Diagnostic Approach for a Young Woman with Constitutional Symptoms
This 25-year-old woman presenting with significant unintentional weight loss (30 pounds), profound fatigue, night sweats, and pruritus requires urgent evaluation for malignancy, particularly lymphoma, as these constitute classic "B symptoms" that significantly increase concern for serious pathology. 1
Immediate Diagnostic Workup
Essential Laboratory Testing
- Complete blood count with differential to evaluate for cytopenias, leukocytosis, or abnormal cell populations that may suggest hematologic malignancy 2
- Comprehensive metabolic panel including electrolytes (sodium, potassium, calcium, magnesium), renal function, and liver function tests 2
- Lactate dehydrogenase (LDH) - elevated levels are associated with lymphoproliferative disorders and tissue breakdown 2
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess for inflammatory processes 2
- Thyroid function tests (TSH, free T4) as thyroid dysfunction commonly causes fatigue and weight changes 2
- HIV testing given the age and presentation, as immunosuppression increases risk of lymphoma 1
- Tuberculosis screening (QuantiFERON or PPD) as TB classically presents with night sweats and weight loss 1
Critical Imaging Studies
- Chest X-ray as initial screening for mediastinal lymphadenopathy, pulmonary masses, or tuberculosis 1
- CT chest/abdomen/pelvis with contrast if initial workup suggests lymphoma or other malignancy to evaluate for lymphadenopathy and organomegaly 2, 1
Physical Examination Focus
- Comprehensive lymph node examination of all nodal chains (cervical, supraclavicular, axillary, inguinal) documenting size, consistency, and mobility 1
- Abdominal examination for hepatosplenomegaly - splenomegaly is a key finding in myeloproliferative disorders and lymphomas 2
- Skin examination to characterize the pruritus pattern and identify any rashes, lesions, or excoriations 2
- Vital signs including temperature (for fever documentation) and weight documentation for baseline 1
Differential Diagnosis Priority
High-Priority Malignant Conditions
Lymphoma (Hodgkin's or Non-Hodgkin's) is the primary concern given the constellation of B symptoms (fever/night sweats, weight loss >10% in 6 months, and fatigue) in a young adult 2, 1. The presence of pruritus further supports this diagnosis as it occurs commonly with lymphomas 2.
Myeloproliferative neoplasms should be considered if CBC shows abnormalities, as these disorders characteristically present with constitutional symptoms including night sweats and weight loss 2.
Infectious Etiologies
Tuberculosis must be excluded given the classic presentation of night sweats, weight loss, and fatigue 1. HIV/AIDS with associated opportunistic infections requires evaluation given the demographic and symptom pattern 1.
Other Considerations
- Hyperthyroidism (weight loss, fatigue, heat intolerance)
- Chronic infections (endocarditis, chronic viral infections)
- Autoimmune disorders (systemic lupus erythematosus, rheumatoid arthritis)
- Occult malignancies (gastrointestinal, ovarian)
Management Algorithm Based on Initial Findings
If Lymphadenopathy Detected
Proceed immediately to excisional lymph node biopsy (not fine needle aspiration) for definitive histopathologic diagnosis, flow cytometry, and molecular studies 2, 1. Core needle biopsy is acceptable if excisional biopsy is not feasible.
If Imaging Shows Masses Without Palpable Nodes
Refer to interventional radiology or surgery for tissue diagnosis via CT-guided biopsy or surgical approach depending on location 2.
If Initial Workup Negative for Malignancy
- Reassess for infectious causes with additional serologies (EBV, CMV, toxoplasmosis)
- Consider bone marrow biopsy if peripheral blood shows unexplained cytopenias or if clinical suspicion for hematologic malignancy remains high despite negative imaging 2
- Evaluate for occult malignancy with age-appropriate cancer screening and consideration of PET-CT if constitutional symptoms persist 1
Critical Pitfalls to Avoid
Do not attribute these symptoms to depression, anxiety, or functional disorders without excluding malignancy first - the combination of significant weight loss, night sweats, and fatigue in a young person warrants aggressive investigation 1, 3.
Do not delay tissue diagnosis if lymphadenopathy is present - fine needle aspiration is insufficient for lymphoma diagnosis; excisional biopsy is required for proper architectural assessment 2.
Do not overlook the significance of "mild" night sweats - any night sweats requiring clothing or sheet changes are clinically significant and constitute a B symptom 1.
Do not perform extensive fatigue evaluation per cancer-related fatigue guidelines 2 until malignancy is excluded, as these guidelines apply to patients with known cancer, not diagnostic workup of new presentations.
Urgency and Referral
This patient requires evaluation within 1-2 weeks maximum given the constellation of B symptoms and significant weight loss 1. If lymphadenopathy or abnormal imaging is identified, immediate referral to hematology-oncology is warranted for expedited biopsy and staging 2.
The 30-pound weight loss over 6-12 months represents >10% body weight loss in most women of this age, meeting criteria for a constitutional symptom that significantly elevates concern for lymphoproliferative disorders 2, 1.