Key words
breast - CT - breast cancer - metastases
Introduction
CT examinations of the chest are being increasingly performed worldwide for diagnostic
purposes in basic patient care. Incidental findings such as coronary calcification,
bronchiectasis, pulmonary emphysema, degenerative spinal column changes, and liver
cysts are common and are described in up to 73 % of all CT examinations depending
on the patient population. In contrast, the frequency of incidental breast findings
relevant to treatment and prognosis in CT examinations of the chest is controversial
due to a lack of epidemiological data [2]
[3]
[4]
[5]
[6]
[7]. Multiple retrospective studies came to the conclusion that previously undetected,
organ-specific, systemic, or metastatic malignancies in the breast visible on computed
tomography can be expected in up to 1.9 % (8) of all CT examinations of the chest
[3]
[6]
[9]
[10]
[11]. In light of this, targeted evaluation of the female breast in CT examinations of
the chest has the potential to be used for secondary preventative care [6]. Statements regarding the frequency of incidental senological CT findings published
to date are all based on retrospective evaluations of written reports electronically
stored in hospital information systems (HIS) [2]
[3]
[4]
[5]
[6]
[8]
[10]. To the authors' knowledge, there are not yet any retrospective CT examination analyses
independent of the written reports and the clinical history and based on the image
documentation. A representative systematic classification of the constellations of
CT findings analogous to the radiologic, sonographic, and MR-mammographic BI-RADS
lexicon is currently not available. Therefore, the percentage of senological lesions
morphologically visible on CT may be higher with targeted evaluation of the breast
region than in the retrospective analysis of diagnostic data extracted from written
reports. The incidence and the differential diagnostic constellations of findings
of benign incidental CT findings in the breast have also not been systematically analyzed.
Therefore, the goal of the present study is to answer the following questions.
-
How high is the percentage of BI-RADS 3 – 5 CT findings in CT examinations of the
chest on the basis of an analysis of the image documentation blinded to the written
reports and the further clinical-radiological course?
-
Were the BI-RADS 3 – 5 findings determined in the retrospective image evaluation mentioned
in the written reports? If yes, what were the diagnostic and/or therapeutic consequences?
-
What effect did the retrospectively recorded BI-RADS 3 – 5 findings have on treatment
and prognosis?
Materials and Methods
Inclusion and exclusion criteria
The study was approved by the responsible local ethics committee. All patients aged
≥ 18 years who underwent CT examination of the chest after i. v. contrast administration
on one of the two CT units at the radiology institute between 1/1/2012 and 12/31/2012
were included in the image assessments. All male patients and all female patients
aged < 18 years, all follow-up CT examinations performed in 2012, and all CT examinations
without i. v. contrast administration were excluded.
Patient and examination data
Patient and examination data were obtained by performing an interactive electronic
query of the radiology information system of the university hospital (RIS Nice®, AGFA HealthCare, NV, Mortsel, Belgium) using the search parameters „CT chest“ and
„CT chest/abdomen“. All CT examinations fulfilling the inclusion criteria and not
the exclusion criteria were interactively entered in a table (Excel®, Microsoft Corp., Redmond, WA, USA). Image data acquisition and reconstruction parameters
were recorded interactively. The clinical history and the radiological course of patients
with findings in the breast were obtained from the hospital information system (HIS)
(ORBIS® OpenMed, AGFA HealthCare, NV, Mortsel, Belgium) and the picture archiving and communication
system (PACS) (ImpaxEE®, AGFA Healthcare, NV, Mortsel, Belgium) of the university hospital.
CT examination technique
Examinations were performed using the CT systems Brilliance iCT and Brilliance 64
(Philips Healthcare, Eindhoven, Netherlands). Tube voltages of 100 kV and 120 kV,
respectively, were used. The tube current intensity varied between 100 mAs and 300 mAs.
The acquired slice thickness was 1 mm with a slice overlap of 1 mm. Transverse thin-slice
image series with a reconstruction slice thickness of 1 mm or 2 mm and transverse
image series with a reconstruction slice thickness of 4 mm with a soft tissue window
(window 360 HU, level 60 HU), lung window (window 1300 HU, level -500 HU) and bone
window (window 1720 HU, level 530 HU) were available for all CT examinations stored
in the PACS. Additional image reconstructions with a slice thickness of 5 mm in a
coronal (soft tissue window) and sagittal slice orientation (soft tissue window and
bone window) were available in the PACS for some of the CT examinations. Reformatting
with any desired spatial direction, slice thickness, and windowing was able to be
performed interactively on the image evaluation console as needed.
Iohexol® (Accupaque 350TM, GE Healthcare Buchler, Fairfield, USA) in a standard dose of 60 ml (examination
region: chest) or 100 ml (examination region: chest/abdomen) was used as the intravenous
contrast agent. The contrast agent was administered via a high-pressure injector pump
(Accutron CTD® or CT2®, Medrad Medizinische Systeme GmbH, Leverkusen, Germany) via a peripheral or central-venous
access with injection rates of 3 – 5 ml/s adjusted to the particular clinical issue
and the scan protocol. Data was acquired in the time interval stored in the scan protocol.
Image assessment
Image documentation was retrospectively evaluated on a dedicated HIS-PACS workstation
(ImpaxEE®, AGFA Healthcare, NV, Mortsel, Belgium). Transverse slices with small reconstruction
slice thicknesses of 1 mm in the soft tissue window were used. All evaluation options
of the image evaluation console including electronic zoom were available.
All 1170 CT examinations fulfilling the inclusion criteria were evaluated in a first
step in an electronic data collection form by a radiologist (C.H. or J.B.) with knowledge
of the electronically stored clinical issue. The written reports and the radiological,
histological, and clinical documents stored in the electronic patient file were not
viewed during this evaluation in order to simulate a primary image evaluation. Whether
the breast region was completely or only partially included in the reconstructed image
datasets was documented for each side (degree of capture 0 % to < 33 %, 33 % to < 66 %,
66 % to 100 %). The density of the parenchyma was categorized according to the ACR
Classification® of the American College of Radiology (ACR) for X-ray and MR mammography [12]. The findings were categorized separately for each side according to the BI-RADS
Classification® of the American College of Radiology (ACR) using the stages BI-RADS 1 through BI-RADS
6. BI-RADS 1 to BI-RADS 5 categorizations were assigned on the basis of CT features.
Ipsilateral intramammary lesions on CT examinations performed according to the clinical
issue for the purpose of staging or surgical preparation in patients with a newly
diagnosed breast carcinoma were classified as BI-RADS 6. Every identified lesion was
characterized analogously to the procedure used for MR-mammographic findings regarding
the criteria „size“ (mm), „shape“ (round-oval, lobulated, irregular), „margin“ (smooth,
unsharp, spiculated), „matrix“ (homogeneous, inhomogeneous), „internal calcifications“,
„density“, (Hounsfield units, HU), and the ratio of the density of the lesion to the
density of the pectoral muscle.
All findings classified as BI-RADS ≥ 3, every 10th of the BI-RADS 2 classifications,
and about every 30th of the BI-RADS 1 classifications were evaluated in a 2nd step
by a radiologist with many years of experience in senological and CT imaging (B.K.)
with knowledge of the previously assigned BI-RADS classifications using the same approach.
Differences in classifications were resolved together with one of the two primary
evaluators (C.H.) in consensus (retrospective consensus assessment).
The CT findings recorded with the electronic data collection form were compared to
clinical, radiological and histological data and documents stored in the HIS and RIS
of the hospital in a 3 rd step (J.B., O.G., B.H., B.K., W.M.). If CT follow-up examinations
were available, the dynamics of the lesion retrospectively diagnosed in the index
examination in 2012 were evaluated. For the further statistical analysis, the diagnostic
statements contained in the written reports of the index examinations were retrospectively
classified according to BI-RADS.
Statistical analysis
The data were recorded in a standardized input screen (Excel®, Microsoft Corp., Redmond, WA, USA). Quantitative variables were provided with the
average, standard deviation, median, minimum and maximum, while qualitative variables
were specified with the absolute and relative frequency (%). Box plots and column
diagrams were used for graphic representation. Pairwise relationships and group comparisons
were evaluated with the Fisher's exact test and the Mann-Whitney U-Test. A p-value
≤ 0.05 was considered statistically significant. A correction for multiple comparisons
was not performed. The statistical analyses were performed with the program SPSS Statistics
(IBM Corp., Armonk, NY, USA).
Results
Clinical history and examination data
1170 CT examinations met the inclusion criteria ([Table 1]). The average age of the included patients was 60 years ± 17 years standard deviation
(minimum 18 years, maximum 94 years). According to the oncological focus of the university
hospital, the most common indications were staging, treatment monitoring and follow-up
of solid organ tumors and malignant lymphomas (701 of the 1170 patients, 60.0 %),
vascular issues (190 patients; 16.2 %), and inflammatory or interstitial pulmonary
diseases (70 patients; 6.0 %). 32 patients (2.7 %) had 2 primary diseases and 2 patients
(0.2 %) had 3 primary diseases.
Table 1
Medical histories, degree of breast coverage and the BI-RADS classifications in all
1170 CT examinations of the chest. Two primary diseases were documented for 32 patients
(2.7 %) and 3 primary diseases for 2 patients (0.2 %).
|
n
|
%
|
|
primary disease (1170 patients)
|
|
staging in breast carcinoma
|
93
|
8.0
|
|
follow-up of a breast carcinoma
|
13
|
1.1
|
|
staging, treatment monitoring and follow-up of other solid organ tumors
|
422
|
36.1
|
|
staging/treatment monitoring of malignant lymphomas
|
173
|
14.8
|
|
inflammatory pulmonary diseases
|
48
|
4.1
|
|
interstitial pulmonary diseases
|
22
|
1.9
|
|
vascular diseases
|
190
|
16.2
|
|
other
|
237
|
20.3
|
|
BI-RADS consensus classifications (1170 patients)
|
|
1 & 2
|
1082
|
92.5
|
|
≥ 3
|
88
|
7.5
|
|
verification of diagnosis (88 patients)
|
|
biological significance known
|
78
|
88.6
|
|
histological verification
|
22
|
25.0
|
|
senologic-sonographic, X-ray-mammographic, and/or MR-mammographic workup
|
10
|
11.4
|
|
CT and/or clinical course of > 1 year
|
46
|
52.2
|
|
retrospective verification of diagnosis not possible
|
10
|
11.4
|
|
biological classification of CT lesions (88 patients)
|
|
benign
|
46
|
52.3
|
|
malignant
|
31
|
35.2
|
|
unknown
|
11
|
12.5
|
75 – 100 % visualization of the right breast was achieved in 985 CT examinations (84.1 %)
and of the left breast in 975 CT examinations (83.4 %). 50 %-< 75 % visualization
of the breast was achieved 86 times (7.4 %) on the right side and 89 times (7.6 %)
on the left side, 25 %-< 50 % visualization 96 times (8.2 %) on the right side and
100 times (8.5 %) on the left side, and 0 %-< 25 % visualization 3 times (0.3 %) on
the right side and 6 times (0.5 %) on the left side. 37 patients (3.2 %) had undergone
ablation of the right breast and 24 patients (2.1 %) of the left breast. ACR density
category 2 (right breast 544 times, 46.5 %; left breast 560 times, 47.9 %) was seen
more often than density categories 1 (right breast 166, 14.2 %; left breast 164, 14.0 %),
3 (right breast 237, 20.3 %; left breast 236, 20.2 %) and 4 (right breast 186, 15.9 %;
left breast 186, 15.9 %).
In the primary evaluation, 924 images of the right breast (79.0 %) and 940 images
of the left breast (80.3 %) were categorized as BI-RADS 1 and 171 images of the right
breast (14.6 %) or 181 images of the left breast (13.8 %) as BI-RADS 2. 52 examinations
of the right breast (4.4 %) and 57 examinations of the left breast (4.9 %) were classified
as requiring further diagnostic workup (BI-RADS 3 – 5) or were histologically confirmed
as malignant (BI-RADS 6). 8 of these findings (0.7 %) were bilateral. 88 CT examinations
with BI-RADS ≥ 3 classifications per patient (7.5 %) were selected in consensus for
further statistical analysis. 13 patients were downgraded to BI-RADS 1 or 2 in consensus
([Table 1]).
The differential diagnosis was confirmed in 77 of the 88 lesions (87.5 %) by histology
(22; 25.0 %), senological workup (breast ultrasound, X-ray mammography or MR mammography)
(9; 10.2 %) or CT (46; 52.3 %) and/or clinical follow-up for at least 1 year. The
biological significance of 10 of 88 lesions (8.8 %) could not be determined retrospectively
since no or only insufficient follow-up was stored in the patient files. 46 of 88
lesions (52.3 %) were able to be retrospectively classified as benign. 20 lesions
(22.7 %) were already histologically verified as breast carcinomas prior to the index
CT examination. 11 lesions were histologically diagnosed as malignant after the index
CT examination. 7 patients (8.0 %) had breast carcinomas, 3 patients (3.4 %) had intramammary
metastases of other organ tumors, and 1 patient had malignant intramammary lymphoma
(1.1 %).
BI-RADS analyses and carcinoma incidence
In Table [2] the BI-RADS classifications of the retrospective consensus evaluations are compared
to the reports of the CT findings for all 88 CT examinations with retrospective BI-RADS
≥ 3 classifications separated according to the classification of the reference diagnoses.
A histologically verified breast carcinoma was present at the time of CT examination
(BI-RADS 6) in 20 of 88 CT examinations (22.3 %). 9 of 11 breast tumors confirmed
as malignant by diagnostic CT imaging (0.8 % of 1170 total CT examinations and 10.2 %
of the 88 CT examinations with BI-RADS ≥ 3 classifications in the consensus evaluations)
were correctly described as requiring further workup in the written reports. 2 cases
classified as BI-RADS 5 in the consensus evaluations (0.2 % or 2.3 % of the 88 CT
examinations) were overlooked in the diagnostic evaluation of the images as evidenced
by the written reports. This affected 2 patients in advanced stages of oncological
disease who had undergone adequate additional senological diagnosis and treatment
independently of the false-negative CT diagnoses so that the false-negative findings
were without therapeutic or prognostic consequence ([Table 3]). Both findings were probably overlooked during the diagnostic CT evaluations due
to their small size ([Fig. 1]) and the multitude of metastases in the other examined organ regions ([Fig. 2]).
Table 2
Tabular comparison of the retrospective consensus evaluations with the reports of
the CT findings for all 88 CT examinations with retrospective BI-RADS ≥ 3 consensus
classifications separately for the 46 CT examinations with benign lesions, the 31
CT examinations with malignant lesions and the 11 CT examinations without verification
of diagnosis.
|
biological significance
|
|
consensus finding
|
total
|
|
|
BI-RADS
|
1
|
2
|
3
|
4
|
5
|
6
|
|
|
benign
|
report
|
1
|
0
|
0
|
28
|
7
|
1
|
0
|
36
|
|
|
2
|
0
|
0
|
1
|
2
|
0
|
0
|
3
|
|
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
4
|
0
|
0
|
4
|
3
|
0
|
0
|
7
|
|
|
5
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
6
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
total
|
0
|
0
|
33
|
12
|
1
|
0
|
46
|
|
malignant
|
|
1
|
0
|
0
|
0
|
0
|
2
|
0
|
2
|
|
|
2
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
4
|
0
|
0
|
0
|
0
|
2
|
0
|
2
|
|
|
5
|
0
|
0
|
0
|
0
|
7
|
0
|
7
|
|
|
6
|
0
|
0
|
0
|
0
|
0
|
20
|
20
|
|
|
total
|
0
|
0
|
0
|
0
|
11
|
20
|
31
|
|
unclear
|
|
1
|
0
|
0
|
3
|
6
|
1
|
0
|
10
|
|
|
2
|
0
|
0
|
0
|
1
|
0
|
0
|
1
|
|
|
3
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
4
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
5
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
6
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
|
total
|
0
|
0
|
3
|
7
|
1
|
0
|
11
|
|
total
|
|
|
0
|
0
|
36
|
19
|
13
|
20
|
88
|
Table 3
Verification of the reference diagnoses in the 13 patients with false-positive consensus
classifications and both patients with false-negative written CT reports.
|
no.
|
age (years)
|
consensus evaluations (BI-RADS)
|
reports (BI-RADS)
|
biological potential
|
verification of diagnosis
|
course of disease
|
|
false-positive consensus evaluations
|
|
1
|
58
|
4
|
1
|
benign
|
course
|
bronchial carcinoma initially diagnosed in 2012, PET-CT 2012 without findings in the
breast, consistent findings in the target lesion in the 4-year CT follow-up period
|
|
2
|
72
|
4
|
1
|
benign
|
senological clarification
|
breast-conserving therapy of a breast carcinoma in 2004, regular senologic-sonographic
and X-ray-mammographic follow-up examinations until 7/2015
|
|
3
|
61
|
4
|
1
|
benign
|
course
|
breast-conserving therapy of a breast carcinoma in 1997, initial diagnosis of osseous
metastases in 2008, no malignant breast tumor in the 1-year clinical course
|
|
4
|
73
|
4
|
1
|
benign
|
senological clarification
|
elevated tumor markers and weight loss of unclear etiology, senologic-sonographic
and X-ray-mammographic diagnosis BI-RADS 2
|
|
5
|
73
|
4
|
1
|
benign
|
course
|
ablation due to breast carcinoma in 2000, pulmonary, osseous, and hepatic metastases,
consistency of findings in the target lesion in the 1.5-year CT follow-up period
|
|
6
|
83
|
4
|
1
|
benign
|
course
|
malignant melanoma Clark level IV tumor thickness 1.5 mm, initial diagnosis in 2012,
consistency of findings in the target lesion in the 2-year CT follow-up period
|
|
7
|
57
|
4
|
1
|
benign
|
senological clarification
|
metastasized bronchial carcinoma initially diagnosed in 2012, biliary sepsis, senologic-sonographic
and X-ray-mammographic diagnostic imaging in 2012, BI-RADS 2
|
|
8
|
70
|
4
|
2
|
benign
|
course
|
malignant melanoma Clark level IV tumor thickness 2.4 mm, initial diagnosis in 2012,
consistency of findings in the target lesion in the 4-year CT follow-up period
|
|
9
|
48
|
4
|
2
|
benign
|
senological clarification
|
breast carcinoma in 2010, with breast-conserving therapy on the left and ablation
on the right, osseous metastasis in 2011, senologic-sonographic and X-ray-mammographic
follow-up 2012: BI-RADS 2, 1-year X-ray-mammographic follow-up period BI-RADS 2, consistency
of findings in 1-year CT follow-up period
|
|
10
|
68
|
4
|
4
|
benign
|
course
|
breast-conserving therapy of a breast carcinoma in 1995, initial diagnosis of leiomyosarcoma
in 2012, no malignant breast tumor in the 2-year clinical course
|
|
11
|
45
|
4
|
4
|
benign
|
course
|
malignant melanoma tumor thickness 1.22 mm, initial diagnosis in 2012, no breast carcinoma
in the 4-year clinical course
|
|
12
|
72
|
4
|
4
|
benign
|
senological clarification
|
breast-conserving therapy of a breast carcinoma in 1994, pelvic leiomyosarcoma in
2012, no breast carcinoma in the 2.5-year clinical course
|
|
13
|
68
|
5
|
1
|
benign
|
senological clarification
|
breast-conserving therapy of a breast carcinoma in 2007, osseous (initial diagnosis
in 2010) and hepatic (initial diagnosis in 2011) metastases, consistency of findings
in the 6-month CT follow-up period, no malignant breast tumor in the 12-month clinical
course
|
|
false-negative written reports
|
|
1
|
73
|
5
|
1
|
malignant
|
histological workup
|
intramammary metastasis of a malignant melanoma Clark level IV tumor thickness 1.74 mm
|
|
2
|
65
|
5
|
1
|
malignant
|
histological workup
|
intramammary metastases of a breast carcinoma, disseminated pulmonary, pleural, hepatic
metastases
|
Fig. 1 74-year-old patient with hematogenous metastasis of a malignant melanoma in the left
breast missed in the written CT report. 2 hematogenous metastases had been resected
in the left breast 16 months before. The index CT visualized a new focal contrast-enhanced
lesion in the axillary part of the left breast a. 10 days later MR mammography indicated as regular follow-up showed a mass lesion
with intense early contrast enhancement typical for malignancy b. After exploratory surgery the histological workup of the operative specimen yielded
a new metastasis of the malignant melanoma. Arrow = mass lesion. a Index CT examination. b MR mammography, T2-weighted image. c MR mammography, contrast-enhanced subtraction image.
Fig. 2 65-year-old patient suffering from intramammary metastases of a bilateral poorly
differentiated invasive ductal breast cancer which were not noted in the written report
of the CT examination. The written report focussed on mediastinal, axillary, chest
wall, hepatic and bone metastases. There was a history of ablation of the right mamma
and of breast conserving therapy of the left mamma. Metastases in the left breast
were diagnosed 4 weeks following index-CT by ultrasonographically guided transcutaneous
breast biopsy. Arrow = mass lesion. a Transverse slice acquired directly caudal to the mammillary plane. b Transverse slice 5 cm caudal to a.
In the retrospective consensus evaluations, 12 of the 46 lesions diagnosed as benign
according to the reference diagnoses were classified as BI-RADS 4 (13.6 % of the 88
CT examinations with BI-RADS ≥ 3 classifications) and 1 lesion as BI-RADS 5 (1.1 %).The
classification as benign was based on senologic-sonographic and X-ray mammographic
examinations performed at the same time as the index CT in 6 of 14 patients with false-positive
consensus evaluations, on consistent findings at > 1-year CT follow-up examinations
in 5 patients, and on normal clinical follow-up examinations of the breast at > 1
year in 4 patients ([Table 4]).
Table 4
Synoptic presentation of our own results compared with the studies published about
this issue to date.
|
author
|
Porter G et al. [11]
|
Hussain A et al. [9]
|
Hussain A et al. [3]
|
Surov A et al. [4]
|
Monzawa S et al. [10]
|
NN et al.
|
|
year
|
2009
|
2010
|
2010
|
2012
|
2012
|
2017
|
|
method
|
|
evaluation basis
|
HIS, reports
|
HIS, reports
|
HIS, reports
|
HIS, reports
|
HIS, reports
|
RIS/PACS, image documentation
|
|
recording period
|
2007 – 2008
|
2007 – 2008
|
1994 – 2008
|
2006 – 2010
|
2006 – 2010
|
2012
|
|
patients
|
|
|
|
|
|
|
|
number (n)
|
no data
|
432
|
no data
|
no data
|
2945
|
1170
|
|
age (years), mean (min-max)
|
69
|
73 (50 – 86)
|
no data
|
62 (39 – 82)
|
no data
|
60 (18 – 94)
|
|
CT examinations
|
|
|
total number (n)
|
3177
|
432
|
5679
|
8105
|
6308
|
1170
|
|
acquisition slice thickness (mm)
|
no data
|
no data
|
2 to 5
|
1
|
5
|
1
|
|
examinations with i. v. contrast agent administration (n, %)
|
3177 (100)
|
no data
|
no data
|
8105 (100)
|
3667 (58.9)
|
1170 (100)
|
|
lesions per patient
|
|
pathological radiological findings (n, %)
|
34 (1.1)
|
33 (7.6)
|
91 (1.6)
|
89 (1.1)
|
31 (0.5)
|
88 (7.5)
|
|
clarified findings (n, %)
|
34 (1.1)
|
33 (7.6)
|
70 (1.2)
|
64 (0.8)
|
32 (0.5)
|
77 (6.6)
|
|
breast carcinomas (n, %)
|
8 (0.3)
|
6 (1.4)
|
22 (0.4)
|
9 (0.1)
|
10 (0.2)
|
27 (2.3)
|
|
metastases of solid organ tumors (n, %)
|
2 (0.1)
|
0 (0.0)
|
0 (0.0)
|
27 (0.3)
|
0 (0.0)
|
3 (0.3)
|
|
malignant lymphomas (n, %)
|
0 (0.0)
|
2 (0.5)
|
0 (0.0)
|
0 (0.0)
|
0 (0.0)
|
1 (0.1)
|
|
benign lesions (n, %)
|
24 (0.8)
|
25 (5.8)
|
56 (1.0)
|
28 (0.4)
|
22 (0.3)
|
46 (3.9)
|
HIS = hospital information system, RIS = radiology information system, PACS = picture
archiving and communication system.
Image analysis of the lesions
The validity of the CT evaluation criteria for determining malignancy was analyzed
in the 77 lesions with verified differential diagnosis or known biological potential
([Fig. 3], [4]). With a median maximum diameter of 8 mm (minimum 3 mm, maximum 25 mm), benign lesions
were statistically noticeably smaller than malignant lesions with a median maximum
diameter of 24 mm (5 mm, 98 mm) (p < 0.001). A round shape was observed more frequently
in benign lesions, while an irregular shape was most commonly seen in malignant processes
(p < 0.004). A smooth margin and a homogeneous matrix were more commonly seen in benign
tumors and an unsharp or spiculated margin and an inhomogeneous matrix were most often
seen in malignant tumors (p < 0.001). Both density measurements within the lesions
and their normalization in relation to the density of the pectoral muscle resulted
in a statistically insignificant tendency toward higher densities in malignant tumors
(p = 0.072; p = 0.071).
Fig. 3 Frequency distribution of the discriminators on benign and malignant findings in
the 78 index lesions with known biological potential. Irregular shapes (p < 0.01),
irregular or spiculated margins (p < 0.001) and inhomogeneous matrices (p < 0.001)
were more often seen in malignant than in benign pathologies.
Fig. 4 Box plot diagrams visualizing the quotient of densities measured in the index breast
lesions and in the pectoralis musculature on the left side as well as the maximum
lesion diameters on the right side stratified according to benign vs. malignant etiology
in the 78 index lesions with known biological potential, respectively. Malignant lesions
showed stronger enhancement compared to the pectoralis musculature (p = 0.071) as
well as larger diameters (p < 0.001). * = statistical outlier.
Discussion
Contrast-enhanced multidetector computed tomography (MDCT) on conventional whole-body
units is not used in the early detection and local staging of breast carcinomas due
to its low spatial resolution compared to X-ray mammography not allowing evaluation
of microcalcifications, its inferior contrast resolution compared to ultrasound and
MR mammography (MRM), and its radiation exposure that is high compared to the other
methods and is not limited to the breast region. Therefore, publications using a prospective
approach to determine the diagnostic value of MDCT in the breast region are rare.
-
Prior to histological verification, Uematsu T et al. performed contrast-enhanced MDCT,
contrast-enhanced MRM, ultrasound, and X-ray mammography in patients with suspicion
of a breast carcinoma. X-ray mammography examinations were evaluated independently
by two radiologists. In the case of divergent classifications, a consensus decision
was made. There were 210 carcinomas in 201 patients. The T-stage ranged from Tis (20
carcinomas; 19 %) and T1 (123; 59 %) to T2 (47; 22 %). 210 carcinomas (100 %) were
detected on MR mammography, 209 carcinomas (99.5 %) on ultrasound, 208 carcinomas
(98 %) on computed tomography, and 195 carcinomas (93 %) on X-ray mammography. In
the visualization of the local tumor size, MRM (76 %) was superior to CT (71 %; p = 0.001),
ultrasound (56 %; p < 0.0001) and X-ray mammography (52 %; p < 0.0001). The tumors
not detected by CT were 2 of 24 ductal carcinomas in situ (DCIS). The most common
indications of malignancy were focal enhancement (n = 21; 21.5 %), ductal enhancement
(22; 23 %), and segmental (33; 34 %) contrast enhancement.
-
Perrone A et al. used an MDCT protocol including data acquisition in minute 1, 3,
and 8 after i. v. contrast agent administration to preoperatively examine 47 patients
with suspicion of a breast carcinoma and contraindications to MRI [14]. Histological workup of the resected specimens yielded 20 benign findings, 6 DCISs,
and 21 invasive carcinomas. On CT, 25 of 27 carcinomas and all benign lesions were
detected and correctly assessed with respect to their biological significance. 2 DCISs
detected on the basis of microcalcifications were not detected by CT. The accuracy
of MDCT was 96 %. The time-density curves after i. v. contrast administration showed
a tendency toward wash out in carcinomas and prolonged enhancement in benign lesions.
-
Inoue M et al. conducted MDCT examinations using a comparable protocol in 149 patients
with suspicion of a breast carcinoma [14]. All 173 detected breast lesions were histologically verified. 131 of 150 mass lesions
(87 %) and 21 of 23 non-mass lesions (91 %) were malignant. 13 invasive breast carcinomas
detected on MDCT were not detected on X-ray mammography and 5 carcinomas detected
on CT were not detected on ultrasound. Analysis of the time-density curves after i. v.
contrast administration confirmed the value of the curve known from MR mammography
for differential diagnosis.
The potential of CT in diagnostic imaging of the breast shown by Uematsu T et al.
[13], Perrone A. et al. [15], and Inoue M et al. [14] is taken into consideration in the current development of CT systems specifically
designed for breast examinations. The first dedicated CT systems for the breast are
currently being introduced by 2 companies (Koning Corporation, New York, USA; CT Imaging
GmbH, Erlangen, Germany). Whole-body MDCT technology cannot be used to evaluate issues
primarily related to the parenchyma because of the comparatively high radiation exposure
of the breast as well as any tissue in the beam path. Typical effective doses are
specified as 0.2 – 0.6 mSv for X-ray mammography examination of both breasts and 5.0 – 7.0 mSv
for CT examination of the chest [16]
[17].
Senological information obtained from CT examinations of the chest performed due to
pulmonary, hilar, and mediastinal issues should be regularly reviewed when evaluating
findings and included in reporting. Probably as a result of the image-based approach,
the percentage of BI-RADS 3 – 5 findings requiring further workup in the present study
(5.8 %) was higher than in the case of Porter G. et al. (1.1 % of 3177 CT examinations),
Moyle P et al. (1.6 % of 5679 CT examinations), Surov A et al. (1.1 % of 8105 CT examinations)
and Monzawa S et al. (0.5 % of 6308 CT examinations) who based their evaluations on
the retrospective analysis of written reports ([Table 5]) [3]
[4]
[5]
[11] Only Hussain A et al. [8] had a comparable result: 7.6 % of 432 CT examinations with incidental findings in
the breast. The number of BI-RADS 3 – 5 findings retrospectively histologically confirmed
as malignant (0.9 %) was similar to that of Hussain A et al. (1.9 %) and higher than
in the case of Porter G et al. (0.4 %), Moyle P et al. (0.4 %), Surov A et al. (0.4 %),
and Monzawa S et al. (0.2 %) [3]
[4]
[5]
[8]
[11]. The differences are probably the result of different inclusion and exclusion criteria.
Table 5
Discriminators for malignancy assessment (Rev. 2, 31 and 32) of masses: Summary of
our own results compared to the publications of Inoue M et al. [16], Porter G et al. [11], Monzawa S et al. [10] and Surov A et al. [4]. The percentages refer to the analyzed discriminator.
|
author/year
|
Inoue M et al. 2002
|
Porter G et al. 2009
|
Monzawa S et al. 2012
|
Surov A et al. 2012
|
NN et al. 2017
|
|
histology
|
benign
|
malignant
|
p
|
benign
|
malignant
|
p
|
benign
|
malignant
|
p
|
benign
|
malignant
|
p
|
benign
|
malignant
|
p
|
|
patients (n, %)
|
no data
|
no data
|
|
24 (71)
|
10 (29)
|
|
21 (67.7)
|
10 (32)
|
|
28 (44)
|
36 (46)
|
|
46 (59.7)
|
31 (40.3)
|
|
|
lesions (n, %)
|
19 (71)
|
131 (29)
|
|
24 (71)
|
10 (29)
|
|
22 (68.8)
|
10 (31)
|
|
31 (32)
|
67 (68)
|
|
46 (59.7)
|
31 (40.3)
|
|
|
diameter (mm)
|
|
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
8 (3 – 25)
|
24 (5 – 98)
|
< 0.001
|
|
|
no data
|
no data
|
no data
|
18
|
17
|
0.2500
|
15 (5 – 70)[1]
|
17 (10 – 24)
|
no data
|
13 ± 9
|
18 ± 10
|
0.2810
|
10 ± 6
|
27 ± 20
|
|
|
shape (n, %)
|
|
|
15 (31)
|
34 (69)
|
no data
|
no data
|
no data
|
no data
|
10 (83)
|
2 (17)
|
no data
|
15 (20)
|
61 (60)
|
no data
|
37 (74)
|
13 (26)
|
< 0.004
|
|
|
3 (100)
|
0 (0)
|
no data
|
no data
|
no data
|
no data
|
2 (40)
|
3 (60)
|
no data
|
16 (73)
|
6 (27)
|
no data
|
5 (100)
|
0 (0)
|
|
|
|
1 (1)
|
97 (99)
|
< 0.0001
|
no data
|
no data
|
no data
|
1 (20)
|
4 (80)
|
no data
|
0 (0)
|
0 (0)
|
< 0.0001
|
3 (27)
|
8 (73)
|
|
|
contour (n, %)
|
|
|
17 (53)
|
15 (47)
|
no data
|
10 (42)
|
0 (0)
|
0.0150
|
8 (80.0)1
|
2 (20)1
|
no data
|
12 (20)
|
48 (80)
|
no data
|
39 (85)
|
7 (15)
|
< 0.001
|
|
|
(58)
|
4 (100)
|
< 0.0001
|
14 (58)
|
4 (40)
|
0.1500
|
5 (42)1
|
7 (58) 1
|
no data
|
6 (35)
|
11 (65)
|
0.777
|
6 (35)
|
11 (65)
|
|
|
|
1 (1)
|
112 (99)
|
< 0.0001
|
0 (0)
|
6 (60)
|
0.0002
|
0 (0) 1
|
0 (0) 1
|
no data
|
13 (62)
|
8 (38)
|
< 0.0001
|
0 (0)
|
3 (100)
|
|
|
matrix (n, %)
|
|
|
no data
|
no data
|
no data
|
17 (71)
|
8 (80)
|
0.3000
|
11 (65) 1
|
6 (35) 1
|
no data
|
22 (29)
|
55 (71)
|
0.289
|
42 (84)
|
8 (16)
|
< 0.001
|
|
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
1 (50) 1
|
1 (50)1
|
no data
|
9 (43)
|
12 (57)
|
no data
|
3 (19)
|
13 (81)
|
|
|
tumor calcifications (n, %)
|
|
|
no data
|
no data
|
no data
|
2 (8)
|
1 (10)
|
0.4600
|
no data
|
no data
|
no data
|
6 (100)
|
0 (0)
|
< 0.0001
|
5 (100)
|
0 (0)
|
< 0.169
|
|
density after i. v. contrast administration (HU)
|
|
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
51 (5 – 135)
|
68 (15 – 134)
|
0.072
|
|
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
43 ± 20
|
64 ± 33
|
0.0080
|
57 ± 31
|
71 ± 31
|
|
|
density quotient breast tumor/pectoral muscle
|
|
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
no data
|
1.0 (0.2 – 9.4)
|
1.4 (0.4 – 7.3)
|
0.071
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1.4 ± 1.5
|
1.9 ± 1.7
|
|
1 13 mass lesions.
The presented evaluations confirm that the discriminators established for MR mammography
[18]
[19] for determining the biological significance of mass lesions and focal contrast enhancement
(non-mass lesions) can be transferred to diagnostic CT imaging ([Table 5]). Only microcalcifications could not be evaluated on CT due to the lower spatial
resolution compared to X-ray mammography. Future prospective studies must determine
the extent to which it is possible to increase the specificity of information regarding
malignancy of an intramammary lesion using innovative CT technologies such as dual-energy
or multi-energy methods.
The presented study had the following method-related limitations with respect to method.
-
The examined population is only representative of a maximum care hospital with a focus
on oncology. In hospitals and radiology practices with a different clinical focus,
changes in the prevalence and differential diagnostic spectrum of intramammary lesions
can be expected due to variations in age distribution and disease rates.
-
The incidence of clinically occult breast carcinomas remains unknown in the examined
1170 patients due to the retrospective approach of the study and the partially incomplete
visualization of the body of the breast due to the CT examination technique used during
treatment. Therefore, it is not possible to specify the number of false-negative CT
findings in the examined population.
-
It was possible to determine the differential diagnosis or the biological potential
of the lesions diagnosed in the retrospective consensus evaluations in approximately
half of the affected patients only on the basis of the clinical course or CT follow-up
examinations.
The percentage of benign BI-RADS 1/2 findings was 92.5 % in the examined population
of 1170 patients. Due to the retrospective approach and the partially incomplete visualization
of the parenchyma, the percentage of undetected or clinically occult breast carcinomas
could not be determined so that the prevalence of malignant breast tumors cannot be
specified. The retrospectively determined BI-RADS ≥ 3 findings were breast carcinomas
(BI-RADS 6) already verified at the time of CT imaging in 1.7 % (20 patients/CT examinations),
BI-RADS 4/5 findings in 2.7 % (32), and BI-RADS 3 findings in 3.1 % (36). 1.1 % (13)
of the retrospectively recorded BI-RADS 4/5 findings were false-positive and 0.2 %
(2) were false-negative. The malignant breast tumors that were overlooked in primary
reporting affected patients in advanced tumor stages and were not therapeutically
and prognostically relevant. The prevalence of malignant breast lesions (940 per 100 000
patients examined with CT) was approximately twice as high as in mammography screening
[20]
[21]. The results of the study highlight the importance of targeted consideration of
incidental senological findings in CT examinations of the chest also in other clinical
settings than that of the included patients in a clinic with a main focus on oncology.