What are the common benign and malignant differential diagnoses for abnormal findings on breast examination, such as a mass, pain, nipple discharge, skin changes, or lymphadenopathy?

Differential Diagnoses for Abnormal Breast Examination Findings

Breast Mass

The differential diagnosis for a breast mass must immediately distinguish between benign and malignant etiologies, with fibroadenoma, cysts, and breast cancer being the most common considerations requiring tissue diagnosis or imaging confirmation. 1

Benign Causes

• Fibroadenoma: Most common benign solid tumor, typically presents as a well-circumscribed, mobile mass in younger women 2, 3
• Cysts: Simple or complicated fluid-filled structures, often multiple and bilateral, may correlate with focal pain 1
• Fibrocystic changes: Nodularity and asymmetric thickening, often cyclic with menses 1
• Fat necrosis: History of trauma, may present as irregular mass mimicking malignancy 4
• Phyllodes tumor: Large, well-circumscribed oval or lobulated mass on mammography 4
• Hamartoma: Well-circumscribed round to oval mass with thin pseudocapsule 4
• Granular cell tumor: Solid, poorly marginated mass with marked posterior acoustic shadowing on ultrasound 4

Malignant Causes

• Invasive ductal or lobular carcinoma: Irregular, spiculated mass with suspicious features on imaging (BI-RADS 4-5) 1
• Ductal carcinoma in situ (DCIS): May present as mass or calcifications 1
• Primary breast lymphoma: Relatively circumscribed or indistinctly marginated uncalcified mass 4
• Metastatic disease: Single or multiple masses with circumscribed margins and low-level internal echoes on ultrasound 4

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Breast Pain (Mastalgia)

Breast pain as an isolated symptom carries a low malignancy risk of only 1.2% to 6.7%, but focal pain requires age-appropriate imaging to exclude underlying pathology. 1

Benign Causes

• Cyclic mastalgia: Hormonal, bilateral, diffuse, related to menstrual cycle 1
• Noncyclic mastalgia: Focal or diffuse, unrelated to menses 1
• Simple cyst: When geographically correlated with focal pain (BI-RADS 2) 1
• Complicated cyst: Probably benign (BI-RADS 3), may cause focal discomfort 1
• Medication-related: Oral contraceptives, hormone therapy, psychotropic drugs, cardiovascular agents 3
• Musculoskeletal: Costochondritis or chest wall pain 3

Malignant Causes

• Breast cancer: Rare presentation with pain alone, but must be excluded with imaging if pain is focal 1

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Nipple Discharge

Pathologic nipple discharge—defined as unilateral, single-duct, spontaneous, and serous or bloody—requires imaging and potential biopsy because underlying malignancy is present in 5% to 21% of cases. 1, 5

Benign Causes

• Intraductal papilloma: Most common cause of pathologic discharge (35-48% of cases) 1
• Duct ectasia: Second most common cause (17-36% of cases) 1
• Galactorrhea: Physiologic, bilateral, milky discharge from multiple ducts; check prolactin and TSH 3
• Physiologic discharge: Bilateral, multiple ducts, white/green/yellow color 1

Malignant Causes

• Ductal carcinoma in situ (DCIS): Most common malignancy associated with nipple discharge 1, 5
• Invasive carcinoma: Less common but possible 1
• Paget's disease: Nipple-centric changes with underlying carcinoma in 80-90% of cases 6, 7

Critical distinction: In males, nipple discharge carries a 23-57% malignancy rate and warrants aggressive evaluation 1

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Skin Changes

Breast skin changes—including erythema, thickening, dimpling, or peau d'orange—mandate immediate bilateral diagnostic mammography with ultrasound to exclude inflammatory breast cancer, which is highly aggressive and accounts for 1-6% of breast cancers. 6, 8

Benign Causes

• Mastitis/abscess: Infectious etiology, but imaging must be obtained before initiating antibiotics 6, 8
• Eczema/dermatitis: Bilateral, superficial, but must exclude Paget's disease 6
• Diabetic fibrous mastopathy: Very dense breast tissue with irregular hypoechoic mass and posterior shadowing 4

Malignant Causes

• Inflammatory breast cancer (IBC): Rapid onset (≤6 months), erythema involving ≥1/3 of breast, peau d'orange, warmth, with or without palpable mass 6, 8
• Paget's disease: Nipple excoriation, scaling, eczema-like appearance, bleeding, ulceration; underlying carcinoma in 80-90% 6, 7
• Locally advanced breast cancer: Skin dimpling, retraction, or ulceration 9

Critical pitfall: Never assume bilateral skin involvement rules out malignancy—both IBC and Paget's can present bilaterally 6

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Axillary Lymphadenopathy

Localized axillary masses are more often benign than malignant, but when cancer is identified, breast cancer is the most common cause, including occult contralateral disease in some cases. 1

Benign Causes

• Reactive lymphadenopathy: Infection or inflammation 1
• Accessory breast tissue: Normal variant in axilla 1
• Breast implant-related: Benign axillary lymphadenopathy 1
• Collagen vascular disease: Systemic lymphadenopathy 4

Malignant Causes

• Metastatic breast cancer: Most common malignant cause; may represent occult primary (including contralateral breast) 1
• Lymphoma: May require special pathologic evaluation or surgical excision 1
• Other metastases: Melanoma, lung cancer, etc. 4

Critical workup: Complete clinical evaluation for systemic disease, age-appropriate imaging (ultrasound with mammogram for ≥30 years; ultrasound alone for <30 years), and core needle biopsy for suspicious findings 1

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Key Diagnostic Principles

Imaging Algorithm

• Age ≥30 years with focal findings: Diagnostic mammogram with or without ultrasound 1
• Age <30 years with focal findings: Ultrasound alone 1
• Skin changes (any age): Bilateral diagnostic mammogram with ultrasound mandatory 6, 8
• Pathologic nipple discharge: Mammography and ultrasound; consider MRI if negative 1, 5

Biopsy Indications

• BI-RADS 4 or 5: Core needle biopsy preferred, with or without punch biopsy for skin changes 1, 6
• BI-RADS 1-3 with persistent clinical suspicion: Punch biopsy of skin or nipple, or short-interval follow-up 1, 6, 7
• Benign biopsy with high clinical suspicion: Reassess, consider MRI, repeat biopsy, or refer to specialist 6, 7

Critical Pitfalls to Avoid

• Never initiate antibiotics for skin changes without obtaining imaging first 6, 8
• Never rely on mammography alone—ultrasound is essential for masses, fluid collections, and lymph nodes 6, 8
• Never assume symptom resolution excludes malignancy—Paget's disease can have a waxing and waning course 7
• Never delay tissue diagnosis when clinical suspicion is high, even with benign imaging 1, 6