What could be causing swollen lymph nodes, nocturnal sweating, and nocturnal urination in a patient?

Urgent Evaluation for Lymphoma or Serious Infection Required

This triad of swollen lymph nodes, night sweats, and nocturnal urination (nocturia) represents classic "B symptoms" that mandate immediate evaluation for lymphoma, tuberculosis, or other serious systemic diseases. 1

Immediate Diagnostic Workup

The combination of lymphadenopathy with night sweats is a dominant symptom pattern in tuberculosis and lymphoma, though these are found less frequently in modern practice than historically expected 2. However, their life-threatening nature demands they be excluded first 3.

Essential Initial Studies

• Complete blood count with differential to assess for hematologic malignancy 1, 2
• Tuberculosis testing (purified protein derivative or interferon-gamma release assay) 2, 3
• HIV testing given the 5-14 times increased risk of lymphoma in HIV-positive patients 1
• Erythrocyte sedimentation rate and C-reactive protein to assess inflammatory burden 2, 3
• Chest radiograph as initial imaging 2, 3
• Thyroid-stimulating hormone to exclude hyperthyroidism 2, 3
• HbA1c and comprehensive metabolic panel to assess for diabetes and renal function 1

Physical Examination Priorities

Examine for lymph nodes >1.5 cm in greatest transverse diameter, which require biopsy 1. Document:

• Number, size, location, and consistency of lymph nodes 1
• Presence of hepatosplenomegaly 1
• Signs of weight loss or cachexia 1
• Peripheral edema suggesting cardiac or renal disease 1

Lymph Node Biopsy Indications

Excisional or incisional biopsy of the most accessible enlarged lymph node is preferred over fine needle aspiration 1. Fresh tissue should be sent in saline for:

• Morphologic examination and immunohistochemistry 1
• Bacterial, fungal, and mycobacterial cultures 1
• Flow cytometry at minimum if patient is critically ill 1

In patients with suppurative lymphadenitis, immunocompromised status, male sex, and prior inadequate antibiotic treatment predict need for surgical drainage 4. Consider melioidosis and actinomycosis in endemic areas 4.

Nocturia Evaluation Using SCREeN Framework

While evaluating for malignancy, simultaneously assess nocturia causes using the European Association of Urology's SCREeN approach 1:

Sleep Medicine Disorders

• Obstructive sleep apnea increases arousals and light sleep, prompting urination upon waking 5
• Ask: "Do you gasp or stop breathing at night? Wake unrefreshed? Fall asleep during the day?" 1

Cardiovascular Causes

• Congestive heart failure causes nocturnal fluid mobilization 1
• Ask about ankle swelling and dyspnea on exertion 1

Renal Disease

• Chronic kidney disease impairs urinary concentration 1
• Obtain urine albumin:creatinine ratio 1

Endocrine Disorders

• Diabetes mellitus causes osmotic diuresis 1
• Diabetes insipidus should be considered with excessive thirst 1

Neurological Conditions

CNS involvement from lymphoma can cause bladder dysfunction and lower extremity weakness 1. This is critical to recognize as it may represent oncologic emergency requiring urgent treatment.

72-Hour Bladder Diary

Complete a 72-hour bladder diary to quantify nocturnal polyuria (>33% of 24-hour urine output at night) 6, 7. This distinguishes primary bladder pathology from systemic causes 1.

Advanced Imaging When Indicated

If initial workup suggests lymphoma:

• Contrast-enhanced CT chest/abdomen/pelvis or PET/CT for staging 1
• Note that HIV-positive patients have increased non-malignant PET-avid lesions that may confound interpretation 1
• Bone marrow biopsy if systemic lymphoma suspected 1

Critical Pitfalls to Avoid

• Do not attribute night sweats to benign causes without excluding malignancy and infection first 2, 3
• Do not delay biopsy of persistent lymphadenopathy >1.5 cm 1
• In HIV-positive patients, 90% of Hodgkin lymphoma is EBV-associated and presents with B symptoms; always investigate for opportunistic infections concurrently 1
• Tuberculosis and tuberculous lymphadenitis can mimic suppurative lymphadenitis; maintain high suspicion in endemic areas 4
• Cat-scratch disease (Bartonella henselae) can cause lymphadenitis with night sweats and low-grade fever; consider metagenomic sequencing if pathogen unclear 8

Treatment Considerations

Treatment cannot begin until diagnosis is established. However:

• If lymphoma confirmed, pediatric aggressive B-cell lymphomas may present with oncologic emergencies (tumor lysis syndrome, spinal cord compression) requiring immediate intervention 1
• Hodgkin lymphoma in HIV patients requires ABVD with growth factor support if CD4 <200 cells/μL 1
• Suppurative lymphadenitis requires surgical drainage plus appropriate antibiotics based on culture 4