Cystic Breast Disease: What to Do When It’s Not So Cystic

Abstract

Cystic breast masses are a common entity encountered by breast radiologists. The imaging features of benign and malignant cystic masses may overlap, causing confusion and miscategorization with the potential to produce diagnostic delay and harm. This article provides a review of key differentiating imaging features that help guide appropriate mass characterization and treatment.

cystic breast mass, complex cystic and solid breast mass, BI-RADS 3

Joint Accreditation Statement:

In support of improving patient care, this activity has been planned and implemented by Amedco LLC and the Society of Breast Imaging. Amedco LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician ACCME Credit Designation Statement:

Amedco LLC designates this live activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™ for physicians. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Key Messages

• Bilateral complicated cysts, clustered microcysts, and multiple bilateral circumscribed masses should be categorized as a BI-RADS category 2 (benign) assessment.

• Isolated oval circumscribed hypoechoic masses (presumed complicated cysts) can be categorized as a BI-RADS category 3 (probably benign) assessment if unaccompanied by suspicious mammographic or clinical features.

• Complex cystic and solid masses identified on US warrant a BI-RADS category 4 (suspicious) assessment with recommendation for biopsy unless correlating with a definitively benign entity on another modality.

Introduction

Cystic breast masses are common. Although they are most prevalent among premenopausal women when hormonal function is at its highest, cystic breast masses may be detected in women of any age.¹ In the ACRIN 6666 trial, cysts were detected in 37.5% of women during the initial round of US screening, and in 47.1% over the course of 3 years.¹ Cysts are frequently detected incidentally on screening examinations at mammography, US, and MRI. On diagnostic examinations, they can be seen when patients present with pain or palpable areas of concern. Although most cystic breast masses are benign, malignant pathologies can present as cystic breast masses, and miscategorization of these masses may lead to diagnostic delays. This educational article will provide a review of cystic breast masses, with an emphasis on key imaging features that help to discriminate between benign and malignant cystic breast masses to guide the radiologist in appropriate lesion characterization and treatment.

Pathophysiology of cyst formation

Wellings defines an epithelial cyst as a “spherical or subspherical cyst lined by a single layer of flattened to cuboidal epithelium; often contains homogenous granular or calcified material.” Benign cyst formation is a part of a larger process known as the fibrocystic breast process. Histologically, cysts result from a dilatation and effacement of the terminal duct lobular unit (TDLU).^2,3 The acini begin producing fluid, which leads to their gradual dilation, ultimately coalescing to result in the formation of a cyst (Figure 1).

Figure 1.

Pathophysiology of breast cyst formation. Breast acini with metaplasia start producing fluid that leads to their gradual dilation. The dilated terminal duct lobular unit produces fluid and begins to coalesce. Once all acini have coalesced, a cyst is formed. Illustration created by Dr. Curtis Simmons.

Benign cystic breast disease can fall under the category of proliferative and nonproliferative subtypes.⁴ A simple cyst falls under the nonproliferative pathway. There is no increase in breast cancer risk for women with nonproliferative masses on breast biopsy. The natural history of cysts is to develop and regress.⁵ It is thought that hormonal variations in estrogen play a role in cyst formation because breast cysts are less often seen in postmenopausal women.³

US technical considerations in assessment of breast cysts

It is important to acknowledge the importance of US technique in the evaluation of cystic breast masses. To accurately assess any breast mass using US, it is crucial to carefully examine the margins in 3 dimensions.⁶ For handheld US, the recommended approach is to obtain orthogonal views, as outlined in the ACRIN 6666 protocol.¹ During the examination, a set of images should be captured with and without calipers to ensure that mass margins are fully visible during interpretation.⁶ One of the images should be taken along the longest horizontal diameter of the mass.⁶ The pectoralis muscle should be at the posterior aspect of the field of view. The focal zone should be placed at or just below the mass being evaluated.^6,7

Gain

Appropriate gain settings for breast US are important for reducing miscategorization of cystic breast masses. The time-gain compensation (TGC) curve should be adjusted so that normal fat appears uniformly gray at any depth in the breast. When the gain is inappropriately decreased, fat will appear anechoic and may cause a solid mass to appear like an anechoic cyst. Conversely, the use of excessive gain could result in miscategorization of a benign cyst as a solid mass. The TGC curve can be set manually or can be automatically adjusted during real-time scanning.⁸

Spatial compounding

Using spatial compounding results in improved lateral edge definition, decreased speckle noise, and better visualization of true internal echoes. However, when using this feature, the radiologist must realize that all posterior features (enhancement and shadowing) are reduced.⁷

Harmonic imaging

Once identified, harmonic imaging is very useful in the focused characterization of breast masses, but use is discouraged during a breast US survey because of a loss of signal past 2 to 2.5 cm of depth and pronounced posterior shadowing from Cooper’s ligaments.⁹ Harmonic imaging uses software that applies a filter to the lower frequencies that are multiples of the fundamental frequencies. The lower frequency superficial reverberation echoes are therefore decreased, and harmonic frequencies are used.⁸ This results in elimination of artifactual internal echoes and better characterization of simple cysts in superficial tissues at a depth <2 to 2.5 cm.

Doppler US

Color and power Doppler US are useful tools in the evaluation of cysts and complex cystic and solid masses. In some cases, high-grade invasive cancers and metastatic lymph nodes can appear anechoic, but the presence of internal vascularity would rule out the possibility of a simple cyst and raise the concern for malignancy. Similarly, the presence of vascularity within an otherwise cystic or complex mass confirms the presence of a suspicious solid component, warranting further investigation with biopsy. Power Doppler is more sensitive than color Doppler in detecting the slow blood flow typically seen within breast masses.⁸ With both power Doppler and color Doppler techniques, it is essential to use light transducer pressure during the Doppler US examination to prevent occlusion of slow blood flow due to compression of the vessel lumen.⁸ Using Doppler US techniques with grayscale imaging can enhance the detection and characterization of cystic breast masses, ultimately improving diagnostic accuracy and appropriate treatment.

Elastography

US elastography is an additional technique that can be used to characterize breast masses, relying on measurements of tissue stiffness within the lesion. In 2012, the BE1 multinational study evaluated 939 breast masses prospectively and found that adding shear-wave (SW) elastography to B-mode US could reduce unnecessary biopsies of low-suspicion Breast Imaging Reporting and Data System (BI-RADS) category 4A masses with lack of stiffness.¹⁰ This study demonstrated that adding SW elastography improved specificity without significant loss in sensitivity. When visual color stiffness was used to selectively upgrade BI-RADS category 3 masses and downgrade BI-RADS category 4A masses, specificity improved from 61.1% to 78.5%.¹⁰ A “bull’s eye” elastography artifact has also been described; the characteristic black ring, central bright spot, and posterior bright spot can reliably indicate the presence of a benign simple or complicated breast cyst and reduce unnecessary biopsies of complicated cysts that appear solid on B-mode US, which is only seen on certain US machines.^8,11

Cystic breast masses

Cystic breast masses can be broadly classified according to their sonographic features into simple cysts, complicated cysts, or complex cystic and solid masses.^6,12 Many cystic breast masses can exhibit a round or oval shape, posterior acoustic enhancement, and avascularity on color Doppler imaging.¹³ Imaging features used to characterize benign and malignant cystic breast masses include margins, echogenicity/heterogeneity of internal contents, and wall thickness (Table 1).

Table 1.

Multimodality Appearance and Management of Simple Cysts, Complicated Cysts, and Complex Cystic and Solid Masses

Category	US description	Mammogram/ DBT appearance	CEM appearance	MRI appearance		BI-RADS	PPV (%)	Management
Simple cyst	Oval or round shape Circumscribed margins Imperceptible wall Anechoic content Posterior enhancement Avascular	Oval or round shape Circumscribed or obscured margins	No internal enhancement	T1	Hypointense	BI-RADS 2	0	Resume screening
				T2/STIR	Hyperintense
				T1FS postcontrast	No enhancement
Complicated cyst	Oval or round shape Circumscribed margins Imperceptible thin wall Uniformly hypoechoic internal contents, mobile debris, or fluid-fluid levels Avascular	Oval or round shape Circumscribed or obscured margins	No internal enhancement May see thin peripheral enhancement	T1	Intermediate or high due to proteinaceous or hemorrhagic contents	BI-RADS 2 If mobile debris or fluid-fluid levels are confirmed at US and/or complicated cyst is characterized at CEM or MRI If seen at screening US in the setting of multiple bilateral oval masses	0	Annual screening
				T2/STIR	Hypo- or intermediate intensity depending on internal contents	BI-RADS 3 If isolated and indistinguishable from a solid mass (ie, mobile debris cannot be confirmed), and no contrast-enhanced modality has been performed for further characterization	<2%	6-month follow-up
				T1FS postcontrast	No enhancement or thin rim enhancement
Complex cystic and solid mass	Contains anechoic and hypoechoic/ echogenic components	Oval or round shape Circumscribed or obscured margins	Enhancement of the walls, thickened septae, and solid mural components	T1	Fat, proteinaceous, and hemorrhagic contents can be hyperintense	BI-RADS 4a	2-95	Biopsy; depending on the type of mass, a vacuum assisted device may be preferred.b
				T2/STIR	Hypointense or intermediate
				T1FS postcontrast	Enhancement of septae, solid mural components

Abbreviations: CEM, contrast-enhanced mammography; DBT, digital breast tomography; FS, fat saturated; PPV, positive predictive value.

^aIf a complex mass corresponds with a fat-containing, encapsulated/ circumscribed area of fat necrosis at mammography BI-RADS 2.

^bSee Figure 12 for a subset of other BI-RADS assessments and management recommendations for complex cystic and solid masses.

The appearance of the tissue surrounding a breast mass on US can impart important clues for differentiating a benign cystic mass (such as a round complicated cyst) from a solid malignant mass (such as a round hypoechoic triple-negative carcinoma). The tissue surrounding benign breast masses should have a maintained normal parenchymal architecture, while malignant masses will infiltrate into and disrupt the surrounding parenchymal architecture. This infiltration is obvious in cases where the margins of the mass are clearly suspicious (spiculated, angular). In more subtle cases, margins may be subtly indistinct or microlobulated, with the surrounding parenchyma losing the normal parenchymal architecture and appearing indistinct on close inspection. The presence of an echogenic rind (also described as an echogenic halo or hyperechoic rim) indicates a disruption of the surrounding normal tissue architecture and raises suspicion for malignancy.⁶

Simple cysts

Simple cysts are fluid-filled round or oval masses lined with epithelial cells. The epithelial lining can be bland or apocrine type, with the apocrine type associated with an indistinct appearance of the inner wall of the cyst on high-resolution US imaging.¹ Cysts commonly fluctuate in size over time and can occur in any quadrant of the breast. They can present diffusely or as an isolated finding. Simple cysts are a common finding, occurring in 20% to 50% of women, with peak prevalence between the ages of 30 and 50.^1,14

Imaging findings

At mammography, simple cysts present as round or oval masses with circumscribed margins. In women with heterogeneously or extremely dense breast tissue, simple cysts also present with obscured margins.

On US, a simple cyst presents as a circumscribed anechoic oval or round mass with an imperceptible wall and posterior acoustic enhancement (Figure 2). Simple cysts lack internal vascularity and contain no internal echoes on US.^1,6

Figure 2.

Simple cyst in a 45-year-old woman with a new palpable right breast mass. Recombined craniocaudal view from a contrast-enhanced mammogram (A) shows multiple round masses (arrows) with no internal enhancement. Targeted US in the transverse plane (B) with color Doppler and in the longitudinal plane (C) in grayscale shows a circumscribed anechoic mass without vascularity, consistent with a simple cyst. Reverberation artifact is present at the superficial aspect of the cyst (A and B).

Sonographic characterization of simple cysts requires careful consideration because high-grade triple-negative invasive ductal carcinomas may also present with anechoic to nearly anechoic internal echogenicity.¹⁵ Attention to detail, including meticulous margin characterization, is essential for accurate diagnoses.^1,6

On MRI, simple cysts will demonstrate oval or round shapes, circumscribed margins, T2/STIR hyperintensity, T1 iso- or hypointensity, and no associated enhancement.^16,17

Although the body of literature on the appearance and treatment of cystic masses at contrast-enhanced mammography (CEM) is still growing, many of the lessons learned at contrast-enhanced breast MRI may be applied to the interpretation and management of cystic masses at CEM. On CEM, simple cysts will present as round or oval masses on the low-energy images but will show no internal enhancement (Figure 2A) on the recombined images.^18-20 The “eclipse sign” is negative enhancement (with or without a thin rim of enhancement) and represents the specific appearance of a cyst on CEM.²¹ Like breast MRI, simple cysts at CEM will present as nonenhancing findings, aiding in assignment of a BI-RADS category 2 assessment.

Management

Simple cysts are benign with no malignant potential and should be issued a BI-RADS category 2 assessment on all imaging modalities.¹³ No dedicated follow-up or intervention is necessary for simple cysts. In certain patients, in whom symptomatic simple cysts present with associated pain or a bothersome palpable lump, therapeutic aspiration can be considered for symptomatic relief.^17,22 In these patients, a recommendation for therapeutic aspiration should not change the BI-RADS category 2 assessment. In addition, patients should be made aware that cyst fluid can reaccumulate after therapeutic aspiration. The management of aspirated fluid is discussed within the next section.

Complicated cysts

On US, complicated cysts are masses that meet the criteria for simple cysts except that they are not anechoic and contain homogenous low-level internal echoes (Figure 3).¹⁷ These low-level internal echoes or debris may layer (fluid-fluid level or fluid-debris level) and shift with positioning (Figure S1).¹³ The echoes can be caused by debris, blood products, milk, and cholesterol crystals.¹⁷ Like simple cysts, complicated cysts can fluctuate in size over time and occur in any quadrant of the breast. Complicated cysts are commonly asymptomatic, demonstrate peak prevalence between ages 30 and 50, and are frequently seen in the setting of other simple cysts, complicated cysts, and clustered microcysts.^1,14

Figure 3.

Complicated cyst in a 50-year-old woman with a new palpable abnormality in the upper-outer quadrant of the right breast. Implant displaced craniocaudal (A) and mediolateral (B) views show a round mass with associated calcifications (arrows). The calcifications change in morphology on the true lateral image. Findings are consistent with layering milk of calcium in a macrocyst. Targeted grayscale US in the radial (C) and antiradial (D) planes shows an oval mass with internal echogenic debris (arrows) corresponding to the mammographic finding.

Imaging findings

Similar to simple cysts, complicated cysts present as round or oval masses at mammography. Layering or “milk of calcium” (MOC) calcifications can occasionally be identified within micro- and macrocysts (Figure 3B) and, when depicted at mammography, aid in diagnosis of a benign cyst. In these cases, the layering calcifications can be clearly depicted on the true lateral view and will change in morphology between mammographic views (Figure 3A and B).¹ Further evaluation with US is not necessary when MOC is present as the sole finding on mammogram. However, ductal carcinoma in situ can occasionally occur near a site of benign MOC, so the characteristics of all calcifications should be carefully examined.

On US, complicated cysts present as oval or round circumscribed masses with imperceptible walls. The 3 varying internal appearances of complicated cysts are illustrated in Figure 4. Complicated cysts may present with (1) mobile internal echoes, (2) fluid-fluid levels, and (3) homogeneous low-level echoes. The third imaging presentation is indistinguishable from a solid mass.

Figure 4.

Complicated cysts. Complicated cysts are oval circumscribed masses with imperceptible walls that can present in 3 common ways at US imaging: with mobile internal debris (A), with a fluid-fluid level (B), and with nonmobile homogenous low-level echoes (C). The third imaging presentation is indistinguishable from a solid mass.

At breast MRI, complicated cysts will be nonenhancing and show shape and margins similar to a simple cyst. However, the internal T1 signal will vary depending on the type of material present within the complicated cyst. Hemorrhagic or proteinaceous cysts may show intrinsic T1 hyperintensity.

As with simple cysts, complicated cysts by CEM will present as round or oval masses on low-energy images but show no internal enhancement on the recombined images.^18-20 The eclipse sign is a negative enhancement (with or without a thin rim of enhancement) and represents the specific appearance of a cyst at CEM.²¹

Management

Bilateral fluctuating complicated cysts, identified sonographically or mammographically, should be assessed as benign (BI-RADS category 2) with routine mammographic screening performed.^1,6 Asymptomatic complicated cysts with mobile internal echoes or fluid-fluid levels should also be assessed as benign (BI-RADS category 2) with routine mammographic screening performed.^1,6

An isolated noncalcified hypoechoic mass with circumscribed margins, either identified at baseline mammography or incidentally discovered sonographically, may represent a complicated cyst but is indistinguishable from a solid mass. Therefore, a probably benign (BI-RADS 3) assessment should be issued in this scenario, with 6-, 12-, and 24-month surveillance recommended.¹³ Many practices also include a follow-up at the 18-month interval timepoint, which is an acceptable alternative. If the mass enlarges or demonstrates suspicious interval change on follow-up, biopsy should be performed.^1,6

A BI-RADS category 4 assessment for presumed complicated cysts is appropriate when (1) suspicious features are present (eg, suspicious calcifications, distortion, or indistinct margins at mammography or US) or (2) the mass is new and enlarging and there is diagnostic uncertainty (ie, the mass could be solid). In these settings, US-guided core biopsy and clip placement should be performed. US-guided diagnostic aspiration may also be considered with an 18- to 20-gauge needle; in this setting, the cyst should be aspirated to resolution.¹ The aspirated cyst fluid should be visually inspected. Benign cyst fluid can be cloudy, yellow, green, brown, or white (nonpurulent). Unless the aspirated cyst fluid is bloody or purulent, the fluid should be discarded to avoid false positive cytological assessments.^1,23 In 1 published series examining 660 cyst aspirates, 5% (33/660) were atypical and 13% (86/660) were nondiagnostic or acellular, but no malignancies were identified at surgery or follow up.²⁴ This supports the practice of discarding cyst contents when they are nonbloody to reduce false positives. If cyst fluid is submitted for cytological assessment, a clip should always be placed at the time of aspiration. Masses unable to be aspirated/aspirated to resolution should undergo core biopsy and clip placement.

Clustered microcysts

Clustered microcysts represent the dilation of multiple acini in the TDLU and fall under the broad spectrum of fibrocystic changes. Clustered microcysts can be lined with bland or apocrine metaplastic epithelium and often present concomitantly with simple and complicated cysts.²⁵ Clustered microcysts are most common in women aged 39 to 50 years and are typically incidental findings detected at mammography or US.^1,26 Over the 3-year ACRIN 6666 study period, clustered microcysts were reported in 104/2662 (3.9%) participants, and only 1 proved to be malignant.^1,14

Imaging findings

At mammography, clustered microcysts present as microlobulated or oval masses with circumscribed or partly obscured margins.¹

Sonographically, clustered microcysts appear as a cluster of tiny anechoic masses that are each less than 2 to 3 mm in size, separated by thin (<0.5 mm) septa, and without a distinct solid component.¹³ While clustered microcysts may appear microlobulated, margins should not be indistinct.

At breast MRI, clustered microcysts will present as T2/STIR hyperintense oval masses that are either iso- or hypointense to the breast parenchyma on T1-weighted imaging.¹ Although rim enhancement at the periphery of the small cystic components may be present on postcontrast sequences, no internal enhancement within the cystic components should be seen.

At CEM, clustered microcysts will appear as oval masses on the low-energy images. Similar to breast MRI, apocrine metaplasia can enhance.¹ Although clustered microcysts should not demonstrate internal enhancement, rim enhancement at the periphery of the small cystic components may be observed.

Management

When clustered microcysts are confidently characterized sonographically and have no associated suspicious findings, a BI-RADS 2 (benign) assessment should be issued. When clustered microcysts are confidently characterized, they have an extremely low risk of malignancy. In 2 published series evaluating over 300 clustered microcyst masses, no malignancies were identified.^27,28

Short-interval follow-up (BI-RADS 3 assessment) can be performed when small or deep masses are difficult to confidently characterize.¹

Masses that mimic clustered microcysts but correlate with a new mass or suspicious calcifications at mammography should be regarded with suspicion, particularly in postmenopausal women because ductal carcinoma in situ or other malignancies may present in this manner.^9,27,28

Inflamed cysts

While simple and complicated cysts are usually asymptomatic, inflamed cysts commonly present with pain, tenderness, warmth, or focal erythema in the breast. Inflamed cysts can present in women of all ages and are most often encountered in the setting of pre-existing fibrocystic change.

Imaging findings

Inflamed cysts will present as round or oval masses at mammography. Due to the associated inflammation, margins of the cysts may be indistinct and surrounding stranding and trabecular thickening may be observed at mammography.

Inflamed cysts can have various sonographic appearances, ranging from thick-walled circumscribed anechoic oval masses to oval homogeneously hypoechoic masses with surrounding inflammatory changes/edema.²⁹

At breast MRI, inflamed cysts can present with pericystic inflammation that may mimic a rim-enhancing mass, presenting a diagnostic challenge.^1,17 In these patients, it is important to define the location of the rim-enhancement in relation to the mass. Careful correlation is necessary to confirm that the size and shape of the dark central cavity of a peripherally enhancing mass at subtraction imaging matches the size and shape at T2/STIR–weighted imaging.³⁰ Thick or irregular rim enhancement would indicate the presence of a complex cystic and solid mass and is a suspicious finding warranting percutaneous sampling. These observations can also be applied to the assessment and characterization of rim-enhancing breast masses at CEM; benign pericystic rim enhancement should be thin and located in the tissue surrounding the mass. If the rim enhancement is thick, irregular, or located within the internal aspect of the mass when correlating with the low-energy imaging, further evaluation with tissue sampling is warranted.¹⁹

Management

Inflamed cysts presenting as definitively benign imaging findings should be issued a BI-RADS category 2 (benign) designation with symptomatic treatment.²⁹ Inflamed cysts accompanied by clinical signs and symptoms of infection require US-guided aspiration or drainage.

For presumed inflamed cysts presenting with suspicious imaging findings (complex cystic and solid mass, thick or irregular rim enhancement, suspicious margins), US-guided biopsy is warranted to exclude a cystic malignancy.

Oil cysts

Oil cysts are a subtype of fat necrosis presenting as round or oval, liquid, fat-containing, encapsulated masses.¹ Oil cysts occur when fat cells are damaged due to trauma and release lipid content into the breast stroma and represent a benign sterile nonsuppurative inflammatory process within the adipose tissue.^1,31 Oil cysts can occur secondarily to physical or iatrogenic trauma (biopsy, surgery, or fat grafting), radiotherapy, and anticoagulation use.³¹ Oil cysts can present clinically as a palpable lump but can often be asymptomatically detected at screening.

Imaging findings

Oil cysts are definitively characterized at mammography and CEM as they have a classically benign appearance. They present as round or oval, circumscribed, fat-containing masses with a thin capsule (Figure 5A and B). Over time, the capsule develops thin rim calcifications, creating the findings pathognomonic of an oil cyst.^1,32 Development of dystrophic calcifications over time represents more densely calcified oil cysts.

Figure 5.

Benign oil cyst in a 40-year-old woman with a new palpable right breast mass. Craniocaudal (A) and mediolateral oblique (B) views show a round circumscribed fat containing mass underlying a skin marker in the inner-upper breast (arrows). Grayscale US in the antiradial (C) and radial (D) planes show a round circumscribed anechoic mass with posterior enhancement. Axial T1 fat-saturated + contrast (E) and T1 non–fat-saturated (F) MRI images demonstrate a nonenhancing round mass with internal fat intensity (arrows).

On US, oil cysts have a variable appearance that is dependent on lesional composition. Oil cysts that are composed of simple liquid fat appear as anechoic, avascular, round or oval masses (Figure 5C and D).¹ Unlike simple cysts, oil cysts typically do not exhibit posterior enhancement and may even demonstrate posterior shadowing.⁶ Oil cysts/fat necrosis with increased complexity and calcifications can present as complex cystic and solid masses and/or masses with fluid-fluid levels.¹

At breast MRI, oil cysts present as round or oval masses with signal intensity following fat on all sequences (Figure 5E and F). Thin rim enhancement may be present on the postcontrast enhanced sequences.¹

Management

Oil cysts are benign (BI-RADS category 2) imaging findings that require no further follow-up. Imaging findings of an oil cyst are pathognomonic at mammography. For indeterminate imaging appearances at US, correlation with the clinical history and mammography or available cross-sectional imaging, such as MRI, is the key to preventing unnecessary biopsies.^17,33,34 Indeterminate sonographic findings suspected to represent an oil cyst/fat necrosis can be correlated with mammography by placing an overlying skin marker at US imaging and obtaining tangential mammography to confirm sonographic-mammographic correlation and the presence of an oil cyst/fat necrosis.

Complex cystic and solid masses

Complex cystic and solid masses (CCSMs) are masses with cystic areas in addition to solid components (thick wall ≥0.5 mm, thick septations ≥0.5 mm, or solid masses).¹³ Complex cystic and solid masses are uncommon, identified in 1.2% (35/2662) of the ACRIN 6666 participants.¹ Although uncommon, ~23% to 31% of CCSMs represent malignancy, and therefore, these masses should be assessed as suspicious (BI-RADS category 4) with recommendation for percutaneous sampling.^16,35 Complex fibroadenomas, fat necrosis, galactoceles, papillomas, papillary carcinomas, and high-grade invasive malignancies (such as triple-negative breast cancers [TNBCs]) can all present as CCSMs.

Imaging findings

Complex cystic and solid masses present as round or oval masses at mammography. If benign entities presenting as CCSMs (eg, galactoceles and fat necrosis) have associated fat density and a pathognomonic appearance at mammography, they can be characterized as benign. Correlation with clinical history and other imaging modalities, such as mammography and breast MRI, is key to the appropriate characterization of CCSMs identified at sonography.

Complex cystic and solid masses are characterized by their sonographic appearance and have been further described and sorted into 4 different imaging categories (Figure 6).^12,22,29 Type 1 CCSMs demonstrate a thick outer wall and thick internal septa that measure >0.5 mm (Figure 6A). Type 2 CCSMs are an intracystic type, with 1 or more discrete solid mural nodules within the cyst (Figure 6B). Type 3 CCSMs are predominantly cystic, with the cystic component representing at least 50% of the mass (Figure 6C). Type 4 CCSMs are predominantly solid, with at least 50% of the mass representing a solid component (Figure 6D).^12,16,29 As expected, the positive predictive value of malignancy for type 4 CCSMs is higher compared with predominately cystic types (41% for type 4 vs 14% to 16% for types 1 to 3), although all types meet the threshold for biopsy.¹²

Figure 6.

Complex cystic and solid masses (CCSMs). A: Type 1 CCSM demonstrating a thick wall >0.5 mm (arrow). B: Type 2 CCSM demonstrating a thick septum >0.5 mm (arrow). C: Type 3 CCSM demonstrating an intracystic component (asterisk) comprising 50% of the mass. D: Type 4 CCSM, a predominantly solid (asterisk) mass with cystic spaces (arrow).

At breast MRI, CCSMs can show enhancement of the solid components; if this is observed, the CCSM should be issued a BI-RADS category 4 assessment with recommendation for percutaneous sampling.^17,36,37 Each breast MRI sequence can be used to evaluate certain aspects of the mass (Table 1). On T1-weighted images, the shape and margin of the mass can be evaluated. Simple fluid will be hypointense on T1-weighted imaging, whereas fat, proteinaceous, and hemorrhagic contents are hyperintense. On the T2/STIR sequence, simple fluid shows high homogeneous signal intensity. Hypointensity on T2 or STIR images suggests proteinaceous or hemorrhagic internal contents.³⁶

At CEM, CCSMs can present with enhancement of thickened walls, septations, and solid mural nodules.¹⁹

Management

Unless the CCSM correlates with a definitively benign entity (such as fat necrosis), a BI-RADS category 4 assessment with recommendation for biopsy is recommended, given the significant risk of malignancy. For masses that are predominantly cystic, vacuum-assisted biopsy is preferred, or if a spring-loaded device is used, then targeting the solid component is recommended.³⁸

Triple-negative breast cancer

Triple-negative malignancies represent 15% to 20% of all breast cancers and account for 35% of breast cancer–related deaths. Given their rapid growth, they can often present clinically as palpable masses. Patients are younger in age and present at an advanced stage that is associated with a reduced overall survival (5-year relative survival of 77.1%).¹⁵ Triple-negative breast cancer disproportionately affects Black women.¹⁵

Care must be made to reduce imaging miscategorization of TNBCs at mammography and US. Triple-negative breast cancers may often present as oval or round masses with erroneously characterized circumscribed margins, hypoechoic or near anechoic internal echogenicity, and posterior acoustic enhancement (Figure 7), contributing to miscategorization of TNBCs as benign or probably benign entities.³⁹ However, this pitfall may be avoided by careful scrutinization of mass margins. Triple-negative breast cancers will often present with subtle microlobulated or indistinct margins (Figure 7B), warranting a BI-RADS category 4 assessment. In addition, the use of color Doppler may show internal vascularity (Figure 7C).

Figure 7.

Triple-negative breast carcinoma in a 31-year-old woman with a BRCA2 mutation and new palpable right breast mass. A: Mediolateral oblique view from a screening examination performed 6 months before shows no findings of malignancy. Grayscale US in the transverse plane (B) shows a round hypoechoic mass with posterior enhancement. Mass margins are indistinct on close inspection. C: Color Doppler US in the longitudinal plane shows peripheral and internal vascularity within the mass. D: Postbiopsy mammogram shows a clip within a round circumscribed mass (arrow). E: T1 fat-saturated + contrast and T2/STIR (F) axial breast MRI shows a heterogeneously enhancing mass (asterisks) with intermediate T2 signal.

Managing cystic breast masses: screening and diagnostic challenges

Screening mammography

Screening examinations are performed on asymptomatic patients to detect malignancy. As with all radiographic examinations, water and soft tissue are indistinguishable at mammography. Therefore, a mass cannot be characterized as a cyst on the basis of mammographic density alone. However, cysts may be inferred by observing fluctuation in the size of similar masses on serial mammographic screening examinations. In addition, benignity of multiple bilateral circumscribed oval/round masses can be inferred at screening, as previously reported by Leung and Sickles.⁴⁰ This landmark study demonstrated that multiple bilateral (at least 3 masses in total with at least 1 in each breast), round or oval, circumscribed or obscured masses can be dismissed as benign findings because these typically represent cysts or fibroadenomas.^40,41 The caveats to this rule are that all the masses should be similar in shape, density, and margin characteristics. If one is enlarging, is greater in density, demonstrates suspicious margins, or represents a palpable finding, that mass should be recalled for further evaluation.⁴⁰

The widespread adoption of digital breast tomosynthesis (DBT) has allowed for enhanced characterization of multiple bilateral circumscribed oval/round masses.⁴² Digital breast tomosynthesis has been shown by multiple studies to reduce false positive recalls and increase cancer detection.^43-45 Digital breast tomosynthesis is particularly useful in providing enhanced visibility of masses and better margin analysis.⁴² In a study by Nakashima and colleagues evaluating 1395 diagnostic mammograms, 83% of the detected circumscribed masses were more visible and better evaluated with DBT compared with mammography alone.⁴⁶ Digital breast tomosynthesis reveals more cases of multiple bilateral circumscribed oval/round masses compared with digital mammography alone; this can contribute to the reduction of false positive recalls by allowing for enhanced confident BI-RADS category 2 assessments at screening.⁴²

Screening breast US

The field of breast imaging saw a marked increase in the use of supplemental screening breast US with the recognition of the limited sensitivity of mammography in dense breast tissue and the introduction of breast density legislation.⁴⁷ The Mammography Quality Standards Act final rule, taking effect on September 10, 2024, will require facilities to inform women whether they have dense or not-dense breasts.⁴⁸ With the increase in screening breast US use comes the challenge of discriminating benign vs malignant asymptomatic breast masses detected at sonography.⁴⁹ Although the incremental cancer detection rate of supplemental screening breast US is reported to be 3 to 4 per 1000 examinations, the low positive predictive value (<10%) of breast US screening creates interpretive challenges.^49-51 With that said, data published on screening breast US programs over time show that false positive examinations can be decreased without compromising cancer detection, with comparison to prior examinations, increased reader experience, and recognition and reclassification of benign sonographic entities.⁵²

There are several findings that may now be assessed as BI-RADS category 2 (benign) at screening breast US that were historically assessed as BI-RADS 3 (probably benign). These BI-RADS category 2 sonographic entities include complicated cysts with debris, clustered microcysts, and multiple bilateral circumscribed masses. Presumed complicated cysts that are solitary, without suspicious features, and indistinguishable from a solid mass should be classified as a BI-RADS category 3 assessment due to the <2% probability of malignancy, particularly in women under 60 years of age.^9,23,42,53 Interval growth or interval development of suspicious imaging features should trigger a biopsy recommendation. However, it must be emphasized that an isolated presumed complicated cyst must be distinguished from the more common presentation of a combination of multiple bilateral complicated cysts, clusters of cysts, and simple cysts warranting a BI-RADS category 2 assessment and recommendation for routine annual screening. Multiple publications have indicated the extremely low malignancy rate, ranging from 0% to 0.44%, among complicated cysts when they are appropriately characterized.^{1,23,52,54,55}

Correlation with mammography is essential when performing and interpreting screening breast US. When a cystic breast mass identified on screening breast US correlates with a stable mass at mammography, it is characterized as benign. Similarly, a new mammographic mass may correlate with a benign cyst at screening breast US, obviating the need for mammographic screening recall.

Other diagnostic considerations

Correlation with other modalities

Correlation with other modalities, imaging studies, and clinical information is critical for increasing interpretive accuracy of cystic breast masses. For example, an isolated presumed complicated cyst can be assessed as a BI-RADS category 3 (probably benign) finding, but if correlation with CEM or breast MRI demonstrates a stable nonenhancing mass, a BI-RADS category 2 designation would be appropriate. Conversely, an isolated presumed complicated cyst correlating with a new indistinct mass at mammography in a postmenopausal woman should be issued a BI-RADS category 4 (suspicious) assessment.

Information gleaned from the clinical and multimodality assessment can impact appropriate categorization of complex cystic and solid breast masses. Differential considerations for CCSMs encompass a wide range of benign, elevated risk, and malignant pathologies (Figures 6–11; Figures S2 to S5). However, careful correlation with other modalities, clinical history, and physical examination allows for appropriate BI-RADS assessment and management of CCSMs (Figure 12).

Figure 8.

Fibrocystic change in a 54-year-old woman with a new palpable right breast lump. Initial mediolateral oblique (MLO) view from diagnostic mammography (A) shows an obscured mass (arrows). Recombined contrast-enhanced mammography MLO view (B) shows rim enhancing mass with enhancing septations (arrows). Color Doppler (C) and grayscale (D) US images show a complex cystic and solid mass with internal vascularity in the septations and nodular components (arrows). Subsequent axial T1 fat-saturated + contrast MR imaging (E) and axial STIR (F) show multiple T2 hyperintense masses (arrows) with associated rim enhancement (chevrons). This palpable mass underwent US-guided core biopsy. (G) Low-power magnification (40×) hematoxylin and eosin–stained section of the core biopsy sample shows fibrocystic changes including apocrine cysts (thin black arrows) and atypical lobular hyperplasia (thick black arrow).

Figure 9.

Invasive ductal carcinoma in a 55-year-old woman with palpable mass and skin dimpling in the right-lower breast. A: Mediolateral oblique recombined images from a contrast-enhanced mammogram examination shows an oval mass with focal internal nodular enhancement (arrowhead). Color Doppler (B) and grayscale (C) US imaging of the right breast at 9 o’clock, 3 cm from the nipple demonstrates a complex cystic and solid mass (arrows). US-guided biopsy specimen yielded invasive ductal carcinoma.

Figure 10.

Papilloma in a 67-year-old woman with a screening-detected mass in the right breast. Full-field digital mammogram mediolateral view (A) shows a round mass (arrow) in the right breast. B: Grayscale US image shows a complex cystic and solid mass containing a solid mural nodule (asterisk). This finding underwent US-guided core-needle biopsy. C: Hematoxylin and eosin–stained image on low-power magnification (40×) demonstrates breast parenchyma with fragments of intraductal papilloma (thin black arrow).

Figure 11.

Papillary carcinoma in a 71-year-old asymptomatic woman presenting for screening mammography. Left craniocaudal (A) and mediolateral oblique (B) mammography views show a round mass (arrows) in the left upper-outer breast. C: Color Doppler US images show a round complex cystic and solid mass containing a solid mural nodule with internal vascularity (asterisk). Core-needle biopsy (D) was performed targeting the solid mural nodule. E: Hematoxylin and eosin–stained histology slide under low-power magnification (40×) shows parts of an encapsulated papillary carcinoma with cystic change.

Figure 12.

Management of complex cystic and solid masses (CCSMs). Complex cystic and solid masses correlating with definitively benign fat necrosis at mammography (MG) (fat-containing, encapsulated, no suspicious imaging features) should be characterized as benign. Complex cystic and solid masses presenting with signs suggesting infection (a presumed abscess) may be assessed as a BI-RADS 3 with recommendation for diagnostic aspiration to aid in therapeutic decision-making. If an aspirate is unable to be obtained, core biopsy should be performed. Complex cystic and solid masses presenting with signs suggesting trauma may be issued a BI-RADS 3 assessment for a presumed hematoma, with short-interval follow-up recommended to ensure resolution and no underlying suspicious mass. For all other CCSMs, a BI-RADS 4 assessment should be issued, with recommendation for tissue sampling. *In the case of clear definitive signs of infection (abscess) and clear definitive signs of trauma (hematoma), a BI-RADS category 2 (benign) assessment may be issued.

Although benign cystic breast masses are more common in pre- and perimenopausal women, they can occur in women of all ages. A more recent study evaluating the frequency of malignancy in complicated cysts in postmenopausal women found no malignancies in their cohort of 114 women.⁵⁴ Indeed, postmenopausal women receiving hormone replacement therapy (HRT) may present with new or increasing benign cystic breast masses, and correlation with the clinical history is useful in this setting.

In postmenopausal women not on HRT, caution must be exercised when characterizing isolated presumed complicated cysts recalled from screening mammography. In a study evaluating the cancer yield of BI-RADS category 3 findings from the National Mammography Database, the frequency of malignancy was found to increase linearly with increasing age.⁵⁶ Specifically, the frequency of malignancy of BI-RADS category 3 findings exceeded 2% for women above the age of 60 and was found to be up to 4.6% for women in their 80s.⁵⁶

Conclusion

Cystic breast masses comprise a broad spectrum of benign and malignant breast entities. Understanding the fundamental distinguishing imaging features of various cystic masses is essential for appropriate BI-RADS assessment and treatment recommendations. Correlation with other modalities, clinical history, and physical examination assists in the decision pathway for certain conditions.

Supplementary material

Supplementary material is available at Journal of Breast Imaging online.

Acknowledgment

Curtis Simmons was the artist for creation of medical illustration Figure 1.

Funding

None declared.

Conflict of interest statement

None declared.

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