What is the recommended workup for a young male with intermittent axillary and groin lymphadenopathy (lymph node enlargement) and intermittent mammary (breast) enlargement and tenderness, with a normal complete blood count (CBC) and no associated symptoms?

Diagnostic Workup for Young Male with Intermittent Axillary and Groin Lymphadenopathy and Mammary Changes

The recommended workup for a young male with intermittent axillary and groin lymphadenopathy and intermittent mammary enlargement/tenderness with normal CBC should include ultrasound as the initial imaging study, followed by targeted diagnostic tests based on ultrasound findings.

Initial Evaluation

Imaging Studies

1. Breast and Axillary Ultrasound (First-line)

   • Ultrasound is the most appropriate initial imaging modality for young males with breast symptoms 1
   • Allows evaluation of both the breast tissue and axillary lymph nodes
   • Can distinguish between gynecomastia and other breast pathologies
   • Can characterize lymph node morphology (size, shape, hilum)

2. Mammography/Digital Breast Tomosynthesis (DBT)

   • Should be performed if ultrasound findings are suspicious or indeterminate 1
   • Not recommended as initial imaging in young males due to low incidence of breast cancer in this population
   • Should be considered if patient is ≥25 years old with suspicious findings

Laboratory Tests

1. Basic Laboratory Evaluation

   • CBC with differential (already normal in this case)
   • ESR and CRP to assess for inflammatory conditions
   • Liver function tests and comprehensive metabolic panel
   • LDH (elevated in lymphoma and other malignancies)

2. Hormonal Studies

   • Testosterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH)
   • Prolactin levels
   • Thyroid function tests (TSH, free T4)

3. Infectious Disease Screening

   • HIV, hepatitis B and C serology 2
   • EBV and CMV serology if clinically indicated

Further Evaluation Based on Initial Findings

If Ultrasound Shows Suspicious Lymph Nodes

1. Core Needle Biopsy

   • Preferred over fine-needle aspiration for definitive diagnosis 2
   • Should be performed for lymph nodes >1 cm without fatty hilum 1
   • Essential for distinguishing between benign and malignant causes

2. Additional Imaging

   • CT scan of neck, chest, abdomen, and pelvis if malignancy is suspected 2
   • PET-CT if lymphoma is suspected based on initial findings

If Mammary Changes Consistent with Gynecomastia

1. Medication Review

   • Assess for medications that can cause gynecomastia
   • Consider drug-induced causes of both gynecomastia and lymphadenopathy

2. Endocrine Evaluation

   • Further hormonal studies if initial tests suggest endocrine abnormalities
   • Consider referral to endocrinologist

Specific Diagnostic Considerations

For Axillary Lymphadenopathy

• Axillary lymphadenopathy may be the first sign of occult malignancy 1
• Lymph nodes >2 cm in short axis are more likely to be pathologic 1
• Benign nodes typically have smooth, well-defined borders and a central fatty hilum 1

For Groin Lymphadenopathy

• Evaluate for local infection or inflammatory conditions
• Consider testicular ultrasound if germ cell tumor is suspected 1
• Measure β-hCG and AFP if retroperitoneal mass or mediastinal adenopathy is present 1

For Mammary Changes

• Intermittent breast enlargement and tenderness in young males is most commonly due to gynecomastia
• Gynecomastia can be physiologic or pathologic
• Rule out underlying endocrine disorders, liver disease, or medication effects

When to Consider Lymphoma or Other Malignancies

• Presence of B symptoms (fever, night sweats, weight loss) 2
• Progressive or persistent lymphadenopathy
• Supraclavicular lymphadenopathy (highest risk of malignancy) 2
• Hard, fixed, non-tender nodes 2
• Multiple nodal regions involved

Diagnostic Pitfalls to Avoid

1. Assuming benign etiology without adequate workup

   • Up to 20% of patients with isolated axillary lymphadenopathy may have underlying malignancy 3

2. Relying solely on fine-needle aspiration

   • Core needle biopsy or excisional biopsy provides more definitive diagnosis 2

3. Overlooking rare causes

   • Consider conditions like Kikuchi-Fujimoto disease which can mimic lymphoma 4
   • Accessory breast tissue with fibroadenoma can present as axillary mass 5

4. Focusing only on breast pathology

   • Systemic causes of both gynecomastia and lymphadenopathy should be considered
   • Evaluate for autoimmune conditions like ALPS if lymphadenopathy is persistent 1

By following this structured approach, clinicians can effectively evaluate young males with intermittent axillary and groin lymphadenopathy and mammary changes, ensuring appropriate diagnosis and management.