D. Scott Lind, M.D., F.A.C.S.; Barbara L. Smith, M.D., Ph.D., F.A.C.S.; Wiley W. Souba, M.D., Sc.D., F.A.C.S.


ACS Surgery 

Breast Biopsy

Cytologic or tissue diagnosis of a palpable breast mass may be obtained by means of FNA biopsy, core-needle biopsy, or open incisional or excisional biopsy. Needle biopsy techniques are less invasive, less costly, and more expeditious than open biopsy but are significantly more likely to yield false negative results. The choice of a biopsy technique should be individualized on the basis of the clinical and radiographic features of the lesion, the experience of the clinician, and the patient's condition and preference.

Fine-Needle Aspiration Biopsy

FNA biopsy permits the sampling of cells from breast lesions for cytologic analysis. It is an appropriate first step in the evaluation of dominant breast masses, but it requires substantial experience on the part of both the operator and the cytopathologist. FNA biopsy is usually the diagnostic procedure of choice for T3 and T4 primary lesions, as well as chest wall and axillary recurrences for which systemic chemotherapy or irradiation is indicated as the first treatment modality. Because of sampling error, the procedure is less useful in evaluating small masses and areas of vague thickening or nodularity. In addition, it often cannot reliably distinguish invasive from noninvasive cancer.

Discrete masses discovered on physical examination may be either cystic or solid. Unless previous ultrasonographic examination has shown the mass to be solid, the needle used should be large enough to permit aspiration of potentially viscous fluid if the lesion proves to be cystic (i.e., 20 or 21 gauge). If the mass is known to be solid, a smaller needle (22 to 25 gauge) is sufficient for obtaining diagnostic tissue and will cause the patient less discomfort. For sufficient suction to be generated, a syringe with a capacity no smaller than 10 ml should be used. A variety of syringe holders are available that facilitate application of suction with a single hand.

Technique. Once informed consent is obtained, the skin of the breast is prepared with alcohol or iodine, and the lesion that is to undergo biopsy is held steady between the thumb and the index finger of the nondominant hand. A local anesthetic is usually not necessary; if it is used, it should be injected so as to create only a small skin wheal, so that there will be minimal distortion of the approach to the lesion. To facilitate visualization of the collected sample, 1 to 2 ml of air is introduced into the biopsy syringe before the needle enters the skin. The tip of the needle is advanced into the lesion before any suction is applied to minimize collection of tissue outside the lesion. Once the tip is in place, strong suction is applied, and the needle is moved back and forth within the lesion repeatedly along a 5 to 10 mm long track to loosen and collect cells. (This oscillation of the needle along the same track is the most effective way of obtaining a cellular, diagnostic specimen.) The back-and-forth movement of the needle within the lesion is continued until tissue becomes visible in the hub of the needle. Suction is released while the needle is still within the lesion (again, to prevent collection of contaminating tissue from outside the lesion).

The needle is then withdrawn from the lesion, and its contents are expelled onto prepared glass slides, spread into a thin smear, and fixed according to the preferences of the cytology laboratory. Additional passes through the lesion may be made to ensure that a sufficiently cellular sample has been obtained, and the syringe may be rinsed so that a cell block can be prepared for further analysis. An adhesive bandage is applied to the biopsy site. If the lesion proves to be cystic, all fluid should be aspirated; this should cause the mass to disappear. The fluid need not be sent for analysis unless it is bloody or a palpable mass remains after as much fluid as possible has been aspirated. If the fluid is to be sent for analysis, it is injected directly into the pathologic preservative.

The patient is reexamined 4 to 8 weeks after successful aspiration. If the same cyst has recurred, it should be aspirated again and the fluid sent for cytologic analysis.

Interpretation of Results. Analysis by an experienced cytologist is critical for accurate interpretation of FNA biopsy results. Many cytology laboratories are able to perform immunohistochemical analysis for hormone receptors on FNA specimens if an appropriate fixative has been used. In most cytology labs, the false positive rate for a diagnosis of malignancy in an FNA biopsy of a breast mass is only 1% to 2%.[11] Thus, a diagnosis of malignancy that is based on cytologic analysis of an FNA specimen may generally be believed, and definitive surgery may be planned without further biopsy. Because FNA biopsy does not distinguish between invasive and in situ breast cancer, intraoperative frozen section should be performed if necessary to determine the need for axillary dissection.

The false negative rate for identifying breast malignancy, however, is high: FNA fails to diagnose as many as 40% of cancers.[11] Any cellular atypia on FNA biopsy is an indication for open biopsy. A diagnosis of normal or fibrocystic breast tissue should also be viewed with suspicion; subsequent open biopsy is usually indicated if the physical examination or a mammogram of the biopsied lesion gives rise to even a minor degree of concern about malignancy. If the cytologic analysis is diagnostic of a specific benign lesion (e.g., a fibroadenoma or a lactating adenoma), it may generally be relied on if it is in concordance with the clinical features of the lesion, and no further workup is necessary. If the evaluation is nondiagnostic, either aspiration should be reattempted or core-needle or excisional biopsy should be performed. If the FNA biopsy results are negative, core-needle or excisional biopsy should be done unless it is also the case that the physical examination suggests a benign lesion and the mammogram is normal (the so-called triple negative criteria). It has been suggested that no further workup is required when the triple negative criteria are present, particularly in younger women.

Core-Needle (Cutting-Needle) Biopsy

In contrast to FNA biopsy, core-needle biopsy removes a narrow cylinder of tissue that is submitted for standard pathologic rather than cytologic analysis; consequently, this technique is preferable if a skilled cytologist is not available for interpretation of FNA biopsy specimens. Core-needle biopsy is highly accurate when successful targeting of the lesion is confirmed by means of breast imaging.[12] The technical difficulty of accurately placing and firing the core needle in small mobile lesions or in lesions surrounded by dense fibrocystic tissue makes other biopsy techniques preferable in these settings. Core-needle biopsy is, however, ideal for sampling large lesions or chest wall recurrences; the larger samples permit more detailed pathologic analysis and easy determination of hormone receptor levels.

Technique. If the mass is palpable, the surgeon can perform the core-needle biopsy in the office. A large needle (usually 14 gauge) is placed either by hand or with a biopsy gun device. Injection of a local anesthetic is usually required -- again, in a quantity that will create only a small skin wheal. A nick is made in the skin with a No. 11 blade to permit easy entry of the biopsy needle into breast tissue and into the lesion. As with FNA biopsy (see above), the lesion is held steady in the nondominant hand while the biopsy needle is advanced into the lesion and a core sample obtained.

Interpretation of Results. Atypia on core-needle biopsy is an indication for open biopsy of the sampled lesion. In addition, any core-needle biopsy (especially one done without stereotactic or ultrasonographic guidance) that yields benign or fibrocystic tissue should be viewed with some suspicion because of the risk of technical or sampling error. Open biopsy should be considered if there is any discordance between a benign core-needle biopsy result and the clinical or mammographic features of the lesion.

Open Biopsy

The vast majority of open breast biopsies are now performed with either local anesthesia alone or local anesthesia with I.V. sedation (monitored anesthesia care [MAC]). General anesthesia is reserved for situations in which multiple lesions must be excised and the amount of local anesthetic required would exceed the maximum safe dose.

Technique. Open biopsy incisions should generally be curvilinear and should be placed directly over the lesion to minimize tunneling through breast tissue (see Figure 1). Resection of a portion of overlying skin is not necessary unless the lesion is extremely superficial. In case the lesion proves to be malignant, all open biopsy incisions should also be oriented so that they can be excised with any subsequent lumpectomy or mastectomy incision. Accordingly, if an open biopsy is to be done at an extremely lateral or medial site, it may be best approached via a radial incision placed over the lesion rather than via a more vertical curvilinear incision.

Open breast biopsy. ( a ) In most cases, a curvilinear incision is preferred. If the mass is close to the areola, a periareolar incision may be used. ( b ) Extremely lateral or medial incisions may be radial. In any case, incisions should be placed directly over the lesion and should be oriented so that they will be included within a subsequent mastectomy incision if margins prove positive and mastectomy is indicated.

The incision should be long enough to provide adequate exposure and to ensure that the mass can be excised as a single specimen with a small margin of grossly normal tissue. The surgeon should orient the specimen, and the pathologist should ink all margins. Meticulous hemostasis should be achieved before closure to prevent the formation of hematomas that could complicate subsequent definitive oncologic resection. Deep breast tissue should be approximated only if such approximation does not result in significant deformity of breast contour. A cosmetic subcuticular skin closure is preferred.

The increasingly widespread use of screening mammography has led to the identification of more and more nonpalpable breast masses and microcalcifications for which tissue diagnosis is required. In most series, 15% to 30% of such lesions prove to be malignant.[12,13,14] Nonpalpable masses and microcalcifications may be approached via core-needle biopsy or open biopsy with wire localization.

Image-Guided Core-Needle Biopsy

Needle biopsy techniques are increasingly being used to diagnose nonpalpable breast lesions. In general, FNA biopsy of nonpalpable lesions is inadvisable because of its high false negative rate. Little is lost by attempting an FNA biopsy of a palpable lesion in the office setting, but performing a stereotactic or ultrasound-guided FNA biopsy of a nonpalpable mass carries a significant cost in terms of time, patient discomfort, and expense. The diagnostic accuracy currently achievable with FNA biopsy in this setting does not justify this cost. Consequently, image-guided core-needle biopsy is the preferred approach for needle biopsy of nonpalpable lesions.

In choosing core-needle biopsy, both patient and physician must be comfortable with the fact that the lesion will only be sampled rather than excised, must recognize that the possibility of a sampling error that will cause the examiner to miss the lesion is higher with core-needle biopsy than with open biopsy, and must realize that equivocal findings will necessitate follow-up with open biopsy. The trade-off for these limitations is that core-needle biopsy generally costs less than open biopsy, takes less time, and leaves only a tiny scar. After a core-needle diagnosis of malignancy, the surgeon may proceed directly to wide local excision and will often be able to obtain clean margins with a single open procedure.

Stereotactic Versus Ultrasound-Guided Core-Needle Biopsy. Whenever feasible, core-needle biopsy is performed with ultrasonographic guidance, which permits real-time documentation of needle position within the lesion. Stereotactic mammography-guided core-needle biopsy is performed if the lesion is not visualized ultrasonographically. Stereotactic biopsy is appropriate for lesions that are favorably located within the breast (i.e., that can be stably positioned in the biopsy window of the machine). Lesions very close to the chest wall or the areola may not be accessible to stereotactic biopsy and are best approached via open biopsy with needle localization (see below).

Clustered microcalcifications may also be approached by stereotactic core-needle biopsy. If the cluster is not large enough for calcifications to remain to guide subsequent wide excision if a malignancy is found, a clip should be placed to mark the biopsy site. Alternatively, if the surgeon has experience with breast ultrasonography, this imaging modality may be used intraoperatively to identify the hematoma that results from stereotactic core-needle biopsy.

Interpretation of Results. The introduction of large core-biopsy needles (11 and 14 gauge), coupled with the use of vacuum assistance to draw additional tissue into the needle, has markedly improved the false negative rate for core-needle biopsy. Currently, false negative rates for this procedure fall into the 1% to 2% range,[13] results that compare favorably with those reported for wire-localized open biopsy. It is now routine to perform radiography of core-needle biopsy specimens to confirm that targeted calcifications have been removed. When the targeted lesion comprises dense tissue rather than calcifications, care must be taken to confirm that the lesion was adequately sampled and thus ensure that the findings can be interpreted reliably. Immediate postbiopsy radiography may be performed to demonstrate that a hole was made in the lesion. A finding of benign or fibrocystic tissue on such a biopsy should be viewed with some suspicion and interpreted in relation to the lesion sampled. One must decide whether the pathologic findings adequately account for the lesion visualized. If any concern remains, open biopsy is indicated.

Because false positive results are rare, a diagnosis of malignancy may be believed and acted on without further biopsy. In planning treatment after core-needle biopsy that shows only carcinoma in situ, one should remember that the lesion was only sampled and that invasive tumor may still be found when the lesion is completely excised. The likelihood of finding invasive tumor on surgical excision after a core-needle biopsy indicative of ductal carcinoma may be as high as 20%.[14]

A finding of atypical ductal hyperplasia on core-needle biopsy is an indication for wire-localized open biopsy. Open biopsy after a core-needle biopsy indicative of atypical ductal hyperplasia may reveal ductal carcinoma in situ (DCIS) in as many as 50% of patients; this may be a less frequent finding when a larger (e.g., 11 gauge) needle was used for the core-needle biopsy.

Follow-Up. Whether short-interval mammographic follow-up is necessary after core-needle biopsy depends on the pathologic findings and the mammographic appearance of the lesion. With a well-circumscribed lesion that pathologic evaluation shows to be a fibroadenoma or with calcifications that pathologic evaluation shows to be located in benign fibrocystic tissue, no special follow-up is required, and routine screening at normal intervals may be resumed. In general, if the pathologic findings are equivocal or discordant with the appearance of the lesion, immediate open excision is preferable to a 6-month repeat mammogram. To ensure appropriate follow-up, there should be close communication between the physician ordering the core-needle biopsy, the physician performing the biopsy, and the pathologist analyzing the specimen.

Open Biopsy with Needle (Wire) Localization

As is the case for open biopsy of palpable lesions, the vast majority of needle-localized breast biopsies are now performed with local anesthesia or local anesthesia with intravenous sedation.[15] General anesthesia is reserved for excision of multiple lesions or other special circumstances.

Technique. The lesion to be excised is localized by inserting a thin needle and a fine wire under mammographic or ultrasonographic guidance immediately before operation. To facilitate incision placement, images should be sent to the OR with the wire entry site indicated on them. With superficial lesions, the wire entry site is usually close to the lesion and thus may be included in the incision. With some deeper lesions, the wire entry site is on the shortest path to the lesion and so may still be included in the incision. The incision is placed as directly as possible over the mass to minimize tunneling through breast tissue. Once the incision is made, a core of tissue is excised around and along the wire in such a way as to include the lesion (see Figure 2). This process is easier and involves less excision of tissue if the localizing wire has a thickened segment several centimeters in length that is placed adjacent to or within the lesion. One then follows the wire itself into breast tissue until the thick segment is reached and only then extends the excision away from the wire to include the lesion in a fairly small tissue fragment.

Needle-localized breast biopsy. ( a ) The mammographic abnormality is localized immediately before operation. The relation between the wire, the skin entry site, and the lesion is noted by the surgeon. ( b ) The skin incision is placed over the expected location of the mammographic abnormality. The dissection is accomplished with the wire as a guide. ( c ) The tissue around the wire is removed en bloc with the wire and sent for specimen mammography. Tunneling and piecemeal removal are to be avoided.

With many lesions, the wire entry site is in a fairly peripheral location relative to the position of the lesion, which means that including the wire entry site in the incision would result in excessive tunneling within breast tissue. In such cases, the incision is placed over the expected position of the lesion (see Figure 3), the dissection is extended into breast tissue to identify the wire a few centimeters away from the lesion itself, and the free end of the wire is pulled up into the incision. A generous core of tissue is then excised around the wire. Again, this process is easier if the thick segment of the localizing wire is placed adjacent to or within the lesion.

Needle-localized breast biopsy. ( a ) It is sometimes necessary to insert the localizing wire from a peripheral site to localize a deep or central lesion. The incision should be placed directly over the expected location of the lesion, not over the wire entry site. ( b ) Once the skin incision is made, the dissection is extended into breast tissue to identify the wire a short distance from the lesion. The free end of the wire is pulled into the wound, and the biopsy is performed as in Figure 2.

Radiography should immediately be performed on all wire-localized biopsy specimens to confirm that the lesion has been excised. The patient should remain on the operating table with the sterile field preserved until such confirmation has been received. If the mass was missed and the surgeon has some idea of the likely location of the missed lesion, another tissue sample may be excised immediately. If, however, the surgeon suspects that the wire was dislodged before or during the procedure, the incision should be closed. After the patient has healed sufficiently to be able to tolerate repeat mammography, another mammogram is obtained, and repeat localization and biopsy are performed.

Directional Vacuum-Assisted Breast Biopsy (Mammotomy)

Directional vacuum-assisted biopsy (DVAB), or mammotomy, is a special procedure for obtaining specimens from single or multiple breast lesions (e.g., microcalcifications, circumscribed masses, and spiculated masses).[16] DVAB is a diagnostic procedure and is not intended for therapeutic purposes. On the whole, it is safe, and the complication rate is acceptably low.

In comparison with core-needle biopsy, DVAB is more successful at removing microcalcifications, can obtain more specimens in the course of a single procedure, and is more sensitive in detecting DCIS and atypical duct hyperplasia. DVAB also appears to diagnose nonpalpable breast lesions more effectively than stereotactically guided core-needle biopsy does. It may, in fact, be helpful to perform DVAB after core-needle biopsy when the diagnosis of atypical duct hyperplasia is being considered; this practice may lead to a decrease in the number of open biopsies performed.

Suitable candidates for DVAB include patients with nonpalpable but mammographically visible clusters of suspicious calcifications, those with well-defined masses that are likely to be benign, and those with suspicious masses. Target lesions must be clearly visible on digital images and identifiable on stereotactic projections. DVAB is not recommended for patients with certain lesions located very posteriorly or very anteriorly in the breast, those with very small or very thin breasts, and those who, for one reason or another, cannot be properly positioned for the procedure or cannot cooperate with the surgeon. The procedure is done on an outpatient basis and usually can be completed in 1 hour or less. Patients are restricted from engaging in strenuous activity for 24 hours after DVAB.

The probe employed for the procedure consists of an outer trocar cannula, a sliding inner hollow coaxial cutter, a so-called knockout shaft, a distal sampling notch, and a proximal tissue retrieval chamber; in addition, it has a thumbwheel, which is used for manual advancement, cutting, and retrieval of biopsy specimens. It must be used under the guidance of an imaging modality (e.g., ultrasonography or roentgenography), and it may be either mounted or handheld. The device is connected to a suction machine, which acts first to draw the target tissue into the sampling notch and then to facilitate retrieval of tissue into the proximal collection chamber.

Stereotactic digital imaging is then performed to visualize the target and calculate its location in three dimensions, and a suitable trocar insertion site is identified. The skin is prepared, and a small amount of buffered 1% lidocaine with epinephrine (usually 10 ml or less) is administered. The skin at the insertion site is punctured with a No. 11 blade, the probe is manually advanced to the prefire site, and the position of the probe is confirmed by means of stereotactic imaging. The device is then fired, repeatedly cutting, rotating, and retrieving samples until the desired amount has been removed. If the lesions being removed are calcifications, the sufficiency of the sampling may be confirmed through x-rays of the specimens.

Once the biopsy is complete, an inert metallic clip is deployed into the biopsy site through the trocar so as to mark the lesion for future reference in case it can no longer be visualized after biopsy; deployment and positioning are confirmed by stereotactic imaging. The biopsy device is then removed, the edges of the skin incision are approximated with Steri-Strips, and a compressive bandage is applied. Any bleeding occurring after removal of the biopsy device should be controlled by manual pressure before the final bandage is applied. Typically, 1 g of tissue (equivalent to approximately 10 to 12 samples with an 11-gauge probe) is sufficient for diagnosis of benign disease, atypical ductal hyperplasia, or carcinoma.

Complications are uncommon. Brisk bleeding may occur during and immediately after the procedure. Bruising and discoloration may result but generally resolve within days. Less frequently still, hematomas may form, fat necrosis may occur, or the patient may note a palpable lump. Caution is advisable in women who are receiving anticoagulants. Surgical site infection has been reported as well, but it is rare.


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