Common and Unusual Diseases of the Nipple

Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for
distribution to your colleagues or clients, use the RadioGraphics Reprints form at the end of this article.
APPLICATIONS OF CURRENT TECHNOLOGY
S65
Common and Unusual
Diseases of the NippleAreolar Complex1
ONLINE-ONLY
CME
See www.rsna
.org/education
/rg_cme.html.
LEARNING
OBJECTIVES
After reading this
article and taking
the test, the reader
will be able to:
䡲 Describe the utility
of US and MR imaging as adjuncts to
mammography in the
evaluation of the
nipple-areolar complex.
䡲 Recognize normal
characteristics of the
nipple-areolar complex on breast images
obtained with various
modalities.
䡲 Identify indications
of common and rare
lesions on US and
MR breast images as
well as on mammograms.
Darlene Da Costa, MD ● Abraha Taddese, MD, PhD ● Marina Luz Cure,
MD ● Deborah Gerson, MD ● Robert Poppiti, Jr, MD ● Lisa E. Esserman,
MD
The nipple-areolar complex is often best evaluated as a separate region
of the breast. Because of the intricacy of the anatomic structures and
their superficial position, the diagnostic techniques required for optimal evaluation of the nipple-areolar complex differ from those routinely used to evaluate the whole breast. Although clinical examination
and screening mammography are still of central importance, the adjunct use of multiple imaging modalities (ultrasonography, contrast
material– enhanced magnetic resonance imaging, or both) as well as
nonstandard mammographic views is often necessary to differentiate
benign abnormalities from malignant ones. For accurate diagnosis,
familiarity with a wide range of appearances of the normal anatomy,
including congenital anomalies (eg, supernumerary nipples), is necessary, as is a thorough knowledge of the features of the benign and malignant processes that commonly occur in the nipple-areolar complex.
Benign abnormalities may include mammary duct ectasia, nipple calcifications, cutaneous horn of the nipple, abscess of the Montgomery
gland, and nipple adenoma. Malignant abnormalities may include
Paget disease and primary lymphoma as well as carcinoma of the
breast. Some conditions, such as nipple retraction and inversion, may
have either a benign or a malignant cause. In such cases, a thorough
radiologic assessment is especially important.
©
TEACHING
POINTS
See last page
RSNA, 2007
RadioGraphics 2007; 27:S65–S77 ● Published online 10.1148/rg.27si075512 ● Content Codes:
1From
the Department of Radiology, Mount Sinai Medical Center, 4300 Alton Rd, Miami Beach, FL 33140. Recipient of an Excellence in Design
award for an education exhibit at the 2006 RSNA Annual Meeting. Received March 9, 2007; revision requested May 1 and received July 6; accepted
July 18. L.E.E. is a consultant with Ethicon Endo-Surgery; all remaining authors have no financial relationships to disclose. Address correspondence to D.D.C. (e-mail: [email protected]).
©
RSNA, 2007
S66
October 2007
RG f Volume 27
●
Special Issue
Figure 1. Supernumerary nipples. (a) Photograph shows bilateral firm tan papules anterior to
the axilla. (b) Mediolateral oblique mammograms from the same patient show bilateral accessory
breast tissue in the axillary tail.
Introduction
Normal and Variant Anatomy
Many articles describe, in a cursory way, one or
another pathologic condition within the nippleareolar complex. Likewise, various reports of
missed and incorrect diagnoses, such as a missed
malignancy or a malignancy mistakenly believed
to represent dermatitis, can be found (1,2). However, to our knowledge, no focused review of conditions affecting this region of the breast exists in
the published literature. Therefore, we offer this
overview of the multimodality approach to diagnostic imaging in this region that is so difficult to
assess (3). Readers can better recognize the abnormal appearance of the nipple-areolar complex
if they have an understanding of the normal anatomy and its appearance at imaging. We therefore
begin with a review of the anatomy and of the
various imaging techniques used to evaluate the
nipple-areolar complex and then proceed with
descriptions of the benign and malignant features
that may be seen at imaging with various modalities.
The normal nipple is in a position slightly medial
and inferior to the center of the breast. The nipple
and areola are composed of pigmented squamous
epithelium. The nipple-areolar complex also contains a layer of circumferential smooth muscle
and sebaceous glands that open through small
prominences (Montgomery tubercles) that surround the periphery of the areola. Hair follicles
around the areola may contain calcification (4).
Milk secretion occurs through approximately
seven to 15 microscopic openings on the surface
of the nipple. Immediately deep to these mammary duct orifices, within each of the major
ducts, are areas of dilatation known as milk sinuses, which have a storage function during lactation. The major ducts have numerous branches,
each of which ends in a terminal duct lobular
unit, where milk is produced during lactation (5).
Common minor congenital malformations,
including a supernumerary nipple or nipples and
related tissue (Fig 1), may be found along the socalled milk line, which extends bilaterally from a
point in the axilla toward the chest, abdomen, and
groin. The most inferior location of such findings
has been in the proximal medial thigh (5).
RG f Volume 27
●
Special Issue
Da Costa et al
S67
Figure 2. Sagittal contrast-enhanced T1-weighted fat-suppressed MR images show various degrees of enhancement in a normal nipple, including none (a), mild enhancement (b), and intense enhancement (c).
Figure 3. Axial contrast-enhanced T1-weighted fatsuppressed MR image of the breasts shows symmetric
bilateral enhancement of the nipple-areolar complex,
with a superficial layer of intense linear dermal enhancement (arrows) and a central region of nonenhancement deep to the dermis.
Normal Imaging Appearances
The nipple, which is normally everted, should be
depicted in profile on at least one standard mammographic view. This orientation allows evaluation of both the nipple-areolar complex and vessels in the normal retroareolar region.
At magnetic resonance (MR) imaging after
the administration of gadolinium, the degree of
nipple enhancement varies; enhancement may be
absent, mild, or intense (Fig 2). Intense enhance-
ment is due to the presence of numerous vessels
(6). Normal nipples show a bilaterally symmetric
enhancement pattern (7). The characteristic twolayered appearance of the nipple-areolar complex
represents a superficial layer of intense linear dermal enhancement (1–2 mm thick) with an underlying region of nonenhancement deep to the dermis (Fig 3) (7). Normal nipples do not show
nodular or irregular enhancement along their posterior borders.
Ultrasonography (US) is useful for differentiating between tissue types and for identifying individual mammary ducts in most patients. The
ducts are linear hypoechoic or isoechoic structures that appear to radiate from the nipple like
the spokes of a wheel from the hub (8).
Mammographic Technique
Because of x-ray overpenetration, the nippleareolar complex is often poorly depicted and thus
overlooked at mammography (9). Moreover, lesions of various kinds may mimic a normal retroareolar density, leading to a false-positive finding; or, in the setting of dense breasts, a lesion
may be obscured and the mammogram therefore
interpreted as negative (10). Additional mammographic views with spot compression and magnification, as well as US images, may be needed to
S68
RG f Volume 27
October 2007
●
Special Issue
Figure 4. Additional work-up for a retroareolar density identified at mammography.
(a) Magnified view of a craniocaudal mammogram shows a well-defined mass in the retroareolar region (arrow). (b) US image of the same region shows an anechoic cyst with a
posterior region of high echogenicity.
Figure 5. Image artifact caused by improper scanning technique. US image
shows a nipple with a large posterior
shadow that simulates a mass (arrows).
better evaluate a retroareolar density or pattern of
microcalcification that arouses suspicion (Fig 4).
The visibility of such features may be further improved with hot-light viewing or with the use of
varied contrast settings during soft-copy interpretation at the digital mammography workstation.
US Technique
Measures for maximizing the quality of depiction
at US include the use of warm gel and the maintenance of a sufficiently warm room temperature
to avoid muscle contraction within the nipple and
areola. In addition, to minimize acoustic shadows, the transducer must be held at an appropriate angle. When scanning is performed with the
transducer held flat to the breast, against the surface of the nipple and areola, the nipple may produce an acoustic shadow with a masslike appearance (Fig 5). Proper scanning technique for US
evaluation of the intranipple and subareolar portions of the mammary duct—an evaluation that is
particularly important in a patient with a nipple
discharge—requires angulation of the transducer
so that the ultrasound beam is perpendicular to
the long axis of the duct during peripheral compression. When the transducer is held at an appropriate angle against the periphery of the
nipple, it is easier to maintain the steady contact
and pressure needed to achieve optimal depiction
of the duct (Figs 6, 7) (8). Other useful maneuvers include the two-handed compression technique and rolled-nipple technique: The twohanded compression technique is used to achieve
better visibility of the duct where it enters the
base of the nipple and to assess intraductal lesions
and ductal compressibility. The rolled-nipple
technique is used to depict the portion of the
mammary duct within the nipple. Both techniques have been well described by Stavros (8).
MR Imaging Technique
Two important technical requirements for evaluation of the nipple-areolar complex with MR imaging are the use of a dedicated breast coil and the
administration of a contrast agent (6). MR images
should be correlated with mammograms and with
US images when the latter are available.
RG f Volume 27
●
Special Issue
Da Costa et al
S69
Figures 6, 7. Importance of the transducer position for US of the intranipple portion of
the mammary ducts. (6) Drawing shows improper scanning technique, with the transducer
held flat against the periphery of the nipple-areolar complex. In this position, the ultrasound
beam roughly parallels the abnormal duct (shown in red), and the nipple casts a posterior
shadow that obscures the intraductal lesion, represented here as a pale spot within the duct.
(7) Drawing shows proper scanning technique, with the transducer held at an angle so that
the ultrasound beam is roughly perpendicular to the long axis of the duct. With the transducer in this position, it is easier to maintain proper contact and pressure, and the abnormal
duct can be viewed clearly without an acoustic shadow from the nipple.
Mammographic Features
Mammographic features that are associated with
abnormalities of the nipple-areolar complex include asymmetry, a subareolar mass, nipple inversion, microcalcification, and skin thickening.
US Features
Figure 8. Intraductal lesion in a 42-year-old
woman with recent onset of a spontaneous
bloody discharge from the nipple. US image
shows a solid lesion (arrow) within the dilated
duct.
Clinical and
Imaging Signs of Abnormality
Skin thickening and nipple retraction are visible
signs of advanced breast cancer that are observable at physical examination. However, more
subtle findings that are associated with pathologic
changes in the nipple-areolar complex may be
seen on mammograms and US and MR images
long before clinical symptoms and signs are manifested.
US depiction of the mammary ducts is particularly useful for the exclusion of intraductal papillary lesions in the subareolar area in patients with
a nipple discharge (Fig 8). It is also useful for the
detection of subtle and frequently missed secondary signs of breast carcinoma, such as one or
more dilated subareolar ductal segments extending 3 cm or more within the breast (3).
MR Imaging Features
On MR images of the breast, findings of bulkiness, bilateral asymmetry, or early, delayed, or
persistent enhancement of the nipple-areolar
complex with a retroareolar mass may be indicative of tumoral involvement of the nipple-areolar
complex (Fig 9). In a study of 35 patients, higher
sensitivity was demonstrated with MR imaging
than with mammography for the diagnosis and
assessment of nipple and retroareolar tumors (7).
S70
October 2007
RG f Volume 27
●
Special Issue
Figure 9. Pathologic nipple enhancement at contrast-enhanced MR imaging for routine screening in a 40-year-old
woman with a family history of breast cancer. (a) Sagittal T1-weighted fat-suppressed image shows subtle irregular
enhancement in the nipple-areolar complex (arrow), a finding that was interpreted as normal. (b) Sagittal T1weighted fat-suppressed image obtained 1 year later shows progressive irregular masslike enhancement of the nippleareolar complex (arrow). (c) Corresponding craniocaudal mammogram shows a retroareolar mass (arrow).
Figure 10. Nipple retraction in the
breast of a 68-year-old woman who
underwent a lumpectomy for infiltrating ductal cell carcinoma 10
years earlier. Photograph (a) and
magnified view from a mediolateral
oblique mammogram (b) show the
postsurgical scar (white arrow) and
retracted nipple (black arrow).
Teaching
Point
Preoperative recognition of nipple involvement
in retroareolar breast cancer may be critical when
nipple-preserving breast conservation therapy is
being considered (7). Breast MR imaging, in
most cases, can help differentiate between a tumor that is confined to retroareolar tissue and one
that involves the nipple-areolar complex (6). Furthermore, it has been suggested that the use of
breast MR images for guidance of nipple-preserving breast-conservation surgery may help reduce
the rate of local recurrence (10,11).
Benign Processes
Nipple Inversion
When nipple abnormalities such as inversion are
identified, it is important for the technologist to
document them in the medical record so that the
radiologist will be aware of the findings and the
relevant medical history (12). Nipple inversion
may be bilateral or unilateral and usually results
from a benign process that takes place gradually,
over a long period (eg, a few years). When nipple
inversion occurs more rapidly (eg, within a few
months), the cause is more likely to be a malignancy. Additional mammographic work-up is
needed in cases in which the history of nipple inversion is not known or in which nipple inversion
developed over a short period of time. The additional work-up should include spot compression
views with the nipple in profile (to determine
whether there is a retroareolar mass) as well as
craniocaudal and lateral spot magnification views
to assess microcalcifications. If the mammographic views are unrevealing, US should be performed. Reported histopathologic findings in
cases of acute nipple inversion with a benign
RG f Volume 27
●
Special Issue
Da Costa et al
S71
Figure 11. Subareaolar abscess
in a 30-year-old woman with pain
and erythema of the areola. Photograph (a) and US image (b) show a
well-circumscribed oval intradermal
mass (arrow). The mass appears
anechoic in b, a finding suggestive of
benignity.
Figure 12. Ductal
ectasia in four different patients. (a) Spotcompression magnification of a mediolateral oblique mammogram shows a
focal linear density
behind the nipple
(arrows). (b) Sagittal
unenhanced T2weighted fat-suppressed MR image
shows high-signalintensity branching
tubular structures
(arrow) that represent fluid-filled ducts.
(c) US image shows
branching fluid-filled
structures behind the
nipple, features representative of dilated
mammary ducts (arrow). (d) US image
shows histopathologically proved inspissated secretions simulating a papilloma in
a dilated duct (arrow).
cause include mammary duct ectasia, postsurgical
changes (Fig 10), fat necrosis, fibrocystic
changes, and Mondor disease (13).
usually helps differentiate an abscess from a neoplasm (Fig 11) (15).
Mammary Duct Ectasia
Inflammation
A subareolar abscess results from the blockage of
a small gland or duct beneath the areola, with the
development of an infection under the skin. Such
abscesses are uncommon and occur mostly in
nonlactating young and middle-aged women
(14). There are no known risk factors.
US features include low-amplitude intracystic
echoes, which may be difficult to differentiate
from those observed in a neoplasm. In this situation, a clinical history that includes fever, or the
observation of a lesion response to antibiotics,
The clinical manifestations of ductal ectasia may
include a nipple discharge, nipple retraction, a
palpable mass, and pain or tenderness. At imaging, ductal ectasia may be more confidently diagnosed if similar features are demonstrated bilaterally. If subareolar ductal dilatation is observed on
mammograms, spot compression and magnification views should be obtained to exclude an underlying mass (Fig 12a) (16). Calcified, inspissated secretions within the dilated subareolar
ducts are a typical mammographic feature. The
S72
October 2007
RG f Volume 27
●
Special Issue
Figure 13. Benign and malignant
nipple calcifications. (a) Magnified
mediolateral oblique view shows
multiple round calcifications with
central lucency suggestive of benign
skin calcifications (arrows) in the
subareolar region. (b) Magnified
mediolateral oblique view obtained
in a patient who underwent previous
reduction mammoplasty shows
coarse calcifications located circumferentially around the nipple (arrow), a configuration that signifies
benign calcifications at a suture site.
(c) Craniocaudal view obtained in
a patient with a history of trauma
to the breast shows a coarse subareolar calcification (arrow), a finding
indicative of fat necrosis. (d) Magnified craniocaudal view shows clustered pleomorphic subareolar calcifications (arrows) that were subsequently excised. The diagnosis in
this case was intraductal carcinoma
without associated Paget disease.
Figure 14. Cutaneous horn and
retracted nipple in the breast of a
78-year-old woman. (a) Photograph
obtained during the physical examination shows a crusted excrescence
emanating from a retracted nipple
(arrow). (b) Craniocaudal mammogram shows dense keratin (arrow),
which resembles calcification.
Teaching
Point
calcifications filling the ducts are coarse, smoothbordered, and shaped like a rod or cigar pointing
toward the nipple (17). On T1- and T2-weighted
MR images, the dilated ducts may be seen as
branching tubular structures that converge toward the nipple, with high signal intensity due to
intraductal proteinaceous material, blood, or both
(Fig 12b) (18). At US, the subareolar ducts appear dilated and fluid filled (Fig 12c). Inspissated
secretions often are visible and may be sufficiently
echogenic to mimic an intraductal tumor (Fig
12d). The observation of movement of the particulate matter in these secretions at real-time US
is another diagnostic feature of ductal ectasia.
RG f Volume 27
●
Special Issue
Da Costa et al S73
Figure 15. Nipple adenoma in a
47-year-old woman. (a) Photograph
shows a small papule (arrow) on the
nipple. (b) US image depicts a dilated subareolar mammary duct and
an intraductal lesion that extends to
the nipple (arrow). Adenoma was
diagnosed at biopsy.
Figure 16. Paget disease of the
breast in a 68-year-old woman.
(a) Photograph shows a pink scaly
eczematous plaque of the nipple (arrow). (b) Magnified craniocaudal
mammographic view shows extensive subareolar pleomorphic calcifications (arrows) with a segmental
distribution.
Calcifications
Nipple calcifications are uncommon. However,
the glands and hair follicles of the nipple-areolar
complex may contain calcifications (4). These
so-called skin calcifications may be extensive and
form a pattern that is spherical with a central area
of lucency (Fig 13a) (4). Other types of calcifications may occur in association with sutures (Fig
13b), fat necrosis (Fig 13c), intraductal papilloma, Paget disease (extension of intraductal carcinoma to the surface of the nipple), and intraductal carcinoma without associated Paget disease (Fig 13d).
Cutaneous Horn
A cutaneous horn is a conical projection of keratin above the surface of the skin, in a configuration that resembles a miniature horn (Fig 14).
The condition is usually asymptomatic; however,
the lesion may grow rapidly and is vulnerable to
trauma (19). Malignant lesions, usually squamous cell carcinomas, may be found at the base
of the horn (20). Other tumors, more rarely
found in that location, include Paget disease of
the breast, sebaceous adenoma, and granular cell
tumor (21).
Nipple Adenoma
Nipple adenoma, also known as florid papillomatosis, erosive adenomatosis, and superficial papil-
lary adenomatosis (22), is an uncommon variant
of intraductal papilloma that involves the nipple
(Fig 15). The clinical manifestations may resemble those of Paget disease of the breast: Patients often present with a bloody discharge,
crusting, nodularity, tenderness, swelling, and
erythema of the nipple. The accepted treatment is
complete local excision (23).
Malignant Processes
Paget Disease
The clinical manifestations usually are suggestive
of the diagnosis and may include a bloody disTeaching
charge from the nipple, itching, erythema, scaly
Point
or flaky skin, nipple erosion or ulceration, nipple
retraction, and a palpable mass. Thickening of
the breast also may occur with or without changes
in the nipple (24).
Mammograms may show malignant calcifications at the level of the nipple or elsewhere in the
breast, skin thickening, nipple retraction, and a
discrete mass or masses (Fig 16). However, the
mammographic appearance is normal in as many
as 50% of patients with Paget disease of the breast
(25,26).
MR imaging may play an important role in
the selection of patients with Paget disease for
breast-conserving therapy, if there is no clinical or
Teaching
mammographic evidence of breast carcinoma.
Point
Abnormal nipple enhancement and linear
clumped enhancement indicative of ductal carcinoma in situ in association with Paget disease
may be seen on MR images (27).
S74
October 2007
RG f Volume 27
●
Special Issue
Figure 17. Subareolar mass mimics a normal nipple. (a) Craniocaudal view obtained at screening mammography in a 70-year-old woman
shows a small subareolar mass (arrow) that has the density of a normal
nipple. The nipple was present
but was obscured by the lesion.
(b) Craniocaudal view obtained at
screening mammography 2 years
later shows enlargement of the mass
(arrow). A biopsy was performed,
and the mass was diagnosed as infiltrating ductal carcinoma.
Figure 19. Nipple necrosis due to infiltrating ductal carcinoma in an 85year-old woman. (a) Photograph obtained at physical examination shows destruction and replacement of the nipple by a 3-cm ulcerated plaque with a
serosanguineous crust (arrow). (b) Mediolateral oblique mammographic
view shows a large, irregular, dense mass with ill-defined borders in the upper
part of the breast (white arrow) and with direct extension to the nipple, causing nipple necrosis. Enlarged lymph nodes are visible in the axillary tail (black
arrow).
RG f Volume 27
●
Special Issue
Da Costa et al
S75
Figure 18. Nipple retraction due to a
malignancy in the right breast of a 68-yearold woman. (a) Mediolateral oblique
mammogram shows a retracted nipple (arrow). (b) US image shows an irregular hypoechoic mass in the subareolar region
(arrows). The diagnosis, based on histopathologic analysis, was infiltrating ductal carcinoma.
Figure 20. Nipple displacement
and retraction due to poorly differentiated infiltrating ductal carcinoma with necrosis in a 75-year-old
woman. (a) Photograph obtained at
physical examination shows a 5-cm
subcutaneous lobulated mass (black
arrow) and an inverted nipple (white
arrow). (b) Mediolateral oblique
mammographic view shows a large
dense mass (arrow) that fills the
breast.
Carcinoma
Teaching
Point
Subareolar carcinomas, which are easily confused
with normal nipple structures, may be more difficult to diagnose than cancers elsewhere in the
breast (Fig 17). Even a small tumor in this location may manifest as a palpable mass (10). Nipple
markers may be necessary during the imaging
evaluation to help distinguish the nipple from the
mass.
At mammography, spot compression with or
without magnification may be used to improve
the visibility of an underlying lesion. On US images, a subareolar mass or intraductal lesion may
be identified. Contrast material– enhanced MR
imaging may be useful if the mammographic and
US findings are suggestive of abnormality but are
inconclusive.
A minority of breast cancers arise in central
mammary ducts near the nipple, in the same location in which intraductal papillomas are found.
Some cancers arise from preexisting papillary
ductal hyperplasia or large intraductal papillomas.
Carcinomas that arise centrally may be intraductal, invasive, or mixed (both invasive and intraductal) (28).
Nipple retraction, a secondary sign of malignancy, generally is associated with cancers that
are large enough to be visible on mammograms
and palpable at physical examination (4,13). The
underlying cancer may be subareolar or may have
arisen at another location in the breast (Fig 18).
Nipple ulceration also may occur with the extension of advanced-stage breast cancer to the skin
surface (Fig 19) (29). If nipple retraction is
caused by cicatrization and the pull is eccentric,
the nipple may deviate in the direction of the cancer; in some cases, it may be fully inverted (Fig
20) (29).
S76
RG f Volume 27
October 2007
●
Special Issue
Figure 21. Primary malignant
lymphoma in the breast of a 75year-old woman. (a) Craniocaudal
mammographic view shows a large
dense retroareolar mass. (b, c) US
images show a homogeneous hypoechoic mass in the retroareolar region (b) and a large lymph node
in the axilla (c). (d) Photograph
obtained at clinical examination
shows a 3-cm shiny reddish tumor
that has encompassed the areola.
Lymphoma
The relative frequency of primary versus secondary breast lymphoma is variably reported; therefore, the preponderance of one type versus the
other is unclear (30). There is no association between specific subtype of lymphoma and mammographic findings (31). If a primary breast lymphoma is subareolar, the nipple may appear enlarged or bulging at physical examination, instead
of retracted as in infiltrating carcinoma (Fig 21).
Since mammographic and US findings are nonspecific and may include single or multiple wellto ill-defined (rarely spiculated) masses of varied
size, the clinical appearance of the nipple may
provide a clue to the diagnosis (32,33).
Conclusions
Clinical examination is particularly important,
and a tailored imaging evaluation with multiple
modalities often is necessary to accurately diagnose an underlying abnormality of the nippleareolar complex. This region of the breast may
not be clearly depicted on conventional mammograms. Supplemental mammographic views often
are needed, and US may be performed to further
characterize a mammographic or clinical finding.
Contrast-enhanced MR imaging may be useful
for additional evaluation in cases in which there is
a substantial suspicion of undiagnosed malignancy or of the extension of a known malignancy
to the nipple-areolar complex.
References
1. Feig SA, Shaber GS, Patchefsky A. Analysis of
clinically occult and mammographically occult
breast tumors. AJR Am J Roentgenol 1977;128:
403– 408.
RG f Volume 27
●
Special Issue
2. Mitnick JS, Vazquez MF, Plesser KP, Roses DF.
Breast cancer malpractice litigation in New York
State. Radiology 1993;189:673– 676.
3. Martin JE, Moskowitz M, Milbrath JR. Breast
cancer missed by mammography. AJR Am J
Roentgenol 1979;132:737–739.
4. Kopans DB. Anatomy, histology, physiology, and
pathology. In: Breast imaging. 2nd ed. Philadelphia, Pa: Lippincott-Raven, 1998; 14 –15.
5. Cardenosa G. Nipple-areolar complex. In: Breast
imaging companion. Philadelphia, Pa: LippincottRaven, 1997; 172.
6. Morris EA. The normal breast. In: Morris EA,
Liberman L, eds. Breast MRI diagnosis and intervention. New York, NY: Springer, 2005; 39.
7. Friedman EP, Hall-Craggs MA, Mumtaz H,
Schneidau A. Breast MR and the appearance of
the normal and abnormal nipple. Clin Radiol
1997;52:854 – 861.
8. Stavros AT. Breast anatomy: the basis for understanding sonography. In: Breast ultrasound. Philadelphia, Pa: Lippincott Williams & Wilkins, 2004;
85– 89.
9. Stefanoyiannis AP, Costaridou L, Sakellaropoulos
P, Panayiotakis G. A digital density equalization
technique to improve visualization of breast periphery in mammography. Br J Radiol 2000;
73(868):410 – 420.
10. Giess CS, Keating DM, Osborne MP, Ng YY,
Rosenblatt R. Retroareolar breast carcinoma:
clinical, imaging, and histopathologic features.
Radiology 1998;207:669 – 673.
11. Douek M, Hall-Craggs MA. Can the use of preoperative MR imaging reduce local recurrence rates
in patients with retroareolar breast cancer who
undergo breast-conservation surgery? Radiology
1999;210:880 – 881.
12. Kalbhen CL, Kezdi-Rogus PC, Dowling MP,
Flisak ME. Mammography in the evaluation of
nipple inversion. AJR Am J Roentgenol 1998;170:
117–121.
13. Berg WA, Birdwell RL, Gombos EC. Nipple retraction. In: Berg WA, Birdwell RL, eds. Diagnostic imaging: breast. Section IV:3– 6. Salt Lake
City, Utah: Amirsys, 2006.
14. Yanai A, Hirabayashi S, Ueda K, Okabe K. Treatment of recurrent subareolar abscess. Ann Plast
Surg 1987;18(4):314 –318.
15. Kopans DB. Ultrasound and breast evaluation. In:
Breast imaging. 2nd ed. Philadelphia, Pa: Lippincott-Raven, 1998; 431.
16. Huynh PT, Parellada JA, de Paredes ES, et al. Dilated duct pattern at mammography. Radiology
1997;204:137–141.
17. Cardenosa G. Major subareolar ducts. In: Breast
imaging companion. Philadelphia, Pa: LippincottRaven, 1997; 184.
18. Berg WA, Birdwell RL, Gombos EC. Lesion imaging characteristics. In: Berg WA, Birdwell RL,
Da Costa et al
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
S77
eds. Diagnostic imaging: breast. Section IV:1– 45.
Salt Lake City, Utah: Amirsys, 2006.
Thornton CM, Hunt SJ. Sebaceous adenoma with
a cutaneous horn. J Cutan Pathol 1995;22(2):
185–187.
Dabski K, Stoll HL Jr. Paget’s disease of the
breast presenting as a cutaneous horn. J Surg Oncol 1985;29(4):237–239.
Yu RC, Pryce DW, Macfarlane AW, Stewart TW.
A histopathological study of 643 cutaneous horns.
Br J Dermatol 1991;124(5):449 – 452.
Kijima Y, Matsukita S, Yoshinaka H, Owaki T,
Aikou T. Adenoma of the nipple: report of a case.
Breast Cancer 2006;13(1):95–99.
Healy CE, Dijkstra B, Walsh M, Hill AD, Murphy
J. Nipple adenoma: a differential diagnosis for
Paget’s disease. Breast J 2003;9(4):325–326.
Ashikari R, Park K, Huvos AG, Urban JA. Paget’s
disease of the breast. Cancer 1970;26:680 – 685.
Ikeda DM, Helvie MA, Frank TS, Chapel KL,
Andersson IT. Paget disease of the nipple: radiologic-pathologic correlation. Radiology 1993;189:
89 –94.
Burke ET, Braeuning MP, McLelland R, Pisano
ED, Cooper LL. Paget disease of the breast: a pictorial essay. RadioGraphics 1998;18:1459 –1464.
Amano G, Yajima M, Moroboshi Y, Kuriya Y,
Ohuchi N. MRI accurately depicts underlying
DCIS in a patient with Paget’s disease of the
breast without palpable mass and mammography
findings. Jpn J Clin Oncol 2005;35(3):149 –153.
Stavros AT. Nontargeted indications: breast secretion, nipple discharge, intraductal papillary lesions: the basis for understanding sonography. In:
Breast ultrasound. Philadelphia, Pa: Lippincott
Williams & Wilkins, 2004; 160.
Kopans DB. The mammographic appearance of
breast cancer. In: Breast imaging. 2nd ed. Philadelphia, Pa: Lippincott-Raven, 1998; 406.
Topalovski M, Crisan D, Mattson JC. Lymphoma
of the breast: a clinicopathologic study of primary
and secondary cases. Arch Pathol Lab Med 1999;
123:1208 –1218.
Liberman L, Giess CS, Dershaw DD, Louie DC,
Deutch BM. Non-Hodgkin lymphoma of the
breast: imaging characteristics and correlation
with histopathologic findings. Radiology 1994;
192:157–160.
Domchek SM, Hecht JL, Fleming MD, Pinkus
GS, Canellos GP. Lymphomas of the breast: primary and secondary involvement. Cancer 2002;
94(1):6 –13.
Firat D, Barista I, Baltali E. Primary breast lymphomas: a retrospective analysis of twelve cases.
Acta Oncol 2000;39(2):135–139.
This article meets the criteria for 1.0 AMA PRA Category 1 Credit . To obtain credit, see www.rsna.org/education/
rg_cme.html.
TM
RG
Volume 27 • Special Issue • October 2007
Da Costa et al
Common and Unusual Diseases of the Nipple-Areolar Complex
Darlene Da Costa, MD, et al
RadioGraphics 2007; 27:S65–S77 ● Published online 10.1148/rg.27si075512 ● Content Codes:
Page S70
Breast MR imaging, in most cases, can help differentiate between a tumor that is confined to
retroareolar tissue and one that involves the nipple-areolar complex.
Page S72
On T1- and T2-weighted MR images, the dilated ducts [in mammary duct ectasia] may be seen as
branching tubular structures that converge toward the nipple, with high signal intensity due to
intraductal proteinaceous material, blood, or both.
Page S73
The clinical manifestations [of Paget disease of the breast] usually are suggestive of the diagnosis and
may include a bloody discharge from the nipple, itching, erythema, scaly or flaky skin, nipple erosion
or ulceration, nipple retraction, and a palpable mass. Thickening of the breast also may occur with or
without changes in the nipple.
Page S73
MR imaging may play an important role in the selection of patients with Paget disease for breastconserving therapy, if there is no clinical or mammographic evidence of breast carcinoma. Abnormal
nipple enhancement and linear clumped enhancement indicative of ductal carcinoma in situ in
association with Paget disease may be seen on MR images.
Page S75
Subareolar carcinomas, which are easily confused with normal nipple structures, may be more
difficult to diagnose than cancers elsewhere in the breast. [...] Contrast material–enhanced MR
imaging may be useful if the mammographic and US findings are suggestive of abnormality but are
inconclusive.
RadioGraphics 2007
This is your reprint order form or pro forma invoice
(Please keep a copy of this document for your records.)
Reprint order forms and purchase orders or prepayments must be received 72 hours after receipt of form either
by mail or by fax at 410-820-9765. It is the policy of Cadmus Reprints to issue one invoice per order.
Please print clearly.
Author Name _______________________________________________________________________________________________
Title of Article _______________________________________________________________________________________________
Issue of Journal_______________________________
Reprint # _____________
Publication Date ________________
Number of Pages_______________________________
KB # _____________
Symbol RadioGraphics
Color in Article? Yes / No
(Please Circle)
Please include the journal name and reprint number or manuscript number on your purchase order or other correspondence.
Order and Shipping Information
Reprint Costs (Please see page 2 of 2 for reprint costs/fees.)
________ Number of reprints ordered
Shipping Address (cannot ship to a P.O. Box) Please Print Clearly
$_________
________ Number of color reprints ordered $_________
________ Number of covers ordered
$_________
Subtotal $_________
Taxes
$_________
(Add appropriate sales tax for Virginia, Maryland, Pennsylvania, and the
District of Columbia or Canadian GST to the reprints if your order is to
be shipped to these locations.)
First address included, add $32 for
each additional shipping address
TOTAL
$_________
$_________
Name ___________________________________________
Institution _________________________________________
Street ___________________________________________
City ____________________ State _____ Zip ___________
Country ___________________________________________
Quantity___________________ Fax ___________________
Phone: Day _________________ Evening _______________
E-mail Address _____________________________________
Additional Shipping Address* (cannot ship to a P.O. Box)
Name ___________________________________________
Institution _________________________________________
Street ___________________________________________
City
________________ State ______ Zip ___________
Country _________________________________________
Quantity __________________ Fax __________________
Phone: Day ________________ Evening ______________
E-mail Address ____________________________________
* Add $32 for each additional shipping address
Payment and Credit Card Details
Invoice or Credit Card Information
Enclosed: Personal Check ___________
Credit Card Payment Details _________
Invoice Address
Please Print Clearly
Please complete Invoice address as it appears on credit card statement
Checks must be paid in U.S. dollars and drawn on a U.S. Bank.
Credit Card: __ VISA __ Am. Exp. __ MasterCard
Card Number __________________________________
Expiration Date_________________________________
Signature: _____________________________________
Please send your order form and prepayment made payable to:
Cadmus Reprints
P.O. Box 751903
Charlotte, NC 28275-1903
Name ____________________________________________
Institution ________________________________________
Department _______________________________________
Street ____________________________________________
City ________________________ State _____ Zip _______
Country ___________________________________________
Phone _____________________ Fax _________________
E-mail Address _____________________________________
Cadmus will process credit cards and Cadmus Journal
Services will appear on the credit card statement.
Note: Do not send express packages to this location, PO Box.
FEIN #:541274108
If you don’t mail your order form, you may fax it to 410-820-9765 with
your credit card information.
Signature __________________________________________
Date
_______________________________________
Signature is required. By signing this form, the author agrees to accept the responsibility for the payment of reprints and/or all charges
described in this document.
RB-9/22/06
Page 1 of 2
RadioGraphics 2007
Color Reprint Prices
Black and White Reprint Prices
Domestic (USA only)
# of
Pages
1-4
5-8
9-12
13-16
17-20
21-24
25-28
29-32
Covers
50
$213
$338
$450
$555
$673
$785
$895
$1,008
$95
100
200
300
$228
$260
$278
$373
$420
$453
$500
$575
$635
$623
$728
$805
$753
$883
$990
$880 $1,040 $1,165
$1,010 $1,208 $1,350
$1,143 $1,363 $1,525
$118
$218
$320
Domestic (USA only)
400
500
$295
$495
$693
$888
$1,085
$1,285
$1,498
$1,698
$428
$313
$530
$755
$965
$1,185
$1,413
$1,638
$1,865
$530
# of
Pages
1-4
5-8
9-12
13-16
17-20
21-24
25-28
29-32
Covers
International (includes Canada and Mexico)
# of
Pages
1-4
5-8
9-12
13-16
17-20
21-24
25-28
29-32
Covers
50
100
200
300
400
500
$218
$343
$471
$601
$738
$872
$1,004
$1,140
$95
$233
$388
$503
$633
$767
$899
$1,035
$1,173
$118
$343
$584
$828
$1,073
$1,319
$1,564
$1,820
$2,063
$218
$460
$825
$1,196
$1,562
$1,940
$2,308
$2,678
$3,048
$320
$579
$1,069
$1,563
$2,058
$2,550
$3,045
$3,545
$4,040
$428
$697
$1,311
$1,935
$2,547
$3,164
$3,790
$4,403
$5,028
$530
International (includes Canada and Mexico))
50
100
200
300
400
500
$263
$415
$563
$698
$848
$985
$1,135
$1,273
$148
$275
$443
$608
$760
$925
$1,080
$1,248
$1,403
$168
$330
$555
$773
$988
$1,203
$1,420
$1,640
$1,863
$308
$385
$650
$930
$1,185
$1,463
$1,725
$1,990
$2,265
$463
$430
$753
$1,070
$1,388
$1,705
$2,025
$2,350
$2,673
$615
$485
$850
$1,228
$1,585
$1,950
$2,325
$2,698
$3,075
$768
Minimum order is 50 copies. For orders larger than 500 copies,
please consult Cadmus Reprints at 800-407-9190.
Reprint Cover
Cover prices are listed above. The cover will include the
publication title, article title, and author name in black.
# of
Pages
1-4
5-8
9-12
13-16
17-20
21-24
25-28
29-32
Covers
50
100
200
300
400
500
$268
$419
$583
$742
$913
$1,072
$1,246
$1,405
$148
$280
$457
$610
$770
$941
$1,100
$1,274
$1,433
$168
$412
$720
$1,025
$1,333
$1,641
$1,946
$2,254
$2,561
$308
$568
$1,022
$1,492
$1,943
$2,412
$2,867
$3,318
$3,788
$463
$715
$1,328
$1,941
$2,556
$3,169
$3,785
$4,398
$5,014
$615
$871
$1,633
$2,407
$3,167
$3,929
$4,703
$5,463
$6,237
$768
Tax Due
Residents of Virginia, Maryland, Pennsylvania, and the District
of Columbia are required to add the appropriate sales tax to each
reprint order. For orders shipped to Canada, please add 7%
Canadian GST unless exemption is claimed.
Ordering
Shipping
Shipping costs are included in the reprint prices. Domestic
orders are shipped via UPS Ground service. Foreign orders are
shipped via a proof of delivery air service.
Multiple Shipments
Reprint order forms and purchase order or prepayment is
required to process your order. Please reference journal name
and reprint number or manuscript number on any
correspondence. You may use the reverse side of this form as a
proforma invoice. Please return your order form and
prepayment to:
Cadmus Reprints
P.O. Box 751903
Charlotte, NC 28275-1903
Orders can be shipped to more than one location. Please be
aware that it will cost $32 for each additional location.
Delivery
Your order will be shipped within 2 weeks of the journal print
date. Allow extra time for delivery.
Note: Do not send express packages to this location, PO Box.
FEIN #:541274108
Please direct all inquiries to:
Rose A. Baynard
800-407-9190 (toll free number)
410-819-3966 (direct number)
410-820-9765 (FAX number)
[email protected] (e-mail)
Page 2 of 2
Reprint Order Forms
and purchase order
or prepayments must
be received 72 hours
after receipt of form.