1. health and fitness
2. disease
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Review Article
Cystic Breast Lesions
Sonographic Findings and Clinical Management
Pierluigi Rinaldi, MD, Carmine Ierardi, MD, Melania Costantini, MD,
Stefano Magno, MD, Michela Giuliani, MD, Paolo Belli, MD,
Lorenzo Bonomo, MD
Objective. This article reviews basic sonographic findings for distinguishing cystic lesions of the breast.
Methods. We describe sonographic features of simple and complicated cysts in comparison with complex masses and intracystic carcinomas. Results. We correlate cystic lesion appearances with histologic patterns and illustrate the diagnostic and therapeutic management of cystic breast lesions.
Conclusions. Sonography is a useful tool in distinguishing simple cysts from complicated cysts and
complex masses of the breast. Key words: breast; complex cyst; cyst; diagnosis; intracystic carcinoma;
sonography.
C
Abbreviations
BI-RADS, Breast Imaging Reporting and Data System;
DCIS, ductal carcinoma in situ; IPC, Intracystic papillary
carcinoma
Received May 26, 2010, from the Departments of
Bioimaging and Radiological Sciences (P.R., C.I.,
M.C., M.G., P.B., L.B.) and Surgery (S.M.), Università
Cattolica del Sacro Cuore, Rome, Italy. Revision
requested June 18, 2010. Revised manuscript
accepted for publication June 24, 2010.
Address correspondence to Carmine Ierardi,
MD, Department of Bioimaging and Radiological
Sciences, Università Cattolica del Sacro Cuore,
Largo Agostino Gemelli 8, 00168 Rome, Italy.
E-mail: [email protected]
ystic breast lesions include a wide spectrum of
breast diseases, from the most frequent simple
cyst to the uncommon papillary intracystic carcinoma. The purpose of this review is to present
basic radiologic findings to distinguish simple cysts from
complicated cysts and complex masses. We describe
mammographic, sonographic, and magnetic resonance
imaging features of cystic breast lesions, correlate imaging with histologic patterns, and illustrate the diagnostic
and therapeutic management of cystic breast lesions.
Gross Cyst Breast Disease
Gross cystic breast disease has been recognized as the
most frequent female benign breast lesion. Up to onethird of women aged 30 to 50 years have cysts in their
breasts. The true frequency is probably much greater
than the clinically recognized entity, and the prevalence
has been estimated to be between 50% and 90%. It most
commonly appears during the third decade of life, reaches its greatest frequency during the fourth decade, and
sharply diminishes after menopause. Gross cystic breast
disease becomes clinically evident during the third and
fourth decades of life, when hormonal function is at its
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peak level, suggesting that steroid and peptide
hormones may be involved in cyst genesis and
evolution.1–4 Because breast cysts are not frequent in postmenopausal women, a cyst developing in a postmenopausal woman should be
viewed with suspicion3 if the patient is not
receiving hormone replacement therapy.
Gross cystic breast disease includes all of the
benign breast pathologic states, comprising
dilatation of ducts and acini to form cysts, proliferation and metaplasia of their epithelial lining,
and multiplication of ducts and acini to give a
picture of adenosis, which taken together, constitute the disease.5 Starting from the common
mechanism of terminal ductal lobular unit
obstruction that generates a gross breast cyst, 2
main gross cyst types may develop:
Type 1, a secretory cyst, is characterized by
metabolically active apocrine epithelial cells that
are able to produce and secrete a variety of biocompounds, which accumulate within the cyst,
increasing cell proliferation and promoting
apocrine cells to undergo atypia, hyperplasia, or
preneoplastic alterations linked to breast cancer.
Type 2, a transudative cyst, is mainly characterized by a biochemical composition similar to
that found in plasma and lined by flattened
epithelium without metabolic hypertrophy. It
may represent a mere retention cyst in which biocompounds are derived from plasma drainage.
Simple needle aspiration resolves the clinical
symptoms, preventing recurrences without any
epidemiologic evidence of breast cancer predisposition.2
Patients with a single cyst are more than 3 times
as likely to have a flattened rather than an apocrine cyst. Multiple cysts, whether simultaneous
or sequential in any individual patient, are usually all of the same type and are more commonly
apocrine than flattened. A comparison of the frequency of subsequent cysts in patients whose
initial cysts were of either the apocrine or flattened type showed that further cysts were greater
than 5 times more common in patients who presented with the apocrine type. These observations suggest that the natural history of cystic
disease is closely related to the cyst type.6
Although some controversies exist about the
relationship between gross cysts and breast cancer, recent evidence suggests that the multidisci1618
plinary study of gross cystic breast disease may
be a powerful tool for predicting the natural history of the multifaceted gross cyst pathologic
characteristics. Many articles have been published on breast cyst fluids concerning biochemical, hormonal, and a variety of other components
(such as ions, lipids, proteins, enzymes, growth
factors, and antigens) and suggesting that their
profiles provide additional knowledge of the
disease.1,7–9
Sonographic Findings
Gross cysts (≥3 mm in diameter) are usually
grossly visible and palpable, round and well
delimited, and relatively movable in the surrounding breast tissue, and occasionally they develop
thick fibrous firm-appearing walls. Gross cystic
breast disease is often asymptomatic. It is a
source of clinical concern for pain and discomfort and because it mimics malignant breast
masses.2,10
Palpation is not sufficient to distinguish benign
from malignant cystic lesions.2,11 Sonography is
the preferred diagnostic modality to distinguish
cystic from solid lesions and to differentiate simple cysts from cysts with intracystic growth.11,12 A
cyst should be anechoic, resembling a black hole
with an imperceptible circumscribed border.
Other criteria for diagnosing simple cysts include
a round or oval shape and posterior enhancement (Figures 1 and 2).13
The differentiation of a simple cyst from one
with internal echoes or even solid lesions can be
problematic at times, particularly if the lesion is
deep or very small. With current transducers,
most simple cysts of 5 mm or larger can be reliably characterized with standard linear array
high-frequency transducers. The use of tissue
harmonic imaging may improve operator confidence in characterizing a lesion as a cyst and is
especially helpful in reducing artifactual internal
echoes.14
Spatial compounding, in which a sonogram
is derived from the input of multiple offperpendicular beams, may also facilitate evaluation of complicated cysts, masses that might be
cystic or solid. Margin definition is similarly
improved with spatial compounding. Spatial
compounding is particularly helpful in decreasing speckle and other sources of noise. As a
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Figure 1. Transverse sonogram of the left breast in a 32-year-old
woman showing a simple cyst appearing as an anechoic circumscribed round mass. For this and all other images, an Antares
ultrasound unit (Siemens Medical Solutions, Mountain View, CA)
with a 10- to 13-MHz linear array transducer was used.
Figure 3. Transverse sonogram of the right breast in a 51-yearold woman showing clustered microcysts appearing as clusters
of tiny anechoic foci, individually smaller than 2 to 3 mm, with
thin internal septations and no discrete solid component.
result, there is better definition of internal structures within the masses. The improved signal-tonoise ratio facilitates recognition of small cysts,
although posterior enhancement is less apparent with spatial compounding.15
Benign cystic lesions include clustered microcysts and complicated cysts. Clustered microcysts
consist of a cluster of tiny anechoic foci, individually smaller than 2 to 3 mm, with thin
(<0.5 mm) internal septations and no discrete
solid component. If they are nonpalpable, clustered microcysts may be assessed as probably
benign, with short-interval follow-up. Causes
include fibrocystic changes and apocrine metaplasia (Figure 3).13 Complicated cysts may have
homogeneous low-level internal echoes that
characterize commonly encountered cysts and
may also have a layered appearance (Figures 4
and 5). Fluid-debris levels may shift slowly with
changes in the patient’s position. A complicated
cyst may also contain brightly echogenic foci
that scintillate as they shift.13,16 Color Doppler
Figure 2. Oblique sonogram of the left breast in a 26-year-old
woman showing a simple cyst appearing as an anechoic oval
mass with an imperceptible circumscribed border and posterior
enhancement.
Figure 4. Transverse sonogram of the left breast in a 48-year-old woman showing a cyst appearing as a round mass with a fluid-debris level. No vascular signals
are present on color Doppler analysis.
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Figure 5. Oblique sonogram of the left breast in a 54-year-old
woman showing a complicated cyst appearing as an oval mass
with brightly echogenic foci.
sonography is a useful tool for distinguishing
complicated hypoechoic cysts from hypoechoic
solid masses (Figures 6 and 7). If aspirated, the cyst
fluid may be clear, yellow, or turbid green. The term
complicated describes the sonographic appearance and does not indicate that pus or blood is
responsible for the internal echoes. Complicated
breast cysts are estimated to be reported in approximately 5% of breast sonographic examinations.17
They should be circumscribed masses and do not
contain solid mural nodules. In fact, a discrete solid
component places the cystic lesion into the cate-
gory of a complex mass, requiring aspiration or
other intervention.
Septations within a cyst are defined as thin
(<0.5 mm, representing the combined thickness
of 2 myoepithelial and epithelial cell layers) or
thick (>0.5 mm). A cyst containing thin septations is benign (Figure 8), but a cyst containing a
thick wall, which is any imperceptible wall, or
thick septations could be malignant, and biopsy
might be required (Figure 9). In a study by Berg et
al,12 invasive ductal carcinoma was found in 30%
of these types of lesions (grade 2 or 3), whereas
simple cysts, fibrocystic changes, abscesses, and
fat necrosis were seen in cases of benign disease.
A complex mass should contain both anechoic
(cystic) and echogenic (solid) components.
Complex masses must be carefully evaluated to
exclude the presence of malignant processes.
Intracystic masses (cystic masses with a solid
component) have a discrete solid mural mass
within a cyst. Grouped with these are mixed cystic and solid masses with at least a 50% cystic
component (Figure 10). In their large series, Berg
et al12 showed 22% malignancy in this category,
including intracystic papillary carcinoma (IPC),
Figure 7. Transverse sonogram of the left breast in a 65-yearold woman showing a complicated cyst appearing as a round
circumscribed cystic lesion with a small hypoechoic component
without vascular signals (hemorrhagic cyst).
Figure 6. Transverse sonogram of the right breast in a 36-year-old woman showing a small oval hypoechoic circumscribed mass. Color Doppler analysis confirms
the solid nature of the lesion.
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intraductal carcinoma, and invasive ductal carcinoma. Benign intracystic masses include galactoceles, fibrocystic changes, and papillomas.12
Masses that are at least 50% solid with eccentric
cystic foci are considered masses with a fluid
component (Figure 11). In the study by Berg et
al,12 solid masses with eccentric cystic foci
included 18% malignancy (differentiated invasive ductal carcinoma, intraductal carcinoma,
invasive lobular carcinoma, IPC, and ductal carcinoma in situ [DCIS]) and various benign diseases (fibrocystic changes, fibroadenoma, fat
necrosis, and lactating adenoma).
In conclusion, sonographic features associated
with a high risk of cancer are thickened walls,
thick internal septations, and a mixture of cystic
and solid components. In these cases, it is feasible to perform preoperative sonographically
guided fine-needle aspiration cytologic examinations or core biopsies of the cystic and solid components for cytologic or histologic verification.11
Figure 9. Transverse sonogram of the left breast in a 59-year-old woman showing a round noncircumscribed cystic lesion with a thick wall and a large vascular
pedicle adjacent to the cystic wall.
Management
A sonographically simple cyst (anechoic with a
well-defined imperceptible wall and posterior
acoustic enhancement) can be dismissed as a
benign American College of Radiology Breast
Imaging Reporting and Data System (BI-RADS)
category13: BI-RADS category 2 for simple cysts
and category 3 for probably benign cystic
lesions. If the patient is symptomatic with pain
or a very large cyst, aspiration can be performed
electively. When the fluid is typical of a benign
cyst, such as cloudy yellow or greenish black, it
can be discarded, as is generally our practice.
Such fluid can be sent for a cytologic examination by patient request or for patients with a personal history of cancer or atypical lesions.
Symptomatic complicated cysts generally warrant aspiration. Generally, complicated cysts are
seen in patients with other simple cysts. An isolated complicated cyst versus a solid mass may
Figure 8. Transverse sonogram of the right breast in a 31year-old woman showing an oval cystic lesion containing thin
septations.
Figure 10. Transverse sonogram of the right breast in a 61-year-old woman
showing an intracystic mass appearing as a cystic lesion (at least 50% cystic component) with a solid vascularized mural portion (invasive intracystic carcinoma).
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Figure 11. Transverse sonogram of the left breast in a 53-yearold woman showing a mass with a fluid component appearing
as a large irregular cystic mass with a prevalent vascularized solid
portion (at least 50% solid with eccentric cystic foci). Invasive
intracystic carcinoma was diagnosed.
In a study by Venta et al,18 the malignancy rate
of lesions classified as complicated cysts was
0.3% (1 of 308). This malignancy rate is lower
than that of lesions classified as probably benign
using BI-RADS criteria.13 Because the accepted
standard practice for management of probably
benign lesions is follow-up studies, the low yield
of malignancy in this series suggests that complex cysts can be managed with 6-month followup imaging studies instead of intervention.13,18
Clustered breast microcysts are relatively common, seen on 5.8% of breast sonograms. In a
study of 79 clustered microcysts with follow-up
by Berg,19 none proved to be malignant. Clusters
of microcysts without discrete solid components
can be considered probably benign and be followed. Follow-up on an annual basis appears
reasonable.19
It is possible that larger cysts with thin septations represent the continuum of a spectrum
from apocrine metaplasia to cysts as the acini
fuse. A thick wall or thick septations in an otherwise cystic lesion without antecedent trauma or
evidence of infection should suggest possible
malignancy and prompt biopsy (Figure 9).12,13
Complex cystic masses with discrete solid components clearly require biopsy (Figures 10–12).11–13
Intracystic Papillary Carcinoma
not have the same risk of malignancy, although
this concept requires further validation (Figures
11–13).2,10
Intracystic papillary carcinoma of the breast is a
rare malignant tumor with a predilection for
postmenopausal women, constituting 0.5% to 2%
Figure 12. Transverse sonogram of the right breast in a 29-year-old woman obtained during fine-needle aspiration showing a complicated cyst that
disappears at the end of the procedure.
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of all breast carcinomas.11,20–25 Women with IPC
may have no symptoms or may present with a
palpable mass or bloody nipple discharge.23,24
Intracystic carcinoma located within large cystic ducts and neoplastic cells has the appearance
of low-grade DCIS. However, it is not clear
whether all lesions histologically categorized as
IPC are truly in situ carcinomas or whether some
such lesions might represent circumscribed or
encapsulated nodules of invasive papillary carcinoma. The lack of a basal myoepithelial cell layer
in these cases suggests a spectrum of progression from in situ to invasive disease and might
help explain distant metastases.21,26
The terminology used for papillary breast
lesions is quite confusing. The older term IPC is
still used quite frequently. This term, although
generally referring to a localized in situ lesion
arising in a cystic and enlarged duct, has been
used in a variety of contexts in which it is often
difficult to determine whether the term refers to
an in situ or invasive lesion.
Papillary carcinomas can be divided into invasive and noninvasive forms (a classification
that seems to correlate with the prognosis).
Noninvasive papillary carcinomas are further
subdivided into 2 subtypes: a diffuse form, the
papillary variant of DCIS, and a localized form,
IPC, a solitary grossly evident tumor in a cystic
and enlarged duct. Intracystic papillary carcinoma can be present in a pure form or can be associated with DCIS or invasive carcinoma.20,24,25
At pathologic examination, IPC is usually a
well-circumscribed mass with a cystic component containing a nodular or papillary inner
surface. The most common histologic feature
is arborization of the fibrovascular stroma.
A monotonous cell population, the presence of
mitoses, and the lack of myoepithelial cells confirm the diagnosis of IPC.24,27
Figure 13. Transverse sonogram of the left breast in a 49-year-old woman
obtained during fine-needle aspiration showing a complicated cyst that gradually
decreases.
A round or oval shape and circumscribed margins
are common findings. An irregular shape and a
noncircumscribed contour can be observed especially in invasive forms (Figures 9–11).11,31,32
Intracystic papillary carcinomas may be
detected and diagnosed sonographically if they
do not occupy the entire cyst; otherwise, they are
not distinguishable from other solid masses. The
differential diagnosis of large predominantly
solid lesions includes fibroadenomas and phyllodes tumors (Figure 14).21,32–34
Figure 14. Transverse sonogram of the left breast in a 53-yearold woman showing an oval circumscribed complex mass with
fluid components (phyllodes tumor).
Sonographic Findings
It is very important for radiologists to diagnose IPC
for proper treatment.22 Intracystic papillary carcinomas often manifest as intracystic masses.28–30
Sonography is the preferred diagnostic modality for distinguishing cystic from solid lesions
and to differentiate simple cysts from intracystic
growths. Generally, IPC appears as a complex
mass with a solid vascularized component.
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Intraductal papillary carcinomas are highly vascular tumors and have a propensity to bleed
spontaneously. A distinct vascular pedicle is identified within the central core with branching vessels. Color and power Doppler imaging is very
useful for showing the vascularization of an intracystic solid component (Figures 10, 15, and 16).35
Larger intracystic lesions frequently have an
irregular shape, indistinct margins, and markedly mural vascularized nodules. A necrotic or
hemorrhagic component may be associated with
a cystic component. These features suggest a
probably invasive form. On the other hand, circumscribed cystic lesions with a smaller solid
nodule and without a necrotic or hemorrhagic
component suggest a noninvasive form.
Management
When a complex mass is visualized, it is feasible
to perform preoperative sonographically guided
fine-needle aspiration cytologic examinations or
core biopsies of the cystic and solid components
for cytologic or histologic verification.11,12 Fineneedle aspirations and core needle biopsies may
be unable to distinguish between in situ and
invasive lesions because the center of the lesion
is often targeted, and invasion is often identified
at the periphery of the tumor.36 Excisional biopsy
represents the better diagnostic and therapeutic
treatment.
Literature reports confirm the excellent prognosis associated with pure IPC. Patients with
low-grade tumors had no recurrence or metastasis and in the absence of invasion may be treated by local excision (complete excision of the
cyst, which should include the intracystic
growth).11,23–25,37 Therefore, it is most prudent to
continue treating patients with these lesions as
they are currently treated (ie, similar to patients
with DCIS) and to avoid categorization of such
lesions as frankly invasive papillary carcinomas.
However, there is a high frequency of DCIS and
invasive carcinoma associated with these lesions,
and the prognosis of these cases is related to the
type, grade, and size of the associated lesions.
Patients with higher-grade tumors have an
increased risk of recurrence and metastasis. The
low frequency of axillary node metastases with
pure IPC does not justify axillary lymph node dissection. Sentinel node biopsy may be an excellent alternative.11,23–25,36
Intracystic papillary carcinoma of the male
breast is a very rare disease with an incidence
rate between 0.5% and 2.4%.38–41 However, in a
recent study, Burga et al42 showed that the frequency of invasive papillary carcinoma in the
Figure 16. Transverse sonogram of the right breast in a 60year-old woman showing a complex mass with a vascularized
solid portion (invasive IPC).
Figure 15. Transverse sonogram of the right breast in the same
patient as in Figure 14 showing an oval noncircumscribed intracystic lesion with markedly vascularized mural nodules (invasive
IPC).
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male breast was higher than in the female breast
(2-fold increase). The prognosis is excellent, as in
female patients, and power Doppler sonographic and dynamic magnetic resonance imaging
findings are very useful for a better diagnosis.38,41
In one report, excisional biopsy was necessary to
confirm the diagnosis and also indicated that
local treatment was adequate.40
11.
Ohlinger R, Frese H, Schwesinger G, Schimming A, Köhler
G. Papillary intracystic carcinoma of the female breast: role
of ultrasonography. Ultraschall Med 2005; 26:325–328.
12.
Berg WA, Campassi CI, Ioffe OB. Cystic lesions of the
breast: sonographic-pathologic correlation. Radiology
2003; 227:183–191.
13.
American College of Radiology. Breast Imaging Reporting
and Data System: Ultrasound. 4th ed. Reston, VA:
American College of Radiology; 2003.
14.
Sklair-Levy M, Muradali D, Kulkarni S. Linear transducer
harmonic imaging: improved characterization of breast
cysts compared to conventional sonography. AJR Am J
Roentgenol 2001; 176:6–7.
15.
Merritt C, Piccoli C, Forsberg F, Wilkes A, Cavanaugh B, Lee
S. Real-time spatial compound imaging of the breast: clinical evaluation of masses. Radiology 2000; 217:491–492.
16.
Mendelson EB, Berg WA, Merritt CR. Toward a standardized breast ultrasound lexicon, BI-RADS: ultrasound. Semin
Roentgenol 2001; 36:217–225.
17.
Houssami N, Irwing L, Ung O. Review of complex breast
cysts: implications for cancer detection and clinical practice. ANZ J Surg 2005; 75:1080–1085.
18.
Chun J, Joseph KA, El-Tamer M, Rundle A, Jacobson J,
Schnabel F. Cohort study of women at risk for breast cancer and gross cystic disease. Am J Surg 2005; 190:
583–587.
Venta LA, Kim JP, Pelloski CE, Morrow M. Management of
complex breast cysts. AJR Am J Roentgenol 1999; 173:
1331–1336.
19.
Mannello F, Tonti GA, Papa S. Human gross cyst breast disease and cystic fluid: bio-molecular, morphological, and
clinical studies. Breast Cancer Res Treat 2006; 97:115–129.
Berg WA. Sonographically depicted breast clustered microcysts: is follow-up appropriate? AJR Am J Roentgenol
2005; 185:952–959.
20.
Markopoulos C, Kouskos E, Gogas H, et al. Diagnosis and
treatment of intracystic breast carcinomas. Am Surg 2002;
68:783–786.
Ganesan S, Karthik G, Joshi M, Damodaran V. Ultrasound
spectrum in intraductal papillary neoplasms of breast. Br J
Radiol 2006; 79:843–849.
21.
Sartorius OW. The biochemistry of breast cyst fluids and
duct secretions. Breast Cancer Res Treat 1995; 35:255–
266.
Hill CB, Yeh IT. Myoepithelial cell staining patterns of papillary breast lesions: from intraductal papillomas to invasive
papillary carcinoma. Am J Clin Pathol 2005; 123:36–44.
22.
Bodian CA. Benign breast diseases, carcinoma in situ, and
breast cancer risk. Epidemiol Rev 1993; 15:177–187.
Lam WW, Tang AP, Tse G, Chu WC. Radiology-pathology
conference: papillary carcinoma of the breast. Clin Imaging
2005; 29:396–400.
23.
Leal C, Costa I, Fonseca D, Lopes P, Bento MJ, Lopes C.
Intracystic (encysted) papillary carcinoma of the breast: a
clinical, pathological, and immunohistochemical study.
Hum Pathol 1998; 29:1097–1104.
24.
Lefkowitz M, Lefkowitz W, Wargotz ES. Intraductal (intracystic) papillary carcinoma of the breast and its variants: a
clinicopathological study of 77 cases. Hum Pathol 1994;
25:802–809.
Conclusions
Correlation with clinical and radiologic findings
is essential in the diagnosis and management of
intracystic breast lesions. Sonography is the
modality of choice for diagnosing the presence
of an intracystic growth and for guiding fineneedle aspiration cytologic examinations or core
biopsies. Local complete excision is the recommended treatment for IPC.
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