What is the diagnosis and treatment for enlarged lymph nodes (1.22cm and 0.75cm) with symptoms of night sweats, shortness of breath, breast pain, and abdominal pain?

Urgent Evaluation for Lymphoma or Metastatic Malignancy Required

This constellation of symptoms—enlarged lymph nodes (1.22cm and 0.75cm), night sweats, and multiple anatomic sites of involvement—strongly suggests systemic malignancy, most likely lymphoma, and requires immediate tissue diagnosis via excisional biopsy rather than observation. 1, 2, 3

Critical Red Flags Present

Your presentation contains multiple concerning features that mandate urgent workup:

• Night sweats are a classic "B symptom" indicating systemic disease, particularly lymphoma 4, 5
• Multiple lymph node regions involved (axillary nodes measuring 1.22cm and 0.75cm, plus popliteal nodes) constitutes generalized lymphadenopathy, which typically indicates underlying systemic disease rather than localized infection 4, 6, 5
• Lymph nodes >1 cm are considered abnormal and warrant investigation, especially when accompanied by systemic symptoms 7, 4, 6
• Duration and progression with systemic symptoms eliminates the option of simple observation 3, 8

Immediate Diagnostic Approach

First-Line Imaging (Within Days)

• CT scan with contrast of chest, abdomen, and pelvis is the essential first imaging study to evaluate the full extent of lymphadenopathy and identify potential primary malignancy 7, 3
• PET/CT scan should follow if CT shows suspicious findings, as it is particularly valuable for identifying malignant lymph node involvement and staging lymphoma 7, 2, 3
• Ultrasound of the axilla can characterize the lymph nodes and guide biopsy if needed 7, 2

Essential Laboratory Studies

Obtain immediately 3, 4:

• Complete blood count with differential (to evaluate for leukemia/lymphoma)
• Comprehensive metabolic panel (liver function, calcium)
• Lactate dehydrogenase (LDH) - elevated in lymphoma
• Erythrocyte sedimentation rate and C-reactive protein

Tissue Diagnosis is Mandatory

Do not observe or treat empirically with antibiotics 3, 8. The American Academy of Otolaryngology-Head and Neck Surgery explicitly recommends that patients with lymphadenopathy without obvious infectious cause present for ≥2 weeks should proceed directly to imaging and biopsy rather than empiric antibiotics 3.

For lymph nodes of this size with systemic symptoms 8, 5:

• Excisional biopsy remains the gold standard when lymphoma is suspected, as it provides the most tissue for accurate diagnosis
• Core needle biopsy with immunohistochemistry and flow cytometry is an acceptable alternative if excisional biopsy is not immediately feasible
• Fine-needle aspiration alone is insufficient for initial diagnosis of suspected lymphoma

Differential Diagnosis Priority

Most Likely: Lymphoma

Both Hodgkin and non-Hodgkin lymphoma characteristically present with painless lymphadenopathy and night sweats 7, 1, 2. The involvement of multiple nodal regions (axillary and popliteal) with systemic symptoms is classic for lymphoma 4, 5.

Also Consider: Metastatic Malignancy

• Breast cancer must be excluded given axillary lymphadenopathy and breast pain 7
• Gastric or other GI malignancy could explain upper quadrant pain and generalized lymphadenopathy 7, 2
• Bilateral mammography should be performed to evaluate for occult breast primary 7

Less Likely but Possible

• Infectious causes (tuberculosis, atypical mycobacteria) typically do not cause this symptom constellation 1
• Autoimmune conditions are possible but less likely with this acute presentation 2

Critical Timing

Do not wait beyond 1-2 weeks for definitive diagnosis. Lymphadenopathy persisting >2 weeks with systemic symptoms requires immediate investigation 3, 4, 8. Any delay in diagnosing lymphoma or metastatic cancer directly impacts curability and survival 7.

Additional Symptoms Explained

• Shortness of breath after eating: May indicate mediastinal lymphadenopathy compressing airways or esophagus, or pleural involvement 7
• Breast pain when supine: Could represent chest wall involvement or referred pain from axillary adenopathy 7
• Left upper quadrant pain with bending: Suggests possible splenic involvement or abdominal lymphadenopathy 2

Proceed immediately to CT imaging and arrange for tissue biopsy within one week. This is not a "watch and wait" scenario.