39.3.Sheth.pptx

Interactive Case-based Review of
Subtle Signs of Breast Cancer at
Mammography
Monica M. Sheth, MD
Suzanne E. McElligott, MD
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Authors’ Affiliation:
Department of Radiology
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Hempstead, NY
Address correspondence to:
Monica Sheth, MD (email: monica.sheth@nyulangone.org)
Current address:
Department of Radiology, NYU Langone Health
60 First Avenue, 3rd Floor, New York, NY 11016.
The authors, editor, and reviewers have disclosed no relevant relationships.
RSNA educational exhibit: BR113-ED-X
Dr. Sheth is a recipient of a 2017 RSNA Education Scholar Grant.
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The purpose of screening mammography is to detect breast cancer prior to the
development of clinical symptoms, hopefully at an earlier and more easily treatable
stage. Although mammography remains the standard of care for the detection of breast
cancer, it is not perfect, as approximately 10%–30% of breast cancers can be missed.1
Multiple factors can contribute to missed breast cancer at mammography, including:
• Dense parenchyma obscuring the finding
• Suboptimal positioning or techniques that make detection of the finding more
challenging
• Perception or interpretation errors, which cause the finding to be overlooked or
dismissed as nonworrisome
Introduction

Through a series of cases in which we compare previously obtained (prior) with
most recent (current) mammograms, we illustrate how radiologists can enhance
their diagnostic accuracy and clinical acumen by adhering to these three broad
concepts:
1. Pay meticulous attention to mammographic technique and positioning.
2. Develop a standard search pattern.
3. Compare the current examination to multiple prior studies, when available.
Introduction

Learning Objectives
At the end of this presentation, the reader should be able to:
1. Identify the five signs of an adequately positioned mammogram.
2. Differentiate benign from suspicious changes at the anterior and posterior fat-
glandular interface.
3. Recognize the four types of asymmetries and understand the risk of
malignancy for each type.
Are you ready to spot the change?

The following cases will review the importance of patient positioning and
technique, as a cancer cannot be detected if it is not included or visible at
mammography.
Concept 1: Pay meticulous attention to mammographic technique
and positioning.

Signs of Appropriate Positioning
Do you see a convex-appearing pectoralis major muscle
at the level of the posterior nipple line (PNL) on the
mediolateral-oblique (MLO) mammograms?
Is there less than or equal to 1 cm difference in the
measurement between the nipple and the pectoralis
major muscle (ie, the PNL) on craniocaudal (CC) and
MLO views?
Is the nipple in profile in at least one view?
Is the tissue well compressed, with the nipple in an “up
and out” orientation (eg, perpendicular to the chest
wall)?
Is the inframammary fold open on the MLO view?
Is the breast pulled straight forward on the CC view? Is
the view not medially or laterally exaggerated?2,3,4
CC (a) and MLO (b) mammograms show color-coded signs of
appropriate patient positioning.
a b

Prior
Current Current Prior
CASE: A 61-year-old woman presented for screening mammography.
Prior
Current Current Prior
Prior
Can you spot the change?
CC CC MLO MLO

Mammograms (a–c) show a subtle posteriorly
located asymmetry, which was overlooked on the
CC mammogram (a). Repeat CC synthesized
mammogram (b) obtained the following year shows
more posterior tissue, exposing a dense spiculated
mass located centrally. The results of a US-guided
biopsy of a corresponding irregular hypoechoic
mass in the right breast (6-o’clock position)
confirmed invasive tubulolobular carcinoma.
This case demonstrates the importance of
including posterior tissue and an open
inframammary fold at imaging and also
evaluating the edge of film. On review of the
original images, there was a greater than 1 cm
difference in the PNL measurement on the CC
and MLO views, and neither MLO projection
had an appropriately opened inframammary
fold.2,3,4
Current
Synthesized CC
Current MLO
Prior CC
Teaching Point: Proper positioning is key to ensure
the most tissue is included on the mammogram. If
the positioning is technically inadequate, cancer
can be easily missed or not depicted at imaging.
a b c
Importance of Positioning: Missed Malignancy

The nipple must be
depicted in profile on
at least one view to
enable proper
visualization of the
nipple-areolar
complex and to avoid
mistaking the nipple
for a mass.5,6
Repeat CC
mammogram (a) with
the nipple in profile
and good compression
over the anterior
breast shows anterior
skin thickening and a
small spiculated
retroareolar mass
(circle), which were
obscured on the initial
CC and MLO views (b,
c) when the nipple was
not in profile.
Initial CC
Repeat CC
Importance of Positioning: Nipple in Profile
Axial MR subtraction
image (d) obtained
after the
administration of
contrast material
(postcontrast) shows
an enhancing
spiculated mass
extending into the
nipple, which is
retracted. The results
of a biopsy confirmed
invasive ductal
carcinoma (IDC).
MLO
b c
a
d

Importance of Positioning: Up-and-Out Imaging Technique
Movies of image stacks of digital breast
tomosynthesis (DBT) MLO and CC
mammograms obtained in a 62-year-old
woman who underwent bilateral lumpectomy
and radiation therapy for breast cancer 3 years
prior demonstrate the up-and-out imaging
technique. A triangular dermal marker placed
over the palpable area showed normal
underlying tissue at workup. Mammograms
were obtained using a good up-and-out
technique, with an open inframammary fold,
convex pectoralis muscle, and good
visualization of the posterior breast tissue.
Performing the proper technique allowed for
this small recurrent invasive mucinous
carcinoma (circle) located in the posterior
lower and inner triangles to be depicted.2,6
MLO CC
Click image to play video clip Click image to play video clip

CC mammograms from a 58-year-old woman
demonstrate the importance of centering the
breast at mammography.
On the CC mammogram obtained 1 year
previously (a), the breast is medially rotated
(note the position of the nipple), which limits
assessment of the posterolateral breast tissue.
On the most recently obtained mammogram (b),
obtained with the nipple in a central position, an
asymmetry (circle) is depicted in the far
posterior and lateral left breast. The results of a
biopsy confirmed invasive mammary duct
carcinoma.
Importance of Positioning:
Centered Breast
One year prior Current
Dermal
marker
a b
Click or Tap on Slide to
Advance

Current Current
Prior Prior
MLO MLO
CC CC

Magnified CC
Initial Follow-up Second follow-up
New Grouped Calcifications
New grouped calcifications must be viewed with suspicion. Mammograms (a, b) show a small group of calcifications evaluated with
spot-magnification views. At follow-up (b), they were thought to be more coarse, suggesting a benign cause. In retrospect, a few new
faint calcifications are also depicted in the surrounding tissue (arrowheads in b) but are obscured by motion artifact. Final
magnification views (c, d) show coarse heterogeneous calcifications in a linear and segmental distribution (arrows in d), findings
concordant with ductal carcinoma in situ (DCIS).
Motion artifact can occur when there is patient motion owing to suboptimal compression of the breasts. It is more common on spot
magnification views owing to the longer exposure time. It is critical to recognize motion (either by blurring of the parenchyma or lack
of sharpness of calcifications, biopsy clips, or skin) and to repeat technically inadequate mammographic views for proper diagnostic
evaluation. Motion-related blurring can create the appearance of a pseudomass, make a true mass difficult to appreciate as distinct
from surrounding fibroglandular tissue, and blur or obscure calcifications, as depicted in this case.2
a b c d

The following cases illustrate the importance of developing and adhering to a
search pattern to avoid satisfaction-of-search misses. Such a search pattern
should include the following areas where cancers can be hard to visualize and
are often overlooked:
● Anterior and posterior fat-glandular interface
● Retroglandular fat
● Lower and inner triangles
● Axilla and low axillary tail
● Edge of images
● Skin
● Nipple-areolar complex
Concept 2: Develop a standard search pattern.

Current Prior Prior
Current
CASE: A 50-year-old woman with no significant history presented for screening mammography.
CC CC MLO MLO

CC and MLO mammograms show a new mass (circles) in
the retroareolar region of the left breast, with associated
nipple retraction and overlying skin thickening. It is
important to ensure the imaging finding is real and not
secondary to poor positioning or technique. In this case,
the nipple is in profile, there is adequate compression of
the retroareolar tissue, and the breast is positioned in an
up-and-out configuration on the MLO image.
US evaluation of the axilla was also performed (not shown)
and demonstrated a lymph node with mild eccentric
thickening. The results of a biopsy confirmed retroareolar
IDC with lymph node metastasis.
The retroareolar region contains a Sappey plexus, a rich
lymphatic plexus with drainage to the axilla. Abnormal
axillary lymph nodes may be depicted in cases with
suspicious retroareolar findings when assessing the axilla as
part of a thorough mammographic search pattern.7
Assessing the Axilla with New Retroareolar Mass
CC MLO

Prior Prior
Current
Current
MLO MLO
CC
CC

Current (d) and previously obtained (e) CC mammograms show
differences between the posterior margins of the glandular tissue
(yellow lines). These margins should be carefully examined for
disruption of the normal scalloped border or new tissue density.
Teaching Point: Subtle changes in contour along the posterior
glandular-fat interface can be easily overlooked and, if
identified, warrant additional workup.8
(a, b) Full-field digital mammogram (a) and DBT image (b) of the left
breast show a developing asymmetry (arrows) along the posterior
glandular-fat tissue interface in the upper inner breast. (c) Coned-down
area of interest from the DBT image shows associated architectural
distortion (circle). The results of a histology examination confirmed IDC.
Prior
Current
Current
a b
c
Assessing the Glandular-Fat Interface
d e

Prior
Current Prior
Current
Mole
marker
Mole
marker
CC CC
MLO
MLO

Teaching Point: Maintain
your search pattern when
viewing mammograms.
Always carefully assess the
fat-glandular tissue margins,
both posteriorly and
anteriorly, for contour
abnormalities.
MLO (a) and CC (b)
mammograms show a subtle
focal asymmetry (circle) in a
patient with scattered
fibroglandular tissue and a
contour deformity with new
anterior convexity (red line in
a). (c) Magnifed area of
interest from the CC DBT
image shows subtle
architectural distortion
(arrow) at this location. The
results of a pathology
examination confirmed
infiltrating carcinoma.
(d) US image of the right
breast shows a
corresponding
hypoechoic mass at the
fat-glandular interface.
a b c
d
Assessing the Glandular-Fat Interface: Continued

Corollary case: A 45-year-old woman with dense breasts and no significant history presented for screening mammography.
Mammograms and DBT images of the left breast show a subtle asymmetry (circle in b and d) in the outer breast, with
architectural distortion causing pulling of the anterior fat-glandular interface (dotted line in b and d). The results of a histology
examination confirmed IDC.
Women with dense breasts normally have a convex contour to the anterior margin of tissue compared to scalloped
appearance in women with scattered fibroglandular tissue. Thus, attention to signs of distortion at the anterior fat-
glandular interface in women with dense breasts, analogous to the appearance created by the pulling of a crochet
hook (yellow line animation in a and b on click), at this location is key.8
Assessing the Glandular-Fat Interface: Continued
a b c d
CC CC DBT MLO MLO DBT

Prior
Current
CC CC

Current CC mammogram (a) shows a
new asymmetry (circle) within the inner
posterior breast that was not depicted
on the previously obtained CC
mammogram (b), highlighting the
importance of evaluating the edge of
the image, as subtle changes in tissue
pattern can be seen. The findings in this
area may represent only a small portion
of the area of concern.
The results of a pathology examination
confirmed infiltrating lobular carcinoma
(ILC).
Prior
Current
a b
Assessing the Edge of Images

Teaching Point: Lesions
within the retroglandular fat
and lower and inner triangles
are suspicious findings. Any
tissue density should raise
concern and be further
evaluated, as only muscle
and fat should be in these
spaces.8
INNER
TRIANGLE
RETROGLANDULAR
FAT
LOWER
TRIANGLE
Assessing Retrograndular Fat and Lower and Inner Triangles
CC MLO

Current Current
Prior Prior
CASE: A 79-year-old woman with a history of right breast cancer 5 years prior who underwent right
lumpectomy, chemotherapy, and radiation therapy presented for mammography.
CC CC MLO MLO

Mammogram on prior slide
shows increased skin
thickening and parenchymal
edema, findings consistent
with expected
postlumpectomy changes.
However, there is a new 8-mm
right axillary lymph node
(circle animation on prior
slide). On subsequent spot-
magnification image (a), a faint
calcification (green arrow in a
and b) is depicted in the lymph
node. The results of US-guided
biopsy were positive for
metastatic adenocarcinoma.
Although this lymph node is
not enlarged, it is new and
demonstrates suspicious
features, calcifications, and
cortical irregularity at US (b).
The axilla should be carefully
evaluated at mammography
in patients who have
undergone breast
conservation surgery, as
recurrence and/or
metastases can first present
here.
Teaching point: Management of a lymph node, even if normal in size, should be determined
by the most suspicious feature (focal cortical thickening, loss of fatty hilum, cortical
irregularity, or calcifications).9
Assessing Lymph Nodes
a b

The following cases highlight the importance of comparing
the current examinations to prior examinations, as this
allows subtle changes in tissue patterns to be noticed. This
can be particularly important for identifying asymmetries
and differentiating benign from malignant changes in
surgically altered breasts.
Concept 3: Compare the current examination to multiple prior
studies, when available.

Current Oldest Current Oldest
CASE: An 89-year-old woman with a palpable concern in the left breast presented for
diagnostic evaluation.
MLO MLO MLO
CC CC CC

If viewed in isolation, the left breast tissue appears dense but normal.
However, when compared to prior mammograms and the contralateral
breast, a new dense global asymmetry in the area of palpable concern
(white BB marker) in the upper central and outer left breast is evident.
Teaching point: Most global asymmetries are benign and present as a
normal variant 3% of the time. However, when associated with a mass,
distortion, calcification, or palpable abnormality, the suspicion for
carcinoma increases.
Prior
Current
Current Prior
This case also illustrates the importance of comparing current
mammograms to prior examinations. The detection of malignancy is
significantly better when prior mammograms for at least 2 years are
available for comparison to determine whether a finding is stable, new
and/or developing, and in need of further evaluation.8, 10, 11

Current Prior Current Prior
CASE: A 53-year-old woman presents for screening mammography.
CC
CC MLO MLO

Although uncommon, developing asymmetries have a moderate chance of malignancy, between 13%–27%, and require
further evaluation with diagnostic imaging. If a definitive benign US correlate or a clinical explanation (trauma, infection,
hormone therapy, weight gain or loss, or differences in technique or positioning) cannot be found, a biopsy is
indicated.12,13,14
(a–d) The developing asymmetry on
two mammograms is subtle but real,
persisting on spot-compression
views (not shown). (e) Targeted left
breast US image shows a
corresponding irregular mass with
posterior shadowing. The results of
a core biopsy confirmed ILC.
Current Prior Current Prior
a b c d
e

Asymmetry:
• Only seen on ONE view
• Lacks a convex border
• +/- interspersed fat
• Involves less than one quadrant
• Likelihood of malignancy = 1.8%
• 83% are secondary to
overlapping tissue or
summation artifact
Focal asymmetry:
• Similar on TWO views
• Lacks convex borders
• +/- interspersed fat
• Common at screening (87%)
• LOW likelihood of malignancy
(0.67%)
Global asymmetry:
• Asymmetric tissue relative to the
contralateral breast
• Occupies more than one quadrant
• Seen on TWO views
• Lacks conspicuity of a mass
• Normal variant 3% of time
• 0% likelihood of malignancy with
no symptoms; 7.5% when
palpable
Developing asymmetry:
• New, larger, or denser focal
asymmetry than at prior
examinations
• UNCOMMON (<1% of
examinations)
• BUT the likelihood of cancer
is between 13% and 27%
Understanding Asymmetries11,14,15

Prior Prior
Current
Are there any subtle
changes in the tissue
pattern on the CC
view?
Don’t fall prey to
satisfaction of search
and miss a smaller
cancer elsewhere in
the breast!
Current
CASE: A 59-year-old woman presents for screening mammography.
MLO MLO
CC
CC

(a, b) Current mammograms show
enlargement of a lymph node
(dashed circle in a). On further
review, a subtle more prominent
asymmetry (circle in b) in the right
retroareolar breast was visualized,
best depicted on the CC view. (c)
US image shows a suspicious mass
at the 12-o’clock position. The
results of a biopsy of the mass and
intramammary lymph node
confirmed IDC and IDC-associated
with lymphoid tissue, respectively.
(d, e) Postbiopsy mammograms
show clip placement at both sites
(arrows), confirming the
mammographic-US correlation.
Interval increase in size of an
intramammary lymph node
should prompt careful inspection
for malignancy. Compare with
prior studies to assess any subtle
mammographic change such as a
new asymmetry, focal asymmetry,
architectural distortion, or low-
density mass.
Missed cancers can also be
minimized by reviewing the images
as mirror images (eg, CC views
placed together and MLO views
placed together).
Teaching point: Even if no
additional mammographic
abnormality is detected,
increasing size of an
intramammary lymph node,
particularly with abnormal
morphology, and no clinical
explanation should prompt a
biopsy.9,16
MLO Postbiopsy MLO
CC Postbiopsy XCCL
US
a
b
c
d
e XCCL= laterally exaggerated CC.

Current Prior
Current Prior
CASE: Patient with a history of right lumpectomy and radiation therapy for breast cancer 7 years earlier
presented for annual mammography.
MLO MLO
CC
CC

Evaluation of the lumpectomy site can be challenging owing to distortion,
calcifications, and increased density frequently seen at the site as normal
posttreatment changes. Postlumpectomy changes evolve over a period of
approximately 2–3 years and then stabilize.17
There are some findings that can suggest cancer recurrence. Current
mammograms (a, c) show a new radiodense mass (arrows) near the lumpectomy
site. The mass maintains a similar configuration on two views and lacks central
lucency, both features suspicious for recurrent disease.
Features
suggesting a
postsurgical scar
Features
suggesting
recurrence
Stable imaging
appearance 2–3
years
posttreatment
Change in imaging
appearance 2–3
years
posttreatment
Absence of a
central mass
Central mass
Radiolucent areas Lack of
radiolucent areas
Thick curved
spicules
Fine straight
spicules
Changing
appearance on
different views
Consistent
appearance on
different views
17
a b c d
CC CC MLO MLO

Conclusion
Mammographic signs of breast cancer can be very subtle. Keep these tips in mind to increase
your diagnostic acumen:
1. Evaluate positioning (nipple in profile, open inframammary fold, adequate posterior tissue
with PNL extending to the pectoralis muscle on the MLO view, <1 cm difference in PNL
measurement comparing CC and MLO views, and up-and-out positioning of breast) and
technique (motion artifact, suboptimal compression).
2. Maintain a standard search pattern (anterior and posterior fat-glandular interface, edge of
the images, axillary tail and/or axilla, retroglandular fat, inner and lower triangles, skin, and
nipple-areolar complex).
3. Compare current mammograms to prior examinations (look for parenchymal asymmetries,
architectural distortion, calcifications, new or enlarging masses or lymph nodes, and changes
in the postsurgical breast).

References
1. Hoff S, Abrahamsen A, Samset J, Vigeland E, Klepp O, MD, Hofvind S. Breast cancer: missed interval and screening-detected
cancer at full-field digital mammography and screen-film mammography—results from a retrospective review. Radiology
2012;264(2):378–386.
2. Majid A, Shaw de Paredes E, Doherty R, Sharma N, Salvador X. Missed breast carcinoma: pitfalls and pearls. RadioGraphics
2003;23(4):881–895.
3. Miller L. Mammography positioning basic and advanced.
https://www.sbionline.org/Portals/0/Breast%20Imaging%20Symposium%202016/Final%20Presentations/201B%20Miller%20%2
0Mammo%20for%20Techs%20Positioning.pdf. Published 2016. Accessed September 10, 2018.
4. Popli M, Teotia R, Narang M, Krishna H. Breast positioning during mammography: mistakes to be avoided. Breast Cancer (Auckl)
2014;8:119–124.
5. Nicholson B, Harvey J, Cohen M. Nipple-areolar complex: normal anatomy and benign and malignant processes. RadioGraphics
2009;29(2):509–523.
6. Bassett LW, Hirbawi IA, DeBruhl N, Hayes MK. Mammographic positioning: evaluation from the view box. Radiology
1993;188(3):803-806.
7. Suami H, Pan W, Taylor G. The lymphatic anatomy of the breast and its implications for sentinel lymph node biopsy: a human
cadaver study. Ann Surg Oncol 2008;15(3):863–871.
8. Harvey J, Nicholson B, Cohen M. Finding early invasive breast cancers: a practical approach. Radiology 2008;248(1):61–76.
9. Net J, Mirpuri T, Plaza M, et al. Resident and fellow education feature: US evaluation of axillary lymph nodes. RadioGraphics
2014;34(7):1817–1818.

References
10. Price E, Joe B, Sickles E. The developing asymmetry: revisiting a perceptual and diagnostic challenge. Radiology
2015;274(3):642–651.
11. Sickles E. Mammographic features of 300 consecutive nonpalpable breast cancers. AJR 1986;146:661–663.
12. Sickles E. The spectrum of breast asymmetries: imaging features, work-up, management. Radiol Clin North Am
2007;45(5):765–771.
13. Leung J, Sickles EA. Developing asymmetry identified on mammography: correlation with imaging outcome and pathologic
findings. AJR 2007;188(3):667–675.
14. Chesbro A, Winkler N, Birdwell R, Geiss C. Developing asymmetries at mammography: a multimodality approach to
assessment and management. RadioGraphics 2016;36:322–334
15. Goergen S, Evans J, Cohen G, MacMillan J. Characteristics of breast carcinomas missed by screening radiologists. Radiology
1997;204:131–135.
16. Lee C, Giurescu M, Philpotts L, Horvath L, Tocino I. Clinical importance of unilaterally enlarging lymph nodes on otherwise
normal mammograms. Radiology 1997;203(2):329–334.
17. Krishnamurthy R, Whitman G, Stelling C, Kushwaba A. Mammographic findings after breast conservation therapy.
RadioGraphics 1999;19:S53–S62.

Suggested Readings
Goergen S, Evans J, Cohen G, MacMillan J. Characteristics of breast carcinomas
missed by screening radiologists. Radiology 1997;204:131–135.
Harvey J, Nicholson B, Cohen M. Finding early invasive breast cancers: a practical
approach. Radiology 2008;248(1):61–76.
Krishnamurthy R, Whitman G, Stelling C, Kushwaba A. Mammographic findings after
breast conservation therapy. RadioGraphics 1999;19(Spec Issue):S53–S62.
Roberts-Klein S, Iuanow E, Slanetz PJ. Avoiding pitfalls in mammographic
interpretation. Can Assoc Radiol J 2011(1); 62:50–59.
Sickles E. The spectrum of breast asymmetries: imaging features, work-up,
management. Radiol Clin North Am 2007;45(5): 765–771.

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