Basics about Microcalcifications in mammography of breast as well as Review of Journal article on Residual Microcalcifications after Neoadjuvant Chemotherapy in Carcinoma Breast.

1. By
DR.BHAVIN VADODARIYA
DNB Surgical Oncology 1st year Resident,
Apollo CBCC Cancer Care,
Ahmedabad
Date-22/06/2017

2. Microcalcificatons
 Breast calcifications are common fundings on
mammography and their frequency increases with
the age of the patient.
 It is important to differentiate the microcalcifications of
benign origin from those that are suspicious, since 55% of
non-palpable cancers are diagnosed by the presence of
microcalcifications and because microcalcifications are the
main form of manifestation of ductal carcinoma in situ (DCIS).

3. Why Microcalcification occurs
 A recent study has shown that the carbonate content of mammary
microcalcifications composed of HA may be associated with lesion
grade(Baker et al, 2010).
 However, despite their value for the early detection of breast cancer and
potential prognostic importance,the mechanisms by which mammary
microcalcifications form are unclear at best.
 It has remained uncertain whether they are produced by an active
cellular process or if calcifications are a sign of cellular degeneration.

7. Diffuse
 Formerly called “scattered”,
these are calcifications randomly
distributed within the breast.
 The punctate and amorphous
calcifications in this distribution
are usually benign, especially if
they are bilateral.

8. Regional
Calcification
•This pattern describes
calcifcations in an extensive
area, greater than 2 cm in their
largest dimension.
• A probability of malignancy is
described as about 26%

9. Grouped
• This term is used when a few
calcifications are found in a small
area of tissue.
• The lower limit for this
descriptor are 5 calcifications in
1 cm or when there is a
definable pattern. The upper
refers to when there are more
micro calcifications present
within 2 cm.


10. Linear
 Calcifications are arranged in a
linear path that can branch,
suggesting calcium deposits
within a duct.
 A probability of malignancy is
described as about 60%.
 It is worth noting that certain
calcifications such as vascular
or thick linear may present this
distribution, however, they
have a characteristically benign
morphology

11. Segmental  It suggests the calcium deposit in
the ducts and its branches,
following the anatomical shape of
a breast lobe, i.e. of triangular
shape with the tip directed
towards the nipple.
 While it may occur in benign
pathology, such as secretory
calcifications, its presentation
may be due to extensive or
multifocal cancer.

12. Calcifications of suspicious
Morphology

13. Coarse Heterogenous
 Also known as rough, heterogeneous, they are
irregular and defined calcifications which tend
to coalesce. Measuring more than 0.5 mm.
 These may be located in the breast stroma or ducts.
 Most of these calcifications originate in benign lesions such as
reactionary fibroadenomas, areas of fibrosis or trauma.

14. Coarse Heterogenous

15. Amorphus Calcification
 Also called “powder”, “cloud” or “cottony” they correspond to such
small calcifications (less than 0.1 mm), it is not possible to count
them nor determine their shape. Hence the name “amorphous”
(shapeless).
 Many of them are benign, such as those originated in fibrocystic
changes, especially when they are diffuse and bilateral.
However, when they are grouped, they present a
segmental or linear distribution.
 They may be due to high-risk lesions or malignant etiology, which
justifies indications for histological studies.
 The positive predictive value is approximately 20%, so they are
included in the 4B category.

16. Amorphus Calcification

17. Fine Pleomorphic
 Also called “crushed stone”. They correspond to calcifications
of different shapes and sizes, angled, heterogeneous, with a
size between 0.5 and 1 mm, smaller than the coarse
heterogeneous .
 Calcifcations. While their predictive value of 29% is
higher than the amorphous and coarse heterogeneous
calcifcations, they are included in the BI-RADS 4B
category and have histological studies indicated

18. Fine pleomorphic microcalcifcations.

19. Fine linear or branched
•These correspond to small calcifications, less than 0.5 mm,
thin, linear, usually discontinuous and with irregular edges,
which originate in calcified necrotic debris within a duct
compromised by carcinoma, i.e., they present calcium molds
in an irregular duct.
• They may branch in different directions forming ‘letters’ (L, V,
Y, X) Of the suspicious calcifications, these are the ones that
have the highest positive predictive value for malignancy
(70%) and correspond to BI-RADS 4C category.
When these microcalcifications are new and present a
segmental distribution they can be considered within the BI-
RADS 5 category.

22. Do Calcifications Seen on Mammography After
Neoadjuvant Chemotherapy for Breast Cancer Always
Need to Be Excised?
Authors-Yara Feliciano, MD(1), Anita Mamtani, MD(2) et al.
1Miller School of Medicine, University of Miami, Miami, FL;
2Department of Surgery, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA;
Published Online- 05/01/2017

23. Introduction
 Pre- and post-NAC imaging is used to evaluate the
patient’s response to NAC and to guide the surgical
approach. This generally includes mammography, ultrasound,
and breast magnetic resonance imaging (MRI).
 Mammography and breast ultrasound, the most commonly
used imaging methods for evaluating tumor size
before and after NAC, have variable accuracy.6

24.  Several studies have demonstrated that contrast-
enhanced MRI is the most accurate breast imaging
technique for evaluating the extent of residual disease
after NAC.
 De Los Santos et al. evaluated the ability of MRI to
predict pathologic complete response (pCR) in invasive
breast cancer patients receiving NAC and reported an
overall accuracy of 74%.

25.  However, pCR is not necessary for BCT, and Jochelson
et al. demonstrated that 88% of patients determined to be
candidates for BCT based on post-NAC MRI were able to be have
their breasts conserved.8
 After NAC, new mammographic calcifications may
develop as tumor cells die, or previously seen calcifications
may decrease or increase without clear correlation with
enhancement seen on MRI. The extent of residual calcifications is
an unreliable indicator of response to NAC
because not all calcifications represent viable tumor.

26.  Current NCCN guidelines require complete excision of
indeterminate or suspicious calcifications,13 sometimes
necessitating a larger lumpectomy or a mastectomy for
complete removal in a patient who otherwise has responded to
NAC.
 This study aimed to determine the
relationship between mammographic calcifications and
MRI tumoral enhancement before and after NAC and to
assess the impact of these findings on surgical treatment.

27. Study Population
 Breast cancer patients who underwent NAC at Memorial
Sloan Kettering Cancer Center between April 2009 and
October 2015. Patients from 2009 to 2012 were identified
retrospectively, whereas those treated from 2012 onward
were included in a prospectively maintained database.

28. Inclusion Criteria
 Patients with both pre and post-NAC MRI as well as
mammograms demonstrating calcifications within the tumor
bed either at presentation or after treatment comprised the
study cohort.

29. Exclusion Criteria
 Patients with inflammatory breast cancer, those undergoing
axillary surgery only, and those with imaging unavailable
for review were excluded from the study.

30. Study Variables
 Pre-NAC imaging findings
 Pre- NAC core biopsy results
 post-NAC imaging findings
 Final post-NAC histopathology
 IHC Markers

31. Outcome measures
 Extent of change on imaging after NAC,
 The correlation between changes seen
on mammogram and MRI,
 The correlation between imaging findings
 The presence of residual tumor associated with
calcifications.
 The rate of mastectomy due to residual calcifications
also was ascertained

32.  Complete response seen on MRI was defined as the
absence of any residual mass or non-mass enhancement.
Similarly, complete response seen on mammogram was
defined as the absence of residual mass, calcifications, or
both.

33. Statistical Analysis
 Comparisons were made using Fisher’s exact test. All
statistical analyses were performed using SAS 9.2 (SAS
Institute, Cary, NC, USA), and p values lower than 0.05
were considered significant

34. Results

35. Results

36. Correlation Between Changes on Mammogram
and MRI
 No statistically significant correlation was seen between
the changes in calcifications on mammogram and the
changes in enhancement on MRI (p = 0.12).
 However, loss of MRI enhancement was strongly
correlated with pCR (p ˂0.0001), with the majority of the
patients with pCR demonstrating complete resolution of
enhancement on MRI (23/29, 79%).

38. ‘
Correlation Between Imaging Findings
and the Presence of Residual Tumor Associated
with Calcifications
 Among the 34 patients with malignant calcifications,
MRI suggested a complete response for 6 patients (18%)
and a partial response for 28 patients (82%).
 Meanwhile, a post-NAC mammogram showed decreased
calcifications in 4 (11.8%) of the 34 patients, no change in
calcifications in 19 of the patients (55.9%), and
increased/new calcifications in 11 of the patients (32.4%)

40. Total Patients =90
BCT=70(78%)
Undergone
BCT=57(81%)
MRM=13(19%)
NO BCT=20(22%)
Extensive
MCs=10(50%)
Size=4(40%)
Multicentric=3(30%)
Discoradant
MRI=1(10%)
Progression=
(20%)

41. Calcification
Malignant=34 Benign=56
MRI Mammo
MRI Mammo
Complete=6
Partial=28
No change=19
Increased=11
Decreased=4 Resolved=34
Decreased=22
No change=23
Increased=19
Decreased=11
Resolved=3

43. Left mediolateral oblique (MLO) view demonstrating
diffuse focal asymmetry with associated calcification
spanning 7 cm.

44. Postchemotherapy magnification MLO view demonstrating a
decrease in focal asymmetry with persistent calcifications
spanning 7 cm.

45. Magnetic resonance imaging (MRI) demonstrating
multiple enhancing masses in two areas including a 2.6-
cm mass at 12 o’clock

46. Postchemotherapy MRI demonstrating complete
resolution of enhancement.

47. Discussion
 Downstaging of large tumors to allow BCT is a major
rationale for the use of NAC in operable breast cancer. In
this setting, determination of candidacy for BCT after
NAC is dependent on the post-NAC evaluation of residual
disease extent.
 The integration of discordant findings on MRI
and mammography remains a significant clinical
problem.

48.  Several studies have demonstrated that contrast-enhanced
MRI is the most accurate technique for evaluating the
extent of residual disease after NAC,6–9 yet indeterminate
or malignant-appearing calcifications on mammography
require surgical excision regardless of MRI findings

49.  In a study previously published by MSKCC by Jochelson et al.,
MRI alone correctly predicted the ability to perform BCT after
NAC for 88% of the patients, whereas the combination of MRI
and mammography after NAC correctly predicted the ability
to perform BCT for 92% of the patients based on using the
extent of residual calcifications seen on the post treatment
mammogram to localize disease extent more accurately.

50.  Weiss et al.11 found that the extent of calcifications on
seen mammography correlated poorly with tumor size on
the final pathology after NAC.
 Adrada et al. reported 41% patient had calcifications
associated with benign pathology after NAC.
 Kim et al. demonstrated that the correlation between
residual mammographic calcifications and residual tumor
extent was lower than the correlation between MRI
findings and residual tumor in all tumor subtypes after
NAC.

51.  Combined assessment of loss of MRI enhancement and
changes in calcifications does not predict the presence of
pCR with sufficient accuracy to be clinically useful.
 .
 Loss of MRI enhancement was the most reliable
predictor of pCR, but in 17 cases with resolution of
enhancement, viable tumor persisted

52.  Although only 38% of calcifications were associated with
malignancy after NAC, neither clinical characteristics,
changes in the extent of calcifications, nor the
combination of changes in calcifications and loss of MRI
enhancement identified a patient subset whose
calcifications could be safely left in place

53. Limitations
 It was in part a retrospective, single-institution study
with a relatively small sample size. However, from 2014
onward, the patients were followed in a prospectively
maintained database.
 Hormone receptor-negative patients were
overrepresented compared with prior studies, likely due
to more frequent selection of these patients for
neoadjuvant treatment given a better expected response

54. CONCLUSION
 Although it is clear that many of the tumor bed
calcifications seen on post-NAC mammography are
associated with benign disease, loss of MRI enhancement
does not predict the absence of residual tumor with
sufficient accuracy to allow calcifications to be left in place.
 Complete excision of all indeterminate or malignant-
appearing calcifications remains standard practice and a
substantial limitation to the use of NAC for downstaging of
patients to BCT

55. Thank You