What is the recommended diagnostic work‑up for an adult woman with a centrally located area of nodularity in the right breast on routine screening mammography?

Diagnostic Work-Up for Centrally Located Breast Nodularity on Screening Mammography

For an adult woman with central breast nodularity detected on screening mammography, proceed with bilateral diagnostic mammography and targeted ultrasound of the area of concern, followed by clinical breast examination to determine if the finding is palpable. 1

Initial Imaging Evaluation

Bilateral diagnostic mammography with targeted ultrasound is the mandatory first step to characterize the nodularity and assess for occult or multifocal disease. 1, 2 The diagnostic mammogram should include:

• Spot compression views to determine if the nodularity represents true architectural distortion, a mass, or simply overlapping normal tissue 1
• Assessment for associated findings including microcalcifications, architectural distortion, or asymmetry 1, 3
• Comparison with prior mammograms when available to determine if this represents a new, enlarging, or stable finding 1, 3

Targeted ultrasound must be performed concurrently to identify any underlying solid mass, as nodularity may represent a palpable correlate of an occult malignancy. 1 Ultrasound can detect lesions that are mammographically occult and has sensitivity reaching 93-100% when combined with mammography. 2

Clinical Correlation

Determine whether the nodularity is palpable on clinical breast examination. 1 This distinction is critical because:

• If palpable: The finding requires more aggressive evaluation regardless of imaging appearance, as clinical examination alone cannot distinguish benign from malignant status 1
• If non-palpable: Management is guided entirely by the BI-RADS assessment category from imaging 1, 4

Management Based on BI-RADS Category

BI-RADS 1-3 (Negative, Benign, or Probably Benign)

If the clinical assessment is benign and imaging shows BI-RADS 1-3, re-examine the patient in 3-6 months. 1 At follow-up:

• If stable: Return to routine annual screening 1
• If clinically progressive: Proceed to tissue biopsy 1, 3

Critical caveat: Even with BI-RADS 1-3, if there is lack of correlation between clinical findings and imaging (i.e., palpable nodularity with negative imaging), further workup is mandatory. 5 Absence of a sonographic correlate does not exclude malignancy—focal asymmetric density carries a 19.4% cancer risk even when sonography shows no focal abnormality. 6

BI-RADS 4-5 (Suspicious or Highly Suggestive of Malignancy)

Proceed immediately to image-guided core needle biopsy (preferred over fine-needle aspiration). 1, 5, 2 Core needle biopsy provides:

• Superior histological architecture assessment 2
• Ability to determine ER, PR, and HER2 status 2
• Better sensitivity and specificity than fine-needle aspiration 2

Women with BI-RADS 4 have a likelihood ratio of 125 for malignancy, while BI-RADS 5 has a likelihood ratio of 2200. 4

High-Risk Features Requiring Biopsy

Biopsy is mandatory regardless of BI-RADS category if any of the following are present:

• Associated cluster of microcalcifications (60% of malignancies present with this feature) 3
• Architectural distortion (exclusively associated with malignancy in focal asymmetric densities) 3
• Palpable mass corresponding to the nodularity (60% of malignancies are palpable vs. 9% of benign lesions) 3
• Solid mass on ultrasound with suspicious features (50% of malignancies vs. 9% of benign lesions) 3
• New or enlarging finding compared to prior examinations 6, 3

Common Pitfalls to Avoid

Do not assume nodularity is benign based solely on negative ultrasound. Two of seven patients (28.6%) with breast cancer presenting as focal asymmetric density had no focal abnormality on sonographic examination. 6 The negative predictive value of ultrasound for breast cancer in focal asymmetric density is only 89.4%. 6

Do not delay biopsy for documented progression. Progressive size increase is a red flag that elevates suspicion for malignancy, as benign lesions typically remain stable. 5 Short-interval follow-up is inappropriate when progression is documented. 5

Do not perform needle sampling before imaging is complete. 1 The complete imaging evaluation must be finished first to properly characterize the extent of disease and guide biopsy site selection. 1, 2

Ensure concordance between pathology, imaging, and clinical findings after biopsy. 5 If biopsy shows benign findings but is discordant with imaging characteristics, surgical excision may be necessary. 5