What is the recommended work‑up and initial management for a 26‑year‑old with confirmed Hodgkin lymphoma, extensive hypermetabolic cervical, mediastinal and axillary lymphadenopathy, indeterminate right pulmonary nodules, and a left upper‑lobe infiltrate suggestive of tuberculosis or pneumonia?

Management of Hodgkin Lymphoma with Concurrent Pulmonary Infiltrate

Before initiating lymphoma-directed therapy, you must definitively rule out active tuberculosis through sputum acid-fast bacilli smears, mycobacterial culture, and GeneXpert MTB/RIF testing, as concurrent TB will fundamentally alter your treatment sequencing and require anti-tuberculous therapy first. 1

Immediate Diagnostic Priorities

Tuberculosis Evaluation (Must Complete Before Chemotherapy)

• Obtain three consecutive early-morning sputum samples for acid-fast bacilli (AFB) smear and mycobacterial culture 1
• Perform GeneXpert MTB/RIF (rapid molecular test for TB and rifampin resistance) on respiratory specimens 1
• Consider bronchoscopy with bronchoalveolar lavage if sputum samples are non-diagnostic but clinical suspicion remains high for TB given the left upper lobe infiltrate pattern 1
• Tuberculin skin test (TST) or interferon-gamma release assay (IGRA) should be performed, though interpretation may be complicated by lymphoma-associated immunosuppression 2

Right Pulmonary Nodule Characterization

• CT-guided biopsy of accessible right pulmonary nodules to distinguish between lymphomatous involvement versus infectious/inflammatory etiology 2
• If nodules are PET-avid and biopsy confirms lymphoma, this represents Stage IV disease requiring more intensive therapy 2

Complete Hodgkin Lymphoma Staging Work-Up

Essential Laboratory Studies

The following must be completed before treatment initiation 2:

• Complete blood count with differential 2
• Comprehensive metabolic panel including renal and hepatic function 2
• Serum albumin (prognostic factor) 2
• Lactate dehydrogenase (LDH) (prognostic marker) 2
• Erythrocyte sedimentation rate (ESR) (prognostic factor) 2
• Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and HIV serology (mandatory before chemotherapy) 2

Cardiac and Pulmonary Assessment

• Echocardiogram with left ventricular ejection fraction measurement (required before doxorubicin-based ABVD chemotherapy) 2
• Pulmonary function tests including DLCO (diffusion capacity of lungs for carbon monoxide) are critical given the pulmonary infiltrate and planned bleomycin therapy 2

Additional Required Studies

• Bone marrow biopsy is indicated in this patient given the extensive nodal involvement (cervical, mediastinal, axillary) suggesting at least Stage III disease, plus the presence of pulmonary findings 2
• Pregnancy test (if female of childbearing age) 2
• Fertility preservation counseling with referral for sperm banking (male) or oocyte/ovarian tissue cryopreservation (female) before alkylating agent chemotherapy 2
• Thyroid function tests (TSH, FT3, FT4) given planned neck irradiation 2
• Dental evaluation and prophylactic care before neck radiation 2

Treatment Sequencing Algorithm

If Active Tuberculosis is Confirmed:

1. Initiate standard four-drug anti-tuberculous therapy immediately (rifampin, isoniazid, pyrazinamide, ethambutol) 1
2. Delay lymphoma chemotherapy for 2-4 weeks until TB treatment is established and clinical improvement documented 1
3. Repeat PET/CT after TB treatment initiation to accurately stage Hodgkin lymphoma once TB-related hypermetabolism resolves 1
4. Coordinate with infectious disease specialists regarding drug-drug interactions between TB medications and chemotherapy 1
5. Continue anti-TB therapy throughout lymphoma treatment (typically 6-9 months total) with careful monitoring for hepatotoxicity given concurrent chemotherapy 1

If Tuberculosis is Excluded:

1. Proceed with risk-stratified Hodgkin lymphoma therapy based on final staging 2, 3
2. For early-stage favorable disease (Stage I-II without risk factors): 2-4 cycles ABVD followed by involved-site radiation therapy 2
3. For early-stage unfavorable disease (Stage I-II with risk factors including bulky mediastinal mass): 4-6 cycles ABVD followed by involved-site radiation therapy 2
4. For advanced-stage disease (Stage III-IV): 6 cycles ABVD with interim PET after 2 cycles to guide therapy escalation/de-escalation 2, 3, 4

Critical Pitfalls to Avoid

Do not start chemotherapy without excluding active TB, as this will worsen TB outcomes, complicate staging accuracy due to overlapping PET hypermetabolism, and increase risk of TB reactivation/dissemination with immunosuppressive chemotherapy 1

Do not assume pulmonary nodules are infectious without tissue diagnosis, as Stage IV lymphomatous involvement fundamentally changes prognosis and treatment intensity 2, 5

Do not proceed with bleomycin-containing ABVD without baseline pulmonary function tests, especially given pre-existing pulmonary infiltrate that increases bleomycin pneumonitis risk 2

Do not delay fertility preservation discussions, as chemotherapy must begin promptly once TB is excluded, and fertility options become limited after treatment initiation 2

Staging Classification

Based on current imaging showing cervical, mediastinal, and axillary involvement, this patient has at minimum Stage III disease (lymph nodes on both sides of diaphragm) 2. If pulmonary nodules represent lymphomatous involvement, this constitutes Stage IV disease (extranodal organ involvement) 2. The mediastinal mass-to-thorax ratio must be calculated from chest X-ray to determine bulky disease status (>1/3 thoracic diameter), which is an adverse prognostic factor 2.