What is the most likely diagnosis and recommended evaluation and management for a bilateral subareolar nodular lesion in a young male?

Bilateral Subareolar Nodular Lesion in Young Male

Most Likely Diagnosis

The most likely diagnosis is physiologic pubertal gynecomastia, which affects approximately 50% of mid-pubertal boys and resolves spontaneously within 24 months in over 90% of cases. 1, 2 Gynecomastia presents as a soft, rubbery, or firm mobile mass directly under the nipple and is bilateral in approximately 50% of patients. 1

Clinical Evaluation Algorithm

Step 1: Confirm True Gynecomastia on Physical Examination

• Palpate for a firm or rubbery, discrete, subareolar ridge of glandular tissue that is symmetrical, freely movable, and nonadherent to skin or underlying tissue. 3, 4
• Differentiate true gynecomastia from pseudogynecomastia (fatty tissue deposition rather than glandular enlargement), especially in patients with elevated BMI. 1
• Rule out suspicious features that would suggest malignancy: hard, fixed, eccentric mass, skin retraction, nipple retraction, or bloody nipple discharge. 1, 5

Step 2: Determine if Imaging is Needed

For young males with clinical findings consistent with bilateral gynecomastia, no imaging is routinely recommended, as most cases can be diagnosed based on clinical findings alone. 1, 5 Unnecessary imaging leads to additional unnecessary benign biopsies without improving outcomes. 1

However, proceed with imaging if:

• The differentiation between benign disease and breast cancer cannot be made clinically 1
• Presentation is suspicious (unilateral, hard, fixed, eccentric, skin/nipple retraction, bloody discharge) 1, 5

Step 3: Initial Imaging Selection (If Indicated)

For males younger than 25 years with indeterminate findings, ultrasound is the initial recommended imaging study. 1, 5 This is due to the extremely low incidence of breast cancer in young males. 5

• If ultrasound shows suspicious or indeterminate features, proceed to mammography or digital breast tomosynthesis before making a biopsy recommendation, as gynecomastia and benign lesions can appear suspicious on ultrasound but are typically diagnosed as benign on mammography. 5

Step 4: Laboratory Evaluation

A comprehensive hormonal workup should be obtained to identify underlying pathology, as proper investigation may reveal an underlying cause in 45-50% of adult cases. 2, 6

Recommended laboratory tests include: 2, 6

• Testosterone (T)
• Estradiol (E2)
• Sex hormone-binding globulin (SHBG)
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Thyroid-stimulating hormone (TSH)
• Prolactin
• Human chorionic gonadotropin (hCG)
• Alpha-fetoprotein (AFP)
• Liver and renal function tests

Testicular ultrasound should be performed to rule out testicular tumors, as detection by palpation alone has low sensitivity. 2

Step 5: Assess for Reversible Causes

Obtain a thorough medical history including: 2

• Onset and duration of gynecomastia
• Sexual development and function
• Administration or abuse of substances associated with gynecomastia (anabolic steroids, marijuana, medications including spironolactone, cimetidine, antiandrogens, antipsychotics)

Examine for signs of systemic disease or under-virilization. 2

Management Algorithm

For Physiologic Pubertal Gynecomastia

Watchful waiting with reassurance is recommended, as spontaneous resolution occurs in over 90% of cases within 24 months. 2, 3 The condition is often painful, especially when present for less than 6 months. 1

For Persistent or Pathologic Gynecomastia

If an underlying pathology is identified, treat the underlying cause or discontinue aggravating substances. 2

If gynecomastia persists despite addressing reversible causes: 2, 3

• Testosterone treatment should be offered only to men with proven testosterone deficiency 2
• Selective estrogen receptor modulators (SERMs), aromatase inhibitors, and non-aromatizable androgens are not recommended in general 2
• Surgical treatment is the therapy of choice for patients with long-lasting gynecomastia that does not regress spontaneously or following medical therapy 2, 3

Special Considerations for Endocrine Referral

Patients with elevated baseline estradiol measurements should be referred to an endocrinologist to determine the underlying hormonal cause. 1

Critical Pitfalls to Avoid

• Do not assume bilateral presentation excludes malignancy entirely. Male breast cancer is rare (median age 63 years, <1% of all breast cancers) but should be ruled out if clinical features are suspicious. 1
• Do not order routine imaging for clear cases of gynecomastia. This leads to unnecessary biopsies and does not improve outcomes. 1, 5
• Do not skip testicular examination and ultrasound. Testicular tumors can present with gynecomastia, and palpation alone has low sensitivity for detection. 2
• Do not prescribe testosterone without confirming testosterone deficiency. Testosterone treatment is only indicated in proven hypogonadism. 2