Mammographic and ultrasonographic features of invasive lobular carcinoma: a review of 16 patients
1 Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
2 Department of Radiology, Phrae Hospital, Phrae, Thailand
3 Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Objectives: To review the mammographic and
ultrasonographic findings of invasive lobular carcinoma (ILC), determine the
role of ultrasonography (US) in the detection of ILC, and determine if ILC is
frequently missed on mammography.
Materials and methods: Approval by Institutional
Review Board was granted. Between January 2000 and July 2008, medical records
and pathological diagnosis of 1,146 invasive breast carcinomas at the authors�
institution were retrospectively reviewed. Only patients with
pathologically-proven pure ILC were included. The initial mammographic reports
were analysed to determine the true-positive and false-negative rates for the
detection of cancer.
Results: There were 37 patients diagnosed as pure
ILC which accounted for 3% of all invasive breast carcinoma. Of the 37
patients, 16 had imaging studies and constituted the material of this study.
The patients ranged in age from 45-76 years (mean age, 56.43 years). Of
the 16 patients, one was asymptomatic, one presented with bleeding tendency and
was found to have factor VIII abnormality (mammography was performed to search
for primary breast carcinoma), one presented with left breast enlargement with
left axillary mass, one presented with right axillary mass, and 12 presented
with palpable breast mass(es). Mammographic breast density was extremely dense
in five, heterogeneously dense in eight, scattered fibroglandular density in
three, and fatty in one. Four patients had bilateral breast carcinoma and one
had multicentricity. The carcinoma was correctly detected on initial
mammographic evaluation in 15 patients (93.75%). The most common mammographic
finding was architectural distortion (8/16 = 50%). The most common US finding was irregular hypoechoic mass (15/18 = 83.3%). There were 18 tumours in 16
patients. Mammography detected 16 tumours but US detected 18 tumours. US was
not better than mammography in the detection of tumours but was helpful in the
detection of multicentricity and guide biopsy.
Conclusion: The most common mammographic feature of
ILC was architectural distortion and the most common US feature of ILC was
irregular or ill-defined hypoechoic mass with acoustic shadowing. These
findings were similar to other studies. The rate of missed diagnosis was not
high but this is likely because most of our patients were symptomatic. US was
not helpful to improve detection of ILC but was helpful to confirm the
suspicious abnormalities on mammograms, detect multicentricity and guide
biopsy. � 2010 Biomedical Imaging and Intervention Journal. All rights
Keywords: breast neoplasms, diagnosis, invasive lobular
Breast carcinoma is a histologically heterogeneous
disease. Invasive lobular carcinoma (ILC) is the second most common breast
malignancy after invasive ductal carcinoma (IDC), accounting for 1% to 20% of
all breast cancers . This wide variation reflects different diagnostic
criteria and the inclusion of variant forms of the cancer. However, most
studies suggest that approximately 7-10% of all invasive breast cancers are ILC
[2-4]. At histopathology, ILC is typically composed of uniform small cells that
diffusely infiltrate in linear fashion (single file) with scarce fibrotic reaction
 leading to difficulty in diagnosis either by clinical examination or
mammography [1,2]. ILC also has a higher rate of mammographically
false-negative results [6,7]. Because mammography has limitation in detecting
ILC, other imaging modalities such as ultrasonography (US) and magnetic
resonance imaging (MRI) have been introduced to improve diagnostic sensitivity
in patients with clinically suspicious lesions [4, 8-13]. This study was
undertaken to review the mammographic and US findings of ILC at the authors�
institution, determine the role of US in the detection of ILC, and determine if
ILC is frequently missed on mammography.
Materials and Methods
The study was approved by the Institutional Review Board.
Between January 2000 and July 2008, medical records and pathological diagnosis
of 1,146 invasive breast carcinomas at the authors� institution were
retrospectively reviewed. Only patients with pathologically-proven pure ILC
were included. Patients with mixed lesions, containing both ILC and ductal
carcinoma were excluded. Mammography was performed using dedicated film-screen
equipments (LoRAD MIII: Damburg, Conn, USA, Siemens Mammomat 3000 Nova, Germany) and the Fuji Computed Radiography System (Fuji Corporation, Tokyo, Japan). Images were obtained in two standard views [mediolateral oblique (MLO) and
craniocaudal (CC)], with additional views as deemed necessary. US was obtained
using a variety of commercially available 5-14 MHz transducers (HDI 5000,
Advanced Technology Laboratories, Bothell, WA, USA, Siemens, Sequoia, Acuson, CA, USA, Toshiba Nemio XG, SSA-580A, Japan and Toshiba Aplio XG, Japan). The initial mammographic reports were analysed to determine the true-positive and
false-negative rates for the detection of cancer. Mammographic images were
retrospectively reevaluated by two breast radiologists with knowledge of the
pathologic report to determine the presence of focal mass, the shape, margin
and density of mass, calcification, architectural distortion, asymmetrical
density, axillary lymphadenopathy and associated features such as skin
thickening, nipple retraction, and breast oedema. In the authors� practice, US
was additionally performed in patients with dense breasts and patients with
suspicious findings on mammogram to confirm the presence of a lesion. If the
lesion was nonpalpable, US was used to guide biopsy since US guided-biopsy is easier, less expensive and avoided radiation compared to mammogram. US images were assessed for the presence of mass, shape, margins, echo pattern, orientation,
posterior acoustic feature, and calcification. Agreement on the imaging
findings was by consensus. The mammographic and US findings were determined
according to the American College of Radiology Breast Imaging Reporting and
Data System (BI-RADS) lexicon . Pathologic review of all lesions was
determined by two pathologists.�����������
There were 37 patients diagnosed as pure ILC which
accounted for 3% of all invasive breast carcinoma. Of the 37 patients, 16 had
imaging studies and constituted the material of this study. The patients ranged
in age from 45-76 years (mean age, 56.43 years). Of the 16 patients, one
was asymptomatic (Figure 1), one presented with bleeding tendency and was found
to have factor VIII abnormality (mammography was performed to search for
primary breast carcinoma) (Figure 2), one presented with left breast
enlargement and left axillary mass (Figure 3), one presented with right
axillary mass, and 12 presented with palpable breast mass(es) (Figure 4). Of
the 12 patients who presented with breast mass(es), one was found to have IDC
on the palpable mass and ILC in the other side which was nonpalpable (Figure
5). The other 11 patients were found to have ILC at the palpable sites.
Mastectomy was performed in 13 patients, breast conservative treatment (BCT)
was performed in two, and one refused further treatment after core biopsy.
Mammographic breast density was extremely dense in four,
heterogeneously dense in eight, scattered fibroglandular density in three, and
fatty breast in one. Four patients had bilateral breast carcinoma. Of these
four patients, three were metachronous and one was synchronous bilateral breast
carcinoma. The first carcinoma was IDC in three and ILC in one. The carcinoma
was correctly detected on initial mammographic evaluation in 15 patients
(93.75%). The missed diagnostic mammogram was retrospectively seen as area of
distortion on both CC and MLO (Figure 6). Multifocal lesions were detected on
US in one (Figure 7). Therefore, 18 tumours were found in 16 patients. The
tumour was more obviously seen on CC view than MLO view (Figures 1 and 5) in
four. The most common mammographic finding was architectural distortion (8/16 =
50%) (Figures 1, 6, 8). The most common US finding was an irregular hypoechoic
mass with ill-defined margins. Tables 1 and 2 summarise the mammographic and US
features of ILC. US was not better than mammography in the detection of tumours
but was helpful in the detection of multifocality and in guiding biopsy.����
Of the different histological types of breast carcinoma,
ILC may be the most difficult to diagnose by mammography because it
characteristically spreads by a single-file infiltration of malignant cells
through the breast stroma with relative paucity of connective tissue reaction,
haemorrhage, necrosis, or calcifications [1, 2, 5, 15]. At mammography, ILC has
a variety of appearances including mass with spiculation, ill-defined or
well-defined margins, asymmetrical density, architectural distortion,
microcalcifications, and normal or benign findings [2, 7, 13, 16]. According to
Hilleren et al. and Lopez et al. [2, 13], the two most frequent
findings were spiculated mass and architectural distortion. In our study,
architectural distortion was the most common finding (50%) and ill-defined mass
was the second most common (25%). Calcifications are often the earliest
manifestation of ductal carcinoma but are less frequent in ILC. Calcifications
were seen in only 2% in the series of Hilleren et al. , 4% in the
series of Helvie et al. , and 24% in the series of Le Gal et al.
. In our study, 31.25% had associated calcifications. The less frequent
calcifications in the series from Hilleren and Helvie may possibly be due to
the poorer quality of the older mammographic machine. Bilaterality and
multicentricity are characteristic features of ILC [1, 2, 5, 15, 17].
Synchronous or metachronous bilateral carcinoma occurs in up to one-third of
patients with ILC [5, 16, 17]. Lobular carcinoma is common in the contralateral
breast but some are ductal . We found four bilateral carcinomas which was
one-fourth of the patients. The contralateral carcinomas in our patients were
ductal more than lobular (3:1). Multicentricity was encountered in only one and
the additional tumours were detected from US. However, the true incidence of
multicentricity is unknown because two had BCT and one was diagnosed by core
biopsy, therefore the entire breast was not sectioned for histologic study. MRI
was also not preformed in this study. The major limitation of using MRI in the
authors� institution is its high cost and long waiting list.
Approximately 20% of ILC are better visualised in one
mammographic view . In the two series [2,19], ILC was better visualised in
the CC view. In this study, four were better seen on CC view than MLO view.
The rate of false-negative findings has been reported to
be as high as 43% [2, 3, 6, 7]. The high false-negative rate may be due to low
opacity with poor margination of the tumour, indirect mammographic signs of
malignancy (architectural distortion, asymmetrical density), and one view
visualisation. The difficulty of making a diagnosis of ILC probably explains
why ILC accounts for a disproportionately large percentage of potential
malpractice suits investigated for failure to diagnose breast cancer . In
this study, only one was initially a missed diagnosis (Figure 6). The low rate
of missed diagnosis in this study may be because most patients were
symptomatic. In a true population-based screening programme or in asymptomatic individuals,
it would be more difficult when there is no �clue� as to the presence of a
Because of the limitations of mammography in detecting
ILC, US and MRI have been used to improve the diagnosis of ILC and to assess
the extent of disease in known cancers [4, 8-13, 20,2 1]. Paramagul et al
 concluded in their study that US was not sensitive and nonspecific in the
diagnosis of ILC but more recent studies showed that US is a useful adjunct to
mammography in the evaluation of ILC [4, 9, 12]. In this study, additional US
was performed in all 16 patients, even in fatty and scattered fibroglandular
breasts, to confirm if there was abnormality over the mammographic suspicious
findings. If the lesion was nonpalpable, US guided-biopsy was used since it was
easier, less expensive and produced no radiation. In this study, the most
common US feature was an irregular hypoechoic mass with acoustic shadowing
which was similar to other studies [4, 8, 9, 12]. Cawson et al.  also
found atypical US feature of hyperechoic mass and a wider than tall appearance.
In this study, one hyperechoic mass was found but it was different from that
found in Cawson et al. The tumour in this study was totally hyperechoic
but in their study tumours were centrally hypoechoic with peripheral
hyperechoic. One patient who had synchronous bilateral breast carcinoma
presented with a palpable mass on the left side and was found to have IDC.
Mammogram of the right breast showed architectural distortion which was seen
only on the CC view. US showed an area of ill-defined heterogeneous echo and
biopsy was performed using US guide which showed ILC. US could not demonstrate
abnormality in one patient who was initially a missed diagnosis.
Retrospectively reviewed mammograms demonstrated an area of architectural
distortion which might show as an abnormality on US if the first reader did not
miss the lesion. Though supplemental US after mammography can increase the rate
of breast cancer detection, it should be performed by specially trained radiologists
since breast US is highly operator-dependent [22, 23]. Though it seems that US
did not improve detection of ILC in this study, it was helpful to confirm the
suspicious lesions from mammography, detect multicentricity, and guide biopsy.
MRI has been introduced as a useful adjunct to mammography
and US in the detection and assessment of the size of ILC [10, 11, 13, 20, 21].
Mann et al. found that MRI was able to detect additional ipsilateral and
contralateral malignant findings not evident at mammography or US in patients
with ILC . Because re-excision rates after breast-conserving surgery (BCS)
of ILC are high, preoperative breast MRI has been proven to reduce re-excision
rates without increasing the rates of mastectomies . However, MRI was not
performed in this study because of its high cost and long waiting list.
In conclusion, the most common mammographic features of
ILC was architectural distortion and the most common US feature of ILC was an
irregular or ill-defined hypoechoic mass with acoustic shadowing. These
findings were similar to other studies. The rate of missed diagnosis is not
high but this is likely because most of the patients in this study were
symptomatic. US was not helpful to improve detection of ILC but was helpful to
confirm the suspicious abnormalities on mammograms, detect multicentricity, and
Figure 1 Metachronous bilateral breast carcinomas. A 54-year-old woman who had history of right mastectomy for IDC 2 years ago came for mammographic screening of the left breast. (A) Left MLO and (B) CC mammograms show an area of mild architectural distortion (arrow) at the outer quadrant which is seen only from CC view. (C) US at the outer quadrant of the left breast shows an irregular hypoechoic mass with acoustic shadowing which proved to be ILC. BCT was performed. (D) Photomicrograph shows slightly large tumour cells arranged in cords and single rows. Mitotic figures are rarely seen (H&E; stain, x400).
Figure 2 A 74-year-old woman presented with bleeding tendency and was found to have factor VIII abnormality, mammography was performed to search for primary breast cancer. (A) Bilateral MLO mammograms show fatty breasts with ill-defined mass (arrow) in the left upper breast. (B) US image of the left breast mass shows an ill-defined high echogenic mass (arrows) with mild acoustic shadowing.
Figure 3 A 62-year-old woman presented with left breast enlargement and a palpable left axillary mass. (A) Bilateral MLO mammograms show heterogeneous dense breasts with diffuse increased breast density and coarse trabeculation on the left side. Scattered micro and macrocalcifications are also seen in the left breast with thickening of the overlying skin. There are multiple enlarged left axillary lymph nodes with increased density and loss of fatty hilum. (B) US of the left breast shows irregular low echogenic mass with calcifications (arrow) and skin thickening.
Figure 4 A 52-year-old woman presented with left breast mass and skin retraction. (A) and (B) Bilateral MLO and CC show a 1.5 cm spiculated mass with faint microcalcifications in the left upper outer quadrant. Skin thickening with retraction (arrow) is shown in the left CC mammogram.
Figure 5 Synchronous bilateral breast carcinomas, ILC on the right side and IDC on the left side. A 56-year-old woman presented with a palpable left breast mass. (A) and (B) Bilateral MLO and CC mammograms show an ill-defined mass at the left upper outer quadrant (arrowheads) which proved to be IDC. There is an area of architectural distortion at the inner quadrant of the left breast seen on CC view (arrow) but no definite distortion or mass on the MLO view. US on the right inner quadrant showed an area of ill-defined heterogeneous echo (not shown) and biopsy was done by US guided which showed ILC.
Figure 6 Metachronous bilateral invasive lobular carcinoma. A 52-year-old woman who was a known case of ILC with left mastectomy one year ago presented with a palpable right axillary mass. The initial mammography was reported as right axillary nodal metastasis without lesion in the right breast. (A) and (B) Bilateral MLO and CC mammograms shows an area of architectural distortion at the upper outer quadrant (arrow). The right axillary node is enlarged and has increased density with loss of fatty hilum. Physical re-examination by the surgeon found a thickening area in the right upper outer quadrant. Biopsy revealed invasive lobular carcinoma.
Figure 7 A 53-year-old woman presented with a palpable right breast mass. (A) Bilateral MLO mammograms show an ill-defined mass with microcalcifications at the right upper outer quadrant (arrow). (B) Composite US images at the right upper outer quadrant show three irregular low echogenic masses with calcifications in the big mass (arrow).
Figure 8 ILC seen as architectural distortion. A 54-year-old woman presented with a palpable mass on the right upper outer quadrant. (A) and (B) Bilateral MLO and CC mammograms show area of architectural distortion at the right upper outer quadrant.
Table 1 Mammographic findings of 16 patients
Table 2 US findings of 18 tumours in 16 patients
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|Received 30 December 2009; received in revised form 29
January 2010, accepted 1 February 2010
Correspondence: Department of Radiology, Chiang Mai University, Chiang Mai, Thailand. Tel.: +66 53945450; Fax: +66 53946136; E-mail: email@example.com (Malai Muttarak).
Please cite as: Muttarak M, Sangchan S, Kongmebhol P, Sukhamwang N, Chaiwun B,
Mammographic and ultrasonographic features of invasive lobular carcinoma: a review of 16 patients, Biomed Imaging Interv J 2010; 6(3):e21