What is the evaluation and management approach for a patient presenting with unilateral gynecomastia?

Evaluation and Management of Unilateral Gynecomastia

Initial Clinical Assessment

For unilateral gynecomastia, most patients can be diagnosed clinically without imaging, but the unilateral presentation requires heightened vigilance to exclude breast cancer, particularly in men over 25 years old. 1

Key Physical Examination Findings

• Palpate for mass characteristics: True gynecomastia presents as soft, rubbery, or firm mobile mass directly under the nipple, often painful if present <6 months 1
• Distinguish from pseudogynecomastia: Assess whether enlargement is glandular tissue versus fatty deposition, especially in elevated BMI patients 1
• Assess for malignancy red flags: Hard, fixed, or eccentric masses; bloody nipple discharge; skin or nipple retraction all mandate immediate imaging 1
• Complete testicular examination: Evaluate testicular size, consistency, masses, and varicocele presence 1
• Body habitus assessment: Calculate BMI or waist circumference; examine body hair patterns in androgen-dependent areas to assess virilization status 1
• Visual field testing: Check for bitemporal hemianopsia suggesting pituitary disorders 1

Critical History Elements

• Medication review: Assess temporal relationship between drug initiation and gynecomastia onset, including spironolactone, antiandrogens, 5-alpha reductase inhibitors, GnRH agonists, ketoconazole, digoxin, and cannabis 2
• Underlying conditions: Screen for hypogonadism, thyroid disease, liver cirrhosis, renal dysfunction, and hyperprolactinemia 3
• Genetic factors: Family history of breast disorders, Klinefelter syndrome (RR 24.7 for gynecomastia), BRCA2 mutations 3

Imaging Decision Algorithm

When Imaging is NOT Needed

• Clinical findings clearly consistent with benign gynecomastia or pseudogynecomastia 1
• No suspicious features on examination 1

When Imaging IS Required

If differentiation between benign disease and breast cancer cannot be made clinically, or if presentation is suspicious (unilateral, hard, fixed, eccentric mass), proceed with imaging immediately. 1

Age-Based Imaging Protocol:

• Men <25 years: Ultrasound as initial study, followed by mammography/digital breast tomosynthesis (DBT) if suspicious features found 1
• Men ≥25 years: Bilateral diagnostic mammography or DBT as initial study (sensitivity 92-100%, specificity 90-96%, NPV 99-100%), with ultrasound to follow if indeterminate or suspicious 1

Laboratory Evaluation

Initial Hormonal Workup

• Serum testosterone levels 1
• Serum estradiol levels: Mandatory in all testosterone-deficient patients before starting testosterone therapy 1
• Luteinizing hormone (LH) 1
• Prolactin levels: If testosterone is low with low/normal LH 1

Mandatory Endocrinology Referral

All men with elevated baseline estradiol measurements must be referred to an endocrinologist to determine the underlying hormonal cause. 1

Biopsy Approach for Suspicious Lesions

Technique Selection

Core needle biopsy is superior to fine-needle aspiration in sensitivity, specificity, and correct histological grading. 1

Guidance Method:

• Ultrasound-visible lesions: Ultrasound-guided core biopsy (preferred for patient comfort, real-time visualization, no radiation) 1
• Mammography-only visible lesions: Stereotactic-guided core biopsy 1
• DBT-only visible lesions: DBT-guided core biopsy 1

Post-Biopsy Protocol:

• Place marker clip to confirm tissue sampling and aid correlation 1
• Perform post-biopsy imaging to document marker placement 1
• Critical: Imaging must precede biopsy as post-biopsy changes confuse image interpretation 1

Treatment Algorithm

Step 1: Observation Period

For physiologic gynecomastia without concerning features, observation is appropriate as spontaneous resolution occurs in up to 50% of patients with noncyclical breast pain. 1

Step 2: Medical Therapy Indications

• Persistent painful gynecomastia in testosterone-deficient patients with low/low-normal LH: Consider selective estrogen receptor modulators 1
• Men developing gynecomastia on testosterone therapy: Undergo monitoring period as symptoms sometimes abate 1
• Timing consideration: Gynecomastia persisting >12 months often becomes fibrotic and less responsive to medical therapy 3, 4

Step 3: Surgical Intervention

For gynecomastia persisting over 12 months, surgical excision is the treatment of choice. 4

Surgical Indications:

• Long-standing symptomatic gynecomastia 5
• Medical therapy failure 5
• Significant psychosocial distress, self-abasement, or social isolation 6
• Fibrotic changes (typically after 12 months duration) 3, 4

Special Populations

Fertility Considerations

Men with gynecomastia interested in fertility must have reproductive health evaluation (testicular exam, FSH measurement) performed prior to treatment. 1

Prophylactic Management

• Patients starting antiandrogen therapy: Breast irradiation (8-15 Gy in 1-3 fractions) given 1-2 weeks before initiation prevents painful gynecomastia 1

Common Pitfalls to Avoid

• Unnecessary imaging in clear benign cases leads to additional unnecessary benign biopsies 1, 3
• Failing to distinguish true gynecomastia from pseudogynecomastia, especially in obese patients 3
• Overlooking medication causes: Spironolactone users with gynecomastia should be switched to eplerenone (significantly lower risk) 2
• Delaying surgical referral beyond 12 months when fibrosis develops and medical therapy becomes ineffective 3, 4
• Missing male breast cancer: Rare (<1% of all breast cancers) but median age 63 years; unilateral presentation in older men requires heightened suspicion 1