- Email: [email protected]
High-resolution sonography of breast carcinoma
EUROPEAN JOURNAL OF
RADIOLOGY ELSEVIER
European Journal of Radiology 24 (I 997) 11~ I9
High-resolution Giorgio
Rizzatto *, Roberta
sonography
of breast carcinoma
Chersevani, Michela Abbona, Donatella Macorig
Vito Luigi Lombardo,
Department qf’Diagnostic Imaging, General Hospital, oia Virtorio Veneto 171, 34170 Gariria, Ital)
Received 5 September 1996; accepted 5 September 1996
Abstract The use of broad band transducers determined a great increase in spatial, contrast and vascular resolution of ultrasound probes dedicated to breast studies. Providing better definition of normal as well as pathologic features, high resolution sonography improves the specificity of the diagnosis for the majority of malignant nodules and allows a better definition of both local and regional staging. The most impressive results have been achieved in the evaluation of multifocal and multicentric carcinomas, in determining the size of the tumor, its degree of invasion of the surrounding tissues and of the ducts. Color and power Doppler offer further characterization that may be particularly useful in evaluating tumor vascularity during therapies that are planned before surgery. These new staging possibilities must push the radiologists to adequate their instruments and their methods to provide up-to-date and more accurate informations to the surgeon. Copyright 0 1997 Elsevier Science Ireland Ltd. Keywords:
Breast carcinoma;
Ultrasound;
Diagnosis; Staging; Therapy; Ultrasound;
1. Introduction
the majority of malignant nodules and allows a better definition of both local and regional staging [2].
High frequency, real-time, hand-held specific transducers ranging from at least 10 MHz up to 15 MHz and more, and focused in the near field, may allow enough resolution to discriminate the very subtle differences of acoustic impedance among these soft tissues. High frequency probes, when compared to those of lower frequency, can improve both spatial and contrast resolutions. The superficial location of breast also makes it possible to increase the frequency of the Doppler signal that is used both for spectrum analysis and color flow mapping; as a result also the vascular resolution may increase [l]. High resolution transducers provide better definition of normal as well as pathologic features; consequently sonography improves the specificity of the diagnosis for
* Corresponding author. Tel.: + 39 481 5922381592240; 481 535346; e-mail: 0720-048X/96/$15.00 PII SO720-048X(96)01
Doppler
fax:
[email protected] Copyright 0 1997 Elsevier 112-6
Science
Ireland
+ 39
2. Technology The use of new composite ceramics with a wider bandwidth improves axial resolution up to its maximum theoretical values, still avoiding to expose the tissue to a too-high peak acoustic intensity. These ceramics offer multiple frequencies in a single transducer and in broad band arrays. This allows the receiver to be tuned to variable frequencies to maximize the sensitivity at various depths. Resolution in the near field is improved and, at the same time, there is enough penetration in the far field. The lateral resolution increases with thin beams and is maximum in the focal zone of the ultrasonic beam. Narrower beams are obtained with the use of higher frequency transducers. Artifacts originating outside the focal zone are important: they may lead to a wrong diagnosis, because of important
Ltd. All rights
reserved
Rndiology
changes in the structural pattern. Lateral resolution and sensitivity can be improved by focusing the ultrasonic beams. Recent dramatic .increases in computing capability allows one to provide several transmit and receive focal zones throughout the field of view, still maintaining adequate frame rates. Using these powerful focusing configurations, some 10 MHz linear arrays are now producing high quality diagnostic images; due to the inherent complexity of the signal processing they are still of lower definition when compared with those obtained with liquid-path transducers. All the techniques that increase the signal-to-noise ratio, enhancing spatial resolution as well as beam penetration, will also increase contrast resolution. Contrast enhancement is also an especially powerful processing technique of the digitized image. Different parameters affect the vascular resolution of an ultrasound system. The intensity of the Doppler signal is related to the number of erytrocytes within the sensitive region of interest; therefore resolution is limited by the lower number of scatterers in small vessels. At the same time the more slowly moving blood in the small vessels acts as the main limiting factor in the current sensitivity to low Doppler frequency shifts. At present the ability to localize flow in superficial structures has increased without significant cost to spatial resolution and frame rate. New broad-band linear array probes permit the imaging of relatively deep-seated areas of interest (up to 4-6 cm) with peak frequencies ranging from 7.5 to 13 MHz; at the same time these probes use frequencies of 4.557 MHz to optimize the Doppler analysis of the lower flow rate (Fig. 1). As the intensity of the scattered wave is proportional to the fourth power of frequency doubling the frequency will result in an echo from the blood that is 16 times stronger [3].
Fig. I. Behaviour of vascular resolution in relation to the Doppler frequency (IO- I3 MHz, linear array. Doppler frequency: 7 MHzleft; 4.7 MHz right).
24 (1997) I1 -19
Fig. 2. Multicentric carcinoma. Mammography identifies three opacities; sonography defines the presence of two carcinomas while the lesion in the retroareolar region is correctly identified as a segmental ductal dilatation (IO mm) with echogenic material (I3 MHz, annular array).
3. Clinical Results Carcinoma is the main breast disease, at the point that the diagnosis of all other benign abnormalities becomes significant because it rules out cancer. Mammography is the main diagnostic tool to detect cancers that are not palpable; pathology is the gold standard to differentiate masses. The role of sonography is to add more diagnostic parameters to those already found with clinical examination and mammography. As with mammography, many sonographic patterns are nonspecific, with a frequent overlap between benign and malignant findings. Nevertheless, the combination of clinical history, physical, mammographic and sonographic findings can be useful to choose the correct approach, and decide to proceed to more invasive biopsy techniques. Cancer may be multifocal, multicentric and bilateral. Multifocality indicates that several unbridged tumors lie in one quadrant; multicentricity indicates that tumors are located in two or more quadrants [4]. Gallager and Martin [5] found a 74% incidence of multicentricity by subserial whole-organ sectioning; 50% were multicentric in situ carcinomas. Rosen et al. [6] confirmed this high incidence and showed a relationship both to the tumor size and its histological type. Residual cancers after operations designed to preserve the breast without other therapy may therefore result in high local recurrence rates, ranging from 18 to 37% [8]. Consequently the attempt of mapping the tumoral growth must be considered a preliminary step in the staging procedure. The high accuracy of sonography in preoperative detection of multicentric carcinomas has already proven [8,9]. In a recent series of 34 histologically confirmed cases, ultrasound was correct in 87%, while only 33% were diagnosed by mammography [lo]. Ultra-
G. Rirratto
Fig. 3. Small infiltrating ligaments are attracted
et al. / European Journal of’Radiology
with a small hypoechoic core and a larger carcinoma towards the tumor (I3 MHz, annular array).
sonic scanning of the whole breast is our standard procedure for treatment planning. Not only with mammography alone a higher number of multicentric carcinomas are occult [l 1,121; furthermore high resolution sonography allows for a reduction of false positive results due to benign changes (Fig. 2). The sonographic description of breast masses includes parameters such as location, number, size, morsound internal structure, posterior phology, transmission and skin changes. With the up-to-date dedicated instruments these parameters are easily and better assessed; with high resolution sonography the presence and type of vascularization must be also considered, along with the demonstration of microcalcifications, the suggestion of ductal spread and of lymphatic [ 131. involvement Most of these parameters may be very useful to evaluate the anatomical extent or degree of advancement of cancer when diagnosed. A greater involvement
Fig. 4. A ‘taller than shadowing, desmoplasia MHz, annular array).
wide’ infiltrating carcinoma with acoustic and alteration of the Cooper’s ligaments (I 3
desmoplastic
13
24 (1997) I I-19
halo; skin is still preserved
while the echogenic
linear
of imaging in the local and regional staging of breast cancer is highly desirable to provide more accurate information for the surgeon. The parameters involved in the local staging of breast tumors are (i) tumor size, (ii) tumor vascularity, (iii) tumor fixation, (iv) local infiltration and (v) ductal invasion. The parameters involved in regional staging of breast tumors are (i) skin invasion, (ii) underlying fascia and muscle invasion and (iii) lymphatics invasion. Several studies indicate a strong correlation between the size of the cancer and prognosis, with a definite decrement in survival associated with an increasing tumor diameter; nodal involvement is also related to tumor size. A correct determination of tumor size is therefore important for patient management, particularly in case of breast conservation therapy. The poor correlation between mammographic and clinical estimates with the size measured on the pathologic specimen is well known. Sonography has shown the best correlation with pathologic cancer size when compared to mammographic and clinical measurements [8,9].
Fig. 5. Speculations with the histologic
as seen with a I3 MHz annular specimen.
array,
compared
Fig. 6. Large medullary carcinoma with regular margins: the skin is (I 5 MHz, annular array). thinner because of compression
High resolution annular arrays show better accuracy in tumor size determination than do lower frequency linear transducers. First, high resolution sonography can accurately differentiate the mass from desmoplasia that is highly echogenic (Figs. 3 and 4); a mixture of strands of collagen fibers, proliferating tumor cells and fatty inclusions is responsible for the high echogenicity [14]. Desmoplasia cannot be differentiated with palpation, and is just as dense as cancer growths on the mammogram. Second, high resolution sonography provides a better assessment of tumor margins. Morphology is the main pattern to clarify the type of tumor growth: expansive or infiltrating. There are two main morphologic patterns for malignant masses: stellate and circumscribed [15,16]. An infiltrating growth shows irregular and spiculated margins, that appear even when associated to reactive desmomore irregular, plasia; high resolution sonography magnifies this characteristic (Fig. 5). Spiculation seems to be the most distinctive pattern of breast cancer, having a 99.4% of specificity and, respectively, a 91.8% and a 88.8% of
Fig. 7. Highly echogenic invasive lobular carcinoma; the pattern corresponds to the different tissue components with distinct acoustic impedance. Ligament on the right is modified and skin is partially infiltrated (I 3 MHz, annular array).
positive or negative predictive value [ 171. In a retrospective evaluation of 65 cancers we have found that the 7.5 MHz transducer missed 18% of spiculations seen with the 13 MHz transducer. Well circumscribed masses have a rounded or oval shape, slightly blurred or well-defined margins that simply push into the surrounding tissues, causing compression, and dislocation, but no distorsion. High resolution probes allow good resolution throughout the whole field of view and permit very clear real time assessment of the rel’ationships between the different tissues. A slight change of shape and a gliding motion inside breast tissues can be shown by probe compression on a circumscribed, non infiltrating mass [13]. The same is not seen with hard, infiltrating masses. The interface may be an irregular, thick, hyperechoic rim, surrounding the mass, and representing desmoplasia; an increased echogenicity of surrounding fat as a reaction to infiltration, and an architectural distorsion, that pulls on the fibrous stroma of the gland. On the contrary, circumscribed carcinomas do not cause changes in the surrounding tissues, besides compression. The borders are quite well-defined, sometimes only blurred or lobulated (Fig. 6). Due to its better contrast, high resolution sonography also provides the best assessment of the L/AP nodular ratio [l&19] and allows a preliminary differentiation between carcinomas and benign nodules. Evaluating the sonographic characteristics of 750 breast nodules, Stavros et al. [17] reported a 41.6”/0 of sensitivity for breast cancer and a 98% of specificity for taller than wide shapes. The odds ratio of this sign turned out to be second only to the spiculated margin, having a very high positive predictive value. Breast carcinomas are usually hypoechoic masses [20]. The sonographic structure is more or less homogeneous, depending on how homogeneous is the pathoon the presence of fibrous tissue, logic structure, calcifications, tumoral vessels and on necrosis. Very heterogeneous histopathologic patterns forming many interfaces are responsible for echogenic growths, more often associated with intense shadowing [14]; this pattern is very well assessed with the high contrast of the dedicated probes (Fig. 7). Posterior sound transmission depends on the amount of fibrous tissue in the mass. For some time distal attenuation has been considered the main characteristic of malignant masses; the specificity of this sign is very high, 94.7% [14]. Differences in tissue interfaces are better appreciated by high resolution sonography; nonetheless there may be no advantage on the lower frequencies because there can be no change of posterior sound transmission or cancer can cause distal sound enhancement, as is the case of medullary and mutinous carcinomas, of carcinomas growing in cysts, but also in some infiltrating ductal carcinomas (Fig. 8) [13].
G. Rirzatto
et al.
! Europrarr Jourrlal qf Rndiology 24 (1997) II-- 19
15
carcinoma with posterior acoustic enhancement. lateral shadows and tumoral vascularity (I 3 MHz. annular array). Fig 8. Intraductal with calcifications and extensive ductal invasion: the interface towards the deeper muscular planes is preserved F1g. 9. Infiltrating ductal carcinoma (I 3 MHz, annular array). Fig. IO. A multifocal carcinoma identified as two small separate hypoechoic areas exibits a very rich vascularity on power Doppler (I3 MHz. annular and lo- I3 MHz linear arrays). Fig. I I. Benign papillary projection from a cystic wall exhibiting rich vascularity (IO-13 MHz, linear array).
Microcalcifications are associated with cancer in 42% of cases and are easily detected with mammography [21]. Sonography has no role in the detection of microcalcifications, nor on evaluating their morphologic features. Nevertheless, the use of high resolution, correctly focalized probes, can show tiny, echogenic spots that
correspond to the mammographic image; visualization increases with the frequency (Table 1). Most small calcifications do not produce acoustic shadowing because of their size (Fig. 9). Microcalcifications cannot be as easily depicted when located inside echogenic, fibroglandular breast tissue, and there is some difficulty
16
G. Rizatto
Table I Percentage of ultrasound tified with mammography
visibility
Located in a nodule Dispersed within the parenchyma
et al.
of microcalcifications
: Europran
already
Jourrd
of’ Radiolog_v 24 (1997)
1 I- 19
iden-
7.5 MHz
10 MHz
13 MHz
96 61
100 87
100 93
in differentiating them from the echogenic interfaces among tissues. At the moment there is no role for sonography, apart from showing the structure where calcifications are located and guiding bioptic procedures [13]. The demonstration of vessels newly produced by tumors, is another sonographic parameter. Color Doppler has been considered a promising adjunct to ultrasound imaging in the differential diagnosis of breast lesions [22]. Semiquantitative evaluations considering the average number of vessels per square centimeter and average density of color pixels, have resulted in the demonstration of vessels in and around a large proportion of cancers, with a larger area being occupied by vessels in cancers compared to benign masses (Fig. 10) [23]. In a first series of 50 carcinomas we have found flow signals in 90% of cases, with bidirectional flow in 93.3%. Flow signals were peripheral in 33.3%, central in 17.8% and irregular in 48.9%. The ratio vascularized area/nodule size was less than 10% in 44.4% of cases, less than 30% in 40% of cases, and more that 30% in 11.6% of cases. The average size of masses showing flow signals was 1.6 cm, while 1.1 cm was the average size of non vascularized masses. More recently, for the last 24 cancers, we have also considered the number of feeding vessels which was 2.1 for malignant nodules,
Fig. 12. Ductal dilatation at the periphery of a small ductal cinoma due to ductal invasion (13 MHz, annular array).
car-
compared to 1.5 for the benign nodules examined. Among the non vascularized tumors (S/SO) we have found two mucoid carcinomas, containing a lot of mucin and scarce stroma [13]. More recently we compared the results obtained with different Doppler frequencies (4.5 and 7 MHz) in the same group of 48 breast lesions. This group included 17 carcinomas and 31 benign lesions (30 fibroadenomas and one phyllodes tumor); their size ranged from 9 to 23 mm (mean 16 mm). This prospective study included the evaluation of the presence of vascularity, of the number of feeding vessels, of the distribution of vessels and of the ratio between the lesion and its
Table 2 Presentation rate of the same color Doppler parameters according to the Doppler frequency (4.5 or 7 MHz), both for benign and malignant nodules Benign
(‘X)
4.5 MHz Vascularity Present Absent Feeding vessels One Two or more Distribution of vessels Peripheral Intranodular Vascularized area < 10% < 30’%1 > 30%
Malignant 7 MHz
(‘A>)
4.5 MHz
7 MHz
41.9 58.1
61.2 38.8
88.2 Il.8
94.1 5.9
84.6 15.4
73.7 26.3
13.3 86.7
6.2 93.8
92.3 15.3
94.7 31.5
73.3 80.0
75.0 93.7
53.3 40.0 6.1
37.5 50.0 12.5
100
100
Fig. 13. Magnification of enlarged ducts at the upper right margin of a ductal carcinoma (K) and its histologic specimen showing neoplastic cells inside the ducts (13 MHz, annular array).
G. Rizzatto et al.
i European Journal of Radiology 24 (1997) I l-19
Fig. 14. Superficial invasive ductal carcinoma interrupting the superficial fascia and infiltrating the skin (I3 MHz, annular array).
vascularized area (Table 2). In all the cases we changed only the Doppler frequency while keeping the same focusing, filter and pulse repetition rate. With the higher frequency most of the nodules exhibited some vascularity (Fig. 11). Still, considering only this parameter there would be no possibility to discriminate benign from malignant lesions. Other Doppler parameters like the presence of more than one feeding vessel and of significant intranodular vascularity make more confident the diagnosis of carcinoma. The higher Doppler frequency makes the separation more evident (Fig. 1). Most benign nodules that exhibit also intranodular vessels are found in young women and may show an active proliferation; the possibility to recognize a larger number of these lesions will result in an earlier and more cosmetic surgery [13]. Infiltrating ductal carcinoma may have an extensive intraductal component which causes local recurrence in case of very conservative surgery. Mammography may have a good predictive value to determine the possibility of an extensive intraductal component; cancers showing calcifications on the mammogram are associ-
Fig. 15. Superficial invasive ductal carcinoma preserving the skin and subcutaneous tissues: Cooper’s ligaments converge towards the tumor ( I3 MHz, annular array).
17
Fig. 16. Magnification of the skin and the subcutaneous fat in a case of lymphatic infiltration (20 MHz, annular array): the hyperechoic tissues enhance visualization of the dilated lymphatic network.
ated with an extensive intraductal component in 65% of cases [24]. High resolution sonography may suggest ductal spread of carcinoma [13]. An asymmetric, dilated duct or stretched and stiff hypoechoic, tubular structures at the periphery of cancer are the most distinctive characters (Figs. 9, 12 and 13). The sonographic pattern of hypoechoic, tubular, structures at the periphery of a mass has been correlated to the pathologic specimen, to ascertain the meaning of such images [25]. The US/ pathologic correlation in 33 TlNO cancers has resulted in 11 true-positive, 14 true-negative, three false-positive and five false-negative findings [26]. Sonography cannot predict the existence of cancer cells inside a duct. Nevertheless, the demonstration of tubular structures at the periphery of a mass must be considered along with the nodule’s size an invaluable information for the surgeon before conservative surgery. Color Doppler may be employed to differentiate vessels from ducts, as both are tubular structures. Regional staging involves evaluation of the skin and the subcutaneous tissues; these structures can be well evaluated only with high frequency, highly focussed transducers. The sonographic pattern of normal skin is a more or less homogeneous band that is more echogenie than the underlying fat tissue. Normal skin thickness varies between 0.5 mm and 2 mm, and is usually maximum in the lower quadrants, towards the inframammary fold. The subcutaneous region contains fat and lymphatics. Subcutaneous fat is crossed by thin, echogenic lines, oblique to the skin surface, that represent Cooper’s ligaments. These ligaments go from the skin to the deep pectoral fascia and are well visualized both in subcutaneous fat as well as in fatty breasts, with a regular orientation and in contrast with hypoechoic fat. Superficial masses, besides causing changes in subcutaneous fat, usually infiltrate the skin, that thickens or changes its echogenicity (Fig. 14). Less superficial
18
G. Rirrutto
et cd. I European Journul q/ Rndiolog~~ 24 (1997) I I
cancers may also cause skin changes by pulling on Cooper’s ligaments, and by changing their orientation (Figs. 3, 4, 7 and 15). As it concerns the possibility of evaluating the invasion of the deeper muscular planes high resolution sonography is still limited if compared to magnetic resonance; nonetheless diagnosis is correct in 95% of the cases (Fig. 9). Underestimation may usually occur in very large glandular breasts. Breast lymphatics form a microscopic network in the superficial areas of the breast, mainly between the skin and subcutaneous tissues and also along ducts. Normal lymphatics cannot be visualized, but in case of dilatation-due to inflammation or carcinomatous infiltrationthey can be demonstrated as hypo-anechoic, thin lines, parallel and perpendicular to the skin, forming a network (Fig. 16) [13]. Axillary and supraclavicular nodes are the most frequent localization of breast cancer, starting from the outer breast quadrants. Sonography can easily detect enlarged lymph nodes, show size and shape, and evaluate if the echogenic hilum is maintained. Node enlargement can result from inflammation, hyperplasia, breast cancer or metastases. A rounded shape and loss of the echogenic hilum suggest infiltration. When compared to mammography and clinical examination, sonography has a higher sensitivity in the detection of axillary lymph nodes [27]; the better contrast provided by high resolution sonography permits a better visualization of nodes dispersed in the fatty tissues of the axilla or of the peripheral breast. Anyway these are preoperative indications and, of course, pathologic examination of lymph nodes after surgery is the only way to rule out cancer diffusion. In summary high resolution sonogrdphy is useful in the characterization of solid masses of the breast. It improves the diagnostic specificity reducing the need for biopsy; furthermore it allows better local and regional staging of tumors. The potential for cost reduction and better treatment planning promotes high resolution ultrasound as a standard procedure to evaluate patients with breast cancer. Radiological departments must upgrade their breast technology with this new facility to enhance the quality of their diagnostic performances.
References PI Rizzatto
PI PI
G. Instrumentation. In: Solbiati L, Rizzatto G, eds. Ultrasound of superficial structures: high frequencies. Doppler and interventional procedures. Edinburgh: Churchill Livingstone 1995; t-21. Rizzatto G, Chersevani R, Solbiati L. High-resolution ultrasound assists in breast diagnosis. Diagnostic Imaging Int 1993; 5: 42245. Burns. PN. Principles of US. In: RiIkin MD, Charboneau JW,
19
Laing FC, eds. Ultrasound 1991. Oak Brook: RSNA 1991: 33-55. V, Prechtel K. Atlas der BrustdrAse und ihrer [41 Barth Erkrankungen. Stuttgart: Enke 1990. [51 Gallager HS, Martin JF. The study of mammary carcinoma by mammography and whole organ sectioning: early observations. Cancer 1969: 23: 8555859. [61 Rosen PP, Fracchia AA, Urban JA, Schottenfeid P, Robbins GF. Residual mammary carcinoma following simulated partial mastectomy. Cancer 1975; 35: 739-747. for breast carcinoma. In: Bland 171 Leis PJ. Prognostic parameters KI, Copeland EM, eds. The breast: comprehensive management of benign and malignant diseases. Philadelphia: WB Saunders: 1993; 331-350. and PI Fornage B, Toubas 0, Morel M. Clinical, mammographic, sonographic determination of preoperative breast cancer size. Cancer 1987; 60: 765-771. [91 Madjiar H, Ladner HA, Sauerbrei W, Oberstein A, Primpeler A. Pfeiderer A. Preoperative staging of breast cancer by palpation, mammography and high resolution ultrasound. Ultrasound Obstet Gynecol 1993; 3: 1855190. H, Sauerbrei W. Ladner HA, Pfeiderer A. Sono[lOI Madjiar graphic detection of occult tumor extension, In: Madjiar H. Teubner J, Hackelier BJ, eds. Breast ultrasound update. Basel: Karger 1994: 140- 146. M. Mammographically [I 11 Holland R, Hendriks JHCL, Mravunac occult breast cancer. A pathologic and radiologic study. Cancer 1983; 52: 1810~1819. M, Hendriks JHCL. HistoST Holland R, Veling SHJ. Mravunac logic multifocality of TIS, Tl-2 breast carcinomas, Implications for clinical trials of breast conserving surgery. Cancer 1985: 56: 9799990. R, Tsunoda-Shimiru H, Giuseppetti GM, Rizzatto [I31 Chersevani G. Breast. In: Solbiati L. Rizzatto G, eds. Ultrasound of superficial structures: high frequencies, Doppler and interventional procedures. Edinburgh: Churchill Livingstone 1995: 141~ 199. J, Bohrer M, van-Kaick G, Georgi M. Echo[I41 Teubner morphologie del Mammakarzinoms. Radiologe 1993; 33: 277286. Feig SA. Breast masses, Mammographic and sonographic evaluation. Radio1 Clin North Am 1992; 30: 67-92. Jackson VP. Sonography of malignant breast disease. Seminars in Ultrasound. CT, and MR 1989; IO: 119~131. Stavros AT, Thickman D, Rapp CL, Dennis MA, Parker SH, Sisney GA. Solid breast nodules: use of sonogrdphy to distinguish between benign and malignant lesions. Radiology 1995; 196: 123-134. BD, Sneige N, Faroux MJ, Andry E. Sonographic U81 Fornage appearance and ultrasound guided fine-needle aspiration biopsy of breast carcinomas smaller than I cm’. J Ultrasound Med 1990; 9: 5599568. BD, Lorigan JG, Andry E. Fibroadenoma of the [I91 Fornage breast: sonographic appearance. Radiology 1989; 172: 67 I 675. C, Soriano RZ, Kurtz AB, Goldberg BB. UltraWI Cole-Beuglet sound analysis of 104 primary breast carcinomas classified according to histopathologic type. Radiology 1983: 147: 191~ 196. [2l] Sickles EA. Mammogrdphic features of 300 consecutive nonpalpable breast cancers, AJR 1986; 146: 661-663. [22] Cosgrove DO, Bamber JC, Davey JB, McKinna JA, Sinnett HD. Color Doppler signals from breast tumors. Work in progress, Radiology 1990; 176: l75- 180. [23] Cosgrove DO, Kedar RP, Bamber JC et al. Breast diseases: Color Doppler US in differential diagnosis. Radiology 1993: 189: 99 104.
G. Rizzatto
et al. i European Journal
features predicting [24] Stomper PC, Connolly JL. Mammographic an extensive intraductal component in early-stage infiltrating ductal carcinoma. AJR 1992; 158: 269-272. [25] Tsunoda-Shimizu H, Ueno E, Tohno E. Echogram of ductal spreading of breast carcinoma. Jpn J Med Ultrasonics 1990; 17: 44449. [26] Tsunoda-Shimizu H, Ueno E, Tohno E, Tanaka H, Aiyoshi Y,
of Radiology 24 (1997) 11-19
19
Itai Y. Breast conservative therapy: the evaluation of ductal spreading of breast cancer by ultrasound. JSUM Proceedings May 1993: 4599460. [27] Pamilo M, Soiva M, Lavast EM. Real-time ultrasound, axillary mammography, and clinical examination in the detection of axillary lymph node metastases in breast cancer patients. J Ultrasound Med 1989; 8: 1155120.
RADIOLOGY ELSEVIER
European Journal of Radiology 24 (I 997) 11~ I9
High-resolution Giorgio
Rizzatto *, Roberta
sonography
of breast carcinoma
Chersevani, Michela Abbona, Donatella Macorig
Vito Luigi Lombardo,
Department qf’Diagnostic Imaging, General Hospital, oia Virtorio Veneto 171, 34170 Gariria, Ital)
Received 5 September 1996; accepted 5 September 1996
Abstract The use of broad band transducers determined a great increase in spatial, contrast and vascular resolution of ultrasound probes dedicated to breast studies. Providing better definition of normal as well as pathologic features, high resolution sonography improves the specificity of the diagnosis for the majority of malignant nodules and allows a better definition of both local and regional staging. The most impressive results have been achieved in the evaluation of multifocal and multicentric carcinomas, in determining the size of the tumor, its degree of invasion of the surrounding tissues and of the ducts. Color and power Doppler offer further characterization that may be particularly useful in evaluating tumor vascularity during therapies that are planned before surgery. These new staging possibilities must push the radiologists to adequate their instruments and their methods to provide up-to-date and more accurate informations to the surgeon. Copyright 0 1997 Elsevier Science Ireland Ltd. Keywords:
Breast carcinoma;
Ultrasound;
Diagnosis; Staging; Therapy; Ultrasound;
1. Introduction
the majority of malignant nodules and allows a better definition of both local and regional staging [2].
High frequency, real-time, hand-held specific transducers ranging from at least 10 MHz up to 15 MHz and more, and focused in the near field, may allow enough resolution to discriminate the very subtle differences of acoustic impedance among these soft tissues. High frequency probes, when compared to those of lower frequency, can improve both spatial and contrast resolutions. The superficial location of breast also makes it possible to increase the frequency of the Doppler signal that is used both for spectrum analysis and color flow mapping; as a result also the vascular resolution may increase [l]. High resolution transducers provide better definition of normal as well as pathologic features; consequently sonography improves the specificity of the diagnosis for
* Corresponding author. Tel.: + 39 481 5922381592240; 481 535346; e-mail: 0720-048X/96/$15.00 PII SO720-048X(96)01
Doppler
fax:
[email protected] Copyright 0 1997 Elsevier 112-6
Science
Ireland
+ 39
2. Technology The use of new composite ceramics with a wider bandwidth improves axial resolution up to its maximum theoretical values, still avoiding to expose the tissue to a too-high peak acoustic intensity. These ceramics offer multiple frequencies in a single transducer and in broad band arrays. This allows the receiver to be tuned to variable frequencies to maximize the sensitivity at various depths. Resolution in the near field is improved and, at the same time, there is enough penetration in the far field. The lateral resolution increases with thin beams and is maximum in the focal zone of the ultrasonic beam. Narrower beams are obtained with the use of higher frequency transducers. Artifacts originating outside the focal zone are important: they may lead to a wrong diagnosis, because of important
Ltd. All rights
reserved
Rndiology
changes in the structural pattern. Lateral resolution and sensitivity can be improved by focusing the ultrasonic beams. Recent dramatic .increases in computing capability allows one to provide several transmit and receive focal zones throughout the field of view, still maintaining adequate frame rates. Using these powerful focusing configurations, some 10 MHz linear arrays are now producing high quality diagnostic images; due to the inherent complexity of the signal processing they are still of lower definition when compared with those obtained with liquid-path transducers. All the techniques that increase the signal-to-noise ratio, enhancing spatial resolution as well as beam penetration, will also increase contrast resolution. Contrast enhancement is also an especially powerful processing technique of the digitized image. Different parameters affect the vascular resolution of an ultrasound system. The intensity of the Doppler signal is related to the number of erytrocytes within the sensitive region of interest; therefore resolution is limited by the lower number of scatterers in small vessels. At the same time the more slowly moving blood in the small vessels acts as the main limiting factor in the current sensitivity to low Doppler frequency shifts. At present the ability to localize flow in superficial structures has increased without significant cost to spatial resolution and frame rate. New broad-band linear array probes permit the imaging of relatively deep-seated areas of interest (up to 4-6 cm) with peak frequencies ranging from 7.5 to 13 MHz; at the same time these probes use frequencies of 4.557 MHz to optimize the Doppler analysis of the lower flow rate (Fig. 1). As the intensity of the scattered wave is proportional to the fourth power of frequency doubling the frequency will result in an echo from the blood that is 16 times stronger [3].
Fig. I. Behaviour of vascular resolution in relation to the Doppler frequency (IO- I3 MHz, linear array. Doppler frequency: 7 MHzleft; 4.7 MHz right).
24 (1997) I1 -19
Fig. 2. Multicentric carcinoma. Mammography identifies three opacities; sonography defines the presence of two carcinomas while the lesion in the retroareolar region is correctly identified as a segmental ductal dilatation (IO mm) with echogenic material (I3 MHz, annular array).
3. Clinical Results Carcinoma is the main breast disease, at the point that the diagnosis of all other benign abnormalities becomes significant because it rules out cancer. Mammography is the main diagnostic tool to detect cancers that are not palpable; pathology is the gold standard to differentiate masses. The role of sonography is to add more diagnostic parameters to those already found with clinical examination and mammography. As with mammography, many sonographic patterns are nonspecific, with a frequent overlap between benign and malignant findings. Nevertheless, the combination of clinical history, physical, mammographic and sonographic findings can be useful to choose the correct approach, and decide to proceed to more invasive biopsy techniques. Cancer may be multifocal, multicentric and bilateral. Multifocality indicates that several unbridged tumors lie in one quadrant; multicentricity indicates that tumors are located in two or more quadrants [4]. Gallager and Martin [5] found a 74% incidence of multicentricity by subserial whole-organ sectioning; 50% were multicentric in situ carcinomas. Rosen et al. [6] confirmed this high incidence and showed a relationship both to the tumor size and its histological type. Residual cancers after operations designed to preserve the breast without other therapy may therefore result in high local recurrence rates, ranging from 18 to 37% [8]. Consequently the attempt of mapping the tumoral growth must be considered a preliminary step in the staging procedure. The high accuracy of sonography in preoperative detection of multicentric carcinomas has already proven [8,9]. In a recent series of 34 histologically confirmed cases, ultrasound was correct in 87%, while only 33% were diagnosed by mammography [lo]. Ultra-
G. Rirratto
Fig. 3. Small infiltrating ligaments are attracted
et al. / European Journal of’Radiology
with a small hypoechoic core and a larger carcinoma towards the tumor (I3 MHz, annular array).
sonic scanning of the whole breast is our standard procedure for treatment planning. Not only with mammography alone a higher number of multicentric carcinomas are occult [l 1,121; furthermore high resolution sonography allows for a reduction of false positive results due to benign changes (Fig. 2). The sonographic description of breast masses includes parameters such as location, number, size, morsound internal structure, posterior phology, transmission and skin changes. With the up-to-date dedicated instruments these parameters are easily and better assessed; with high resolution sonography the presence and type of vascularization must be also considered, along with the demonstration of microcalcifications, the suggestion of ductal spread and of lymphatic [ 131. involvement Most of these parameters may be very useful to evaluate the anatomical extent or degree of advancement of cancer when diagnosed. A greater involvement
Fig. 4. A ‘taller than shadowing, desmoplasia MHz, annular array).
wide’ infiltrating carcinoma with acoustic and alteration of the Cooper’s ligaments (I 3
desmoplastic
13
24 (1997) I I-19
halo; skin is still preserved
while the echogenic
linear
of imaging in the local and regional staging of breast cancer is highly desirable to provide more accurate information for the surgeon. The parameters involved in the local staging of breast tumors are (i) tumor size, (ii) tumor vascularity, (iii) tumor fixation, (iv) local infiltration and (v) ductal invasion. The parameters involved in regional staging of breast tumors are (i) skin invasion, (ii) underlying fascia and muscle invasion and (iii) lymphatics invasion. Several studies indicate a strong correlation between the size of the cancer and prognosis, with a definite decrement in survival associated with an increasing tumor diameter; nodal involvement is also related to tumor size. A correct determination of tumor size is therefore important for patient management, particularly in case of breast conservation therapy. The poor correlation between mammographic and clinical estimates with the size measured on the pathologic specimen is well known. Sonography has shown the best correlation with pathologic cancer size when compared to mammographic and clinical measurements [8,9].
Fig. 5. Speculations with the histologic
as seen with a I3 MHz annular specimen.
array,
compared
Fig. 6. Large medullary carcinoma with regular margins: the skin is (I 5 MHz, annular array). thinner because of compression
High resolution annular arrays show better accuracy in tumor size determination than do lower frequency linear transducers. First, high resolution sonography can accurately differentiate the mass from desmoplasia that is highly echogenic (Figs. 3 and 4); a mixture of strands of collagen fibers, proliferating tumor cells and fatty inclusions is responsible for the high echogenicity [14]. Desmoplasia cannot be differentiated with palpation, and is just as dense as cancer growths on the mammogram. Second, high resolution sonography provides a better assessment of tumor margins. Morphology is the main pattern to clarify the type of tumor growth: expansive or infiltrating. There are two main morphologic patterns for malignant masses: stellate and circumscribed [15,16]. An infiltrating growth shows irregular and spiculated margins, that appear even when associated to reactive desmomore irregular, plasia; high resolution sonography magnifies this characteristic (Fig. 5). Spiculation seems to be the most distinctive pattern of breast cancer, having a 99.4% of specificity and, respectively, a 91.8% and a 88.8% of
Fig. 7. Highly echogenic invasive lobular carcinoma; the pattern corresponds to the different tissue components with distinct acoustic impedance. Ligament on the right is modified and skin is partially infiltrated (I 3 MHz, annular array).
positive or negative predictive value [ 171. In a retrospective evaluation of 65 cancers we have found that the 7.5 MHz transducer missed 18% of spiculations seen with the 13 MHz transducer. Well circumscribed masses have a rounded or oval shape, slightly blurred or well-defined margins that simply push into the surrounding tissues, causing compression, and dislocation, but no distorsion. High resolution probes allow good resolution throughout the whole field of view and permit very clear real time assessment of the rel’ationships between the different tissues. A slight change of shape and a gliding motion inside breast tissues can be shown by probe compression on a circumscribed, non infiltrating mass [13]. The same is not seen with hard, infiltrating masses. The interface may be an irregular, thick, hyperechoic rim, surrounding the mass, and representing desmoplasia; an increased echogenicity of surrounding fat as a reaction to infiltration, and an architectural distorsion, that pulls on the fibrous stroma of the gland. On the contrary, circumscribed carcinomas do not cause changes in the surrounding tissues, besides compression. The borders are quite well-defined, sometimes only blurred or lobulated (Fig. 6). Due to its better contrast, high resolution sonography also provides the best assessment of the L/AP nodular ratio [l&19] and allows a preliminary differentiation between carcinomas and benign nodules. Evaluating the sonographic characteristics of 750 breast nodules, Stavros et al. [17] reported a 41.6”/0 of sensitivity for breast cancer and a 98% of specificity for taller than wide shapes. The odds ratio of this sign turned out to be second only to the spiculated margin, having a very high positive predictive value. Breast carcinomas are usually hypoechoic masses [20]. The sonographic structure is more or less homogeneous, depending on how homogeneous is the pathoon the presence of fibrous tissue, logic structure, calcifications, tumoral vessels and on necrosis. Very heterogeneous histopathologic patterns forming many interfaces are responsible for echogenic growths, more often associated with intense shadowing [14]; this pattern is very well assessed with the high contrast of the dedicated probes (Fig. 7). Posterior sound transmission depends on the amount of fibrous tissue in the mass. For some time distal attenuation has been considered the main characteristic of malignant masses; the specificity of this sign is very high, 94.7% [14]. Differences in tissue interfaces are better appreciated by high resolution sonography; nonetheless there may be no advantage on the lower frequencies because there can be no change of posterior sound transmission or cancer can cause distal sound enhancement, as is the case of medullary and mutinous carcinomas, of carcinomas growing in cysts, but also in some infiltrating ductal carcinomas (Fig. 8) [13].
G. Rirzatto
et al.
! Europrarr Jourrlal qf Rndiology 24 (1997) II-- 19
15
carcinoma with posterior acoustic enhancement. lateral shadows and tumoral vascularity (I 3 MHz. annular array). Fig 8. Intraductal with calcifications and extensive ductal invasion: the interface towards the deeper muscular planes is preserved F1g. 9. Infiltrating ductal carcinoma (I 3 MHz, annular array). Fig. IO. A multifocal carcinoma identified as two small separate hypoechoic areas exibits a very rich vascularity on power Doppler (I3 MHz. annular and lo- I3 MHz linear arrays). Fig. I I. Benign papillary projection from a cystic wall exhibiting rich vascularity (IO-13 MHz, linear array).
Microcalcifications are associated with cancer in 42% of cases and are easily detected with mammography [21]. Sonography has no role in the detection of microcalcifications, nor on evaluating their morphologic features. Nevertheless, the use of high resolution, correctly focalized probes, can show tiny, echogenic spots that
correspond to the mammographic image; visualization increases with the frequency (Table 1). Most small calcifications do not produce acoustic shadowing because of their size (Fig. 9). Microcalcifications cannot be as easily depicted when located inside echogenic, fibroglandular breast tissue, and there is some difficulty
16
G. Rizatto
Table I Percentage of ultrasound tified with mammography
visibility
Located in a nodule Dispersed within the parenchyma
et al.
of microcalcifications
: Europran
already
Jourrd
of’ Radiolog_v 24 (1997)
1 I- 19
iden-
7.5 MHz
10 MHz
13 MHz
96 61
100 87
100 93
in differentiating them from the echogenic interfaces among tissues. At the moment there is no role for sonography, apart from showing the structure where calcifications are located and guiding bioptic procedures [13]. The demonstration of vessels newly produced by tumors, is another sonographic parameter. Color Doppler has been considered a promising adjunct to ultrasound imaging in the differential diagnosis of breast lesions [22]. Semiquantitative evaluations considering the average number of vessels per square centimeter and average density of color pixels, have resulted in the demonstration of vessels in and around a large proportion of cancers, with a larger area being occupied by vessels in cancers compared to benign masses (Fig. 10) [23]. In a first series of 50 carcinomas we have found flow signals in 90% of cases, with bidirectional flow in 93.3%. Flow signals were peripheral in 33.3%, central in 17.8% and irregular in 48.9%. The ratio vascularized area/nodule size was less than 10% in 44.4% of cases, less than 30% in 40% of cases, and more that 30% in 11.6% of cases. The average size of masses showing flow signals was 1.6 cm, while 1.1 cm was the average size of non vascularized masses. More recently, for the last 24 cancers, we have also considered the number of feeding vessels which was 2.1 for malignant nodules,
Fig. 12. Ductal dilatation at the periphery of a small ductal cinoma due to ductal invasion (13 MHz, annular array).
car-
compared to 1.5 for the benign nodules examined. Among the non vascularized tumors (S/SO) we have found two mucoid carcinomas, containing a lot of mucin and scarce stroma [13]. More recently we compared the results obtained with different Doppler frequencies (4.5 and 7 MHz) in the same group of 48 breast lesions. This group included 17 carcinomas and 31 benign lesions (30 fibroadenomas and one phyllodes tumor); their size ranged from 9 to 23 mm (mean 16 mm). This prospective study included the evaluation of the presence of vascularity, of the number of feeding vessels, of the distribution of vessels and of the ratio between the lesion and its
Table 2 Presentation rate of the same color Doppler parameters according to the Doppler frequency (4.5 or 7 MHz), both for benign and malignant nodules Benign
(‘X)
4.5 MHz Vascularity Present Absent Feeding vessels One Two or more Distribution of vessels Peripheral Intranodular Vascularized area < 10% < 30’%1 > 30%
Malignant 7 MHz
(‘A>)
4.5 MHz
7 MHz
41.9 58.1
61.2 38.8
88.2 Il.8
94.1 5.9
84.6 15.4
73.7 26.3
13.3 86.7
6.2 93.8
92.3 15.3
94.7 31.5
73.3 80.0
75.0 93.7
53.3 40.0 6.1
37.5 50.0 12.5
100
100
Fig. 13. Magnification of enlarged ducts at the upper right margin of a ductal carcinoma (K) and its histologic specimen showing neoplastic cells inside the ducts (13 MHz, annular array).
G. Rizzatto et al.
i European Journal of Radiology 24 (1997) I l-19
Fig. 14. Superficial invasive ductal carcinoma interrupting the superficial fascia and infiltrating the skin (I3 MHz, annular array).
vascularized area (Table 2). In all the cases we changed only the Doppler frequency while keeping the same focusing, filter and pulse repetition rate. With the higher frequency most of the nodules exhibited some vascularity (Fig. 11). Still, considering only this parameter there would be no possibility to discriminate benign from malignant lesions. Other Doppler parameters like the presence of more than one feeding vessel and of significant intranodular vascularity make more confident the diagnosis of carcinoma. The higher Doppler frequency makes the separation more evident (Fig. 1). Most benign nodules that exhibit also intranodular vessels are found in young women and may show an active proliferation; the possibility to recognize a larger number of these lesions will result in an earlier and more cosmetic surgery [13]. Infiltrating ductal carcinoma may have an extensive intraductal component which causes local recurrence in case of very conservative surgery. Mammography may have a good predictive value to determine the possibility of an extensive intraductal component; cancers showing calcifications on the mammogram are associ-
Fig. 15. Superficial invasive ductal carcinoma preserving the skin and subcutaneous tissues: Cooper’s ligaments converge towards the tumor ( I3 MHz, annular array).
17
Fig. 16. Magnification of the skin and the subcutaneous fat in a case of lymphatic infiltration (20 MHz, annular array): the hyperechoic tissues enhance visualization of the dilated lymphatic network.
ated with an extensive intraductal component in 65% of cases [24]. High resolution sonography may suggest ductal spread of carcinoma [13]. An asymmetric, dilated duct or stretched and stiff hypoechoic, tubular structures at the periphery of cancer are the most distinctive characters (Figs. 9, 12 and 13). The sonographic pattern of hypoechoic, tubular, structures at the periphery of a mass has been correlated to the pathologic specimen, to ascertain the meaning of such images [25]. The US/ pathologic correlation in 33 TlNO cancers has resulted in 11 true-positive, 14 true-negative, three false-positive and five false-negative findings [26]. Sonography cannot predict the existence of cancer cells inside a duct. Nevertheless, the demonstration of tubular structures at the periphery of a mass must be considered along with the nodule’s size an invaluable information for the surgeon before conservative surgery. Color Doppler may be employed to differentiate vessels from ducts, as both are tubular structures. Regional staging involves evaluation of the skin and the subcutaneous tissues; these structures can be well evaluated only with high frequency, highly focussed transducers. The sonographic pattern of normal skin is a more or less homogeneous band that is more echogenie than the underlying fat tissue. Normal skin thickness varies between 0.5 mm and 2 mm, and is usually maximum in the lower quadrants, towards the inframammary fold. The subcutaneous region contains fat and lymphatics. Subcutaneous fat is crossed by thin, echogenic lines, oblique to the skin surface, that represent Cooper’s ligaments. These ligaments go from the skin to the deep pectoral fascia and are well visualized both in subcutaneous fat as well as in fatty breasts, with a regular orientation and in contrast with hypoechoic fat. Superficial masses, besides causing changes in subcutaneous fat, usually infiltrate the skin, that thickens or changes its echogenicity (Fig. 14). Less superficial
18
G. Rirrutto
et cd. I European Journul q/ Rndiolog~~ 24 (1997) I I
cancers may also cause skin changes by pulling on Cooper’s ligaments, and by changing their orientation (Figs. 3, 4, 7 and 15). As it concerns the possibility of evaluating the invasion of the deeper muscular planes high resolution sonography is still limited if compared to magnetic resonance; nonetheless diagnosis is correct in 95% of the cases (Fig. 9). Underestimation may usually occur in very large glandular breasts. Breast lymphatics form a microscopic network in the superficial areas of the breast, mainly between the skin and subcutaneous tissues and also along ducts. Normal lymphatics cannot be visualized, but in case of dilatation-due to inflammation or carcinomatous infiltrationthey can be demonstrated as hypo-anechoic, thin lines, parallel and perpendicular to the skin, forming a network (Fig. 16) [13]. Axillary and supraclavicular nodes are the most frequent localization of breast cancer, starting from the outer breast quadrants. Sonography can easily detect enlarged lymph nodes, show size and shape, and evaluate if the echogenic hilum is maintained. Node enlargement can result from inflammation, hyperplasia, breast cancer or metastases. A rounded shape and loss of the echogenic hilum suggest infiltration. When compared to mammography and clinical examination, sonography has a higher sensitivity in the detection of axillary lymph nodes [27]; the better contrast provided by high resolution sonography permits a better visualization of nodes dispersed in the fatty tissues of the axilla or of the peripheral breast. Anyway these are preoperative indications and, of course, pathologic examination of lymph nodes after surgery is the only way to rule out cancer diffusion. In summary high resolution sonogrdphy is useful in the characterization of solid masses of the breast. It improves the diagnostic specificity reducing the need for biopsy; furthermore it allows better local and regional staging of tumors. The potential for cost reduction and better treatment planning promotes high resolution ultrasound as a standard procedure to evaluate patients with breast cancer. Radiological departments must upgrade their breast technology with this new facility to enhance the quality of their diagnostic performances.
References PI Rizzatto
PI PI
G. Instrumentation. In: Solbiati L, Rizzatto G, eds. Ultrasound of superficial structures: high frequencies. Doppler and interventional procedures. Edinburgh: Churchill Livingstone 1995; t-21. Rizzatto G, Chersevani R, Solbiati L. High-resolution ultrasound assists in breast diagnosis. Diagnostic Imaging Int 1993; 5: 42245. Burns. PN. Principles of US. In: RiIkin MD, Charboneau JW,
19
Laing FC, eds. Ultrasound 1991. Oak Brook: RSNA 1991: 33-55. V, Prechtel K. Atlas der BrustdrAse und ihrer [41 Barth Erkrankungen. Stuttgart: Enke 1990. [51 Gallager HS, Martin JF. The study of mammary carcinoma by mammography and whole organ sectioning: early observations. Cancer 1969: 23: 8555859. [61 Rosen PP, Fracchia AA, Urban JA, Schottenfeid P, Robbins GF. Residual mammary carcinoma following simulated partial mastectomy. Cancer 1975; 35: 739-747. for breast carcinoma. In: Bland 171 Leis PJ. Prognostic parameters KI, Copeland EM, eds. The breast: comprehensive management of benign and malignant diseases. Philadelphia: WB Saunders: 1993; 331-350. and PI Fornage B, Toubas 0, Morel M. Clinical, mammographic, sonographic determination of preoperative breast cancer size. Cancer 1987; 60: 765-771. [91 Madjiar H, Ladner HA, Sauerbrei W, Oberstein A, Primpeler A. Pfeiderer A. Preoperative staging of breast cancer by palpation, mammography and high resolution ultrasound. Ultrasound Obstet Gynecol 1993; 3: 1855190. H, Sauerbrei W. Ladner HA, Pfeiderer A. Sono[lOI Madjiar graphic detection of occult tumor extension, In: Madjiar H. Teubner J, Hackelier BJ, eds. Breast ultrasound update. Basel: Karger 1994: 140- 146. M. Mammographically [I 11 Holland R, Hendriks JHCL, Mravunac occult breast cancer. A pathologic and radiologic study. Cancer 1983; 52: 1810~1819. M, Hendriks JHCL. HistoST Holland R, Veling SHJ. Mravunac logic multifocality of TIS, Tl-2 breast carcinomas, Implications for clinical trials of breast conserving surgery. Cancer 1985: 56: 9799990. R, Tsunoda-Shimiru H, Giuseppetti GM, Rizzatto [I31 Chersevani G. Breast. In: Solbiati L. Rizzatto G, eds. Ultrasound of superficial structures: high frequencies, Doppler and interventional procedures. Edinburgh: Churchill Livingstone 1995: 141~ 199. J, Bohrer M, van-Kaick G, Georgi M. Echo[I41 Teubner morphologie del Mammakarzinoms. Radiologe 1993; 33: 277286. Feig SA. Breast masses, Mammographic and sonographic evaluation. Radio1 Clin North Am 1992; 30: 67-92. Jackson VP. Sonography of malignant breast disease. Seminars in Ultrasound. CT, and MR 1989; IO: 119~131. Stavros AT, Thickman D, Rapp CL, Dennis MA, Parker SH, Sisney GA. Solid breast nodules: use of sonogrdphy to distinguish between benign and malignant lesions. Radiology 1995; 196: 123-134. BD, Sneige N, Faroux MJ, Andry E. Sonographic U81 Fornage appearance and ultrasound guided fine-needle aspiration biopsy of breast carcinomas smaller than I cm’. J Ultrasound Med 1990; 9: 5599568. BD, Lorigan JG, Andry E. Fibroadenoma of the [I91 Fornage breast: sonographic appearance. Radiology 1989; 172: 67 I 675. C, Soriano RZ, Kurtz AB, Goldberg BB. UltraWI Cole-Beuglet sound analysis of 104 primary breast carcinomas classified according to histopathologic type. Radiology 1983: 147: 191~ 196. [2l] Sickles EA. Mammogrdphic features of 300 consecutive nonpalpable breast cancers, AJR 1986; 146: 661-663. [22] Cosgrove DO, Bamber JC, Davey JB, McKinna JA, Sinnett HD. Color Doppler signals from breast tumors. Work in progress, Radiology 1990; 176: l75- 180. [23] Cosgrove DO, Kedar RP, Bamber JC et al. Breast diseases: Color Doppler US in differential diagnosis. Radiology 1993: 189: 99 104.
G. Rizzatto
et al. i European Journal
features predicting [24] Stomper PC, Connolly JL. Mammographic an extensive intraductal component in early-stage infiltrating ductal carcinoma. AJR 1992; 158: 269-272. [25] Tsunoda-Shimizu H, Ueno E, Tohno E. Echogram of ductal spreading of breast carcinoma. Jpn J Med Ultrasonics 1990; 17: 44449. [26] Tsunoda-Shimizu H, Ueno E, Tohno E, Tanaka H, Aiyoshi Y,
of Radiology 24 (1997) 11-19
19
Itai Y. Breast conservative therapy: the evaluation of ductal spreading of breast cancer by ultrasound. JSUM Proceedings May 1993: 4599460. [27] Pamilo M, Soiva M, Lavast EM. Real-time ultrasound, axillary mammography, and clinical examination in the detection of axillary lymph node metastases in breast cancer patients. J Ultrasound Med 1989; 8: 1155120.