What is the appropriate diagnostic and treatment approach for a 46-year-old female patient with leukocytosis and a unilateral breast mass?

Management of a 46-Year-Old Female with Leukocytosis (WBC 19.07) and Unilateral Breast Mass

This patient requires urgent diagnostic imaging with bilateral mammography and targeted ultrasound of the affected breast and axilla, followed by core needle biopsy of any suspicious findings, while simultaneously ruling out inflammatory breast cancer or infectious mastitis given the elevated white blood cell count. 1, 2

Immediate Diagnostic Priorities

Rule Out Inflammatory Breast Cancer vs. Infectious Mastitis

The elevated WBC count (19.07) combined with a unilateral breast mass creates diagnostic urgency to distinguish between:

• Inflammatory breast cancer (IBC): Presents with rapid onset (<6 months), erythema occupying ≥1/3 of breast, peau d'orange, and may have elevated inflammatory markers 2
• Infectious mastitis: Typically responds to antibiotics within 1 week; failure to respond should raise suspicion for malignancy 2

Critical examination findings to document:

• Erythema, edema, or peau d'orange skin changes 2
• Skin dimpling or attachment to deep fascia 2
• Asymmetry compared to contralateral breast 2
• Axillary lymphadenopathy 1
• Nipple retraction, discharge, or crusting 2

Diagnostic Imaging Algorithm

Step 1: Bilateral Diagnostic Mammography ± Digital Breast Tomosynthesis

For this 46-year-old patient, diagnostic mammography is the initial imaging study of choice 1. Mammography sensitivity for palpable masses is 86-91% in this age group 1.

• Bilateral views are mandatory to evaluate for occult disease in the contralateral breast 1
• Digital breast tomosynthesis (DBT) improves lesion characterization and reduces false positives from overlapping tissue 1

Step 2: Targeted Ultrasound of the Palpable Mass and Ipsilateral Axilla

Ultrasound must be performed even if mammography is negative, as the negative predictive value of combined mammography and ultrasound is 97.4-100% 1. However, negative imaging never overrules a clinically suspicious mass 1.

Ultrasound evaluation should include:

• Characterization of the breast mass (solid vs. cystic, margins, orientation) 1
• Assessment of ipsilateral axillary lymph nodes for morphologic abnormalities 1
• Ultrasound-guided biopsy planning if suspicious features identified 1

Tissue Diagnosis: Core Needle Biopsy is Mandatory

Core needle biopsy (CNB) is strongly preferred over fine-needle aspiration because it provides:

• Superior sensitivity and specificity 3
• Histologic grading and architecture assessment 1
• Hormone receptor (ER, PR) and HER2 status 1
• Differentiation between in situ and invasive disease 4

Biopsy should be performed on:

• Any solid mass with suspicious imaging features (BI-RADS 4 or 5) 1
• Any clinically suspicious mass regardless of imaging findings 1
• Suspicious axillary lymph nodes (ultrasound-guided FNA or core biopsy) 1

If inflammatory breast cancer is suspected clinically, add skin punch biopsy to evaluate for dermal lymphatic invasion 2.

Laboratory Workup

Given the leukocytosis, obtain:

• Complete blood count with differential to characterize the leukocytosis 1
• Blood cultures if fever or systemic signs of infection present
• Liver function tests, alkaline phosphatase, calcium (baseline staging labs if malignancy confirmed) 1

Management Based on Biopsy Results

If Benign and Concordant with Imaging:

• Physical examination at 6-12 months with or without imaging for 1 year to ensure stability 1
• Return to routine screening if stable 1

If Indeterminate, Discordant, or High-Risk Lesion:

• Surgical excision is required 1
• High-risk lesions include: atypical ductal hyperplasia (ADH), papillary lesions, radial scars, suspected phyllodes tumor 1

If Malignant:

• Proceed according to NCCN Breast Cancer Treatment Guidelines 1
• Multidisciplinary tumor board evaluation 1

Critical Pitfalls to Avoid

Never rely on imaging alone to exclude malignancy in a clinically suspicious mass - the sensitivity of mammography is not 100%, and up to 10-15% of breast cancers may have negative mammography 1, 5.

Do not delay biopsy for a trial of antibiotics unless infectious mastitis is clearly the diagnosis - inflammatory breast cancer can mimic mastitis, and failure to respond to 1 week of antibiotics mandates biopsy 2.

Do not perform needle sampling before imaging - biopsy-related changes can obscure or alter imaging interpretation 1.

Ensure concordance between clinical, imaging, and pathology findings - discordance requires surgical excision 1.

Special Consideration: Axillary Adenopathy

If axillary lymphadenopathy is present on examination or ultrasound:

• Ultrasound-guided biopsy of abnormal nodes provides definitive diagnosis with 98-100% specificity 6
• Benign reactive adenopathy from infection/inflammation is common with elevated WBC 6
• However, metastatic breast cancer or lymphoma must be excluded 1, 6