226
CYTOPATHOLOGY
Stereotaxic Aspiration Biopsy in the Evaluation of
Mammographically Detected Clustered
Microcalcification
Joan Cangiarella, M.D.1
Cecilia L. Mercado, M.D.2
W. Fraser Symmans, M.D.1
Gillian M. Newstead, M.D.2
Hildegard K. Toth, M.D.2
Jerry Waisman, M.D.1
1
Department of Pathology, New York University
Medical Center, New York, New York.
2
Department of Radiology, New York University
Medical Center, New York, New York.
Presented in part at the International Academy of
Pathology, Orlando, Florida, March 1–7, 1997.
Address for reprints: Joan Cangiarella, M.D., New
York University Medical Center, 530 First Avenue,
Skirball Building, Suite 7S, New York, NY 10016.
Received May 16, 1997; revision received July 3,
1997; accepted July 10, 1997.
© 1998 American Cancer Society
CANCER
BACKGROUND. Stereotaxic fine-needle aspiration biopsy (SFNA) of mammographi-
cally detected nonpalpable lesions of the breast provides accurate diagnosis and
may eliminate many unnecessary excisional biopsies of areas of microcalcification.
METHODS. SFNA of microcalcification of indeterminate radiologic significance was
performed on 125 patients (1991–1994), yielding 130 specimens (2 sites in 2
patients and bilateral aspirations in 3 patients). Stereotaxic localization was per-
formed, and samples from within the area of microcalcification were obtained
using 22-gauge needles. Smears stained with a Giemsa-type stain were prepared
and studied by a cytopathologist during the procedure to determine the adequacy
of each specimen.
RESULTS. Of 130 specimens, 104 (80%) were cytologically benign, 13 (10%) were
atypical, 6 (4.6%) were suspicious, and 7 (5.3%) were malignant. All malignant
diagnoses were confirmed by subsequent operative biopsy. Follow-up was avail-
able in 74 of 104 benign cases (71%): surgical excisions (all benign) in 8 cases and
follow-up mammograms at 6 months to 5.8 years in 66 cases (no radiologic change
in 64 cases and 2 [1.9%] cases with new radiologic findings [SFNAs of the new
radiographic abnormality revealed adenocarcinoma in both]).
CONCLUSIONS. SFNA is a reliable and cost-effective method of evaluating indeter-
minate microcalcification; however, mammographic follow-up is indicated be-
cause of the possibility of subsequent and independent cancers. [See editorial on
pages 197–9, this issue.]Cancer (Cancer Cytopathol) 1998;84:226 –30.
© 1998 American Cancer Society.
KEYWORDS: aspiration biopsy, cytology, microcalcification, breast, stereotaxic,
mammography.
M ammary microcalcification is commonly found on routine mam-
mography to account for approximately 50% of the biopsies of
nonpalpable mammary lesions.1 The Breast Imaging Reporting and
Data System of the American College of Radiology categorizes mam-
mographic microcalcification into three main groups: benign, inde-
terminate, and high probability of malignancy.2 Several reports have
shown that radiologic characterization of the calcification can provide
clues for estimating the risk of adenocarcinoma; however, biopsies of
suspicious microcalcification showed adenocarcinoma in only 55–
75% of cases.3–5 When three radiologic criteria depicting the micro-
calcification were assessed (vermicular calcification, linear or
branched forms, and irregularity of size), adenocarcinoma could be
predicted in 88% of cases.6 Obviously, more precise classification of
areas of microcalcification requires study of samples from the breast.
Stereotaxic aspiration biopsy of indeterminate microcalcification can
 Aspiration in Calcification of the Breast/Cangiarella et al.
provide diagnostic samples; thus, an operative biopsy
is not required for every patient. However, concern
over insufficient sampling with false-negative diag-
noses has led many to question the results of aspira-
tion biopsy. We investigated the use of stereotaxic
fine-needle aspiration biopsy (SFNA) in 125 patients
with clustered microcalcification on mammographic
examination to evaluate the accuracy of the procedure
in identifying patients with mammary cancer.
MATERIALS AND METHODS
Our files were searched for patients who underwent
stereotaxic aspiration biopsy of a single cluster of
mammographically evident microcalcification with no
evidence of a density (mass) during the period 1991–
1994. One hundred twenty-five patients were identi-
fied, all female, with an age range of 31–72 years
(mean, 54 years). Among these patients, a total of 130
procedures were performed (3 patients had bilateral
stereotaxic aspirations, and 2 patients had 2 sites as-
pirated in the same breast). The clusters of microcal-
cification were evaluated by contact and magnifica-
tion mammography. Stereotaxic localization involved
taking two views to establish three-dimensional coor-
dinates of the mammary lesion using a Lorad Digital
Spot Mammography System (Lorad, CT). All localiza-
tions were performed by full-time mammographers
assisted by full-time mammographic technologists. All
aspiration biopsies were performed by cytopatholo-
gists who specialized in aspiration cytology. Two or 3
samples were then taken from at least 3 different sites
within each area of microcalcification (for a minimum
of 6 samples), using standard 22-gauge spinal needles.
Syringes were not used.7 The sites were confirmed by
stereoradiography to assure correct placement of the
needle within the area of microcalcification. Diagnos-
tic material from the needle was expelled onto glass
slides. The aspirates were then smeared thin and fixed
by immersion in 95% ethyl alcohol and stained with
hematoxylin and eosin, or air-dried and stained with a
modified Giemsa stain (Diff-Quik, Baxter, McGaw
Park, IL) or by a rapid Papanicolaou method.8 Air-
dried smears stained with Diff-Quik were evaluated by
the on-site cytopathologist for adequacy of the speci-
men, and the patient remained on the mammography
table until calcific debris was obtained. This proce-
dure eliminated nondiagnostic specimens. A speci-
men was considered adequate if it contained calcific
debris; thus, epithelial groupings were not present in
every case. Calcific debris was identified by routine
microscopy of uncoverslipped smears stained with
Diff-Quik. Calcific debris was less discernable on al-
cohol-fixed smears.
Diagnoses were reported in standard terms, as in
227
surgical pathology. For the purpose of this study, le-
sions were classified as benign, atypical, suspicious, or
positive for carcinoma (i.e., negative aspirates were
those with definitive benign findings, and positive as-
pirates were those with definitive malignant findings).
The diagnoses in benign cases were divided into fibro-
cystic change, nonproliferative, or proliferative type;
microcalcification only; and miscellaneous other diag-
noses. The nonproliferative group often contained
large, regular, monolayered groups of uniform ductal
epithelial cells; numerous bare oval nuclei (from myo-
epithelial and stromal cells); and fragments of stroma.
The proliferative group consisted of cellular aspirates
with cohesive, monolayered, small, and less regular
sheets of uniform epithelial cells with bare, oval nuclei
and rare, single, intact ductal epithelial cells. The mi-
crocalcification-only category included aspirates with
calcific fragments and stromal fragments but no mam-
mary ductal epithelial cells. The other category in-
cluded one case of fat necrosis. The atypical category
showed scattered single epithelial cells with enlarged
and pleomorphic nuclei admixed with small, uniform
ductal epithelial cells and scattered, bare, oval nuclei.
The “suspicious” category contained single or clus-
tered atypical epithelial cells, but these were of insuf-
ficient quantity or were associated with confusing
factors that precluded a definitive diagnosis of carci-
noma. The malignant group generally contained
abundant, dissociated, intact epithelial cells with en-
larged nuclei and irregular nuclear contours, an in-
creased nucleocytoplasmic ratio, prominent nucleoli,
necrotic debris, and other features of malignancy. In a
small number of cases, a stereotaxic 14-gauge core
needle biopsy using a disposable biopsy gun was ob-
tained immediately after the aspiration biopsy. Re-
gardless of diagnosis, all patients were asked to have a
follow-up mammogram in 6 months. Thirty patients
had a subsequent wire localization procedure fol-
lowed by resection of the area of microcalcification.
RESULTS
Of the 130 stereotaxic aspiration biopsies, 104 (80%)
were benign, 13 (10%) were atypical, 6 (4.6%) were
suspicious, and 7 (5.3%) were positive for adenocarci-
noma. Because a cytopathologist was present during
the performance of the SFNA to evaluate the specimen
adequacy and to ensure the presence of microcalcifi-
cation on the smear, all specimens were satisfactory
(that is, all contained calcific debris).
In the benign category, 69 specimens were diag-
nosed with fibrocystic changes of nonproliferative
type, and 15 specimens showed fibrocystic changes of
proliferative type. Nineteen specimens contained mi-
228 CANCER (CANCER CYTOPATHOLOGY) August 25, 1998 / Volume 84 / Number 4
crocalcification only. One specimen showed fat nec-
rosis.
In the group with fibrocystic changes of nonpro-
liferative type, seven patients had core needle biopsies
at the time of SFNA and one patient had an excisional
biopsy; all cases showed fibrocystic changes of non-
proliferative type on microscopic examination. Two
patients were followed by repeat SFNA of mammo-
graphically unchanged microcalcification 2 years lat-
er; both had cytologic findings of nonproliferative-
type fibrocystic changes. Twenty patients were lost to
follow-up. All other patients have been followed for
6 – 69 months (mean, 23.9 months) with no radio-
graphic changes in microcalcification.
In the proliferative group of 15 patients, 4 had
subsequent excisional biopsies (1 patient had bilateral
biopsies) and 1 patient had a core needle biopsy. The
core needle biopsy and four of the excisional biopsies
showed the same findings (proliferative-type fibrocys-
tic changes) on histology. One excisional biopsy
showed only microcalcification. One patient was lost
to follow-up. The remaining 9 patients had no change
in their mammographic findings for a period of 6 – 61
months (mean, 24.8 months).
In the microcalcification-only group of 19 pa-
tients, 8 were lost to follow-up. Three patients had
core needle biopsies, which showed calcification in
one, fibrocystic change in one, and normal mammary
parenchyma in one. One of these three patients had a
subsequent excisional biopsy, which showed fibrocys-
tic changes and microcalcification. Two patients had
SFNAs of new radiographic abnormalities 1 year later
and were both diagnosed with mammary adenocarci-
noma. In one case, the cluster of microcalcification
initially sampled by aspiration biopsy was unchanged
radiographically; however, a new, discrete area of mi-
crocalcification was noted. In the other case, a new
density developed in a different (axillary) portion of
the breast. Eight patients were followed radiographi-
cally for a period of 14 – 43 months (mean, 30.8
months) with no change in their cluster of microcal-
cification.
In the “other” category, the patient with fat necro-
sis of the breast had a 6-month post-SFNA mammo-
gram, which was unchanged.
In the atypical category of 13 patients, follow-up
was unobtainable for 1 patient. One patient refused
biopsy and has been followed with mammographic
examination for 31 months with no radiographic
change. One patient had a core needle biopsy, which
showed atypia, followed by an excisional biopsy,
which showed proliferative changes. Ten additional
patients had excisional biopsies; 6 had carcinoma, and
4 had proliferative changes (3 with sclerosing adeno-
TABLE 1
Comparison of Cytologic and Histologic Findings in Six Cases in
Which Subsequent Local Excision Failed to Confirm the Cytologic
Diagnosis of “Atypical” or “Suspicious of Carcinoma”
Cytologic
Case no. diagnosis Histologic diagnosis
1 Atypical Sclerosing adenosis, fibrocystic change
2 Atypical Sclerosing adenosis, fibrocystic change
3 Atypical Sclerosing adenosis
4 Atypical Fibrocystic change, proliferative type
5 Atypical Fibrocystic change, proliferative type
6 Suspicious Fibrocystic change, nonproliferative type
sis). Thus, 50% of the patients with atypical smears
had cancer.
Of the six suspicious cases, one patient was lost to
follow-up, one patient had a core needle biopsy with a
subsequent excisional biopsy, and three had exci-
sional biopsies only. The core needle biopsy showed
only microcalcification; however, excisional biopsy
showed in situ ductal adenocarcinoma of the comedo
type. The other excisional biopsies showed fibrocystic
changes in one, atypical ductal hyperplasia in one,
and lobular adenocarcinoma in situ in one. One pa-
tient refused biopsy and has been followed mammo-
graphically for 24 months with no change in the area
of microcalcification. Thus, in five patients with a sus-
picious SFNA and with follow-up information, three
had cancer or a precancerous lesion.
All seven cases diagnosed as adenocarcinoma on
SFNA had excisional biopsies confirming the diagno-
sis.
In our series of 130 SFNAs, follow-up was avail-
able in 98 (75%) of the cases. Follow-up was attempted
in the remaining cases but was unsuccessful.
Six cases were apparently “overcalled” (Table 1);
that is, subsequent local resection failed to confirm
the diagnosis of atypia or suspicion of cancer. Two
patients diagnosed with microcalcification and no
other findings had additional SFNAs 1 year later in the
same breast because their follow-up mammograms
showed a radiographic change (a new area of micro-
calcification in one and a new density in the other).
The original area of microcalcification was considered
unchanged mammographically. SFNA of the new le-
sions revealed adenocarcinoma in both patients. One
of these patients developed an intraductal adenocar-
cinoma with a 0.3 cm focus of invasion; the other had
a 0.8 cm infiltrative adenocarcinoma with an intraduc-
tal component (comedo-type) representing 25% of the
tumor. These two patients illustrate the importance of
follow-up mammograms for patients with indetermi-
nate microcalcification.
 Aspiration in Calcification of the Breast/Cangiarella et al.
TABLE 2
Comparison of Cytologic and Histologic Diagnoses in 40 Cases in
Which an Excisional or Core Needle Biopsy Was Performed
Histologic diagnosis by core or excisional biopsy (n)
Cytologic
diagnosis (n) Benign Atypical Suspicious Malignant
Benign(14) 14 0 0 0
Calcification(4) 4 0 0 0
Atypical(11) 5 0 0 6
Suspicious(4) 1 1 0 2
Malignant(7) 0 0 0 7
Correlation between cytologic findings and histo-
logic findings in the 40 patients for whom both were
available is summarized in Table 2.
DISCUSSION
Microcalcification is commonly seen on mammo-
graphic evaluation. Characterization of microcalcifica-
tion regarding size, shape, and distribution may dis-
tinguish benign from malignant calcification;4 – 6,9
however, the precise classification of microcalcifica-
tion requires study of samples of involved tissue from
the breast. Stereotaxic aspiration biopsy has been
used to evaluate nonpalpable lesions of the
breast.3,10 –14 Our study suggests that, with the pres-
ence of an experienced cytopathologist at the proce-
dure working in conjunction with the mammographer
and the surgeon, stereotaxic aspiration biopsy is a
reasonable procedure in the evaluation of mammary
microcalcification.
A major criticism of the use of stereotaxic aspi-
ration biopsy has been the large number of nondi-
agnostic specimens, with a reported range of 8.6 –
36%.3,12,14 –15 The high rate of insufficient sampling
can be lowered to essentially zero by the presence of
an experienced cytopathologist at the time of the pro-
cedure to evaluate the adequacy of the specimen, as
our study has shown. Multiple samplings, with imme-
diate radiologic assessment of stereotaxic mammo-
grams after needle placement and a trained cyto-
pathologist’s assessment of aspirates by on-site
microscopic examination, will permit diagnostic spec-
imens to be obtained in every case. In our study,
assuming that a negative aspirate showed definitive
benign findings (the benign or microcalcification-only
category), the false-negative rate was 0%. The false-
positive rate was 0.76% (1 case called “suspicious” on
cytology proved benign on resection, and after 2 years
the patient has no evidence of cancer). On review, this
case showed intact, small, single epithelial cells with
scant cytoplasm evocative of lobular carcinoma ad-
mixed with scattered, bare, oval nuclei representing
229
stromal and myoeithelial cells, belying a benign le-
sion. For cases with available follow-up data (based on
subsequent excisional biopsy or mammographic fol-
low-up), the calculated sensitivity and specificity were
100% and 99%, respectively, in our study. These fig-
ures were slightly higher than those previously re-
ported in another series in which stereotaxic aspira-
tion biopsy of mammary microcalcification was
evaluated (sensitivity of 87% and specificity of 93%).15
Even with these reported findings, many individuals
and institutions are now advocating the use of stereo-
taxic core needle biopsy for the evaluation of micro-
calcification. Supporters of core needle biopsy argue
that the procedure produces tissue for diagnosis and
the results are more specific. Supporters of aspiration
biopsy indicate that this procedure is more sensitive in
finding epithelial atypia. Published reports have
shown core needle biopsy to yield more specific diag-
noses than fine-needle aspiration biopsy in cases of
lobular carcinoma16 and in patients with a palpable
mass and an initially unsatisfactory cytologic speci-
men.17 However, a comparative study of the use of
core needle biopsy and fine-needle aspiration biopsy
in the diagnosis of palpable breast masses showed
fine-needle aspiration biopsy to be more sensitive in
detecting malignant neoplasms.18 Preliminary studies
at our institution have also shown stereotactic aspira-
tion biopsy to be slightly more sensitive and specific
than core needle biopsy in the evaluation of a variety
of nonpalpable mammary lesions.19
The risk of hemorrhage is higher with core needle
biopsy, and the only reported case of malignant seed-
ing after a stereotaxic procedure occurred after a 14-
gauge core needle biopsy.20 Another potential prob-
lem with core needle biopsy is the removal of the
entire area of microcalcification with multiple biop-
sies,21 as operative management of these cases be-
comes difficult or impossible if the lesion is no longer
visible on the post– core needle biopsy mammogram.
Comparison of core needle biopsy and needle aspira-
tion biopsy has shown that cytologic assessment is
more useful than core needle biopsy in the evaluation
of malignant microcalcification,22 wherein 45% of ma-
lignant microcalcifications were falsely reported as be-
nign by core needle biopsy in contrast to 10% by
needle aspiration biopsy. Studies have shown an in-
sufficient rate of less than 1% with core needle biopsy;
however, this accuracy required multiple passes with a
14-gauge needle.23 Thus, multiple cores (3–11 core
biopsies) are necessary to obtain reliable diagnostic
material; 6 core specimens were required to obtain
diagnostic material in 92% of cases in one series.24
Specimen radiographs of all core needle biopsies in
230 CANCER (CANCER CYTOPATHOLOGY) August 25, 1998 / Volume 84 / Number 4
cases of microcalcification must be performed to con-
firm the deposits of calcium salts.25
Our study shows that stereotaxic aspiration biopsy
can be used in the evaluation of mammary microcal-
cification as an alternative to core needle biopsy or
resection, and we encourage institutions that have
good results with stereotaxic aspiration biopsy to con-
tinue to use this procedure. It clearly indicates that
success is not guaranteed and requires a committed
team with training and ongoing experience. In our
opinion, the “ideal” team would include a radiologist
who specializes in mammography, a cytopathologist
who has performed and interpreted at least 100 mam-
mary aspirates, a mammographic technologist with
good interpersonal skills, and a surgeon or clinician
with good clinical judgement and an understanding of
mammary pathology. It is critical to perform the triple
test; that is, all negative aspirates must be interpreted
in conjunction with clinical and mammographic find-
ings to eliminate false-negative diagnoses. Stereotaxic
aspiration biopsy can also provide the patient with an
immediate on-site diagnosis and results, with sub-
stantial savings as compared with conventional local-
ization and open biopsy.12 The use of SFNA can pro-
vide accurate diagnoses and avoid unnecessary
surgical excisions in most patients with benign lesions
under the appropriate circumstances. SFNA, followed
by excision when necessary, offers a logical stepwise
approach to the diagnosis of patients with mammary
microcalcification.
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