Image-Guided Breast Biopsy

Section VI

BREAST SURGERY Shawna C. Willey, MD It is on our own failures that we base a new and different and better success. —Havelock Ellis

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Image-Guided Breast Biopsy Richard E. Fine, MD and Kenneth J. Bloom, MD

INTRODUCTION Increased utilization of mammography screening is believed to have resulted in a relative increase in breast abnormalities of sufficient risk to warrant a biopsy. It is estimated that approximately 1.5 million breast biopsies are performed each year in the United States. Many of these biopsies are for nonpalpable lesions and, therefore, require some type of image guidance. A significant number of these biopsies will be performed for benign disease because the average positive predictive value for mammography is only 20% (range 15%–35%).1–4 If traditional methods for histologic confirmation were utilized, all women with nonpalpable breast lesions would proceed to the operating room after a wire localization procedure was performed in the radiology suite. Percutaneous imageguided breast biopsy has become an effective minimally invasive alternative to open surgical breast biopsy for the diagnosis of both palpable and nonpalpable imagedetected abnormalities.5–7 Although the risk of bleeding and infection may be comparable with those of open surgical breast biopsy, some potential difficulties are unique to image-guided breast biopsy.8 With the early introduction by the Karalinski Institute in 1989 of stereotactic-guided fine-needle aspiration cytology of nonpalpable breast abnormalities,9 imageguided percutaneous breast biopsy has been shown to provide a secondary level of screening in a less-invasive,

cost-effective manner to obtain a histologic diagnosis without sacrificing accuracy.5–7,10 The evolution of the biopsy tools used with image guidance (stereotaxic, ultrasound, and recently, magnetic resonance imaging [MRI]) has added to the accuracy of minimally invasive imageguided breast biopsy,11,12 keeping a greater portion of women with probably benign disease out of the operating room for a diagnostic procedure. However, advancement in technology has also added to the potential procedural risks.13

INDICATIONS Almost any palpable or nonpalpable, indeterminate breast abnormality, which is visualized with imaging modalities (ultrasound, mammography, MRI), can be evaluated with image-guided breast biopsy. The lesions will fall into the following categories established by the American College of Radiology (ACR) lexicon14: ● BI-RADS 3 (probably benign, short-interval follow-up

[6 mo], <2% risk of malignancy) abnormalities identified in a patient with a strong family history, difficult clinical and imaging examination, or a high level of anxiety. ● BI-RADS 4 (suspicious abnormality, biopsy should be considered) abnormalities, which require biopsy, may

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avoid a trip to the operating room for an abnormality with perhaps only a 20% risk of malignancy. ● BI-RADS 5 (highly suggestive of malignancy, appropriate action should be taken) abnormalities can provide a histologic diagnosis for preoperative patient consultation.

Stereotactic Breast Biopsy Stereotaxis mammography determines the position of a nonpalpable breast abnormality by utilizing computerized triangulation of the targeted lesion visualized with two stereo images, separated by a 30° arc.5,15 The equipment for performing a stereotactic breast biopsy is either a dedicated prone table or an add-on unit, which utilizes a targeting and biopsy platform attached to a standard upright mammogram system.15,16 Add-on stereotactic breast biopsy units have been traditionally less popular because the upright patient position and patient visualization of the procedure have the potential for producing increased syncopal episodes.5,17 The advantages of the prone position include gravity to assist the technologist with posterior lesions and a greatly enhanced workspace beneath the table.18 Both are important for positioning and access, which limit many of the potential difficulties in achieving a successful biopsy.

OPERATIVE STEPS Evaluate mammogram and lesion as well as patient and choose image approach to breast (craniocaudal [CC], mediolateral [ML], lateromedial [LM]) Step 2 Position patient on stereotactic biopsy table for visualization of image-detected abnormality Step 3 Obtain scout and stereotactic digital images Step 4 Target lesion on stereo images Step 5 Anesthetize skin and breast parenchyma and make skin incision after appropriate antiseptic skin preparation Step 6 Insert biopsy device based on calculated coordinates Step 7 Assess appropriate alignment between lesion and biopsy device on prebiopsy and/or postbiopsy alignment stereo digital images Step 8 Adequately sample lesion for diagnosis and/or potential therapeutic removal Step 9 Place postprocedure marker and obtain postprocedure/clip placement stereo images Step 10 Obtain specimen radiograph Step 11 Obtain adequate hemostasis and apply appropriate dressing and/or wrap Step 1

Step 12 Check pathology for concordance with radiologic impression Step 13 Obtain follow-up imaging

OPERATIVE PROCEDURE Evaluating the Mammogram and the Patient and Choosing the Approach to the Breast Choosing an Inappropriate Mammogram Lesion Type for Biopsy ● Consequence It is important to anticipate that some patients and some lesions will be difficult to biopsy. The characteristics of certain lesions (low-density nodules, faint microcalcifications, and vague asymmetrical densities) make them more difficult to visualize with digital imaging despite postprocessing features. Also, when the field of view of the breast is limited to a 5 × 5-cm area (the size of the biopsy window in the front compression paddle), the abnormality is not visualized in relation to the remainder of the breast as it is on the mammogram. An asymmetrical density may represent only a summation shadow of overlapping fibroglandular tissue. Loosely clustered calcifications may become more diffuse on stereo images and be impossible to target with any certainty because of varying depth. Grade 2 complication ● Prevention Recognizing these demanding lesions may avoid unnecessary scheduling and the possibility of procedures being canceled. Complete diagnostic workup, including spot compression views and possibly ultrasound for asymmetrical densities and microfocus magnification for microcalcification, is essential. A true lateral (90°) view may successfully demonstrate “tea cup” calcifications associated with “milk of calcium,” in which benign calcium deposits layer out within microcysts. It is sometimes prudent to send patients with a complete diagnostic evaluation and a persistent but questionable imaging abnormality to the stereotactic suite ahead of time to see whether the lesion can be successfully visualized.

Failure to Recognize Patient Characteristics that Will Result in an Unsuccessful Stereotactic Breast Biopsy ● Consequence There are also patient characteristics that will interfere with the success of a stereotactic breast biopsy. Patients with neurologic or musculoskeletal conditions may not tolerate positioning on the already-uncomfortable stereotactic biopsy table. Any condition that increases the

43 IMAGE-GUIDED BREAST BIOPSY likelihood of patient movement will cause a greater risk of missing the target lesion. This includes patients with acute or chronic respiratory conditions with associated coughing and patients with a high level of anxiety, especially those suffering from claustrophobia or agoraphobia. A history of bleeding abnormalities or use of anticoagulants, as with any biopsy, creates the potential for bleeding and complications such as hematoma. Grade 2 complication ● Prevention When recognizing the kyphotic patient or those who may not tolerate the table positioning, it is helpful to ask the patient to try lying on the floor at home, with her head turned to one side for approximately 20 to 30 minutes. Having cough suppressants available will deal with most respiratory conditions. Although most stereotactic breast biopsies are performed with only local anesthesia, it may be helpful to use a diazepam for sedation in those anxious patients. If time allows, schedule the biopsy after 10 days of restriction from anticoagulants working on platelet function and allow for the reversal of warfarin. However, because the patient facing a possible diagnosis of breast cancer may not want to wait 10 days or if reversal of warfarin is medically inadvisable, most procedures can still be accomplished with only marginal risk. Using a smallergauge biopsy device and wrapping the patient with a pressure-style dressing may be helpful.

Not Choosing the Ideal Approach to the Breast ● Consequence The shortest skin-to-lesion distance and the ability to clearly visualize the imaged abnormality are both factors the technologist and physician consider when working together to choose the correct approach (CC, LM, ML, and with the Hologic Multi-Care Platinum table, caudocranial) to the breast. Once the shortest skin-tolesion distance is chosen, the lesion must be well visualized. The visibility of the breast abnormality may occasionally take priority over the shortest distance from the skin to the lesion. Although a lesion in the breast at 12 o’clock may suggest a CC approach, if the lesion is seen better on the patient’s mediolateral oblique (MLO) mammogram view, then an ML approach may be preferable. A situation may arise (on the Fischer Mammotest table) in which the abnormality is best seen in the CC view but the lesion appears to be in the inferior aspect of the breast on the MLO mammogram view. Therefore, it may not be possible to insert the biopsy instrument without traversing most of the breast tissue and striking the back of the patient’s breast (negative stroke margin), because in contrast to the Hologic Multicare Platinum table, the Fischer Mammotest table does not provide a caudocranial approach. Grade 1 complication

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● Repair/Prevention Determining the true position of the lesion within the breast starts with an understanding of the virtual position of the lesion created by the usual 60° MLO mammogram. A lesion that is in the lateral breast appears to be higher on the MLO view than its true position and a medial lesion appears lower on the MLO view than its true position. Therefore, if the patient’s abnormality is visualized best in the CC view, but the lesion is in the medial aspect of the breast, the biopsy using this approach will be successful and may not impale the underside of the breast because the medial lesion is actually more superior in the breast than it is perceived on the MLO mammogram view.

Failure to Recognize the Position of the Lesion in the Breast ● Consequence The technologist may have difficulty in locating a lesion for biopsy when positioning the patient on the stereotactic table if the correct position of the lesion in the breast is not appreciated. Grade 1 complication ● Repair Remember that when positioning a patient on a prone stereotactic table for an LM or ML approach that this is a 90° angle to the breast compared with the 60° angle associated with the traditional MLO mammogram view. Therefore, the lesion in the lateral aspect of the breast will “move” to a more inferior position with the LM stereotactic approach compared with its apparent position on the MLO mammogram. A lesion in the medial aspect of the breast will “move” to a more superior position with an ML (90°) stereotactic approach compared with its apparent position on the MLO mammogram.

Failure to Visualize the Lesion on Both Stereo Images ● Consequence When a lesion well visualized on the scout image lacks visibility on both stereo images, another difficulty arises, especially when the physician has already considered the shortest skin-to-lesion distance and the clarity of the image on each mammogram view. This is most often due to fibroglandular tissue that superimposes itself over the target lesion in one of the stereo images because of the angle of exposure. Grade 1 complication ● Repair A technique known as target on scout can be utilized to resolve the issue of limited clarity of the lesion on one of two stereotactic images. The stereo image, with poor lesion visibility, is replaced by the original scout image in which the lesion is clearly identified. The

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targeting is then performed on the one remaining stereo image and the scout image. The software is able to recognize the 15° separation between the two targeted images and then calculate the appropriate coordinates. It is important to maintain all follow-up prefire and postfire images consistent with the targeting images. On the replaced scout image on the Hologic Multi-Care Platinum table, with the biopsy device in position, it is more difficult to visualize the targeted lesion because of the cartesian targeting platform.

Patient Positioning Failure to Image a Lesion that is Deep against the Pectoral Muscle

Obtain Scout and Stereo Digital Images Acquisition of the first digital image is the 0°, scout image. Regardless of the approach to the breast (CC, ML, LM, or caudocranial), this image is taken perpendicular to the compressed breast. Next, the technologist obtains a set of stereo images by rotating the tube head to the +15° and the –15° positions to yield an arc of separation between the two stereo images of 30°.

Not Correctly Positioning the Breast Lesion within the Compression Window

● Consequence The position of certain lesions, including those against the chest wall or in the tail of the breast or axilla, may require innovative positioning by the experienced technologist. Grade 1 complication

● Consequence Failure to position the breast so that the lesion to be biopsied falls within the 5 × 5 cm opening of the compression paddle such that it appears in the middle third of the scout image will result in the lesion being “thrown” outside the visualization/targeting window on one of the two stereo images (Fig. 43–2). Grade 1 complication

● Repair One commonly used positioning technique involves placing the patient’s arm and part of the shoulder through the table aperture with the breast. This allows compression with the paddles of the most posterior aspect of the breast (Fig. 43–1).

● Repair Repositioning the patient and the breast so that the breast abnormality falls within the middle third of the compression paddle–biopsy window should correct the problem. The technologist will frequently recognize and correct this problem.

Failure to Recognize the Depth of a Lesion in the Breast

Figure 43–1 The patient is positioned with her arm through the table aperture so the surgeon can gain access to a posterior lesion.

● Consequence A lesion that is too superficial may interfere with the successful function of certain biopsy devices that may require the sampling portion of the device to be within the skin. A vacuum-assisted biopsy (VAB) device requires maintaining a suction vacuum to pull tissue toward the sampling portion of the device. If the entire sampling portion is not beneath the skin because the lesion is too superficial, the vacuum is unable to maintain enough suction to pull the tissue in for biopsy (Fig. 43–3). The newer large, intact sampling devices utilize radiofrequency-activated tissue cutting and must, therefore, be a certain distance beneath the skin to avoid any inadvertent burns. If a lesion is too deep, insertion of the biopsy device without encroaching on the backside of the breast will be difficult, and a stroke margin problem will be encountered. This is especially true for devices that have a springloaded mechanism to advance the biopsy portion of the device forward into the breast. A stroke margin is the distance from the device tip after advancing forward to the back of the breast. There is a problem when this distance is less than the stroke (forward motion) of the particular device (negative stroke margin) (Fig. 43–4). Grade 1 complication

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Correct positioning Image receptor Scout

Stereo

⫹15

⫺15

Incorrect positioning Image receptor Scout

Stereo

⫹15

⫺15

Figure 43–2 Correct positioning with the lesion in the middle third of the biopsy window. Incorrect positioning will cause the lesion to be taken out of view on one of the stereo images.

Negative Stroke Margin Stroke (mm) Stroke (⬍0) margin

Post-fire

Lesion

Figure 43–3 The back end of the sampling portion of a vacuumassisted biopsy device is shown outside the skin during an attempt to biopsy a superficial lesion.

● Repair The use of skin hooks can retract the skin so the back of the VAB device is covered; thus, there will be adequate suction for biopsy and the skin can be protected from the heat of the radiofrequency-activated large intact sample device (Fig. 43–5). Repositioning the patient for a different approach to the breast may be all that is required (e.g., changing from a CC to an ML or LM approach) to deal with lesions that are determined to be too deep.

Compression thickness

Figure 43–4 A negative stroke margin occurs when the stroke margin is less that the forward motion (stroke) of the biopsy device.

● Prevention The ability to recognize the significance of lesion movement from one stereo image to the next can alert the astute physician to the depth (superficial or deep) of the lesion and further predict a problem of a lesion too close to the skin or too deep against the back of the breast or rear image receptor.

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SECTION VI: BREAST SURGERY sary amount of tissue behind the lesion. Using a biopsy device that has a shorter-throw (forward movement of an automated device) or a biopsy tool that has a shorter sample notch can reduce the required breast thickness. Manual insertion of the biopsy instrument (avoiding the automated firing) allows a controlled forward motion of the sampling notch into appropriate position. Use of the lateral arm allows insertion of the biopsy device through the side of the compressed breast, parallel to the compression paddles. Also, use of the double-paddle technique adds an additional buffer between the back of the breast and the back compression paddle.

Figure 43–5 Skin hooks are one method to adjust for potential complications related to the biopsy device and a superficial lesion.

Targeting the Lesion A target is chosen on the abnormality in each of the stereotactic images. The computer software determines the horizontal, parallax shift of the lesion from stereo image number one to stereo image number two. The software then calculates the horizontal, vertical, and depth coordinates. The software can either use the 30° separation of stereo images or substitute the 15° between the stereo and the scout images when using the “target on scout” technique. It may be important to consider the biopsy device type when placing the target on the lesion in each of the stereo images. If the abnormality in the breast is small, the size of certain devices when inserted into the breast may hinder visualization of the lesion. Therefore, placing the targets inferior to the lesion will allow the lesion to appear superior to the biopsy device once it is in position and easily visualized.

A Negative Stroke Margin ● Consequence Once the target information is acquired, whether there will be an adequate stroke margin becomes evident. The stroke margin again is the distance from the postfired position of the biopsy probe to the back of the breast or rear-image receptor. A negative stroke margin is encountered when the breast is very thin or the lesion is in a posterior position in the breast. This situation may result in the biopsy needle striking the rear-image receptor and piercing the back of the patient’s breast skin (see Fig. 43–4). Grade 1 complication ● Repair Several methods are available for eliminating the negative stroke margin. Taking a different approach to the breast lesions (e.g., changing from a lateral approach to a medial approach) may actually provide the neces-

● Prevention Small or ptotic breasts create one of the most common difficulties in stereotactic breast biopsy. A minimal compression thickness is required to avoid stroke margin problems. This minimal compression thickness varies between biopsy devices. It is important to recognize the patient with these characteristics. Once again, the ability to accurately access the position of the lesion and appropriately position the patient for the correct approach will limit these difficulties.

Prepare the Breast: Skin Preparation, Local Anesthesia, and Skin Incision The appropriate level of local anesthesia is crucial to limit patient discomfort and resultant movement. The position of the biopsy device to the calculated horizontal and vertical coordinates determines the entry site into the breast. The physician makes a small skin incision with usually a No. 11 blade scalpel. The incision size may vary from just a few millimeters to slightly greater than 1 cm, depending on the biopsy device and whether the incision is oriented vertically.

Using Local Anesthetic with Epinephrine in the Skin ● Consequence The skin wheal is raised, usually with 1% lidocaine. For stereotactic biopsy, it is important to avoid the use of local anesthesia combined with epinephrine. The constant pressure of the 5 × 5 cm biopsy window (in the compression paddle) on the breast for the entire length of the procedure (sometimes >30–45 min) will cause a decrease in blood flow and result in skin necrosis at the entrance site. Local anesthesia with epinephrine (1 : 100,000) is commonly used with the deeper injection into the breast parenchyma. Grade 1 complication ● Repair The area of necrosis is usually limited to the size of the skin wheal. Local wound care is sufficient and rarely requires surgical excision of the necrotic skin.

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Injecting Too Much Local Anesthetic ● Consequence Too much local anesthetic injected into the biopsy site can also pose potential problems. The injection is not performed in real time as is done with ultrasoundguided procedures and, therefore, can cause inadvertent lesion movement, and faint, noncalcified lesions can become difficult if not impossible to see on additional imaging. Grade 2 complication ● Repair If the injection is too large, a quantity of local anesthetic results in the movement of the lesion such that adequate sampling may be altered; in this situation, it will be necessary to remove the biopsy device from the breast and retarget the lesion. If the lesion is faint and/or noncalcified, correction is more difficult. Occasionally, waiting a few minutes for reabsorption or dilution of the local anesthetic is sufficient. Sometimes, a review of the stereo digital images taken for initial targeting can help judge the correct position of the lesion by comparing the surrounding breast architecture. A last resort would be postponing the procedure and rescheduling. ● Prevention Physicians have employed different techniques for providing the patient with adequate anesthesia and avoiding the difficulties outlined. One technique utilizes a skin wheal followed by injection of deep local anesthetic at the four quarters of the clock (12, 3, 6, 9 o’clock positions) positioned at the lateral aspect of the skin wheal. The 1½ inch needle is inserted to the hub and the local anesthetic is injected gently as the needle is withdrawn. This technique disperses the local anesthetic evenly and provides a region of anesthesia where tissue sampling will occur. Another technique involves placing local anesthetic directly at the biopsy site only after a skin wheal has been raised. A spinal needle can be directed with stereotactic guidance to the correct x-, y-, and z-axis (depth) coordinates, and 1 or 2 ml of local anesthetic is directed in a limited fashion to the biopsy site. However, the most accurate prevention starts with recognition of which lesions will be difficult to visualize when larger amounts of local anesthetic are injected (faint asymmetrical densities and microcalcifications). Prior to injecting larger quantities of local anesthetic, deploying a metallic clip in the lesion will eliminate nonvisualization. In addition, allowing injection of deep local anesthesia only after the biopsy device is in position and visually aligned with the target lesion will usually accomplish the goal.

Insertion of the Biopsy Device The physician inserts the biopsy device into the breast to the depth determined by the system software.

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Failure to Recognize Specific Insertion Depths for Different Devices ● Consequence Certain devices require placement at a depth less than that calculated by the system software. The “pullback” is calculated by the individual manufacturers because of the device mechanics such as the forward motion or throw with the amount of “dead space” at the front of the needle along with the length of the sampling portion of the needle. If the required pullback in depth is ignored for a particular device, the device may be too deep or not aligned correctly with the lesion and adequate tissue sampling will not occur. Grade 1 complication ● Prevention It is crucial not only to be familiar with the biopsy mechanism of the device but also to know the specifications from the manufacturers for stereotactic targeting, including the pullback depth. The Fischer MammoTest table allows the specifications for all the biopsy devices physicians will use to be programmed into the system. The Lorad Multi-Care table requires calibration of each device to the system on each patient (z-axis = zero), and the physician manually sets the depth.

Inability to Avoid a Negative Stroke Margin ● Consequence If a negative stroke margin cannot be prevented by changing the positioning or approach to the breast or utilizing any of the other previously discussed options, the negative stroke margin must be recognized and manipulated to prevent injury to the patient or the equipment. Grade 1 complication ● Repair The most commonly employed correction method is pulling back the prefire position of the biopsy needle a determined number of millimeters until the calculated stroke margin is adequate. Care must be taken not to pull back the biopsy device to a distance that places the sampling notch or biopsy mechanism too far in front of the lesion such that the lesion will be missed.

Assess Appropriate Alignment between the Lesion and the Biopsy Device on Prebiopsy and/or Postbiopsy Alignment Stereo Digital Images Failure to Recognize Targeting Errors ● Consequence Interpretation of the stereotactic digital images allows the physician to determine whether the breast-imaged abnormality is within the range required by the device for adequate sampling. Correct targeting demonstrates

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Vertical error 12

9

3

6

Probe is above

12

9

3

6

Probe is below

Figure 43–6 Y or vertical axis targeting error: The device is visualized above or below the lesion. The directed sampling is illustrated by the shaded areas on the clock.

symmetrical alignment of the lesion and the biopsy portion of the device in each stereo image. There are three types of targeting errors that can occur: x-, y-, and z-axis targeting errors. X-axis deviation occurs when the lesion is pushed to the right or the left of the biopsy needle. Y-axis errors represent movement of the lesion above or below the needle/probe. Z-axis error occurs when the sampling notch or biopsy mechanism is too proximal or too distal to the depth of the breast abnormality. Grade 1 complication ● Repair Fortunately, most x- and y-axis targeting errors that present a problem with stereotactic needle-core biopsy have a limited effect on the success of a stereotactic biopsy performed with either a VAB or a large-intake sample device because these devices can be directed for specific sampling (Fig. 43–6). However, if the deviation from the target is significant enough to risk a poor biopsy, the lesion must be retargeted. After the device is removed from the breast, it is redirected and inserted with new coordinates. ● Prevention To avoid missing a lesion because of an incorrect depth (z-axis) coordinate caused by forward motion of the lesion because of the “plowing” effect as the biopsy device is inserted; targets can be placed on the lesion in each of the new stereo images and the resultant zaxis depth compared with the original z-axis depth. The

position of the target in each stereo image can also be helpful in preventing lesion movement and improve the probability of being able to easily visualize a very small lesion once the biopsy needle/probe is fully inserted into the breast. By targeting beneath the lesion, some of the plowing effect is dispersed, and because the lesion will be elevated above the device, even a very small lesion will not be hidden and its position will be easily assessed.

Adequately Sample the Lesion for Diagnosis and/or Potential Therapeutic Removal Failure to Choose the Correct Biopsy Device ● Consequence The tools for specimen acquisition have evolved from fine-needle aspiration, automated Tru-Cut core needle, VAB devices to large-intact sampling instruments, and the technologic advancements have closely paralleled the acceptance of image-guided breast biopsy.19 Fineneedle aspiration has long been recognized to have several potential pitfalls. This includes insufficient sampling, as high as 38% in some series, with sensitivity ranges between 68% and 93% and specificity between 88% and 100%.18,19 Cytology rarely provides a specific benign diagnosis and cannot distinguish between invasive and in situ carcinoma. The automated Tru-Cut core needle has a lower false-negative rate compared with that of fine-needle aspiration.5–7 Standard use of the 14-gauge needle essentially eliminated the issue of insufficient sampling.

43 IMAGE-GUIDED BREAST BIOPSY Several different gauge needles have been evaluated for Tru-Cut biopsy. The lower rate of insufficient sampling and increased sensitivity, without increased complications, has led to a minimum size of 14-gauge as a standard.5,19 The issue of how many cores are needed was addressed by Dr. Laura Lieberman from Sloan-Kettering in New York.20 In this study, 145 lesions were biopsied: 92 were nodular densities, and 53 were microcalcifications. Five cores with a 14-gauge automated Tru-Cut needle yielded a diagnosis in 99% of biopsies for breast masses. Five cores yielded a diagnosis in only 87% of the microcalcification cases, and more than six cores yielded a diagnosis in 92% of the cases. The accuracy of needle-core biopsy of microcalcifications came into question. Studies demonstrated upgrading to carcinoma from 48% to 52% of atypical hyperplasia identified on stereotactic core biopsy.21–23 Not surprisingly, atypical hyperplasia diagnosed at stereotactic core biopsy has become an indication for open biopsy. Grade 2 complication ● Repair The VAB device was developed to satisfy the requirement of increasing the size of the core sample and the contiguous nature of the sampling as a proposed solution to the upgrading issue.24,25 The VAB system was ideal for performing an image-guided biopsy of calcifications under stereotactic guidance. The spring-loaded mechanism to advance the biopsy probe could eliminate the potential z-axis targeting error by rapidly penetrating the tissue and avoiding the plowing effect of pushing the lesion forward. But the ability to manually insert the device without having to utilize the firing mechanism could help deal with the small breast and potential stroke margin issues. The vacuum applied to the sampling portion of the device eliminates the pinpoint accuracy required with automated Tru-Cut biopsy needles by pulling the lesion toward the sampling chamber, and the ability of the VAB sampling to be directional is helpful in dealing successfully with mild x-axis and y-axis targeting errors.18,24 The improved accuracy with the directional VAB device lowered the upgrading of diagnosis compared with that of needlecore biopsy technology.11,12

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large intact sample devices. Fortunately, the vacuum associated with these devices will continue to pull blood from the biopsy site and allow the inherent biopsy mechanism the opportunity to continue to obtain tissue samples. Therefore, from personal experience, the most important step in dealing with bleeding during a stereotactic breast biopsy is to continue to take core samples with appropriate rapidity. The injection of additional local anesthesia with 1 : 100,000 epinephrine can be helpful. ● Prevention During the imaging phase of the procedure, it should be determined whether there are vessels near the lesion that may be in the pathway of the biopsy device. This is accomplished by placing a target on the vessel in each stereo image to check whether the depth is the same as the lesion. If the lesion and the vessel are at the same depth, the patient should be repositioned to try to manipulate the breast so the approach to the lesion avoids the vessel.

Place a Postprocedure Marker and Obtain Postprocedure/Clip Placement Stereo Images Postprocedure digital images are required to document removal of the microcalcifications and, at the same time, to verify the presence of residual calcifications. If the postprocedure images are taken after clip placement, it is important to verify accurate and successful clip deployment. In addition, accuracy is improved when calcifications are documented within the core samples on a digital specimen radiograph.26,27 Even in open biopsy surgical literature, pathologic assessment has identified atypical hyperplasia and ductal carcinoma in situ (DCIS) at a “distance” from the targeted calcifications.28

Clip Placement and Migration

● Consequence During the course of any image-guided breast biopsy procedure, bleeding can occur. An excessive amount of intraprocedural bleeding can potentially interfere with sampling and, as a result, an accurate biopsy. Grade 2 complication

● Consequence At the conclusion of a stereotactic breast biopsy, the placement of a marker has become standard. The marker has two purposes. The first and foremost is to be able to localize a stereotactic biopsy site when all image evidence of the target lesion has been removed, and second, to track the site on future mammograms. The initial clip (Micromark; Ethicon Endosurgery) was developed as an adjunct to the Mammotome VAB device to mark the complete removal of calcifications where pathology resulted in the need for follow-up surgery.29 Clip migration was a reported event.30 The result would be a failure to accurately localize a biopsy site. Grade 1 complication

● Repair When performing a stereotactic breast biopsy, the most common biopsy devices used include VAB devices and

● Prevention The prevention of clip migration involved careful technique, including pulling the device back to position the

Failure to Appropriately Manage Intraprocedural Bleeding

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ramping up of the clip into the center of the biopsy cavity, applying active suction to pull the tissue in the breast toward the clip applier, and rotating and closing the device away from the clip position (to avoid accidental removal). Postprocedure mammograms could accurately ensure good clip placement. The issue of clip migration has also been avoided by the use of clips or markers that do not require attachment to the breast tissue. The newer markers include a metallic component along with an absorbable component such as Vicryl or collagen that can be visualized by ultrasound. These newer markers are simply deposited into the biopsy cavity. As the biopsy site heals, the cavity contracts and the clip is trapped at the biopsy site.

Obtain a Specimen Radiograph Postprocedure digital images and specimen radiographs of calcifications and the relationship to diagnostic upgrading have been addressed earlier. Additional sampling to remove a greater portion of the targeted lesion can easily be accomplished if inadequate calcifications are visualized on postprocedure images.

Obtain Adequate Hemostasis and Apply Appropriate Dressing and/or Wrap Techniques to avoid hematomas are discussed in the section on “Image-Guided Breast Biopsy with Ultrasound Guidance,” later.

Check Pathology for Concordance with Radiologic Impression This topic is addressed in the section on “Pathologic Pitfalls in Image-Guided Breast Biopsy,” later.

Image-Guided Breast Biopsy with Ultrasound Guidance

Adequately sample lesion for diagnosis and/or potential therapeutic removal Step 8 Place postprocedure marker and obtain postprocedure/clip placement mammogram Step 9 Obtain adequate hemostasis and apply appropriate dressing and/or wrap Step 10 Check pathology for concordance with radiologic impression Step 11 Obtain follow-up imaging Step 7

Evaluate the Ultrasound Failure to Recognize a Possible Cystic Lesion ● Consequence The ultrasound characteristics of a complex cyst frequently mimic those of a solid lesion. If the complex cystic lesion is not recognized and the physician moves forward with an image-guided biopsy of a presumed solid lesion, the physician may waste a more costly disposable biopsy device instead of a simple syringe or a needle that would be adequate for a cyst aspiration. By evaluating the ultrasound images and appreciating the depth (superficial or deep) of the lesion or its relationship to an implant, the patient can be better positioned (see the section on “Position the Patient and Equipment [Ultrasound and Biopsy System], later) and the optimal biopsy device chosen. To be discussed further in the section on “Sample the Lesion for Diagnosis and/or Potential Therapeutic Removal,” later, certain biopsy instruments are more ideally suited for a very deep or very superficial lesion. Grade 1 complication ● Prevention Careful evaluation of the diagnostic ultrasound performed at an outside institution can sometimes eliminate the unnecessary wasting of an expensive disposable biopsy tool for a lesion that may actually turn out not to be solid and can be aspirated. Any suggestion of posterior enhancement or other characteristics of a possible complex cyst should first lead to an attempt at aspiration, even with a larger-gauge needle. Occasionally, duct ectasia may be associated with cystic fluid that requires a needle as large as 14-gauge to aspirate the contents.

OPERATIVE STEPS Step 1 Step 2 Step 3 Step 4 Step 5 Step 6

Evaluate ultrasound Position patient and equipment (ultrasound and biopsy system) Identify lesion with ultrasound and optimize image Anesthetize skin and make skin incision after appropriate antiseptic skin preparation Insert biopsy device Confirmation scan for alignment of lesion with biopsy device

Position the Patient and Equipment (Ultrasound and Biopsy System) Poor Positioning of the Patient and Equipment ● Consequence/Prevention Regardless of the imaging modality, the most significant error in image-guided breast biopsy is of course missing the lesion or a failure to accurately sample the breast abnormality and providing the patient a false sense of security. With ultrasound intervention, the ability to perform a successful procedure starts with

43 IMAGE-GUIDED BREAST BIOPSY comfort for the patient and the physician. Positioning of the physician, the patient, and the ultrasound equipment will greatly facilitate the required alignment of the biopsy device with the lesion. Standing opposite to the ultrasound unit will eliminate the physician from turning his or her head away from the biopsy field to see the ultrasound monitor. The optimal setup to provide the best visualization of the advancing biopsy device is a straight line between the physician’s vision and the physician’s arm down the length of the biopsy device, along the long axis of the ultrasound transducer, and up to the ultrasound monitor. Grade 1 complication

Identify the Lesion with Ultrasound and Optimize the Image Inappropriate Gain and Focal Zone Setting ● Consequence/Repair Optimal scanning is achieved by adjusting the time gain compensation slope to provide a uniform gray scale. An altered overall gain setting may change the appearance of the internal echo pattern and limit the ability to distinguish solid from cystic lesions. To achieve the optimal lateral resolution, the sonographer must align the focal zone with the target lesion as illustrated in Figure 43–7. This will better demonstrate the retrotumoral characteristics such as posterior enhancement. Grade 1 complication

Poor Optimization of the Lesion Position for Biopsy ● Consequence If the ultrasound transducer is not positioned so that the greatest diameter of the lesion is within the ultrasound plane, the needle-core biopsy device may miss the lesion by veering off the edge of a solid mass. If the lesion is not positioned correctly on the ultrasound

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monitor, the shortest skin-to-lesion distance will not be achieved. Grade 2 complication ● Prevention Two scanning techniques are crucial for identifying the area of greatest lesion diameter and positioning the lesion on the ultrasound monitor to limit the skin-tolesion distance. Movement of the transducer perpendicular to the long axis of the transducer allows the scanner to visualize the lesion from end to end and find the widest portion of the lesion. Sliding the transducer in the direction parallel with the long axis will change the position of the lesion on the ultrasound monitor.

Prepare the Breast: Skin Preparation, Local Anesthesia, and Skin Incision Failure to Judiciously Administer Local Anesthetic ● Consequence Too much local anesthetic injected into the breast parenchyma carries the risk of the inability to visualize a smaller target lesion. In addition, the injection of too much local anesthetic in one area can create a false lesion that mimics a cyst. This can be especially frustrating when the target lesion is cystic. Grade 2 complication ● Repair If the visibility of the target lesion has been hindered by the local anesthetic administration, few alternatives are available to continue the biopsy. A very skilled sonographer could use an aspiration needle to aspirate any collections of local anesthetic that are interfering with the biopsy. However, the usual course of action would be to wait until the local anesthetic has been reabsorbed. Attempting to perform the biopsy without optimal visualization of the lesion could result only in

Figure 43–7 Alternating the focal zone, as seen with this breast phantom, will alter the lateral resolution. The ideal lateral resolution occurs when the focal zone is aligned with the target.

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an inadequate sampling of the lesion and a diagnosis that may falsely reassure the patient. ● Prevention After a sterile or “clean” preparation of the skin and the ultrasound transducer, local anesthetic (usually 1% lidocaine) is injected at the proximal end of the ultrasound transducer. Once a skin wheal is made, intraparenchymal injection of local anesthetic is performed under direct ultrasound visualization. By monitoring the injection with ultrasound, adequate anesthesia is obtained without compromising visibility. The technique of injection under direct visualization is discussed further with prevention of inadvertent biopsy of the skin and prevention of pneumothorax below.

Insert the Biopsy Device Failure to Visualize the Advancing Biopsy Device Tip ● Consequence Pneumothorax, hemothorax, and biopsy of pectoral muscle (with associated increased bleeding and pain) are among the potential problems associated with the inability to confirm the position of the advancing biopsy device. Grade 2 complication ● Repair The details of treatment of a rare pneumothorax or hemothorax, and the placement and management of chest tubes are not discussed in this section. Management of “Bleeding and Hematoma” are discussed later. ● Prevention To avoid potential advancement of the device into the pectoral muscle or lung, multiple issues are addressed. The key to visualizing the advancing tip of any device resides in both maintaining alignment of the device with the ultrasound scan plane and keeping the advancing device as parallel with the face of the ultrasound transducer as possible. To achieve parallel positioning with the transducer, regardless of the lesion depth, will require that the patient be positioned in lateral decubitus with a pillow behind the shoulder. In addition, the ultrasound transducer can be gently tilted into the breast away from the advancing device. Local anesthesia can also be injected under direct ultrasound visualization; by directing the needle beneath the lesion, it can be raised off or away from the pectoral muscle. Another way to avoid inadvertent pneumothorax is to use a nonfiring device. The VAB as well as the large intact sample devices are positioned below a lesion without a spring-loaded firing mechanism and the acquisition of tissue is directed superiorly.

Confirmation Scans for Alignment of the Lesion with the Biopsy Device Failure to Align the Lesion with the Biopsy Device ● Consequence Failure to confirm with ultrasound imaging that the biopsy device tip or its sampling area is aligned correctly with the lesion will of course lead to inadequate biopsy of the lesion and potentially falsely reassuring a patient of a benign diagnosis. Grade 2 complication ● Prevention To avoid missing significant portions of the lesion with ultrasound-guided needle core biopsy, by the forward movement of the inner and outer cannula, the needle tip is brought just to the front edge of the lesion and does not penetrate into the lesion prior to firing. When performing a needle-core biopsy, in which it is crucial to know whether the needle has penetrated the lesion, a confirmation scan is needed to avoid a false image created by the overlap of the narrow ultrasound scan plane with the needle just at the edge of the lesion (image averaging). The physician may view the ultrasound image and interpret it as a successful biopsy although the needle has not actually penetrated the lesion (Fig. 43–8). By moving the ultrasound transducer perpendicular to its long axis, the lesion can be visualized from one end through its middle to the other end of the lesion. It is necessary to see a portion of the lesion without the needle, followed by the needle with the lesion, and then continuing the scan in the same direction to again visualize the lesion without the needle. This will confirm that the needle is in the lesion. The success of ultrasound-guided VAB or large intact biopsy is enhanced by careful attention to the technical aspect of the procedure. Patient positioning (lateral decubitus), injection of local anesthetic posterior to the lesion for a lifting effect, and torquing down of the biopsy device handle as the probe approaches the underside of the lesion all serve to provide a shallow angle of insertion and easier access underneath the lesion, especially when the lesion is deep within the breast parenchyma. When the biopsy device is in position for a biopsy, ensuring an adequate sampling requires a confirmation scan to assess the relationship of the device and the lesion. VAB devices and one of the large intact sample devices (Rubicor Medical, Halo, Redwood City, CA) are positioned below the lesion. If these are not positioned beneath the breast target lesion, the artifact created by the device would eliminate visualization of any portion of the lesion below the biopsy probe. To confirm that the device is centered beneath the lesion, the ultrasound transducer is rotated 90°. The device is then visualized in crosssection, and it becomes obvious whether it is centered underneath the lesion, also seen in cross-section.

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Figure 43–8 When the biopsy needle and the edge of a lesion are both within the ultrasound scan plane, image averaging occurs and creates the perception that the needle is in the lesion.

Sample the Lesion for Diagnosis and/or Potential Therapeutic Removal Failure to Choose the Appropriate Biopsy Device for Ideal Sampling ● Consequence Cytologic or histologic confirmation of malignancy is the minimum requirement for ultrasound-guided biopsy of “indeterminate” or suspicious solid lesions. Fine-needle aspiration biopsy is a quick, inexpensive technique to delineate benign from malignant solid breast masses. However, the same issues surrounding the use of fine-needle aspiration in stereotactic imageguided breast biopsy apply to ultrasound-guided procedures. Grade 2 complication ● Prevention Ultrasound fine-needle aspiration is ideally suited to evaluate lesions in areas such as the axilla where more invasive biopsy devices may be difficult or dangerous. The diagnosis of lymph node metastasis by fine-needle aspiration can assist with preoperative staging in consideration of neoadjuvant chemotherapy or eliminating sentinel lymph node biopsy by confirming positive cytology in clinically suspicious lymph nodes. The use of automated Tru-Cut needle-core biopsy eliminates the same problems with fine-needle aspiration that are seen with stereotactic breast biopsy such as insufficient sampling and the inability to provide the histologic type and grade of a diagnosed cancer. VAB and large intact sample technology are also available with ultrasound guidance. The indications for an ultrasound-guided VAB are similar to those for needlecore biopsy, including any indeterminate, ultrasoundvisible, palpable or nonpalpable solid masses. If the physician is interested in the potential therapy of probably benign breast abnormalities, VAB devices or large intact sampling devices would be required. Both of these device categories have successfully demonstrated their ability to

Figure 43–9 A postprocedure hematoma after a vacuum-assisted biopsy. No surgical intervention was required.

remove image evidence and especially palpability of probably benign solid masses.31

Place a Postprocedure Marker and Obtain Postprocedure/Clip Placement Mammogram Clip placement and potential pitfalls have been addressed previously.

Obtain Adequate Hemostasis and Apply Appropriate Dressing and/or Wrap Bleeding and Hematoma ● Consequence The incidence of hematoma with image-guided breast biopsy is reported to be 2% to 8% (Fig. 43–9). It is extremely rare for bleeding or hematoma to result in any post–image-guided surgical procedures. This author’s experience is that no patient has required operative intervention. Bruising and small hematoma

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formation are common, especially near the biopsy insertion site. The size of the hematoma will, of course, contribute to the level of pain and discomfort. Grade 1 complication ● Prevention/Repair Manual compression is the mainstay for achieving hemostasis in image-guided breast biopsy and preventing hematomas. It is important for the pressure to be applied across the biopsy track created by the device. When a VAB or large intact sample device has been used to remove the image evidence of the lesion, a larger biopsy cavity is created and there is a greater risk of bleeding/hematoma. It is important that the manual pressure and the pressure dressing, in particular, be applied to the site of the lesion and not only at the incision. Prevention of a hematoma can also be influenced by placing the patient in a chest wrap. Conservative management with ice and pressure wraps is sufficient.

Check Pathology for Concordance with Radiologic Impression This topic is addressed in the section on “Pathologic Pitfalls in Image-Guided Breast Biopsy.”

PATHOLOGIC PITFALLS IN IMAGE-GUIDED BREAST BIOPSY Not Performing a Further Procedure with a Diagnosis of Benign Papillary Lesion on Core Biopsy ● Consequence The pathologist is confronted with the following decision points when presented with a papillary lesion: 1. Distinguishing benign, atypical, and malignant papillary lesions with limited material. 2. Establishing a diagnosis with the realization that the sample may not contain the most worrisome histology present in the lesion. 3. Distinguishing invasive carcinoma from a fragmented and distorted sclerosing papillary lesion. Papillary lesions of the breast can be divided into benign and malignant categories. Benign lesions include solitary intraductal papilloma, multiple papillomas, and atypical hyperplasia within a papilloma. If a diagnosis of atypia is mentioned, further surgical excision needs to be performed. What is less clear is whether or not complete surgical excision is required for a diagnosis of benign intraductal papilloma. Solitary intraductal papilloma usually presents as a well-defined mass, whereas multiple intraductal papillomas typically present as a nodular mass or with microcalcifications.32 In both instances, a cystic component may be identified on ultrasound examination.

The significance of either diagnosis is an increased risk of developing breast cancer. Based on a review of 372 solitary papillomas and 41 multiple papillomas published from the Mayo clinic, there is an approximately twofold increased risk in the case of solitary papilloma and a threefold increase in the case of multiple papillomas.33 Atypia, when present, is more often associated with multiple papillomas than with solitary central papillomas.34 The atypia in papillary lesions is frequently unevenly distributed and is usually present in less than 50% of the papilloma.35 The relative risk of developing carcinoma when atypia is present versus when atypia is not identified is a 7.5-fold increase.36 In addition, that risk is in the ipsilateral breast as opposed to a more generalized risk associated with atypical intraductal hyperplasia (AIDH). Studies have demonstrated the presence of atypia and/ or malignancy in 0% to 44% of excision specimens when a diagnosis of benign papillary lesion is rendered on a core biopsy.37–46 In general, a relationship exists between the presence of atypia and/or malignancy in excisional specimens and the amount of residual lesion remaining after core biopsy. This is not surprising given the focal nature of atypia, when present. Because of the possibility of missing the most worrisome histology and the fact that papilloma with atypia is a precursor lesion, most experts recommend complete radiographic excision of the imaging abnormality if a diagnosis of benign papillary lesion is rendered by the pathologist. When sclerosing papillary lesions are removed in small fragments, they can be difficult to distinguish from radial sclerosing lesions and invasive carcinomas. The sclerosis can entrap benign epithelial elements, simulating an invasive carcinoma. The use of immunostains can effectively demonstrate the presence or absence of a myoepithelial cell layer to aid in the differential diagnosis of an invasive cancer but cannot help to distinguish a radial sclerosing lesion. It should be noted, however, that most malignant papillary lesions behave in a relatively indolent manner.47 Whereas they occasionally metastasize to lymph nodes, distant metastasis is rare. ● Prevention Complete removal of the imaging abnormality should be performed.41,42,45,46,48 The biopsy device chosen by the surgeon may dictate further procedures. For example, if a lesion, highly suspicious for a papilloma, is sampled with a 14-gauge spring-loaded biopsy device, a second procedure will need to be performed even if a diagnosis of a benign papillary lesion is rendered. Limited sampling of a papillary lesion may miss atypia, which is usually present only focally, and atypia is believed to be a precursor lesion. Therefore, when the probability of a papillary lesion, such as a welldefined subareolar mass, is high, a large-core biopsy device or whole intact excisional biopsy device should be used.

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Figure 43–10 Low-power hematoxylin and eosin (H&E) microscopic image of a completely resected intraductal papilloma. The biopsy was obtained using a whole intact biopsy device, preserving the architecture and eliminating the need for further surgery.

A second factor in selecting a biopsy device is preservation of tissue architecture. Biopsy devices can be thought of as providing puzzle pieces to the pathologist. The larger the pieces, the less the architecture is distorted and the easier it is for a pathologist to establish a diagnosis. In addition to deciding how much tissue should be sampled, the radiologist or surgeon must also decide whether to remove the lesion in one piece (whole intact), to optimally preserve the architecture, or in pieces. If the lesion is to be sampled in pieces, the size of the pieces must be determined. Because architecture is critical in differentiating a sclerosing papillary lesion from other lesions, larger pieces allow the pathologist to obtain a better overall assessment of the architecture. Removing all imaging evidence of a potential papillary lesion will greatly reduce the need for further surgery if a diagnosis of benign papillary lesion is rendered (Fig. 43–10).

Obtaining a HER-2 Result on a Core Biopsy Specimen ● Consequence HER-2 is an oncogenic protein that may be overexpressed in up to 20% of high- and intermediate-grade invasive breast carcinomas. It is rarely overexpressed in low-grade ductal or classic invasive lobular carcinomas.49 Patients with HER-2 overexpression benefit from targeted anti–HER-2 therapies, such as trastuzumab, in both the adjuvant and the metastatic settings.50–52 The assessment of HER-2 overexpression is most commonly performed by immunohistochemistry, and patients whose tumor cells show 3+ overexpression have the greatest likelihood of response to anti–HER-2 therapy.

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The ability of a pathologist to accurately assess a HER2 immunostain can be compromised by four major artifacts: tissue crush, tissue retraction, thermal injury, and edge artifact. These artifacts can cause the HER-2 antibody to diffuse unevenly, causing the tumor cells in the area of artifact to see a higher concentration of antibody than expected. Tissue crush is caused when a thin needle is forced into tissue and the cells along the edge are crushed. The cytoplasm becomes streamed and distorted. Tissue retraction is defined as the separation of breast epithelial cells, benign or malignant, from stromal elements, creating a cleftlike space. The use of VAB devices can accentuate this artifact, but it may also occur as part of routine tissue processing. Thermal injury is caused by the use of cautery. It causes the cells to take on a windswept appearance and increases nuclear chromasia. Edge artifact is seen in all tissues and is caused by antibody pooling along the edge of a specimen, affecting tissue located within 1 mm of the edge. Thus, a core biopsy measuring 2 mm in diameter is mostly edge artifact, with the exception of the exact middle of the core. Core biopsies with a small diameter, such as a 14-gauge springloaded core, are virtually all edge artifact. Fluorescence in situ hybridization (FISH) is a method that allows detection of the HER-2 gene.53 The technique involves exposing the tumor nuclei via digestion of the cell membrane and cytoplasm, heating the DNA until it uncoils, flooding the sample with a fluorescently tagged complementary sequence to the HER-2 gene, and then cooling the DNA allowing it to recoil with the HER-2 gene now fluorescently tagged. The number of HER-2 genes in each tumor nucleus can then be enumerated. Because two HER-2 genes are present in all normal cells, one from mom and one from dad, it is essential that only tumor nuclei be assessed. The key to counting only the tumor nuclei is preservation of tissue architecture. It has been noted that approximately 18% of breast tumors scored as 3+ by HER-2 immunohistochemistry and 12% of breast tumors assessed as having gene amplification do not show overexpression or gene amplification when repeated in a central reference laboratory.54,55 This high rate of error has resulted in the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) issuing joint guidelines in an effort to improve HER-2 assessment in breast cancer.56 ● Prevention The artifacts caused by core biopsy all lead to potential overstaining by immunohistochemistry. Thus, tumors assessed as 3+ may be truly 3+ or may be falsely positive as a result of an artifact. If the diameter of the biopsy core is less than 2 mm, cores assessed as 3+ should be confirmed with FISH testing or be repeated on the lumpectomy specimen, because the majority of the core is edge artifact. Even if large-core biopsy devices are used, care must be taken to avoid scoring artifacts because these will still be present in the biopsy.

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Figure 43–11 Low-power HER-2 immunostained slide shows apparent strong expression of the protein. However, the staining cannot be clearly visualized on the membrane and is the result of both edge and crush artifact typical of a core biopsy specimen.

Before relying on the results of a FISH test, you must be assured that the correct cells were examined. Because only tumors can show amplification of the HER-2 gene, if gene amplification is detected, tumor cells must have been examined. The only possibility for error is if in situ and invasive carcinoma are both present and only the in situ carcinoma shows amplification of the HER-2 gene. Although this does occur, it is unusual. More problematic is when FISH testing does not show amplification of the HER-2 gene. In this circumstance, one must always question whether tumor cells were observed. It can be difficult to distinguish tumor cells from normal cells on fluorescence microscopy, especially when the tumor is limited and intermixed with benign pathology such as adenosis. The pathologist relies on architecture and comparison with an adjacent hematoxylin and eosin (H&E)–stained section to select the tumor cells. As a general rule, if the pathologist is struggling to establish the diagnosis on the H&E slide, it will be difficult to identify the tumor cells by fluorescence. The larger the core biopsy, the better the preservation of tissue architecture, and the more reliable the FISH result (Fig. 43–11).

Not Obtaining an Estrogen Receptor Immunostain on a Core Biopsy Specimen ● Consequence The determination of estrogen receptor (ER) should be performed on all breast carcinomas. The accurate determination of ER status is largely dependent on the amount of tumor assessed, tissue fixation, and the assay used. Currently, ER status is usually assessed by immunohistochemistry. Unlike HER-2, which is a membrane protein, ER is a nuclear stain and is not affected by the artifacts such as edge artifact, tissue crush, tissue retraction, or cautery artifact.

Studies have shown that ER status is an excellent predictor of response to antiestrogen therapy.57,58 The initial studies were performed by ligand-binding assay. This assay requires a large amount of fresh tissue, which is ground up and assessed quantitatively. Assessment of ER on formalin-fixed paraffin-embedded tissue was found to be even more predictive of response to antiestrogen therapy when using a specific immunohistochemical assay with a specific scoring system.58 This is not surprising because the tissue included in the ligand-binding assay usually included a mixture of tumor cells, stroma, and often, benign breast epithelial cells. Unfortunately, in current practice, many different immunohistochemical assays and scoring systems are used to assess ER status, leading to significant errors in ER testing results. These errors can be broken down into several problems including tissue fixation, tissue processing, antigen retrieval methods, antibody clones, amount of tissue assessed, scoring system, and cutoff levels. With respect to core biopsies, tissue fixation and the amount of tissue examined are of most concern. ER determination is greatly affected by tissue fixation. Underfixation of breast tissue can cause a marked decrease in the ability of immunohistochemistry to detect ER.59 Because core biopsies tend to be significantly smaller than excisional specimens, they fix more rapidly, which is optimal for ER assessment. It is not unusual to see weak expression of ER on a core biopsy while no expression is noted on the excision specimen. ● Prevention ER determination should be performed on all core biopsies because of more optimal tissue fixation.60 If no expression of ER is noted, ER status should be reassessed on the excisional specimen. Expression in as little as 1% of the invasive tumor cells is associated with significantly greater responsiveness to antiestrogen therapy than those tumors showing no expression. Because the amount of tissue examined in a core biopsy is typically less than the amount examined in an excisional specimen, lack of expression in a core biopsy may be the result of incomplete sampling.

Not Performing a Further Procedure with a Diagnosis of AIDH on Core Biopsy ● Consequence The diagnosis and significance of AIDH are defined based on the follow-up of patients who underwent excisional biopsy. When AIDH is found on a core biopsy, the question is whether it is representative of the entire lesion or whether it is indicative of a more worrisome pathology. On a molecular level, AIDH and low-grade intraductal carcinoma are undistinguishable.61–63 The two lesions are sometimes difficult for the pathologist to separate, even on excisional specimens, let alone on core biopsy samples in which more limited tissue is available. Even when a definitive diagnosis of

43 IMAGE-GUIDED BREAST BIOPSY AIDH can be rendered on core biopsy, it is frequently associated with low-grade DCIS. When diagnosed on core biopsy, AIDH is frequently upgraded to DCIS or invasive carcinoma once the lesion is excised.21,64–68 In general, the more tissue removed at core biopsy, the smaller the percentage of cases that will be diagnosed as carcinoma on excision. Approximately 40% of core biopsies diagnosed as AIDH using a 14-gauge biopsy device will show carcinoma on excision whereas only about 20% will show carcinoma when AIDH is diagnosed with an 11-gauge VAB device.69 Recently, it has been suggested that it may be important to note the number of foci of AIDH on core biopsy and that the number of foci may be predictive of the presence of carcinoma on the excisional biopsy.70 When AIDH was limited to only one or two foci, carcinoma was not seen on the subsequent excisional biopsy specimen; the incidence of carcinoma was 50% when three foci of AIDH were identified and 87% when four or more foci were identified. I believe this approach is too simplistic and that attention should be paid to the type and extent of the mammographic lesion. If the lesion presents as microcalcifications, carcinoma is more often detected if the mammographic lesion is not completely removed. However, even if the mammographic microcalcifications are completely removed, carcinoma may still be found at excision. If the mammographic lesion presents as a mass, there is only a 5% incidence of carcinoma at excision.71 It has been noted that when a micropapillary pattern is identified, most excisional specimens will contain a micropaillary DCIS.70 ● Prevention Whereas there continues to be much interest in defining a subset of AIDH patients who do not require subsequent excision, no such category can be defined reliably. AIDH has similar molecular alterations to those seen in low-grade DCIS and should be treated. It is frequently found at the periphery of DCIS, and thus, a concurrent carcinoma can be truly excluded only if the surrounding tissue is examined and no carcinoma is seen.66 AIDH is a significant risk factor for the development of invasive breast cancer, conferring a relative risk of four to five times and is about equal in both breasts.72,73

Not Performing a Further Procedure with a Diagnosis of Angiolymphoid Hyperplasia/Lobular Carcinoma In Situ on Core Biopsy ● Consequence When angiolymphoid hyperplasia (ALH) or lobular carcinoma in situ (LCIS) is found on excisional biopsy, no further surgery is performed because the lesions are believed to be markers of a generalized increased risk of developing invasive breast carcinoma that occurs

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with equal frequency in both breasts.74–80 LCIS/ALH is not typically associated with a mammographic or ultrasound abnormality and, thus, is usually an incidental finding rather than the pathology that led to the core biopsy. It has an incidence of less than 2% in most core biopsy studies.42,79,81–84 Because of its low incidence, our knowledge of ALH/LCIS on core biopsy is mostly derived from retrospective trials. Pooling these studies, approximately 19% of excisional biopsies after a diagnosis of ALH/LCIS show carcinoma.85 Approximately 55% of these show invasive carcinoma (30% invasive lobular), and 45% show intraductal carcinoma. Liberman and coworkers84 put forth criteria strongly recommending surgical excision if there is radiologicpathologic discordance, if another lesion requiring excisional biopsy (such as atypical ductal hyperplasia [ADH]) is also present, or if the histologic features of the ALH/ LCIS cannot be easily distinguished from DCIS.84 ● Prevention Because ALH/LCIS is not associated with a radiographic abnormality, there is likely to be radiologicpathologic discordance. Although concern has been raised that these studies might be biased because not all patients who were diagnosed with ALH/LCIS on core biopsy underwent excisional biopsy, until further studies are available, excisional biopsy seems prudent.

Not Performing a Further Procedure with a Diagnosis of Flat Epithelial Atypia (Atypical Columnar Cell Alteration) on Core Biopsy ● Consequence Columnar cell lesions are the most common cause of pleomorphic microcalcifications seen on core biopsy. These lesions have been described under a number of different names ranging from “blunt duct adenosis” on the benign side to “clinging carcinoma” on the malignant side. The significance of columnar cell lesions is the company they keep. Atypical columnar cell lesions (flat epithelial atypia) have been associated with lowgrade in situ and invasive ductal and/or lobular carcinomas.86 In one review, 95% of cases of pure tubular carcinoma were associated with atypical columnar cell lesions.87 On a molecular level, columnar cell lesions frequently show loss on chromosome 16 similar to those seen in low-grade carcinomas.88 For years, these lesions were largely ignored when identified in excisional biopsy specimens and the association with lowgrade carcinomas was not appreciated. Retrospective studies looking at benign breast biopsies containing overlooked atypical columnar cell lesions did not show a subsequent invasive carcinoma. When columnar cell alterations were present without an associated carcinoma, the lesions did not appear to confer an increased risk of malignancy.

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Figure 43–12 H&E-stained microscopic slide shows flat epithelial atypia. The nuclei in the lining cells are more vesicular with visible nucleoli. They have lost their polarity and have a much more uniform and focally rounded appearance.

● Prevention Columnar cell alterations are commonly seen because of their frequent association with pleomorphic microcalcifications. If a dedicated breast pathologist is not available at your institution, it is worth asking your pathologists if they are aware of this entity and the current histologic criteria. It is essential that the pathologist be familiar with the terminology and criteria. If atypia is present, complete surgical excision of the lesion is advised because of the possible association with an in situ or invasive carcinoma. If no associations are found, the probability of developing into an invasive carcinoma is exceedingly low (Fig. 43–12).

Pathology Does not Correlate with Imaging Findings?/No Calcifications Found on Pathology When Calcifications Were Identified on Your Imaging Study (Tissue Processing in General) ● Consequence Although they are not encountered very often, the inability to demonstrate microcalcifications on histologic examination can be problematic. If calcifications cannot be demonstrated, and the lack of microcalcifications cannot be explained, complete excision of the lesion should be performed, assuming microcalcifications are still remaining in the breast. When performing an image-guided biopsy for microcalcifications, large-core or whole intact biopsy devices should be utilized. Studies have shown that larger biopsy samples and more cores will remove more of the calcifications and require few excisional biopsies owing to radiographic-pathologic discrepancies.89–91 ● Prevention This is definitely the case in which an ounce of prevention is worth a pound of cure. The radiologist/surgeon

should radiograph all of the removed cores as well as obtain a postbiopsy film to ensure that the calcifications have been removed and a specimen radiogram to ensure that they are present in the core biopsy specimens. Once documented, the cores containing the microcalcifications should be submitted separately from the cores that do not show radiographic evidence of calcifications. This will allow the pathologist to concentrate on the more suspicious cores and potentially examine more levels on sections thought to contain calcifications. If microcalcifications are not identified by the pathologist, several steps should be taken. The first step is for the pathologist to polarize the H&E slides. Calcifications composed of calcium oxylate are not easily demonstrated on the H&E stain but are easily demonstrated on polarization.92,93 This type of calcification is most commonly seen associated with apocrine metaplasia. Assuming that calcifications are still not identified, the next step should be to x-ray the tissue block. If no calcifications are identified within the block, but preprocessing radiographs demonstrated the microcalcifications, it can be assumed that the calcifications dissolved in processing. This happens very rarely. If calcifications are still demonstrated in the paraffin-embedded block, deeper sections should be obtained. The sections should be cut on a fresh microtome blade, if possible. Occasionally, microcalcifications cannot be cut by a microtome blade and the calcifications are launched as small projectiles rather than being cut. These can be detected as holes in the tissue that represent remnants of where the microcalcifications used to reside.

Lack of Radiographic and Pathologic Correlation, Whatever the Cause, Requires Complete Surgical Excision Not Performing a Further Procedure with a Diagnosis of Radial Scar on Core Biopsy ● Consequence Most radial scars are incidental findings measuring approximately 4 mm in size. Based on data from the Nurses’ Health Study, women with radial scars demonstrate a twofold increase in risk of invasive breast cancer; this risk increases with the size of the radial scar.94 The risk is believed to be bilateral, but larger radial scars may be associated with DCIS and invasive carcinomas. Carcinomas arising in association with radial scars are frequently located at the periphery of the lesion, causing them to be missed if the center of the lesion is targeted. It is important to note whether a radial scar is an incidental finding or whether it is the targeted lesion. There is a significantly higher association of carcinoma and AIDH in lesions identified mammographically than those lesions found incidentally. There does not appear to be any distinguishing mammographic feature that allows

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Figure 43–13 Triple immunostaining for P63, cytokeratin 5/6, and cytokeratin 18 in the same radial sclerosing lesion as seen on the H&E stain. P63 and cytokeratin 5/6 highlight cells with myoepithelial/basal differentiation. Both antibodies are visualized with diaminobenzidine (DAB) (brown). P63 is a nuclear, and cytokeratin 5/6 is a cytoplasmic. Cytokeratin 18, a cytoplasmic stain, is visualized with fast red. The presence of two cell types confirms the proliferation as benign.

radiographic separation of radial scars harboring carcinomas from those that do not harbor such foci.95 ● Prevention All mammographically detected radial scars and all radial scars measuring 6 mm or larger should undergo excision. Sloane and Meyers96 reported a 30% incidence of carcinoma when the radial scar measures 6 mm or larger and an incidence of only 2.6% with smaller radial scars. Given the small number of radial scar studies and the low incidence of radial scars in general, it seems prudent to recommend excision for all mammographically detected radial scars and certainly all radial scars measuring larger than 6 mm (Fig. 43–13).

REFERENCES 1. Kopans DB. The positive predictive value of mammography. AJR Am J Roentgenol 1992;158:521–526. 2. Sailors DM, Crabtree JD, Land RL, et al. Needle localization for non-palpable breast lesions. Am Surg 1994;60: 186. 3. Wilhelm NC, DeParedes ES, Pope RT. The changing mammogram: a primary indication for needle localizaiton biopsy. Arch Surg 1986;121:1311. 4. Miller ES, Adelman RW, Espinosa MH. The early detection of non-palpable breast carcinoma with needle localization. Experience with 500 patients in a community hospital. Am Surg 1992;58:195. 5. Parker SH, Lovin JD, Jobe WE, et al. Nonpalpable breast lesions: stereotactic automated large-core biopsies. Radiology 1991;180:403–407. 6. Elvecrog EL, Lechner MC, Nelson MT. Nonpalpable breast lesions: correlation of stereotaxic large-core needle

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