In a 21‑year‑old transgender woman on estrogen therapy presenting with a several‑week history of unilateral right nipple discharge that began clear and is now yellow, worsened by nipple manipulation and associated with mild itching, dryness, tenderness, without fever or infection signs, what are the likely causes and recommended evaluation and management?

Evaluation and Management of Unilateral Nipple Discharge in a 21-Year-Old Transgender Woman on Estrogen Therapy

This presentation most likely represents physiologic discharge exacerbated by nipple manipulation, and the primary recommendation is to stop all breast compression and manipulation with clinical reassessment in 3-6 months. 1

Discharge Characterization

The discharge characteristics in this case suggest a physiologic rather than pathologic etiology based on several key features:

Physiologic features present:

• Initially clear, now yellow discharge (physiologic discharge is typically white, green, yellow, or clear) 2
• Non-spontaneous nature—worsened by squeezing/manipulation and improves when manipulation stops 2, 1
• No fever, warmth, or clear infectious signs 2

Concerning features to note:

• Unilateral presentation (right breast only) is typically associated with pathologic discharge 2
• However, the provoked nature and improvement with cessation of manipulation strongly favor physiologic discharge despite unilaterality 1

The associated itching, dryness, and mild tenderness likely represent local irritation from repeated manipulation rather than underlying pathology 1.

Special Considerations for Transgender Women

Transgender women on estrogen therapy develop breast tissue identical to cisgender females, with increased lobules, ducts, and acini, and face an increased breast cancer risk compared to cisgender males 2. However, at age 21, the pretest probability of malignancy remains extremely low 2.

The ACR Appropriateness Criteria specifically addresses transgender women, noting that imaging may be considered regardless of hormone therapy duration if pathologic features are present 2. In this case, the predominantly physiologic features argue against immediate imaging.

Recommended Management Approach

Initial management (most appropriate):

• Patient education to completely stop all breast compression and manipulation 1
• Instruct patient to report any development of spontaneous discharge (discharge occurring without touching the breast) 1
• Monitor for change in discharge characteristics to bloody or serous appearance 1
• Clinical reassessment in 3-6 months if discharge persists despite stopping manipulation 1

Imaging is NOT routinely indicated at this time because:

• The discharge is provoked rather than spontaneous 2, 1
• Patient is under 30 years of age with dense breast tissue limiting mammography sensitivity 2, 1
• No palpable mass is present 1
• The overall presentation favors physiologic discharge 2, 1

When to Escalate Evaluation

Proceed with imaging (ultrasound as initial modality) if: 2, 1

• Discharge becomes truly spontaneous (occurs without manipulation)
• Discharge changes to bloody, serous, or serosanguineous appearance
• A palpable mass develops
• Discharge becomes clearly single-duct in origin
• Clinical suspicion increases during follow-up

Ultrasound is the appropriate initial imaging modality for patients under 30 years of age with concerning features, as it avoids radiation and is more sensitive in dense breast tissue 2, 1. Mammography or digital breast tomosynthesis would only be added if ultrasound shows suspicious findings 2.

Critical Pitfalls to Avoid

Do not proceed directly to surgical duct excision without first stopping manipulation and observing the clinical course, as physiologic discharge does not require surgery 1, 3. Studies show that only 0.3% of patients with non-spontaneous discharge have carcinoma 2.

Do not dismiss the presentation solely based on age—while malignancy risk is low at age 21, transgender women on estrogen therapy warrant careful evaluation given their unique breast cancer risk profile 2. However, this careful evaluation begins with proper discharge characterization, not reflexive imaging.

The key distinguishing feature is spontaneity: if the patient must squeeze or manipulate the nipple to produce discharge, this is physiologic until proven otherwise 2, 1. The yellow color and unilaterality, while initially concerning, are overridden by the provoked nature of the discharge.

Follow-Up Protocol

If discharge persists after 3-6 months of avoiding manipulation, ultrasound of the retroareolar region becomes appropriate as the next step 2, 1. The malignancy rate for pathologic nipple discharge ranges from 11-16% in larger studies, but this applies to truly pathologic (spontaneous) discharge 2, 3. For provoked discharge in young patients, the cancer risk approaches zero 2.