What causes the formation of breast cysts?

Breast Cyst Formation: Pathophysiology and Clinical Significance

Breast cysts arise as an aberration of normal lobular involution (ANDI) associated with active secretion of apocrine epithelium under hormonal stimulation, representing the most common cause of benign breast masses in adult women. 1

Mechanism of Cyst Development

Breast cysts form through a process of abnormal lobular involution where terminal duct lobular units become obstructed and dilate with fluid accumulation. 1 This process is fundamentally driven by:

• Hormonal fluctuations: Cysts develop primarily in response to fluctuating estrogen and progesterone levels, explaining their predominance in premenopausal women 2
• Apocrine metaplasia: The epithelial lining undergoes apocrine changes with active secretion into the obstructed lobular units 1
• Ductal obstruction: Blockage of terminal ducts prevents normal fluid drainage, leading to progressive accumulation and cyst expansion 1

Epidemiology and Risk Factors

• Clinical macrocysts occur in approximately 7% of adult women, making them one of the most frequent benign breast lesions 1
• Premenopausal women are predominantly affected due to higher estrogen levels and active hormonal cycling 2
• Postmenopausal occurrence is rare unless the patient is on hormonal replacement therapy 2
• Conditions causing hormonal imbalances (such as polycystic ovarian syndrome) increase the risk of fibrocystic changes and cyst formation 2

Cyst Classification and Characteristics

The NCCN guidelines classify breast cysts into three distinct categories based on ultrasound characteristics, each with different malignancy risk profiles: 3

Simple Cysts

• Anechoic (completely fluid-filled), well-circumscribed, round or oval with imperceptible walls and posterior acoustic enhancement 3
• Considered benign (BI-RADS 2) with essentially no malignancy risk 3
• Require no further evaluation beyond routine screening if concordant with clinical findings 3

Complicated Cysts

• Contain low-level internal echoes or debris but lack solid components, thick walls, or thick septa 3
• Associated with very low malignancy risk (<2%) 3, 4
• Represent an intermediate category between simple and complex cysts 4

Complex Cysts

• Contain discrete solid components including thick walls, thick septa, and/or intracystic masses 3
• Carry significantly higher malignancy risk (14-23%) 3, 5
• Sonographic features predictive of malignancy include thick cyst walls, lobulation, and hyperechogenicity 5
• Two or more suspicious criteria combined increase malignancy risk 13.6-fold 5

Cyst Fluid Composition

The intracystic fluid contains a diverse array of components that reflect the underlying pathophysiology: 6

• Ions, lipids, proteins, and enzymes secreted by apocrine epithelium 6
• Growth factors and hormonal components 6
• The biochemical profile of cyst fluid provides insight into the physiopathology and may help identify cysts at higher breast cancer risk 6

Clinical Implications

Malignancy Risk

• Simple cysts are not associated with subsequent breast cancer development 3
• Multiple recurrent cysts may be associated with a small but significant increase in breast cancer risk 1
• Complex cysts require immediate tissue biopsy due to their 14-23% malignancy rate 3, 5

Management Principles

• Most cysts can be managed by aspiration alone 1
• Multiple recurrent cysts causing significant symptoms may justify short-term therapy with danazol 1
• Complicated cysts require either aspiration or short-term follow-up every 6-12 months for 1-2 years 4

Common Pitfalls

The key clinical challenge is distinguishing benign simple cysts from complex cysts that harbor malignancy. 5 Failure to adequately assess complex breast cysts can result in missed or delayed diagnosis of malignancy, particularly when multiple suspicious sonographic features are present. 5 Always obtain tissue biopsy for complex cysts rather than relying on aspiration alone. 3