Magnetic Resonance of the Breast 15

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15.1

Before Getting Started

For successful breast magnetic resonance imaging (MRI), one of the most important steps is to interview the patient before she proceeds to the magnet. This serves two important purposes: (1) to obtain patient history data, which are indispensable for adequate image interpretation, and (2) to explain to the patient what is going to happen, to ensure her cooperation (particularly to reduce motion, thus, subtraction artifacts). Typically, this part of the exam takes longer than the part in the magnet. A thorough patient history should focus on issues related to breast diseases and physiology. Questions to be answered are:

1. Previous breast cancer, including stage, age at diagnosis

2. If applicable, type of breast cancer treatment: breast conservation or mastectomy; previous radiation therapy, reconstructive surgery, chemotherapy, antihormonal therapy

3. Family history of breast or ovarian cancer, including age at diagnosis

4. Previous fine-needle aspiration cytology/core biopsy/excisional biopsy of benign lesions

5. Menstrual/menopausal state 6. Hormonal-replacement therapy

7. Pregnancy or lactation (if yes, do not do breast MR) 8. Present complaints, in particular:

9. Nipple discharge (note texture/color) 10. Mastodynia (cycle phase dependency?) 11. Palpable abnormalities

Inspect the breast to check for any nipple discharge or skin changes. Note any inflammatory changes, because they may cause substantial differential diagnostic difficulties. If there is any inflammation, consider postpon- ing the imaging until this has resolved. A clinical exam-

Magnetic Resonance of the Breast 15

C. Kuhl

Contents

15.1 Before Getting Started . . . 469

15.2 Hardware Requirements . . . 470

15.3 Patient Positioning . . . 470

15.4 Imaging: Pulse Sequence Parameters and Documentation . . . 471

15.5 Kinetic Analysis . . . 473

15.6 Reading the Breast Magnetic Resonance Study . . . 474

15.6.1 Diagnostic Criteria in Dynamic Breast Magnetic Resonance . . . 474

15.6.2 The Normal Breast . . . 474

15.6.3 Breast Cancer . . . 476

15.6.3.1 Invasive Breast Cancer . . . 477

15.6.3.2 Ductal Carcinoma-In-Situ . . . 479

15.6.4 Cystosarcoma Phyllodes: Phyllodes Tumors . . . . 483

15.6.5 Fibroadenoma . . . 484

15.6.6 So-called ‘Mastopathic’ or Fibrocystic Changes . . 484

15.6.7 Guidelines for Diagnostic Problem Cases . . . 487

Further Reading . . . 487

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ination of the breasts is an integral part of any breast MR imaging studies and needs to be performed thoroughly to identify any palpable abnormalities.

It is necessary to have previous conventional imaging studies (mammograms, US studies) available before beginning. If the patient’s case is unknown, be sure that the problem that is to be explored by breast MR is well understood. In particular, if there is an equivocal mammographic finding, identify it on the mammograms, because the MR exam may have to be tailored accordingly, e.g., in case the finding is in the axillary tail, this may require a change of image orientation to rotate the heart-pulsation artifact band out of the way.

It is important to check the indications for breast MR. Many diagnostic difficulties can be avoided by proper indication and patient selection. Appropriate indications for breast MR can be divided into two main categories.

1. Clarification of equivocal clinical or conventional imaging findings (mammography, breast ultrasound), particularly in the post-treatment breast, or in high-risk patients with very dense breasts. This includes cases for follow-up after breast conservation surgery and radiation therapy (differentiation of scar versus recurrent tumor), follow-up after reconstructive or implant surgery, monitoring of primary or adjuvant chemotherapy, and search for primary breast cancer in patients with axillary lymph- adenopathy.

2. Preoperative breast MR in patients scheduled for excisional biopsy of a suspicious focus (BI-RADS 4 or 5). This serves to improve the preoperative local staging to assess the true tumor extent, to demonstrate an extensive intraductal component (EIC) or infiltration of the chest wall or the nipple, and to rule out multifocal, multicentric or contralateral disease before a breast-conserving therapy is initiated.

According to a recent study by Fischer and co-work- ers, systematic preoperative breast MRI in patients with presumed solitary BI-RADS category 4 or 5 lesions will reveal additional multicentric breast cancer foci in 14% of patients.

It should be kept in mind that, for clarification of palpable or conventional imaging abnormalities (mammography or ultrasound guided), core biopsy is a safe and inexpensive alternative to breast MR. It should go without saying that breast MR cannot be used to spare a patient a mammogram. A mammogram must accompa-

ny the reading of any breast MR study – this is not a for- mal requirement, but it is necessary to check the indication, to ensure the sensitive diagnosis of in-situ cancers, and to avoid diagnostic errors secondary to breast cancers with atypical MR imaging presentation (e.g., cancers with shallow enhancement).

15.2

Hardware Requirements

To image the breast, a dedicated breast surface coil is an indispensable prerequisite. Usually, this is a double- breast surface coil that allows imaging of both entire breasts simultaneously. It is not important to extend the range of the surface coil to include the axilla. Diagnosis of lymph-node involvement is not necessarily an integral part of breast imaging with MR, because there are no criteria to distinguish involved from normal lymph nodes anyway. If the radiologist still wishes to screen for enlarged lymph nodes, this can be done with the body coil.

Concerning the MR system used for breast MR, a simple rule of thumb applies: the higher the field and the stronger the gradients, the better. The higher signal- to-noise ratio (SNR) offered by magnets with 1.5 T is better able to fulfill the specific technical requirements of breast MR. However, if suitable pulse sequences and strong gradients are available, breast MR is feasible with 1.0-T or 0.5-T systems.

15.3

Patient Positioning

Imaging must be performed with the patient in the prone position. The arms should be placed alongside the body. Raising them up above the head does have advantages in terms of reducing fold-over artifacts;

however, in this position, the blood circulation tends to become restricted, which in turn may lead to patient movements. Moreover, with her arms over her head, the patient is more likely to push herself out of the coil.

A venous line (18–20 G) is placed into an antecubital vein and kept patent via a saline infusion. Before mov- ing her into the bore, explain to the patient again that she must lie perfectly still – also in between scans (when the scanner noise stops) – and explain to her why this is so important. Explicitly instruct her not to turn

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her head from side to side, and not to move her arms, particularly during the injection of contrast material.

Movements of the upper extremities are almost always associated with pectoral muscle contractions, which in turn translate into changes of the cross-sectional aspect of the entire breast, thus giving rise to severe motion and subtraction artifacts.

15.4

Imaging: Pulse Sequence Parameters and Documentation

In the past, two different ‘schools’ evolved in breast MRI. The ‘European approach’ was to perform dynamic imaging to assess the lesions contrast-enhancement characteristics. The ‘US approach’ favored static, high- spatial-resolution imaging to characterize lesion morphology. As a consequence, the two different schools advocated completely different imaging techniques.

Depending only on the diagnostic criterion that was given priority, and given the limitations of the MR equipment, the proposed imaging sequences were designed to allow optimal spatial or optimal temporal resolution.

To date, among those who perform breast MR clinically, there is broad agreement that both concepts should be integrated. This means that MRI of the breast must consider both lesion morphology and lesion contrast-enhancement kinetics. However, as yet, with cur-

rent MR systems and pulse-sequence software, any proposed pulse sequence is only a compromise on the diverging demands of temporal and spatial resolution.

Accordingly, there is no such thing like an ‘optimal pulse sequence’. All parameters given here are sugges- tions and should be understood as such. We perform breast MRI with 1.5-T systems with pulse sequences that provide adequate temporal and high spatial resolution.

Before discussing the various technical issues, it is important to realize that personal practical experience with breast MR should be considered an absolute prerequisite for using breast MR imaging clinically, and this has most definitively more impact on the technique’s accuracy rates than any other single factor, including choice of imaging technique. Also, in this respect, breast MR is in no way different from conventional breast imaging techniques. All pulse sequences recommended for breast MRI are heavily T1-weighted (T1-W), two-dimensional (2D) or 3D, gradient-echo (GRE) sequences (Table 15.1). As the echo times (TEs) are more or less given by field-dependent in-phase settings of fat and water resonance frequencies, improving the sequences’ T1-contrast is only possible by reducing the repetition time (TR). The flip-angle has then to be adapted to the TR; in general, it must be set smaller with shorter TRs.

At 1.5 T, we use a transaxial (2D GRE pulse sequence with TR/TE/FA 290/4.6/90°, with a 512×400 imaging matrix. The field of view (FOV) should be adjusted to

Table 15.1. Pulse sequence parameters recommendations for diagnostic breast magnetic resonance

Sequence WI Plane No. of TR TE Flip Echo Slice Matrix FOV recFOV No. Acq.

slices (ms) (ms) angle train thickness of time

length (mm) acq. (min)

TSE^a T2 Axial 20–35 2500–4000 90–110 90 12–15 3–4 512×512 270–320 100 2 4

TSE^b T2 Axial 25–35 2500–4000 90–110 90 12–15 3–4 512×512 270–320 100 2 4

SE^c T1 Coronal 25–35 300–500 10–15 90 3–4 256×256 350 60 2 2

2D or 3D T1 Axial 20–35 250 (2D) in phase 90 (2D) 3–4 512×5400 270–320 100 1 1:50 per

dynamic or 15 (3D) (4.6 ms at 1.5 T) or dynam-

GRE^d (always as (6.9 ms at 1.0 T) 25 (3D) ic scan

short as (3.0 ms at 0.5 T) possible)

aStandard sequence to use without fat suppression

bOptional sequence to use with spectral-selective fat suppression

cOptional sequence to cover the chest wall including axilla with cranio-caudal phase encoding direction

dStandard sequence to use as a dynamic study pre- and 5–8 times postcontrast (Gadolinium)

Abbreviations: WI weighting of images; TR repetition time (ms); TE echo time (ms); Matrix phase × frequency matrix; FOV field of view (mm); recFOV rectangular field of view (%); Acq. acquisition(s)

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the size of the breast (not chest), typically 280–300 mm (for bilateral acquisition). The section thickness should be 3 mm or less without gaps between sections. With this parameter setting, about 30–35 sections are needed to cover the entire breast parenchyma. A total of 5–7 dynamic scans are obtained in a series, i.e., one precontrast and 4–6 times after bolus injection of 0.1 mmol/kg gadopentetate dimeglumine. The temporal resolution should be kept at 1–2 min per dynamic scan; we do not recommend improving the temporal resolution beyond the 1-min margin, because there is no additional diagnostic information to be expected. Instead, the temporal resolution should be set at 1–2 min, and all remain- ing scanner capacity should be invested to improve the spatial resolution.

If breast MRI has to be performed at 0.5 T, the shorter tissue T1-relaxation times need to be compensated for by use of a pulse sequence with a substantially shorter TR. This is why a 3D pulse sequence is manda- tory for breast MR at this field strength. At 0.5 T, in- phase TE for fat and water resonance frequencies is 14 ms; however, this is too long to maintain an adequate temporal resolution, and, moreover, the long TE would introduce some T2-contrast. Therefore, a TE of 3.0 ms is recommended to reduce phase-cancellation effects while preserving dynamic imaging capabilities. At 1.0 T, in-phase imaging settings dictate a TE of 7.0 ms, a necessity that limits the image acquisition speed con- siderably.

Concerning the choice of image orientation, the following facts are important. With current magnets, sagittal imaging is feasible only in single breast protocols.

For bilateral protocols, one needs to decide between the axial or coronal image orientation. We prefer the axial orientation because we believe that it is easier to assess the retro-areolar and pre-pectoral region in these images, and because fewer sections are needed to cover the parenchyma. Coronal imaging may be advantageous, especially to compensate for the limited temporal resolution secondary to the long in-phase TE settings at 1.0 T: With coronal imaging, with the feet-head phase- encoding direction, a rectangular field-of-view can be used to reduce the number of phase-encoding steps at a given spatial resolution.

In all protocols for breast MR, the signal from fatty tissue must be suppressed to improve the detection and delineation of contrast-enhancing lesions. In principle, fat suppression can be achieved by active (frequency- or spectral-selective prepulses) or passive (subtraction)

techniques. For dynamic breast MR imaging, fat suppression must be obtained via image subtraction, which is done off-line and, as such, does not affect the temporal resolution. A spectral- or frequency-selective fat suppression takes too much time to allow image acquisition in a rapid, dynamic pattern.

We do not recommend obtaining images in comple- mentary orientations after the dynamic series, because the lesion-to-parenchyma contrast deteriorates rapidly in the intermediate and late postcontrast period, such that it would be difficult to detect the lesion in question in these images. To elucidate the lesion’s location in, for example, the sagittal and coronal planes, it is much more useful to obtain maximum intensity projection (MIP) or multiplanar reconstruction (MPR) views of the early postcontrast subtracted images.

Prior to the dynamic series, we regularly obtain a T2- W turbo spin-echo (TSE) pulse sequence (TR/TE/TF 2800/110/16) with geometric parameters corresponding to those of the subsequent dynamic series. The T2- W images are obtained to improve the detection of (residual) interstitial edema after, for example, radiation therapy or the diagnosis of inflammatory changes, to improve the delineation of lymphangiosis or cystic lesions, and also to help categorize solid enhancing tumors.

If regional (axillary, internal mammary) or remote (supraclavicular) lymph node involvement or osseous metastases are to be evaluated, we use the built-in body coil to acquire coronal T1-W SE images prior to the dynamic series. This should be done before the contrast-enhanced study, because lymph nodes or bone- marrow metastases are visible only on the precontrast image as hypointense lesions against the adjacent hyperintense subcutaneous or bone-marrow fatty tissue.

Documentation should at least include hard copies of early, intermediate, and late postcontrast fat-suppressed (subtracted) images and nonsubtracted, precontrast and postcontrast images. In addition, any time/intensity curves (see below) should be document- ed together with the corresponding lesion.

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15.5

Kinetic Analysis

For analysis of lesion-enhancement kinetics, a small region of interest (ROI) should be placed in the lesion to obtain the time course of signal intensity over the dynamic series. The ROI must be placed selectively into vital tumor components, because only here can mean- ingful time courses be obtained. Vital tumor should be identified by searching for the area where enhancement appears first on the early postcontrast image, i.e., by identifying the area with the fastest and strongest enhancement, at wide window settings. Parametric images may be helpful in identifying tumor areas with the most rapid enhancement. It is not useful to include the entire lesion in a ROI or to place a large region that encircles most of a lesion, because then necrotic or hypovascular tumor areas are averaged together with the vital parts. Two different kinetic parameters may be derived from the ROI-based signal intensity (SI) curves:

1. The initial SI rise in the early postcontrast period (‘upstroke’ of the curve) provides the lesion’s enhancement rate (quantified as ‘enhancement velocity’).

2. The behavior of SI in the intermediate and late postcontrast period (time course or shape of the time course) is visually assessed and classified as type I–III.

Regarding the enhancement rate: the SI increase in the early postcontrast period may be used to quantify the early phase-enhancement rate (or ‘enhancement velocity’); to do this, SI increase is given relative to base- line SI.

The rationale of calculating enhancement rates is based on the observation that malignant lesions tend to have enhancement kinetics that differ from those of benign lesions. On average, malignant lesions exhibit higher enhancement velocities and a different time course kinetic (see below) than benign ones. However, the concept of an ‘enhancement threshold’ to separate benign from malignant lesions, which was propagated in early studies in the field of dynamic breast MR, cannot be maintained any more (see below). Still, enhancement should be quantified routinely in all enhancing lesions in order to be used as one diagnostic criterion among others.

Regarding the shape of the time course, according to the SI changes in the intermediate and late postcontrast

period, the time courses may be visually classified as type I–III:

1. Type I: straight or curved type. Signal continues to increase over the entire dynamic period. In the curved type, the time course is flattened in the late postcontrast period due to saturation effects.

2. Type II: plateau type. After initial upstroke, enhancement is abruptly cut off, and the signal plateaus in the intermediate and late postcontrast period.

3. Type III: wash-out type. After the initial upstroke, enhancement is abruptly cut off, and the signal decreases (washes out) in the intermediate postcontrast period (2–3 min post injection).

The rationale of evaluating the lesions’ SI time courses is in terms of the differential diagnosis of enhancing solid lesions. A type I time course indicates the presence of a benign lesion, as it is mostly found in benign tissues (9:1 benign versus malignant), such as normal breast tissue, fibrocystic disease, and fibroadenomas. A type-I course may rarely occur in malignant lesions with poor angiogenetic activity, such as some lobular or scirrhotic ductal cancers or ductal carcinoma-in-situ (DCIS). A type-II time course increases the suspicion of malignancy of a lesion, as it is obtained more often in malignant than in benign tissues (3:2 malignant versus benign). A type-III time course is highly suspicious, because it is seen much more often in breast cancers than in benign lesions (6:1 malignant versus benign). A type-III time course in benign lesions may occur in hypervascularized tissues such as inflammatory lesions and, rarely, in hypervascular fibroadenomas, papillo- mas, or focal adenosis. It is important to understand that the diagnostic information provided by the kinetic analysis may only be used for the differential diagnosis in lesions with strong enhancement. Lesions with slow or gradual enhancement, i.e., those that lack significant angiogenic activity, including slow-enhancing breast cancers, will almost always exhibit ‘benign’, steady signal time courses. A wash-out or plateau time course will be obtained only in lesions with extensive hypervascu- larity and arteriovenous shunts. So while absence of a plateau or wash-out time course can be used to support the diagnosis of a benign lesion in cases with rapid and strong enhancement, it cannot be used to do the same in a lesion with slow and shallow enhancement.

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15.6

Reading the Breast Magnetic Resonance Study

15.6.1

Diagnostic Criteria

in Dynamic Breast Magnetic Resonance

When a contrast-enhancing lesion is identified on the postcontrast subtracted images, the process of the lesion differential diagnosis is initiated. To distinguish benign and malignant enhancing lesions, the following diagnostic criteria may be considered: morphology (configuration, borders, internal architecture); enhancement kinetics (early-phase enhancement rate, degree of enhancement, shape of time/signal intensity curve, spatial progression of enhancement); and lesion SI in T2-W TSE images.

15.6.2

The Normal Breast

Because the breast is a hormone-reactive organ that responds to endogenous (ovarian hormones) or exogenous (replacement therapy) hormonal stimuli, what is looked upon as ‘the normal breast’ changes steadily, depending on the patient’s age, menstrual/menopausal state, and hormone/antihormone intake. When starting with breast MR in general, it is of the utmost impor- tance to be familiar with the variable aspect of the breast parenchyma in MRI.

Particularly in the very young premenopausal patient (at or below the age of 35 years), strong, spontaneous, focal contrast enhancement may be found which can mimic benign and malignant lesions. These ‘lesions’ correspond to the hormone-reactive part of the parenchyma and should not be mixed up with true lesions requiring biopsy (Fig. 15.1). According to a

Fig. 15.1. A Young premeno- pausal volunteer underwent breast magnetic resonance (MR) during the first week of her men- strual cycle (day 3). B Same vol- unteer 1 week later (day 10).

Upper left precontrast; upper right first postcontrast; bottom left sec- ond postcontrast; bottom right early postcontrast subtracted image of her dynamic series. Note the focal, nodular lesion with rapid enhancement visible during the first week of the menstrual cycle (A), which completely resolves by the second week (B).

This is what we would call an

‘unidentified breast object’

(UBO). No biopsy indicated or required

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recent series, the incidence of spontaneous contrast- enhancing ‘lesions’ or ‘unidentified breast objects’

(UBOs) is highest in weeks 1 and 4 of a menstrual cycle, whereas significantly less enhancement is encountered in week 2.

A distinction of UBOs and serious pathology is often difficult enough, because the morphology of these ‘lesions’ may appear quite suspicious. Enhancement rates may also be well beyond any ‘enhancement threshold’.

To solve this problem, we recommend the following:

1. Avoid MRI of very young premenopausal patients, because here, diagnostic difficulties can be predicted to occur.

2. Be conservative with the indication to biopsy a young patient with ‘MR-only’ lesion. Our rationale is that if, in a premenopausal patient, a contrast- enhancing lesion has no correlate on conventional imaging and has no wash-out time course (type-III TIC), we recommend follow-up after 2–4 menstrual cycles, during the second week of her menstrual period.

Fortunately, these very young patients are not routinely subjected to breast MR; yet, they are increasingly seen owing to the increasing number of patients who are BRCA1/BRCA2 gene carriers or who, on the basis of their family history, are identified as high-risk patients.

Moreover, evidence exists that with exogenous hormone-substitution therapy, the premenopausal situa- tion is restored (as is intended by the medication).

Accordingly, in patients receiving replacement therapy, if contrast enhancement is seen that is not clearly suspicious, it is dealt with like the ‘UBOs’ in premenopausal patients. We ask the patients to discontinue hormone medication for at least 6 weeks and schedule a follow-up exam.

In many patients, a streak of (early) contrast enhancement is seen in the parenchyma just adjacent to the subcutaneous fat, i.e., in the most peripheral parts of the parenchymal volume. This is a normal finding – probably due to the centripetal vascular supply of the parenchyma – and should not be confused with regional or segmental enhancement (see below).

Fig. 15.1B

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15.6.3 Breast Cancer

Histologically, biologically, prognostically, and also in terms of breast MR, breast cancers are not all alike.

First, a fundamental histologic and, thus, diagnostic dif- ference exists between DCIS and invasive breast cancers

(IBCs). Among the invasive cancers, many different histologic subtypes exist, including ductal invasive cancers not otherwise specified (NOS; about 80% of invasive cancers), lobular invasive cancers (10%–15% of cancers), and rare invasive cancers, such as medullary, mucinous, or tubular cancers (5%–10% altogether).

Fig. 15.2A–E. Breast MR appearance of ductal invasive breast cancer in a 52-year-old patient. A Precontrast, B early postcontrast, C early postcon- trast subtracted, D time/inten- sity curve, E T2-weighted (T2- W) TSE image. There is a focal lesion with rapid and strong enhancement, lobulated shape, partly indistinct borders, homogeneous enhancement.

Time course of signal intensity (SI) shows a clear wash-out phenomenon (type III). In the T2-W TSE image, the lesion is about iso- to hypointense to the remainder of the parenchyma. Although the lobulated shape and the homogeneous enhancement might suggest fibroadenoma, the wash-out time course clinches the diagnosis. Moreover, the somewhat indistinct margin and the low SI on T2-WI clearly support the diagnosis of a malignant lesion

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15.6.3.1

Invasive Breast Cancer

Owing to their high neo-angiogenetic activity, IBCs induce capillary sprouting and the formation of new vessels, mostly with leaky vessel linings. Accordingly, in IBCs, an increased vessel density is associated with an increased vessel permeability. Both effects account for the rapid and strong SI increase observable on breast MR of IBCs.

In the ‘typical’ ductal invasive breast cancer, enhancement is usually well beyond 80% signal increase in the early postcontrast period, followed by a type-II (plateau) or type-III (wash-out) SI time course (Figs. 15.2–15.5). Concerning lesion morphology, every- thing that has been found useful in mammography or ultrasound also applies for breast MR; IBCs tend to appear as a focal mass with irregular morphology, indistinct margins, and an inhomogeneous internal architecture. In about 15%–20% of cases, a rim

enhancement is seen – a finding that is almost pathognomonic for breast cancer. The rim corresponds to the vital tumor periphery around a more or less fibrotic or necrotic tumor center. If a dynamic imaging technique is used with good temporal resolution, it is possible to monitor the progression of enhancement, starting in the tumor periphery in a centripetal fashion (Fig. 15.3).

In T2-W TSE images, IBCs tend to exhibit a low SI, iso- intense or even hypointense, with respect to the adjacent parenchyma (Fig. 15.2).

Lobular breast cancers tend not to form focal nodules, but to grow more or less diffusely, with gradual replacement of the preexisting breast parenchyma (Fig. 15.6). This is also the reason why lobular invasive cancers may go undetected by mammography until they become very large: they often do not form masses or nodules, and in the vast majority, they do not exhibit microcalcifications. One should be prepared to see lobular breast cancer more often on MR than one would expect based on its natural prevalence – this tumor is

Fig. 15.3A–D. Progression of enhancement in a ductal invasive breast cancer. First, second, third, and fourth postcontrast subtracted image (at 40, 80, 120 and 160 s postbolus injection of gadopentetate dimeglumine). Note the irregular morphology and the ring enhancement, which is particularly evident in the earliest postcontrast image. Note the centripetal progression of enhancement, with filling-in of the central fibrotic tumor parts in the intermediate and late postcontrast period

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difficult to diagnose mammographically and may cause nonspecific mammographic changes, which may prompt a referral to breast MR. Accordingly, in our series of breast cancers detected by breast MR, lobular cancers make up as many as 27% of cases. In breast MR, more than 80% of lobular invasive cancers enhance rapidly and strongly – as one would expect a breast cancer to enhance. In these cases, the diagnosis is quite straightforward and simple. However, due to their particular ‘Indian-path-like’, diffuse growth pattern, some 20% of lobular IBCs are not particularly hypervascular.

Accordingly, this fraction of lobular invasive cancers may enhance gradually – well below any ‘enhancement threshold’. For the same reason (lack of hypervascular- ity), time course assessment tends to be of little use for a correct classification in these cases, because they usually exhibit a steady (type I) or a plateau (type II) time

course. However, other diagnostic criteria, particularly morphologic features, should still allow the correct diagnosis to be reached.

Medullar IBCs, an uncommon entity with a relative- ly favorable prognosis, is the most important differential diagnosis of myxoid fibroadenomas. Medullary cancer is seen in younger patients (Fig. 15.7), it is a roundish, very well circumscribed tumor, with intermediate but usually heterogeneous enhancement, and high SI in T2-W TSE images. Fortunately, it is rather rare, accounting for less than 7% of all IBCs. It is important, however, to consider this diagnosis in patients with a strong family history of breast cancer (in particular patients with family members who were diagnosed with breast cancer at age 35 or younger), or patients in whom a genetic predisposition has been identified (BRCA1 or BRCA2 mutation carriers).

Fig. 15.4A–D. A 51-year-old woman referred for preoperative breast MR. She was scheduled for excisional biopsy of microcalcifications in her upper outer quadrant that were suspicious of breast cancer. She underwent breast MR to check whether she would be a candidate for possible breast conservation therapy. A Precontrast, B early postcontrast, C late postcontrast, D early post-

contrast subtracted image. Breast MR confirms the presence of a malignant lesion in her upper outer quadrant, but detects a second tumor manifestation between both upper quadrants. Histology confirmed a multicentric invasive breast cancer, 8 mm and 6 mm in size. Mastectomy was performed

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Inflammatory breast cancer is a clinical rather than a distinct pathologic entity. It is diagnosed in cases where an invasive breast cancer (usually of ductal origin) is associated with clinical findings of inflammation, i.e., cutaneous edema and erythema. On histopathology, there is extensive tumor lymphangiosis. The MR findings are as variable as the clinical presentation. What is visible clinically appears as dermal thickening and edema, interstitial edema (best appreciated on T2-WI), and variable cutaneous enhancement. The underlying cancer usually enhances strongly, but there are also reports of nonenhancing or very slowly enhancing inflammatory cancers. In addition, abscess formation does occur in inflammatory cancer. To conclude, in no

way can MR be used to distinguish (puerperal or non- puerperal) mastitis from inflammatory breast cancer.

The only role of MR (if any) is to demonstrate the extent of the disease and to monitor the response to chemotherapy.

15.6.3.2

Ductal Carcinoma-In-Situ

Although there are reports in the current literature stat- ing that microcalcifications can be visualized by high- resolution breast MR, for current clinical practice, there is ample evidence confirming that microcalcifications (particularly the relevant, tiny ductal calcifications) are

Fig. 15.5A–E. A 61-year-old woman with right axillary lymphade- nopathy, unknown primary. A The maximum intensity projection (MIP) image of the early postcontrast subtracted images of her dynamic series reveals three lesions. In her right breast, there is an irregular lesion immediately adjacent to the chest wall and another lesion in her upper outer quadrant. In her left breast, there is a small lesion in the retro-areolar region. B Early postcontrast subtracted image of the prepectoral lesion, C corresponding time/intensity curve. D Dynamic series over the small lesion in the upper outer quadrant of her right breast (upper left precontrast;

upper right early postcontrast; bottom left late postcontrast; and bottom right early postcontrast subtracted image). E Signal inten- sity time course of the lesion in D. There is a multicentric invasive breast cancer (IBC) in her right breast plus a contralateral small IBC in her left breast. With irregular morphology, rapid and strong enhancement and wash-out time course, the diagnosis is straightforward in the prepectoral lesion. The small additional foci in the same and the contralateral breast are well circumscribed, yet also here, the wash-out time course allows the correct diagnosis

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Fig. 15.5D, E.

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not visible on MRI. One could even go beyond this and state that, as soon as a calcification is detected on an MRI, it cannot be a suspicious calcification. However, accordingly, while the in-situ cancers’ propensity to form microcalcifications constitutes the basis of DCIS diagnosis in mammography, this feature cannot be exploited for MRI of DCIS. Moreover, the criteria perti- nent to the diagnosis of IBC in dynamic MR may not be transferred to the diagnosis of DCIS (rather, the absence of these features may not be used to exclude

DCIS). Probably due to the variable angiogenic activity of in-situ cancers, enhancement in breast MR can be anywhere between strong to moderate to even absent.

Accordingly, diagnostic criteria based on contrast- enhancement kinetics are not reliable enough to exclude DCIS. Enhancement rate, degree of enhancement, and time course of SI may (but not necessarily will) be misleading. A recent study revealed that DCIS exhibits nonspecific or even delayed enhancement in about two-thirds of cases, and that in about 10% of Fig. 15.6A–C. Lobular invasive

cancer with slow and shallow enhancement in a 57-year-old woman. Precontrast (A), early postcontrast (B), early post- contrast subtracted images (C). Note that the tumor has replaced the entire residual parenchyma. On the precon- trast image (A), there is homo- geneous, low-signal-intensity tissue, no interspersed fatty tissue. In an otherwise involut- ed breast, this is suspicious.

Note the shallow enhancement rate, not exceeding 50% in the early postcontrast period.

However, the particularly irregular morphology and the very inhomogeneous enhancement do allow the correct diagnosis

Fig. 15.7A,B. Precontrast (A) and early postcontrast (B) images. This is a 27-year-old woman who underwent preoperative breast MR. Note the well-circumscribed, nodular lesion in her upper quadrant.

However, enhancement is inhomogeneous with peripheral rim. Excisional biopsy revealed medullary invasive cancer

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cases, no enhancement is obtained at all – in our series, we found nonenhancing DICS less often, i.e., in 3% of all cases. So, unlike IBC, DCIS may be missed by breast MR. As a result, a recent state-of-the-art mammogram must be available when a breast MR study is read. If a mammogram shows suspicious microcalcifications, it is not possible to avoid biopsy due to a negative breast MR study. Accordingly, it is not useful to attempt a clarification of mammographically suspicious microcalcifications by an MR study. What can be done in this setting is to see whether there is multifocal or multicentric tumor growth before breast-conserving therapy is initiated (Figs. 15.4 and 15.5).

While enhancement kinetics may be misleading in DCIS, there are some morphological features that may be used to establish the diagnosis prospectively, even in cases where no specific findings suggest DCIS on mammography. In DCIS, tumor growth is confined to the

distribution of a single duct or a ductal system; therefore, there are specific MR findings that are very suggestive of DCIS irrespective of the enhancement kinetics:

1. A segmental enhancement (isolated regional enhancement with triangular configuration, tip towards the mammilla, corresponding to the distribution of a ductal system) (Fig. 15.8).

2. A dendritic, branching enhancement, sometimes with arborizing configuration, corresponding to the enhancement within a single duct.

3. Any diffuse, regional enhancement around an invasive breast cancer is suggestive of an intraductal component.

DCIS may also present as a focal lesion with strong and rapid enhancement, with or without wash-out, indistin- guishable from an invasive breast cancer.

Fig. 15.8A–C. A 32-year-old woman who underwent mastectomy on her right breast 2 years previously due to invasive breast cancer. Routine follow-up breast MR was performed in this high-risk patient: no clinical or conventional imaging findings. A Dynamic series on her left breast (upper left precontrast; upper right early postcontrast; bottom left late postcontrast; and bottom right late postcontrast subtracted image). B,C Two other postcontrast sub- tracted sections obtained cephalad from the position of the sec-

tion in A show that the enhancement occupies the entire lower outer quadrant. Note the extremely dense, homogeneous parenchyma in this very young patient. Note the slowly progressive enhancement in her lower outer quadrant. Enhancement rate is 30% in the early postcontrast period. However, the enhancement has an isolated regional, segmental configuration (tip towards mammilla). This is suspicious of a large ductal carcinoma in situ (DCIS), which was confirmed by excisional biopsy

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15.6.4

Cystosarcoma Phyllodes: Phyllodes Tumors

This is a rare fibroepithelial tumor that can have benign and malignant variants. The benign variant can behave in a semimalignant pattern owing to a local recurrence rate of up to 20%; the malignant version metastasizes as IBCs. Clinically, these are rapidly growing tumors, usu-

ally of considerable size at the time of presentation.

Histologically, phyllodes tumors are hypercellular, hypervascular, with internal cystic (or necrotic) areas and with (macroscopically) expansive growth pattern.

On MR, these tumors are well circumscribed, exhibit a very rapid and strong enhancement, and show (sometimes huge) internal cysts or central tumor necrosis (Fig. 15.9).

Fig. 15.8B, C.

Fig. 15.9A–D. Malignant cysto- sarcoma phyllodes. A huge tumor affects virtually the entire right breast and bulges the breast contours. A Precontrast, B early postcon- trast, C late postcontrast, D early postcontrast subtracted image. Note the strong, rapid, inhomogeneous enhancement with multifocal, nonenhancing, central necrosis

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While it is already difficult to distinguish benign and malignant cystosarcoma histologically, breast MR cannot be expected to deliver this information. Moreover, if no internal cysts or necrosis have evolved yet in a small cystosarcoma, it cannot be distinguished from a fibroadenoma on the basis of MR.

15.6.5 Fibroadenoma

Fibroadenomas represent a frequent finding in breast MR – much more frequent than is detected on mammograms. Fibroadenomas constitute one of the major differential diagnostic problems for MRI, as they do in mammography or breast ultrasound. There are a varie- ty of diagnostic criteria to distinguish fibroadenoma from breast cancer; however, none of them are 100%

specific. Accordingly, it is up to the practical experience of each radiologist, to his or her degree of diagnostic confidence in the individual case, and to his or her personal preferences in terms of aggressiveness or conser- vativeness whether or not, eventually, a biopsy is recommended.

In general, the MR appearance of fibroadenomas varies strongly with the degree of fibrosis; there are myxoid fibroadenomas with a large extracellular/interstitial fraction filled with a gelatinous matrix. With increasing age, regressive changes take place, the interstitial matrix undergoes fibrosis, resulting in a sclerotic fibroadenoma.

Typically, a myxoid fibroadenoma is a well-circumscribed lesion with rapid and strong, ‘carcinoma-type’

enhancement and type-I time course of SI (steady increase or bowing of TIC, Fig. 15.10). Ideally, it has low- SI internal septations (often best seen on T2-WI) (Fig. 15.11). However, with the limited spatial resolution available with double-breast imaging techniques, these are only visible in about 15% of cases; if seen, they are almost pathognomonic for fibroadenoma. Otherwise, fibroadenomas show a homogeneous internal enhancement. The enhancement starts in the center of the lesion and progresses from there to the tumor periphery, such that the lesion seems to grow from one dynamic scan to the other (‘blooming fibroadenoma’, Fig. 15.10). In T2-W TSE images, the lesion has a hyperintense signal with respect to parenchyma.

In sclerotic fibroadenomas, the enhancement is reduced or even absent, and the SI in T2-WI is low. As a

consequence, internal septations are hardly visible. If enhancement is present, the time course of SI corresponds to a type-I shape. Enhancement may be somewhat heterogeneous due to regressive clumps of calcifications and the slow progression of enhancement.

According to our experience, the diagnosis can be established with sufficient confidence if all criteria support the diagnosis of either myxoid or sclerotic fibroadenoma.

An important differential diagnosis of myxoid fibroadenoma, however, is medullary breast cancer, and breast MR may not be useful to distinguish these two entities further. The same holds true for the differentiation of fibroadenoma and a (small) phyllodes tumor.

15.6.6

So-called ‘Mastopathic’ or Fibrocystic Changes In breast MRI, so-called ‘mastopathic’ or fibrocystic changes appear as diffuse, bilateral, patchy, and heterogeneous enhancement. The histopathological correlate of the small enhancing dots has been shown to be focal adenosis, i.e., proliferation of the glandular epithelium.

It is important to realize that there is no correlation of the presence of enhancement with the presence or absence of atypias. Accordingly, it is not possible to distinguish ductal hyperplasia from atypical ductal hyperplasia (ADH) by breast MRI.

The heterogeneity of enhancement that is seen in patients with fibrocystic disease is due to the presence of areas with predominant epithelial proliferation next to areas with predominant regressive changes (fibrosis) and associated cysts. The enhancement is usually steady (type-I curve) but may become rapid and strong. Often, there are small dots of rapidly enhancing foci interspersed within the diffusely enhancing parenchymal tissue, owing to small fibroadenomas or nodes of focal adenosis. Hence, it may be difficult, if not impossible, to distinguish fibrocystic changes from ‘serious pathology’, such as DCIS or invasive cancer. In turn, small foci of cancer or DCIS may be masked by enhancement secondary to focal adenosis. The following hints have emerged from clinical practice and may prove helpful.

First, if diffuse spotty enhancement is present, it is not useful to attempt quantification or time-course analysis of each and every enhancing spot. However, note that as opposed to DCIS, mastopathic changes are diffuse, usually more or less symmetric on both breasts;

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Fig. 15.10A–E. Myxoid fibroadenoma in a 37-year-old woman with typical breast MR presentation. A Precontrast, B early postcon- trast, C intermediate postcontrast, D late postcontrast image of her dynamic series, obtained before and 40, 80, and 200 s postbolus injection of gadopentetate dimeglumine. E Time/intensity curve of the same lesion. Note the ovoid lesion shape, the smooth lesion borders, the homogeneous enhancement, the centrifugal progression of enhancement (‘blooming’ fibroadenoma; it seems to grow between the dynamic scans). Note the rapid and strong enhancement, followed by a type-I time course of signal intensity

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they are not confined to the territory of a distinct duct.

Symmetry is the clue to the diagnosis. As opposed to invasive cancer, mastopathic changes tend to exhibit a gradual and steady SI increase. On follow-ups, mastopathic changes, in fact, change their appearance and location, reflecting the cyclical rebuilding of the breast parenchyma. Last, always remember that bilateral, diffuse, multifocal breast cancer is rare; fibrocystic disease

is not. So, if in doubt, follow-up examinations should be performed.

Concerning the clinical use of the term ‘mastopathic’

or ‘fibrocystic disease’, it is important to understand that according to biopsy results, what is histologically called a ‘mastopathy’ or a ‘fibrocystic disease’ seems to be so ubiquitous that the terms easily qualify as a mis- nomer. Similarly, in imaging studies, it is a frequent Fig. 15.11A–E. Myxoid fibro-

adenoma in a 39-year-old woman with chronic renal fail- ure. A Precontrast, B early postcontrast, C late postcon- trast, D early postcontrast sub- tracted image of her dynamic series. E T2-weighted turbo spin-echo (TSE) image of the lesion. Note the somewhat inhomogeneous, rapid and strong enhancement. However, there is a type-I time course, the lesion’s signal on the T2- weighted TSE image is increased, and there are internal low signal-intensity septations visible on the T2-weighted TSE image. The diagnosis ‘- fibroadenoma’ was confirmed by sonographic follow-up over the past 4 years

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habit that almost anything that is apparently benign but does not correspond to a ‘completely negative study’ is generously (and somewhat thoughtlessly) categorized as ‘mastopathic’ or ‘fibrocystic’. However, it should be well understood that contrast enhancement – to a variable degree – may be one facet of normal, healthy breast parenchyma and is by no means necessarily a sign of (‘mastopathic’ or ‘fibrocystic’) disease. The diagnosis of

‘mastopathic changes’ should be avoided or reserved for cases where cysts and diffuse, spotty enhancement suggest a true imbalance of tissue formation and regenera- tion.

15.6.7

Guidelines for Diagnostic Problem Cases

It is important to note that, of course, not every breast cancer behaves as expected in every aspect. The following guidelines can be used to help make decisions in cases where the diagnostic criteria point in different directions.

1. A wash-out (type III) time course overrides any other diagnostic criterion and should prompt biopsy. Make sure that no ‘fake wash-out’ is produced by motion; make sure that the ‘lesion’ is not a vessel.

2. An irregular morphology (stellate lesion shape) overrides any other diagnostic criterion, as long as there is at least intermediate enhancement; in our setting, 30%–40% early postcontrast. Make sure that the lesion is not, in fact, an island of residual normal parenchyma – with normal enhancement – that is entirely surrounded by fatty tissue, producing a

‘pseudo-mass’ on subtracted images.

3. Rim enhancement overrides any other diagnostic criterion and should prompt biopsy. Make sure that the ‘rim’ is within the lesion. A ‘fake rim enhancement’ may be seen on subtracted images of

complicated cysts; however, on the nonsubtracted images, it is readily obvious that the ‘rim’, in fact, corresponds to reactive enhancement in the parenchyma adjacent to the cyst.

4. In a lesion with well-circumscribed morphology and rapid enhancement, a low SI on the T2-W TSE image should increase suspicion.

5. If no enhancement is seen in the location of a presumed lesion, the presence of IBC can be definitely excluded, because non-enhancing IBCs are too rare to be mentioned as a reasonable differential diagnosis. However, make sure that contrast material reached the arterial circulation in a timely manner by checking the enhancement of parenchymal vessels. Please note that the absence of enhancement does not exclude the presence of DCIS.

6. An isolated regional segmental enhancement or a linear-branching enhancement overrides any other diagnostic criteria; a biopsy to rule out DCIS is indicated. However, make sure by checking the nonsubtracted images that no subtraction artifacts at fat/parenchyma interfaces produce a ‘fake’ linear enhancement.

Further Reading

Fischer U (1999) Lehratlas der MR-Mammographie. Thieme Verlag. ISBN 3131185813

Fischer U, Kopka L, Grabbe E (1999) Breast carcinoma: effect of pre-operative contrast-enhanced MR imaging on the thera- peutic approach. Radiology 213 : 881–888

Ikeda D, et al. ACR-Imaging and Reporting System-Magnetic Resonance Imaging™: Illustrated BI-RADS®-MRI™. American College of Radiology, in press

Kuhl CK (2000) MRI of breast tumors. European Radiology 10 (1) : 46–58

Kuhl CK, Schild HH (2000) Dynamic image interpretation of MRI of the breast. J Magn Reson Imaging 12 : 965–974

Orel SG (2001) MR imaging of the breast. Magn Reson Imaging Clin N Am 9 : 273–288