Cystic lesions are some of the most commonly encountered entities in the breast. They can often be a diagnostic challenge to the radiologist, given their myriad appearances and a wide variety of benign and malignant pathologies. Ultrasound (US) plays an important role in their characterization, categorizing them into simple, complicated or complex cysts, each with different management strategies and prognostic outcomes.

Simple cysts are essentially well-defined anechoic lesions, having imperceptible walls and increased through-transmission. No intervention is required for these BI-RADS 2 lesions, except for large, painful cysts aspirated for symptomatic relief.

Complicated cysts contain internal echoes, due to cellular debris, blood, proteinaceous material, cholesterol, and other content. While no solid component or internal vascularity is present, differentiating these from a solid lesion may be difficult. These BI-RADS 3 lesions are rarely malignant, with a cancer risk of <2% [1]. It is recommended for them to establish stability, with intervention considered if they are symptomatic or growing.

Complex Cystic Breast Masses (CCBMs), containing anechoic as well as echogenic components, result in a variety of imaging appearances. Doshi et al. [1], adapting criteria previously described by Berg et al. [2], classified these into four types (Table 1), based on their sonographic features. Type 1 lesions show a thick outer wall, internal septa, or both. Type 2 masses contain one or more intracystic masses. Type 3 masses have mixed cystic and solid components, and are at least 50% cystic. Type 4 masses are at least 50% solid. As interpreting these descriptions of type 2 and 3 masses may result in some overlapping findings in practice, we add a clarification to the definition of type 2 masses, in that the intracystic masses are peripheral and nodular.

This pictorial essay aims to describe many benign, atypical and malignant breast pathologies presenting as CCBMs (Table 2). We contribute and describe a number of such examples, encountered at our institution over the past decade. The imaging was performed on a variety of ultrasound machines used at our institution including Philips iU22 xMATRIX, Toshiba Aplio 500 and GE LOGIQ E9.

Fibroadenomatoid hyperplasia

This rare benign lesion, featuring an increased number of intralobular ductules and sclerosis of the intralobular connective tissue, most commonly occurs in younger patients as a focal palpable lesion, or breast pain/tenderness. A

*DCIS: ductal carcinoma in situ.

circumscribed, heterogeneously hypoechoic mass may be seen, with internal echogenic septations and vascularity [3] (Figure 1).

Flat epithelial atypia

This refers to an alteration of native intraductal epithelial cells, replaced by cuboidal/columnar cells with mild cytologic atypia. Absence of architectural atypia distinguishes this from Atypical Ductal Hyperplasia (ADH) and Ductal Carcinoma InSitu (DCIS), and may present as an irregular microlobulated lesion, with hypoechoic or complex cystic features [4] (Figure 2).

Fibrocystic change

This is a benign change in the Terminal Ductal Lobular Unit (TDLU), sometimes with fibrosis. It presents with a cyclic pattern of recurring and remitting pain and tenderness, tied to the menstrual cycle, with diffuse or regional areas of firmness. There may be prominent fibroglandular tissue with progressively coarsened echotexture from cumulative fibrotic changes, along with small cysts, sometimes clustered [5] (Figure 3).

Apocrine metaplasia

This benign epithelial alteration in the lobular portion of the TDLU is associated with fibrocystic change. Secretory columnar cells replace the normal cuboidal epithelium, and the resulting apocrine secretions form microcysts. As these gradually increase in size, several adjacent acini fuse to form larger cystic

spaces [6]. Typically, clustered small anechoic foci with intervening septations and posterior acoustic enhancement are seen (Figure 4).

Intraductal papilloma

These are the most common mass lesions in the major lactiferous ducts, usually presenting in the late reproductive or menopausal years, with serous or serosanguinous discharge. They appear as well-defined solid vascularized stalks or masses in the subareolar region (Figure 5), frequently within dilated ducts. Multiple lesions occur in 10% of cases, more common in younger patients, and confer an increased risk of malignancy [7].

Intracystic papilloma

As an uncommon manifestation of intraductal papilloma, this is comprised of a branching central fibrovascular core covered by epithelium, and extends out from the ductal wall into the lumen. The duct becomes obstructed and dilated as the papilloma continues to grow. The resulting cystic lesion is usually well-circumscribed and septated, with an irregular macrolobulated hypoechoic internal nodule [8] (Figure 6).

Atypical ductal hyperplasia

This refers to an intraductal proliferation of epithelial cells, having some of the histological features of DCIS, thus considered borderline. Groups of indeterminate microcalcifications are the common mammographic feature. Sonographically (Figure 7), it is a mildly hypoechoic, microlobulated mass, associated with a fluid-filled duct [9].

Papillary carcinoma

Comprising 1% - 2% of breast malignancies, these may manifest most commonly in post-menopausal women as palpable retroareolar masses or nipple discharge. They can present as a hypoechoic solid mass, or complex cyst with septations or mural-based nodularity. Anechoic regions represent cystic components or haemorrhage [8] (Figure 8).

Breast abscess

Typically with these, there is antecedent mastitis, though certain underlying conditions such as diabetes or rheumatoid arthritis may be contributory. Irregular, thick-walled and multi-loculated collections with debris may be demonstrated (Figure 9 and Figure 10). Overlying skin thickening and peripheral vascularity are common. Ultrasound plays an important role in guiding aspiration, helping to relieve symptoms and enhancing response to antibiotic therapy.

Fat necrosis

Localized inflammation causes saponification and necrosis of fatty tissue, due to causes such as trauma, post-surgery, or radiation therapy, resulting in oily fluid and cellular debris. During the reparative phase, encapsulation by fibrosis occurs, sometimes with wall calcification. Appearances vary depending on the degree of fibrosis, but usually show well-defined anechoic or hypoechoic lesions, with mural nodules or echogenic bands [10] (Figure 11). Correlation with mammography is recommended to confirm the presence of fat, helping avoid unnecessary biopsy.

Post-operative seroma

Post-surgical collection of serous fluid can occur as an early complication,

from potential spaces left following lumpectomy/mastectomy or axillary dissection. These are typically anechoic, and as they mature, result in a thickened and almost nodular appearance of the wall (Figure 12).

Adenomyoepithelioma

These rare tumors feature proliferation of epithelial and myoepithelial elements in the breast lobules and ducts, manifesting clinically as non-tender palpable masses. Most are deemed benign, though if presenting with rapid enlargement, malignant change may be considered. They are microlobulated and hypoechoic, with posterior acoustic enhancement and increased peripheral vascularity (Figure 13). Cystic components, as well as surrounding ductal dilatation, have also been reported [11].

Papillary DCIS

As a variant of DCIS, this features prominent papillae with fibrovascular cores, and is frequently seen with other architectural patterns of DCIS. Multiple ducts can be involved, as with all other variants. The regions involved may be sonographically occult, or show ill-defined hypoechoic masses or small calcifications [8] (Figure 14).

Granulomatous mastitis

This inflammatory reaction, centered on the lobules, usually affects women of child-bearing age or using oral contraceptives; no specific causative agent has been described. Most commonly presenting with masses, patients may also report pain, erythema, axillary lymphadenopathy, and draining sinus tracts. It appears as an irregular hypoechoic lesion, sometimes with tubular extensions (Figure 15). Associated fat necrosis and abscess formation can result in cystic appearance.

Galactocoele

This develops from ductal obstruction over weeks to months, usually painless in lactating women. The appearance is variable (Figure 16), usually anechoic, but increasingly echogenic based on higher milk/fat content, occasionally with fat-fluid levels. Atypically, they may exhibit microlobulated margins, irregular shape, and posterior shadowing [12], mimicking sinister lesions, requiring multi-modality imaging for further characterization.

Lymphangioma

These are rare entities in the breast and axilla, known to occur in the subareolar region, upper outer quadrant, and tail of Spence [13], consisting of dilated lymph channels lined by endothelium. They are lobulated and anechoic, with variably thick internal septa and internal debris (Figure 17).

Foreign body granuloma

These can mimic soft tissue neoplasms on imaging, often causing diagnostic difficulty. Clinical history is therefore of major importance in considering reasonable differentials and management. There is typically an echogenic structure, and surrounding hypoechoic changes from granulomatous tissue response; in some cases, this can result in cystic foci (Figure 18).

Myxoid fibroadenoma

Breast fibroadenomas feature proliferation of stromal and epithelial components of the TDLU. Myxoid fibroadenomas represent a histologic variant, where the stromal component is distinctly hypocellular with an abundant myxoid matrix. Classically they are well-defined, with rounded contours, generally hypoechoic (Figure 19); intralesional calcifications may be observed, as well as degenerative cystic foci.

Benign phyllodes tumor

Phyllodes tumors are rare fibroepithelial neoplasms, exhibiting rapid proliferation of epithelial and stromal cells. A benign mass may feature an inhomogeneous hypoechoic solid appearance, with well-defined, microlobulated margins and cleft-like cystic spaces internally (Figure 20) [14].

Invasive ductal carcinoma (IDC)

The most common breast malignancy, comprising up to 80% of cases, this presents as a firm, palpable and painful mass, sometimes with skin thickening and erythema, nipple retraction and discharge. Originating in the duct and infiltrating its basement membrane, it grows and replaces the surrounding tissues indiscriminately. Suspicious features include the following: ill-defined/angular margins, spiculated pattern, anti-parallel configuration, with internal microcalcifications. Occasionally they are mixed solid-cystic, which confers a higher malignancy grade on histology [15] (Figure 21).

Invasive mucinous carcinoma

Accounting for 2% of breast malignancies, these are divided into pure and mixed mucinous subtypes. The former features a larger amount of mucin, and is

less aggressive with lower rates of axillary nodal metastases. They demonstrate mixed cystic and solid components, with microlobulated margins; posterior acoustic enhancement is common (Figure 22). The pure subtype tends to be more homogeneous, reflecting its less aggressive nature [16].

Ductal carcinoma in situ (DCIS)

Accounting for 15% - 20% of breast malignancies, this frequently asymptomatic condition exhibits proliferation of malignant cells within ducts, without basement membrane invasion. If suspicious microcalcifications are detected on mammogram, features allowing for US-guided biopsy may be sought, which is generally preferred over stereotactic biopsy. Calcified DCIS may appear with echogenic foci located within a mass or a duct, sometimes distributed in a branch pattern. Non-calcified DCIS features rounded/irregular hypoechoic masses, with indistinct or microlobulated margins (Figure 23) [17].

Encysted papillary carcinoma

This rare subtype of papillary carcinoma comprises 1% - 2% of breast malignancies. It usually presents post-menopausally as a slow-growing, palpable retroareolar mass with nipple discharge. A complex cystic mass is seen, sometimes with septations, and vascular solid papillary components projecting into the cyst lumen [18] (Figure 24).

Malignant phyllodes tumor

Imaging features favoring malignant phyllodes include large size (generally larger than 3 - 7 cm [14] ), irregular margins with an echogenic rim, inhomogeneous hypoechoic echotexture and vascularized solid components (Figure 25). Cleft-like anechoic spaces within suggest focal necrosis or cystic degeneration.

Metaplastic breast carcinoma

This rare, heterogeneous group of malignancies accounts for <1% of all mammary tumors. Histologically diverse, they are divided into subtypes exhibiting varying patterns of metaplasia and differentiation with epithelial and/or mesenchymal components. Patients present with rapidly growing large masses, with

infrequent axillary nodal involvement. These are well-circumscribed, and may be rounded or microlobulated, exhibiting complex internal echogenicity, with anechoic components indicating necrosis or cystic degeneration (Figure 26 and Figure 27) [19].

Angiosarcoma

This exceedingly rare malignant tumor of endovascular origin accounts for about 0.04% of breast cancers. Primary and secondary angiosarcomas have been described, the former occurring sporadically from 20 - 40 years of age, and the latter in older patients after breast radiotherapy [20]. Sonographically it is non-specific, appearing circumscribed or ill-defined, with hypoechoic, hyperechoic, or heterogeneous echotexture and presence of vascularity (Figure 28). As existing post-therapy changes can complicate the findings, radiologists should be cognizant of prior history.

We conclude by summarizing a few teaching points. First, CCBMs with a higher risk of malignancy (20% - 30%), are generally classified under the BI-RADS 4 category. Second, CCBMs have a wide range of differential diagnoses, with a variety of benign, borderline and malignant histologies. Classifying these lesions based on ultrasound morphology can be useful in assessing common imaging features, helping to draw attention to their differences and their clinical implications. Type 3 and type 4 CCBMs are more likely to be malignant compared to types 1 and 2. Third, biopsies should be done under ultrasound guidance to target the solid component and to avoid false negative results. Radiology pathology concordance is of utmost significance in these cases. Finally, clinical history and mammographic correlation may help to narrow the differential diagnoses and prevent unnecessary biopsies in certain CCBMs, such as post-operative seromas and galactoceles.

This paper was not supported by any financial grants or funding body.

No potential conflict of interest relevant to this article was reported.

Chotai, N.C., Yim, H., Fok, E.C.M., Loke, S.C. and Lim, H.M.Y. (2022) Complex Cystic Breast Masses: An Ultrasound Imaging Review. Advances in Breast Cancer Research, 11, 31-49. https://doi.org/10.4236/abcr.2022.111002