphoma diagnosis depends on assessment of overall lymph node architecture (e.g., identifying Reed-Sternberg cells in the correct background for Hodgkin lymphoma), which requires an open excisional biopsy. FNA disrupts architecture and is inadequate for definitive diagnosis and subclassification.

Why the others are wrong A — repeating the same inadequate technique won't fix the fundamental architectural limitation. C — empiric antibiotics are inappropriate without an infectious source identified and would delay diagnosis of a concerning, enlarging, painless node. D — imaging alone (PET/CT) is for staging, not tissue diagnosis; treatment should never start without histologic confirmation. E — core biopsy can sometimes suffice, but is not automatically definitive and may still be inadequate to fully assess architecture; excisional biopsy remains the gold standard when core/FNA are non-diagnostic.

Exam Pearl Architecture is everything in lymphoma diagnosis. FNA gives cytology only — it cannot show the nodal architecture needed to identify Reed-Sternberg cells in their reactive background. Whenever FNA is "suspicious but non-diagnostic," the answer is escalate to excisional biopsy.

Q9Age-Based Treatment●●●○ Hard

A 68-year-old man with multiple comorbidities is newly diagnosed with stage III classic Hodgkin lymphoma. His family asks why his oncologist is recommending a multidisciplinary "shared care" approach rather than standard full-intensity chemotherapy alone. What is the best explanation?

A. Hodgkin lymphoma is untreatable after age 60
B. Patients over 60 have worse outcomes with standard treatment, so a shared, individualized approach balancing efficacy and toxicity is recommended
C. Radiotherapy alone is preferred in this age group to avoid chemotherapy toxicity
D. Age alone is a contraindication to any staging workup
E. He should be treated identically to a 30-year-old with the same stage

Reveal Answer

Correct answer: B

Patients >60 years old have historically worse outcomes with standard Hodgkin lymphoma regimens due to reduced treatment tolerance and higher comorbidity burden — this warrants a shared-care, individualized treatment approach rather than reflexively applying the same intensive protocol used in younger patients.

Why the others are wrong A — Hodgkin lymphoma remains treatable in older adults; the approach is adjusted, not abandoned. C — radiotherapy alone is never appropriate regardless of age; chemotherapy (alone or combined with RT) remains standard. D — age doesn't preclude staging; accurate staging still guides treatment decisions. E — identical treatment ignores the well-documented age-related difference in tolerance and outcomes.

Exam Pearl "Shared care" for age >60 doesn't mean withholding treatment — it means individualizing intensity based on comorbidities and functional status while still treating with chemotherapy (± RT).

Q10Secondary Malignancy●●●●● Extreme

A 39-year-old woman, 14 years post mantle-field radiation for Hodgkin lymphoma given at age 19, presents with a new, slowly growing, scaly, ulcerated lesion on her upper chest within the prior radiation field. She has been adherent to breast MRI/mammography surveillance, which has been negative. What is this lesion most consistent with, and what should happen next?

A. Radiation dermatitis; reassurance only, no biopsy needed
B. A secondary radiation-field malignancy (e.g., cutaneous squamous or basal cell carcinoma); biopsy is warranted
C. Recurrent Hodgkin lymphoma; proceed directly to PET/CT without biopsy
D. Normal skin change of aging; no further workup indicated
E. Contact dermatitis; trial of topical steroids first

Reveal Answer

Correct answer: B

Secondary malignancies — including skin cancers — within a prior radiation field are a recognized long-term complication of lymphoma treatment. A new, non-healing, ulcerated or scaly lesion in a previously irradiated field warrants biopsy to rule out a radiation-induced secondary malignancy, distinct from breast cancer (which her MRI/mammography surveillance already covers).

Why the others are wrong A/D/E — a new, non-healing/ulcerated lesion should never be dismissed as benign without tissue diagnosis, particularly within a known high-risk radiation field. C — nodal/mediastinal recurrence doesn't typically present as an isolated cutaneous ulcerated lesion, and any suspicious lesion requires tissue diagnosis before imaging-based conclusions are drawn.

Exam Pearl Documented long-term secondary malignancy risk after lymphoma treatment spans breast, lung, skin, and colon cancers — surveillance isn't limited to breast MRI/mammography alone. Any new lesion in a prior radiation field deserves a low threshold for biopsy, regardless of how long ago treatment occurred.