Mark
A. Stein,
MD
#{149} Mitchell
Calcifications Discrepancies Identification’
S. Karlan,
MD
in Breast Biopsy in Radiologic-Pathologic
To analyze the effectiveness and accuracy of the diagnostic process from screening mammography to final diagnosis at pathologic examination, the authors conducted a prospective study of 277 consecutive patients who underwent 291 mammographically directed biopsies of nonpalpable lesions. Of the 170 lesions that demonstrated findings consistent with calcification on preoperative mammograms and radiographs of specimens, 12 (7.1%) were not described by the pathologist as being calcified. These discrepancies were due to inadequate sampling in three cases (25%), lack of explicit descniption by the pathologist in four (33%), presence of oxalate crystals that required examination with polanizing lenses in two (17%), and unexplained loss of tissue probably related to processing in three (25%). Of the 121 lesions that did not demonstrate findings consistent with calcification at radiography, eight (6.6%) were described as calcified by the pathologist. The authors recommend a protocol for avoiding these discrepancies that involves performance of a more comprehensive examination of histologic sections by the pathologist, including the use of polarizing lenses, if necessary, and radiographic reexamination of paraffin-embedded tissue blocks with subsequent step sectioning by the pathologist when results are positive.
I
in the techniques of preoperative needle localization of nonpalpable breast lesions that have been detected at mammognaphy, coupled with the surgical biopsy of smaller volumes of breast tissue and the use of local anesthesia have produced a more aggressive attitude toward early biopsy of lesions that are suspicious for malignancy. Advances in the diagnosis of nonpalpable lesions include the use and refinement of radiography of specimens (1-8) and localization techniques (9-16) and reduction in radiation dose at mammography (1719). As a result, the number of biopsies performed to evaluate nonpalpable disease has disproportionately contributed to the increase in the number of breast biopsies performed. In a previous madiologic-pathologic
graphs, and radiologic and pathologic meports for the presence or absence of calcifications. All discrepancies in reporting were analyzed. The surgical specimens of all lesions underwent radiographic examination, generally with compression and magnification, on a dedicated mammography unit (Diagnost U-M; Philips, Shelton, Conn) at 25 kVp. When calcifications occupied a small volume of the specimen or when specimens consisted of multiple fragments, the location of the calcifications was indicated to the pathologist by serial sectioning and radiography of the tissue, with use of a needle as a marker, and by direct verbal communication. After routine processing and embedding of the specimen in paraffin blocks approximately 5 mm thick to allow histologic examination, 5 1-sm-thick sections were obtained from each block for microscopic analysis. Pathology reports were systematically reviewed by the authors to
correlation
correlate
MPROVEMENTS
study
MATERIALS consecutive
terms:
Breast, biopsy, 00.125, 00.12986, Breast, calcification, 00.3291, 00.81 #{149} neoplasms, 00.31, 00.32 #{149} Breast neodiagnosis, 00.12986, 00.99
Radiology
1991;
179:111-114
of the
METHODS
a prospective patients
who
study
of
underwent
preoperative needle localization of 291 mammographically suspicious, nonpaipable breast lesions, with use of methylene blue stain, with or without the use of hook wires as markers. We examined the
From
(M.A.S.)
#{149}
3.5%
AND
We conducted 277
I
Index
(20),
breast tissue specimens that demonstnated the presence of microcalcifications on specimen nadiognaphs did not have these findings confirmed at pathologic examination. The diagnosis of one of these “missed” cases was converted from benign to malignant after examination of deeper portions of the tissue blocks.
mammograms,
00.99 Breast plasms,
Specimens:
the and
surgical
Departments
specimen
radio-
of Radiology
Surgery (M.S.K.), Beverly Hills Medical Center, 1 177 5 Beverly Dr. Los Angeles, CA 90035. Received July 3, 1990; revision requested August 21; final revision received November 16; accepted November 26. Address reprint requests to M.A.S. RSNA, 1991
the
microscopic
findings
with
the findings at specimen radiography. If specimen radiographs confirmed that the suspicious microcalcifications originaily present on the preoperative mammogram had been removed at surgery, and if the pathologist did not report their presence in the biopsy specimen, then this was recorded as a “forward” discrepancy. These paraffin-embedded blocks then underwent radiographic examination with use of the same mammography unit at 25 kVp. The technique described by Rebner et al (20) was modified to provide two exposures for each set of blocks to distinguish dust from calcification. Only those blocks that contained microcalcifications
were
then
step
sectioned
more deeply and reexamined by the pathologist. If the microcalcifications were still
not
seen,
then
this
process
was
me-
peated until the calcifications were identified in the histologic specimen. In all cases, the original histologic sections were reviewed. If the reports of the findings on the preoperative mammogram and specimen radiograph did not indicate the presence of microcalcifications, but the pathologist reported their presence, then this was recorded as a “reverse” discrepancy. In these cases, the preoperative mammograms and surgical specimen radiographs 111
.
a.
c.
Figure
1.
Radiographs
lesion. (a) Left lateral sion of the calcification.
were
reanalyzed
these
discrepancies.
demonstrating mammogram (c) Paraffin
localization, shows block
in an attempt
localization radiograph
to explain
Of the
291 preoperatively the
overall
mate
was 6.9% (20 of 291). The rate cmepancy was essentially the the 170 calcified lesions seen ogmaphy (7J%; 12 of 170) as 121 noncalcified lesions seen ogmaphy (6.6%; eight of 121). tnibution of malignancies these lesions is shown
of dissame for at radifor the at radiThe dis-
among in the Table.
Radiographic analysis of the 12 cases of calcifications that were not seen at histologic examination (forward discrepancies) showed that in seven cases (58%) calcifications were present
in the
paraffin
block
(Fig
1).
In four of these cases, calcifications were also present in the original sue
slides
tion and
but were required
light
for
used
their
at histologic
missed the use
tis-
examina-
in two cases of polarized
identification
in the
other two. The slides of the remaining three cases did not contain calcifications, requiring targeted resectioning of their paraffin blocks for repeat histologic examination. Radiographs of five of the 12 cases showed no calcifications in the specimens
prepared
in paraffin
blocks.
these, two showed calcifications the slides that were reviewed. fications
112
were
#{149} Radiology
never
identified
needle confirms
sions
localized
discrepancy
and
paraffin
in place presence
block
for examination
to direct biopsy of calcification
Of
in Calciin the
preserved
in the
uncut
portion
of the paraffin blocks were step sectioned until the calcifications were definitely identified on histologic sections. However, the original diagnosis was not altered in any of these cases. In the analysis of the eight reverse discrepancies that occurred in the group of 121 lesions that did not demonstrate calcifications at radiogmaphy but did demonstrate calcifications
at histologic
examination,
asymptomatic
dengo breast mammography nonpalpable
cancer and lesions,
cused
on
graphic direct
localization the surgeon
improvements
the
in radio-
that and
shows
exci-
of breast
tissue
a higher percentbe benign, it is im-
perative to minimize the frequency of inadequate biopsies. Our data demonstrate a 6.9% ovenall discrepancy nate between the findings at the final radiographic confirmation of lesion excision and
findings
at pathologic
when
they
nadiognaphs.
ward
of fo-
Four
examina-
are seen causes
discrepancies
were
in specimen of these
for-
identified.
The most common cause of forward discrepancies (four cases [33%]) resulted from a decision not to describe benign and incidental calcifications and from a lack of complete scrutiny of the histologic material. Another common and connectable cause of forward discrepancies (three cases [25%]) was inadequate sampling that resulted from standard procedures for handling tissue at histologic examination. Excised tissue that is embedded in paraffin blocks is
typically
techniques to the lesion
amount
removed. Because age of lesions will
even
un-
screening with require biopsy attention has
in a nonpalpable radiograph
These discrepancies are of two types. The first and most important type was calcified lesions may not be identified at histologic examination
me-
patients
calcifications Specimen of tissue.
tion.
DISCUSSION more
(b) portion
minimize
the
view of the preoperative mammogram and surgical specimen madiogmaphs revealed diffuse scattered punctate calcifications in one patient (12%). However, in the other seven patients (88%), no calcifications were seen; evidently the size of these calcifications was beyond the nesolving capability of the radiography equipment.
As
of breast
of calcifications. in the uncut
remaining three cases, which suggests that they may have been lost during preparation. The seven cases that contained micmocalcifications in the original le-
RESULTS
lesions,
specimen,
sampled
causes
the
only
a small
in sections,
pathologist
percentage
which
to examine
of the
tissue.
Another connectable cause of forward discrepancy was the presence of calcium in the form of oxalate in the tissue. Although present in only two of the 170 lesions (1.2%), the presence
April
1991
Distribution Nonpalpable
of Malignancies Breast Lesion
as a Function Lesions
D emonstnating at Radiography
No Discrepancy
Parameter
in parentheses
Calcifi
Correlation
cations
Not
of Calcifications
Reverse Discrepancy
113 15 (13.3)
170 45 (26.5)
in a
CaIc ifications
Demonstrating at Radiography
No Discrepancy
Total
12 3 (25)
of the Presence Lesions
Forward Discrepancy
158 42 (26.6)
No.ofpatients No. of malignancies Note-Numbers
of Radiographic-Pathologic
Total
8 0
121 15 (12.4)
are percentages.
MAMMOGRAM SUSPICIOUS Positive
1
NONPALPABLE
PRE-OPERATIVE
NEEDLE
LESION
DIRECTED
C)
0 z
Positive
BIOPSY
I
m
z
$ Calctfied
on
Spectmen
Mammogram
,..
Postoperative
Mammogram
Calcified
on
Specimen
Radiograph I Positive
Negative
Immediate
Non
-I
Mammogram
0
z
Radiograph Negative Immediate Postoperative
Posdive
+
Pathologist Polarizing
Use Lens
END
Mammogram
Nenative
___
Positive
Review
Positive
Negative
Histology
___
Report
for
Calcifications Positive
I
Negative
X-ray Paraffin
Blocks
for
Calcification Neoative Positive -
Figure
2.
Proposed
protocol
for
Step-Section diagnostic
sequence
to confirm
of calcium oxalate accounted for two (17%) of the 12 forward discrepancies. The routine use of polarizing lenses by the pathologist, as suggested by Lagios (21), could eliminate
the radiologist eliminating,
this
in were
error.
The
final
cause
of forward
discrepancy (three cases [25%]) was the loss of material. Calcium may be leached when acidic fixative is added or may be shattered from the paraffin blocks when the surfaces are shaved flat or when they are sectioned (21). Better techniques for handling tissue are needed to reduce these sources of error.
Except for loss of material, over which the pathologist has control, Volume
179
#{149} Number
1
these
histologic
identification
can be instrumental detecting, or correcting
forward
discrepancy
initially
nosis
found reported
diagnosed
the
potential
of these
lesions
in
errors.
The three malignancies forward discrepancies However,
of excised
in the here-
correctly.
for misdiagas benign
is
tissue.
malignancies
common.
pathologic
cases)
and
at sungi-
cal specimen radiography should be a routine part of the diagnostic process this missed
in these correlation
patients, will
carcinoma.
even rarely There
though reveal were
no
a
eight
ings at radiologic and examinations of breast
real and has been reported (20). Our data support the conclusion that conrelation between the findings at examination
in the
reverse
dis-
crepancy lesions; these microcalcifications are often below the resolving capability of the mammographic equipment and, therefore, cannot be depicted. Discrepancies between the find-
Seventy-five
discrepancies
that
in a missed
in our
had
the
diagnosis
at pathologic lesions are
percent study
of the
(nine
potential
of
12
to result
of carcinoma
are connectable. The flow chart in Figune 2 offers a protocol designed to meduce these errors. More compnehensive examination of the histologic Radiology
#{149} 113
sections the use sary,
and
by the pathologist, of polarizing lenses radiographic
including if neces-
Acknowledgments: We express our gratitude to Linda Sylvia, ART, for her meticulous attention to detail in locating the lesions and obtaining immediate postoperative mammograms, as
well as in data accumulation ing; dite MD, sistent and script
114
and record
2.
Bauermeister DE, McClure HH. Specimen radiography: a mandatory adjunct mammography. Am J Clin Pathol 1973; 59:782-789. Rosen P, Snyder RE, Foote FW, Wallace
Detection parently specimen 3.
4.
5.
6.
7.
8.
9.
keep-
to Gary R. Gray, MD, for succinct and erueditorial comments; to Charles Panchani, for his patience and acceptance of our perdemands on the pathology department; to June Storch for her assistance in manutranscription.
#{149} Radiology
1.
reexamination
of the paraffin-embedded tissue block with subsequent step sectioning by the pathologist if results are positive may be necessary to accomplish this goal. Still, in a small percentage of patients (three of 291 [1.0%] in our series), the intended tissue is lost and cannot be reexamined by the pathologist. When microcalcifications are depicted in a cancer screening mammogmam, we believe that the radiologist can serve a pivotal role in assuring successful completion of the diagnostic loop from screening mammography to accurate histologic diagnosis of a nonpalpable mass. By assuming the initiative to correlate the pathologic and radiographic findings and to direct the meexamination of excised tissue by the pathologist when discrepancies are found, errors will be minimized. U
12.
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21.
Lagios MD. Pathologic examination and tissue processing for the mammographically directed breast biopsy. In: Proceedings of mammographically directed breast biopsies: problems and pitfalls. San Francisco: California Society of Pathologists, 1989.
April
1991