Advances in Anatomic Pathology:
Update on Percutaneous Needle Biopsy of Nonmalignant Breast Lesions
Johnson, Nicole B. MD; Collins, Laura C. MD
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Reprints: Laura C. Collins, MD, Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215 (e-mail: email@example.com).
All figures can be viewed online in color at http://www.anatomicpathology.com.
Certain nonmalignant lesions encountered on percutaneous breast biopsies pose dilemmas with regard to the most appropriate clinical management subsequent to needle biopsy (ie, surgical excision vs. follow-up). These lesions include columnar cell lesions, atypical ductal hyperplasia, lobular neoplasia, papillary lesions, radial scars, fibroepithelial lesions, and mucocele-like lesions. As minimally invasive diagnostic procedures are now standard it is more important than ever to be aware of the limitations of percutaneous biopsy, particularly with regard to apparently benign lesions because of the risk that the radiologically detected lesion may harbor malignant disease not represented in the biopsy specimen. This underscores the importance of radiologic-pathologic correlation. Increasingly, radiologists are adopting vacuum-assisted devices using larger gauge needles. The changing practices among radiologists are reflected in recent studies which have enriched the literature. In addition, magnetic resonance imaging is being used more frequently in breast imaging, resulting in pathologists more often encountering benign biopsies with uncertain imaging correlation. These changes prompted evaluation of the recent literature and its possible effect on management concerns. This review focuses on management issues following the diagnosis of nonmalignant lesions diagnosed on percutaneous breast biopsy and highlights imaging terms commonly used in breast radiology reports to facilitate accurate radiologic-pathologic correlation.
Percutaneous needle biopsy methods are now the standard at most institutions in the United States for the initial evaluation of breast lesions. These biopsies are most often performed using large core needles with guidance by stereotactic mammography, ultrasound (US) or, more recently, magnetic resonance imaging (MRI). In general, US guidance is preferred over stereotactically guided biopsy for cases in which the lesion can be visualized by US, as the US-guided procedure is faster than the stereotactic procedure and eliminates the need for a mammography unit. A variety of different biopsy devices are available for this purpose.1–15 Newer directional vacuum-assisted biopsy devices (eg, Mammotome, Suros) employ vacuum assistance to draw the tissue into the needle and permit the use of larger needles (12 gauge to 8 gauge), thereby resulting in larger specimens. For ease of reading, in this article the term core needle biopsy (CNB) will be used to encompass the spectrum of percutaneous biopsy sampling devices.
CNB was developed with two goals in mind: (1) to eliminate the need for open biopsy in patients with benign lesions and (2) to provide a nonsurgical means to definitively diagnose breast cancer, given the limitations of fine needle aspiration cytology (FNAC) in this regard. In particular, in contrast to FNAC, the CNB procedure rarely results in insufficient material for evaluation, generates the type of specimen most pathologists feel comfortable interpreting, provides tissue for possible diagnostic immunohistochemical stains and for biomarker studies (eg, E-cadherin, myoepithelial cell markers, estrogen receptor, etc.) and more often results in a definitive diagnosis than FNAC.16–22
Experience to date has indicated that there is excellent correlation between the findings on CNB with those on open biopsy.1–4 Furthermore, the level of diagnostic agreement among pathologists in the interpretation of CNB specimens is extremely high. For example, in a study examining over 2000 CNB specimens initially diagnosed by multiple pathologists at 22 hospitals around the United States followed by central review by one of 3 reference pathologists, the original diagnosis and the central review diagnosis were concordant in 96% of the cases. This level of agreement was comparable with that observed among over 550 open surgical biopsies obtained from the patients in that study.23
This review focuses on management issues following the diagnosis of nonmalignant lesions diagnosed on percutaneous breast biopsy and highlights imaging terms commonly used in breast radiology reports to facilitate accurate radiologic-pathologic correlation.
Critical to accurate diagnosis and management of patients undergoing CNB procedures is correlation of clinical and radiologic findings with the findings on pathology (“the triple test”). In that regard, some basic guidelines to radiology reporting may be of value. Currently, the Breast Imaging Reporting and Data System (BIRADS) (Table 1) is required in the United States for mammography reporting and may be applied to US and MRI as well. For those patients with mammographically detected lesions that fall into BIRADS categories 1 and 2, normal interval screening is recommended. For category 3, shorter follow-up is suggested (4 or 6 months for solid masses and calcifications, respectively). For categories 4 and 5, CNB or excision is usually performed. For mammographically detected lesions, category 4 is further broken down into 3 subdivisions (4a-4c; Table 2), which is where histopathologic-radiologic correlation is most critical. Although some argue that patients with category 5 lesions should go directly to surgical excision and sentinel lymph node biopsy (SLNB),24 a CNB can help differentiate in situ and invasive carcinomas, especially for patients presenting with calcifications only, and such patients may not require an SLNB. The category 6 refers to biopsy confirmed malignancy. Therefore, pathologists are most likely to encounter CNB specimens from BIRADS category 4 and 5 lesions.
There are several key words in breast imaging reports that should raise the pathologist's level of concern when reviewing a CNB and prompt further evaluation of the tissue (additional levels) or discussion with the radiologist when radiologic-pathologic correlation is not met. Mammography reports will describe the characteristics of the mass (shape, border, density, etc.) or the presence of calcifications and their features (distribution and form). In general, worrisome features include irregular masses with spiculated borders and pleomorphic linear or branching calcifications.25–27 Amorphous calcifications, referring to calcifications too small to further characterize, are of intermediate concern and are usually biopsied.26,28
Like mammography, US is another modality used to evaluate mass lesions. Similar features as those described in mammography are reported (shape, margin, and boundary). Rather than density, echogenicity in relation to subcutaneous fat is studied. “Isoechoic” describes imaging findings with the same echogenicity as fatty tissue. “Anechoic” often correlates with cysts and “hyperechoic” correlates with fibroglandular tissue. Most cancers are described as “hypoechoic.” Additionally, the orientation of the mass in relation to the cutaneous surface (parallel vs. nonparallel) is important. Posterior acoustic patterns (no features, enhancement or shadowing) are also reported. Worrisome features of breast lesions on US studies include a hypoechoic pattern, irregular shape, nonparallel orientation (the lesion is taller than it is wide) and posterior shadowing.29
MRI of breast lesions is predicated on tumor angiogenesis in neoplasia. This tool is used to observe the morphologic features and the kinetics of contrast-enhancement within a lesion. The shape, border and enhancement characteristics are evaluated for masses. Two phases of kinetics are described, initial (within 2 min of contrast administration) and delayed (more than 2 min after contrast administration.) Initial phase kinetics is reported as slow, medium or fast. Delayed phase kinetics, referring to a signal intensity curve, is reported as persistent, plateau or wash-out. In short, masses with irregular margins, rim enhancement, fast initial phase kinetics and plateau or washout delayed kinetics are suspicious findings.30,31 Mass lesions smaller than 5 mm and non–mass-like enhancement have lower likelihood of malignancy. However, these guidelines should be used with caution. Invasive lobular carcinoma and ductal carcinoma in situ (DCIS) may present as non–mass-like lesions. Invasive lobular carcinomas may also present with persistent kinetics, typically a low-risk MRI finding.30 With any uncertainty, communication with the radiologist is encouraged. Imaging features characteristic of radiologically suspicious lesions are summarized in Table 3.
There are several technical aspects of CNB that merit specific comment. First, the sensitivity of the CNB procedure is in large part related to the size of the needle. Most studies have evaluated the sensitivity of CNB from the perspective of underestimation of malignancy (or upgrade rates). Not surprisingly, the underestimation rates vary with gauge of the needle used and range from 18% to 60% with 14-gauge needles.14,32–35 These rates are reduced significantly with the newer 11-gauge and 9-gauge needles to between 8% and 39%.8,9,14,35–37
Second, if the CNB is performed because of the presence of mammographic calcifications without a soft tissue density, specimen radiography should be performed to confirm the presence of calcifications within the specimens. In fact, the likelihood that the pathologist will be able to render a specific diagnosis on this type of specimen is significantly greater when calcifications are identified on the specimen radiograph compared with when they are not.38,39 In one study, a specific diagnosis was rendered in 81% of core biopsies in which calcifications were present on the specimen radiograph compared with only 38% of cases in which calcifications were not radiographically identified in the core biopsy specimens.38 It is of great value for the radiologist to submit separately cores with and without radiographically identified calcifications. Furthermore, the calcifications must be identified by the pathologist microscopically and their location indicated in the final pathology report. More telling perhaps, is the likelihood of a missed malignant diagnosis on CNB for targeted calcifications. It has been shown that malignant diagnoses are missed only 1% of the time in the presence of calcifications, but are missed significantly more frequently (11%, P<0.001) when microcalcifications are absent on the specimen radiograph.35 Importantly, it must be kept in mind that only those calcifications at least 100 microns (0.1 mm) in size correlate with those seen by mammography.40 If calcifications large enough to correlate with those seen on imaging studies are not seen on the initial levels of the CNB samples, additional efforts should be pursued to identify them, including a search for calcium oxalate crystals with polarized light, radiographing the block and cutting additional levels.41,42 If these efforts fail to identify calcifications histologically when they were confirmed to be present on the specimen radiograph, the possibility that the calcifications were lost in processing exists (eg, calcifications fractured out of block by microtome during sectioning).38,43
Finally and most importantly, radiographic-pathologic correlation is absolutely essential in every case in which CNB is performed. The pathologic diagnosis on a CNB should be concordant with the impression from the imaging studies. Discordant diagnoses must be reconciled, and this may require repeat core biopsies or open surgical biopsy.14,44,45 The use of interdisciplinary pathology-breast imaging correlation conferences is particularly useful in this regard.
There are a number of recurring diagnostic problems encountered in CNB specimens. These are generally similar to those encountered in open surgical excision specimens and include classification of columnar cell lesions, distinguishing atypical ductal hyperplasia (ADH) from low-grade DCIS, identifying foci of stromal microinvasion in cases of DCIS, distinguishing solid DCIS from lobular carcinoma in situ (LCIS), distinguishing between tubular carcinoma, microglandular adenosis and benign sclerosing lesions, distinguishing among benign papillomas, atypical papillomas and papillary forms of DCIS, distinguishing mucocele-like lesions (MLLs) from mucinous carcinomas, and distinguishing low-grade phyllodes tumors from cellular fibroadenomas. However, rather than focusing on diagnostic criteria and tools of value in making these distinctions, as mentioned above, the following discussion will center around management issues concerning nonmalignant diagnoses made on CNB. The most prudent approach for the pathologist in the face of any of the above diagnostic uncertainties is to provide enough diagnostic information without overdiagnosing the lesion. Whether or not the pathologist should specifically recommend an excision in the surgical pathology report is a contentious issue among pathologists, radiologists, and clinicians at some institutions.
There are several nonmalignant lesions that generate considerable discussion as to the appropriate management subsequent to CNB (ie, surgical excision vs. follow-up). Strong data to aid in decision making for these particular lesions are lacking as most centers have insufficient numbers to provide sound recommendations, and the majority of studies are retrospective in nature with the inherent biases attributable to that study design.46,47 Lesions encountered in CNB specimens for which management issues commonly arise include columnar cell lesions, ADH, lobular neoplasia [atypical lobular hyperplasia (ALH) and LCIS], papillary lesions, radial scars, fibroepithelial lesions, and MLLs. Additional management options aside from surgical excision, such as excision by large bore en bloc percutaneous vacuum-assisted devices (eg, SiteSelect)48–55 and radiofrequency ablation,56–58 also contribute to the discussion; however, review of these options is beyond the scope of this article.
Columnar Cell Lesions
Columnar cell lesions are now encountered frequently in both excisional biopsies and CNBs performed for mammographic microcalcifications. Included in this spectrum of columnar cell lesions are columnar cell change and columnar cell hyperplasia and also those lesions that exhibit low-grade cytologic atypia and referred to by the World Health Organization working group as flat epithelial atypia (FEA).59 The major concern with FEA on CNB is that it is frequently associated with more worrisome lesions, including DCIS (particularly low-grade DCIS), lobular neoplasia and invasive tubular and lobular carcinomas.60–67 Therefore, the possibility of missing such lesions due to limited sampling is a concern when FEA alone is encountered in CNB samples (Fig. 1). Very limited available data suggest that about one-quarter to one-third of patients who have FEA on CNB show a more advanced lesion at excision.65,68–72 However, a more recent study has challenged these observations. This study included samples obtained by an 11-gauge vacuum-assisted device from patients with mammographic calcifications only, and showed no instances of carcinoma on subsequent excision for 64 patients with columnar cell lesions without atypia, 38 patients with FEA, and 3 patients with “extensive” FEA diagnosed on CNB. Fifty-four percent displayed FEA, ADH, or lobular neoplasia on excision.73 However, given the small number of patients in this latter study and the preponderance of data suggesting close associations between FEA and low-grade carcinoma (either in situ or invasive), we continue to recommend excision when FEA is identified on CNB. Currently, we do not recommend excision for patients with columnar cell change or columnar cell hyperplasia identified on CNB.
Atypical Ductal Hyperplasia
CNB specimens in which ADH is the most significant diagnosis are the source of a great deal of controversy. The targeted lesion is most often mammographic microcalcifications and the issue of concern is whether the diagnosis of ADH is representative of the entire lesion. Numerous studies have reported upgrades to a worse lesion (ie, DCIS or invasive carcinoma) on excisional biopsy when ADH is found on CNB. Rates vary from 18% to 87% of patients using a 14-gauge device.15,32–35,74,75 Rates are approximately halved to between 10% and 39% with the use of 11-gauge or 9-gauge needles.8,9,11,14,35–37 In the majority of cases the carcinoma found at excision is DCIS, and in about one-quarter of cases an invasive cancer is identified.8,9,11,76–78
The identification of patients with ADH on CNB who can be spared surgical excision continues to be an area of active investigation. In an analysis of pathologic features of ADH on CNB, Ely et al79 noted that the likelihood of finding carcinoma on excision was related to the extent of ADH on the CNB. None of the patients in which ADH involved 2 or fewer foci on CNB had carcinoma on excision. In contrast, of the cases with 4 or more foci of ADH on core, 87% had carcinoma on excision. Others have reported that for ADH on CNB confined to less than 3 lobules or ducts and/or in whom all of the mammographic microcalcifications had been removed, none had DCIS or invasive carcinoma on subsequent excision.80,81 The architectural pattern of ADH has also been studied in this regard and significant associations between the presence of micropapillary pattern of ADH and the presence of DCIS on subsequent excision have been reported.79,81 More recent studies have placed greater emphasis on mammographic-pathologic correlation as a way to stratify patients who may be spared excision. One study evaluated the particular type of calcifications and found that underestimations occurred more often when the ADH was associated with linear, branching, or granular calcifications on mammography. In contrast, there were no instances of upgrade to DCIS on excision when the mammogram showed fine rounded calcifications.82 In another recent study, Forgeard et al83 stratified patients according to the number of foci of ADH (≤2 or >2), the mammographic size of the lesion (<6 mm, ≥6 mm but <21 mm or >21 mm) and whether or not the lesion had been completely excised according to postprocedure imaging studies in an effort to identify patients with ADH on CNB who could safely avoid surgical excision. In this retrospective study of patients with targeted microcalcifications found to have ADH on CNB, the authors identified 3 subsets of patients: one group with no worse lesion found on excision (imaging lesion size <6 mm and complete removal of lesion by imaging studies), a second group with a low rate of upgrade (4%; ≤2 foci of ADH with either imaging lesion size <6 mm with incomplete removal or size ≥6 mm and <21 mm), and a third group with a high rate of upgrade to a worse lesion (up to 38%; >2 foci of ADH with either imaging lesion size >6 mm with incomplete removal or size ≥6 mm and <21 mm or lesion size >21 mm). On the basis of these findings the authors developed an algorithm for managing patients with ADH on CNB whereby only the third group of patients would need to undergo excision with follow-up for the first 2 groups of patients.83 In contrast, a study in which the CNB was performed using vacuum-assisted devices with 9-gauge or 11-gauge needles showed no significant difference in the rate of upgrade regardless of the extent of the ADH, though the numbers in this study were small. Seven (12.5%) of 56 cases with focal ADH were upgraded to carcinoma on excision compared with 11 (22.4%) of 49 patients with ADH, not otherwise specified and 8 (44%) of 18 classified as suspicious for DCIS.12 Importantly, in this study postbiopsy imaging had not been performed to assess the extent of residual calcifications.8,12
The studies cited above are all limited by small numbers. At this time, reliable radiologic, technical, and pathologic factors predictive of which patients with ADH will likely have a worse lesion remain elusive. As such, we currently continue to recommend excision for all patients in whom ADH is identified on a CNB specimen.
Ductal Carcinoma In-situ
As with ADH, the issue of contention when DCIS is identified on CNB is the underestimation rate of invasive carcinoma. Underestimation rates of invasive carcinoma for CNB showing DCIS range from 10% to 38%.14,24,84–93 The clinical concern in this situation is that the patient will require a second procedure to pursue SLNB if invasion is found upon excision. Whether or not to perform SLNB at the time of excision has been questioned.24 As well as requiring an additional surgical procedure, when SLNB is performed after excision there is often compromised surgical lymph node mapping.94,95 In an effort to choose patients with DCIS on CNB that would be best served with SLNB, many retrospective studies have been performed examining pathologic and mammographic features of CNB that may predict invasion on excision. These features include the presence of a mammographic mass,85,87,88,92,96 tumor size 1.5 to 5 cm,84,93,96 DCIS of high nuclear grade,24,92,93,96 the presence of comedo necrosis,97 lobular involvement by DCIS,96,97 the presence of periductal inflammation,24,89 and microinvasion.85,92 As discussed above, many studies report lower underestimation rates with the use of vacuum-assisted biopsy devices and larger gauge needles.
Extensive involvement of the CNB by DCIS has been shown to correlate with increased likelihood of surgical margin involvement at excision.98 One study showed that those cases of invasive ductal carcinoma with a high proportion of DCIS were more likely to require wider excision. Other predictive features of DCIS associated with compromised margins on univariate analysis include high nuclear grade, solid pattern and comedo necrosis.98
All patients with DCIS identified on CNB require surgical excision of the area of mammographic abnormality. It is not our practice to perform SNLB at the time of initial excision unless microinvasion is present in the CNB. If there is a very high index of suspicion for invasive carcinoma, repeat CNB may be indicated before definitive surgery.
Lobular Neoplasia (ALH and LCIS)
As ALH and classical forms of LCIS do not typically present with clinical or radiologic findings, these diagnoses on CNB are, therefore, incidental. A histopathologic correlate to the radiologic abnormality should be pursued. If the correlating lesion is benign and would not by itself require excision (such as a fibroadenoma), the management of the lobular neoplasia remains a matter of debate. It could be argued that as these lesions are generally considered to be markers of a bilateral increase in breast cancer risk, surgical excision is not indicated. However, there is a paucity of adequate data regarding the findings in subsequent surgical excision specimens from patients who have ALH or LCIS identified on CNB. To date, most studies are retrospective and are clouded by selection bias based on concomitant imaging features or patient history. In a recent review of the literature by Cangiarella et al,99 cases in which lobular neoplasia on core biopsy were upgraded to invasive carcinoma or DCIS on excision ranged from 0% to 67% with no significant difference between ALH (0% to 67%) and LCIS (0% to 50%). In another review of the literature, Elsheikh and Silverman100 report that the incidence of subsequent cancer on CNB of pure lobular neoplasia (ie, unassociated with other high-risk lesions) is 18%. However, some of the cancers identified on subsequent excision in this review had been associated with mass lesions on imaging studies (i.e. represent radiologic-pathologic discordance) or lobular neoplasia with atypical features (pleomorphic LCIS). Brem and colleagues reported on a multi-institutional study of lobular neoplasia on CNB. Two hundred and seventy eight patients had lobular neoplasia as their worst lesion. Excision was performed in only 164 of these cases and a worse lesion was found in 22% of women with ALH and 25% of those with LCIS.101 In this study, a higher likelihood of underestimation was associated with the presence of a radiologic mass or calcifications, a higher BIRADS category, the use of a non–vacuum-assisted CNB device and fewer specimens obtained. However, there was no group in which the risk of upgrade on excision was sufficiently low, and these authors recommended that all women with ALH or LCIS on CNB undergo excision. In contrast, Nagi and colleagues conducted a very careful mammographic-pathologic correlation study and found that of 98 cases of purely incidental classical lobular neoplasia (ie, with no mammographic abnormalities or atypical pathologic features such as pleomorphic nuclei or comedo necrosis), there was a 93% correlation with the pathology findings on excision.102 In only three cases were worse lesions found in the excision specimen.
It has been proposed that rather than group all cases of incidental lobular neoplasia under one treatment arm, the pathologic appearance of the lesion be considered when determining the clinical management. Under this rubric, lobular neoplasia of the classic type A (small, uniform, bland nuclei) may not require excision.102 Additional studies are needed to evaluate this proposal and to assess interobserver agreement using this classification. Certainly, for patients with a diagnosis of pure ALH or LCIS on CNB, a surgical excision is warranted if there is radiologic-pathologic discordance or if the LCIS has atypical features such as pleomorphic nuclei or necrosis (Fig. 2) which would result in difficulties in distinguishing the lesion from DCIS.102–104 Immunostaining for E-cadherin may be of value in determining whether the cells have a lobular or ductal phenotype105–107; although, in this situation we believe it is prudent still to recommend excision if the features on routine histologic sections are not those of classical LCIS. In the meantime, our current practice is for all patients with lobular neoplasia on CNB to undergo excisional biopsy.
The management of patients with papillary lesions diagnosed on CNB is also an unresolved issue. Papillary lesions are endowed with a myriad of names with different diagnostic criteria defined by multiple experts. Further complicating this realm of breast pathology on CNB is the focal nature of involvement of some papillary lesions by atypia and the tissue fragmentation inherent in CNB, making the already complex architecture of papillary lesions more difficult to interpret. The primary distinction to be made with papillary lesions on CNB is to differentiate those lesions with from those without atypia, especially for institutions that do not routinely excise all benign papillomas diagnosed on CNB. Further classifying an atypical papillary lesion into atypical papilloma, papilloma with DCIS, papillary DCIS, encapsulated papillary carcinoma (intracystic papillary carcinoma) and frankly invasive papillary carcinoma can be quite difficult on CNB due to the limited, often fragmented tissue available and the likelihood that the periphery of the lesion is not evaluable (Fig. 3). In some cases, immunohistochemical studies for myoepithelial markers or high molecular weight cytokeratins (CK 5/6, CK 14, 34βE12) and estrogen receptor may help to sort out this differential diagnosis. Lesions with low or intermediate nuclear grade DCIS will lack staining with high molecular weight cytokeratins and will show strong expression of estrogen receptor; whereas benign papillomas will show a mosaic staining pattern with high molecular weight cytokeratins and will have only focal expression of estrogen receptor.108–110 However, tissue sampling will still be an issue. Fortunately, this distinction is not as critical on CNB as most experts would agree that a papillary lesion with any degree of atypia calls for surgical excision for complete evaluation and definitive classification. In addition, special attention should be paid to the surrounding tissue, as atypia outside the papillary lesion may serve as a better prognostic indicator.111,112
The issue of whether to excise benign papillomas found on CNB remains controversial. Some more recent studies have cautiously suggested that patients with a diagnosis of a benign papilloma on CNB may be followed if the imaging studies are concordant. In one study, none of the 18 patients (0%) who had a benign papilloma on CNB and who had a subsequent surgical excision were found to have carcinoma. In contrast, 2 of 7 cases (29%) with papilloma with separate foci of atypia and 12 of 13 cases (92%) diagnosed as severely atypical papilloma suspicious for carcinoma were found to have carcinoma on excisional biopsy.113 In another study, 6 of 30 (20%) patients with benign papillomas on CNB underwent subsequent excisional biopsy, all of which revealed no atypia. The remaining patients (those without surgical excision) had no evidence of disease progression on clinical and radiologic follow-up.114 Carder et al115 reported 16 benign or indeterminate papillomas on CNB of which 4 displayed ADH at excision, but no carcinoma was identified at excision in any of these cases. In contrast, in other studies, unexpectedly high rates of atypia or malignancy were identified at excision among patients with diagnoses of benign papilloma on CNB (eg, 5 of 28 patients, 17.9% in one study116 and 15 of 80 patients, 19% in another117). Of note, these studies only included patients with 14-gauge automated needle biopsy specimens. More recent studies evaluating this issue have reported upgrade rates varying between 6% and 36%, although it should be pointed out that several of these studies are limited by lack of pathologic review.118–123. It has been suggested that for those benign papillomas without atypia diagnosed on CNB, complete removal by large gauge vacuum-assisted device could be considered, offering a less invasive method of excision for patients with a low probability of cancer while allowing for further evaluation of the remaining papillary lesion along with some surrounding tissue.49 Thus, while some studies suggest that patients with benign papilloma diagnosed on CNB may be spared excision, currently we recommend that all radiologically targeted papillary lesions diagnosed on CNB should be excised.
Radial Scars/Complex Sclerosing Lesions
The occurrence of invasive or in situ carcinoma involving radial scars or in close proximity to radial scars is well known, with rates ranging from 0% to 34%,124–130 and with variable association with older patient age and larger lesion size.128,131 Although the association with carcinoma is known, the possibility of underdiagnosis on CNB is not surprising given that involvement of the radial scar by carcinoma is often only focal or peripheral (Fig. 4).131 Retrospective studies examining surgical excision following a diagnosis of radial scar without atypia diagnosed on CNB reveal rates of upgrade to invasive carcinoma ranging from 0% to 12%.124–130,132 As discussed above for other lesions associated with an upgrade rate, missed carcinomas after a diagnosis of radial scar on CNB are more likely with 14-gauge automatic spring-loaded biopsy devices versus larger gauge vacuum-assisted devices and with fewer than 12 tissue samples.124,132,133 This suggests the possibility that excision by vacuum-assisted devices with careful clinical follow-up may be feasible for those patients with radial scars without atypia on vacuum-assisted biopsy and pathologic-mammographic correlation.132
However, given the very limited data available at this time, we believe it is prudent for all patients with radial scars diagnosed on CNB to undergo surgical excision to exclude the possibility of concomitant carcinoma.
When a fibroadenoma is diagnosed on CNB and the imaging findings are concordant with that diagnosis, no further surgery is required. Issues arise when the CNB shows a fibroepithelial lesion with increased stromal cellularity for which the differential diagnosis includes benign phyllodes tumor or phyllodes tumors of uncertain malignant potential. Malignant phyllodes tumors are not usually a diagnostic problem. Features on CNB that have been shown to be associated with phyllodes tumor include markedly increased stromal cellularity, stromal cell atypia, and mitoses and also a high proportion of stroma to epithelium.134 Further features that suggest phyllodes tumor on CNB are increased stromal cellularity compared with that of a typical fibroadenoma in at least 50% of the specimen, stromal overgrowth (ie, at least one 10× field with no glands), adipose tissue within the stroma and tissue fragmentation135 (Table 4). However, none of the above mentioned features can predict with absolute reliability the likelihood of having a benign phyllodes tumor versus a fibroadenoma on excision (Fig. 5). Therefore, any fibroepithelial lesion in which the differential diagnosis includes phyllodes tumor must be excised for complete evaluation.134–139 Repeat biopsy does not seem to be helpful.135 Histologic features strongly suspicious for phyllodes tumor should be reported so that clear margins can be attempted in these cases. Regarding fibroadenomas, aside from excluding phyllodes tumors, features of “complex” fibroadenomas which include sclerosing adenosis, calcifications associated with epithelium, cysts greater than 3 mm and papillary apocrine metaplasia, might be mentioned due to the slight increase in risk for subsequent carcinoma that these lesions incur.140
MLLs are composed of mucin containing cysts which may rupture, with extravasation of mucin into surrounding stroma (Fig. 6).141 The imaging target may be indeterminate calcifications or a nodular mass. The epithelium lining the cysts of MLLs is often attenuated but may range from benign to ADH to DCIS.142 The reason management issues arise in this scenario are the concern as to whether there may be undersampling of areas of mucinous carcinoma. Of note, the presence of epithelial cells floating in pools of mucin may be attributable either to stripped epithelium from a benign MLL in a fragmented CNB specimen or to mucinous carcinoma. One small study reported that 30% of MLLs were found to be mucinous carcinoma on exision,143 though others have claimed that mucinous lesions can be accurately classified on the basis of the CNB.91,144 The largest study to date by Wang et al91 reviewed the CNB and surgical excision of 32 mucinous lesions, of which 29 diagnoses made on CNB were unchanged with excision. The remaining cases were diagnosed as MLL without atypia on CNB and only showed fibrocystic change on excision. In those cases that display disrupted mucin pools, the presence of capillaries within the mucinous stroma may offer a clue to the malignant nature of the lesion.145 Given the very small numbers in these studies, it is recommended that an excision to rule out mucinous DCIS or mucinous carcinoma be performed after the identification of MLL or stromal pools of mucin on CNB.
Other Benign Mass-like Lesions
With the strong emphasis on radiologic-pathologic correlation when interpreting CNB specimens, it is important to keep in mind other entities that may form mass lesions aside from malignancy and those described above. Cysts, pseudoangiomatous stromal hyperplasia, fat necrosis and nodular adenosis can form a palpable mass or a mass lesion identified on imaging studies. Recognition of these lesions and their careful correlation with the imaging findings can prevent an unnecessary surgical excision. Table 5 summarized the non-malignant breast lesions for which excision is recommended.
In conclusion, when rendering an opinion on a CNB of the breast, the pathologist should always correlate the radiologic findings with those seen on the histologic sections and provide sufficient information to ensure the patient is triaged into the appropriate management pathway.
The authors wish to express their thanks to Dr Stuart Schnitt for reviewing and commenting on this manuscript during its preparation.
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core needle biopsy; flat epithelial atypia; atypical ductal hyperplasia; lobular neoplasia; papilloma; radial scar
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