Adequate histologic sampling of breast magnetic resonance imaging--guided core needle biopsy.
Abstract: * Context.--The increasing use of contrast-enhanced magnetic resonance imaging (MRI) of the breast as a valuable adjunct to mammography and ultrasound in the detection of breast lesions, in association with needle core biopsy taken from the suspicious areas, has major workload implications for histopathology laboratories wherever breast MRI is practiced.

Objective.--To establish the number of histologic levels necessary for the evaluation of breast MRI-guided needle core biopsy specimens taken from suspicious areas on breast MRI examination.

Design.--Retrospective histologic review of a series of breast MRI-guided core needle biopsies, initially examined routinely at 4 levels, in the Pathology Department at Mount Sinai School of Medicine in New York, New York.

Results.--Accurate diagnostic classification was possible after examination of the first level in 95.4% of cases. For a small group of patients (4.4%), 4 levels were considered to provide additional useful information, although this information did not alter the diagnosis. In only a single case (0.2%) was it likely that routine examination of 4 levels could have led to an incidental finding of a very small intraductal papilloma (0.15 cm) present only at the second histologic level. However, this incidental finding would have not changed the patient outcome.

Conclusions.--Needle core biopsies for MRI-detected abnormalities should be routinely examined at only 1 level. Further levels may be needed in occasional cases to identify more conclusively an associated pathologic abnormality and may be of particular value when assessing atypical intraductal proliferative epithelial lesions.
Article Type: Report
Subject: Magnetic resonance imaging (Usage)
Mammography (Usage)
Breast examination
Authors: Cornea, Virgilius
Jaffer, Shabnam
Bleiweiss, Ira J.
Nagi, Chandandeep
Pub Date: 12/01/2009
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 College of American Pathologists ISSN: 1543-2165
Issue: Date: Dec, 2009 Source Volume: 133 Source Issue: 12
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 230246910
Full Text: Within the last 10 years, contrast-enhanced magnetic resonance imaging (MRI) of the breast has gained recognition as a valuable adjunct to mammography and ultrasound in the detection of breast lesions that might otherwise be clinically, sonographically, and mammographically occult. There is general agreement among investigators that the sensitivity of breast MRI is excellent, ranging between 88% and 100%, with more variable specificity ranging from 37% to 97%. Despite the use of several criteria in the classification of MRI-detected lesions and the interpretation of contrast-enhancement kinetics, suspicious BIRADS (breast imaging reporting and data system) IV and V lesions still require histologic diagnosis.

Two different approaches to the histologic verification of MRI-detected breast lesions are feasible. The first is MRI-guided wire-localized open breast biopsy. Although open breast biopsy yields good results, the surgery is costly, invasive, and associated with a certain perioperative risk. As an alternative, percutaneous breast biopsy techniques under MRI guidance have been developed. Under mammographic and sonographic guidance, percutaneous biopsy techniques have already been carefully evaluated and have been shown to be safe and accurate methods. When compared with open breast biopsy, percutaneous biopsy is less invasive, faster, and can be performed at lower cost.1 This category of specimens currently accounts for approximately 20% to 30% of the breast needle core biopsies at our institution, and usually the amount of tissue removed is 3 to 4 times greater than that removed with stereotactic or ultrasound breast needle core biopsies. Thus, the routine examination of these specimens (cutting, staining, and reading of 4 levels, ie, 4 slides of tissue), necessitates a considerably greater amount of work by the pathology laboratory personnel (histology technicians as well as resident and attending pathologists). To decrease the cost and workload to our laboratory, while maintaining the same quality of patient care, we retrospectively reviewed all of our breast MRI-guided core needle biopsies to determine the optimal number of levels needed for accurate diagnosis.

MATERIALS AND METHODS

The results of breast core needle biopsy specimens as interpreted from January 10, 2006, to February 17, 2008, at Mount Sinai School of Medicine in New York, New York, were reviewed. Each biopsy, performed under MRI guidance, consisted of 9- and 11-gauge core needle biopsy specimens. All specimens received were fixed in formalin and were processed routinely. Up to 5 core cylinders were embedded in a single paraffin block; if more than 5 cores were present, an additional block was prepared. Each block was sectioned to produce 4 slides with 1 level per slide. Each consecutive slide contained 1 histologic level, 20 [micro]m apart.

In this study, the reports and slides (with increased focus on the first and the last level) comprising 505 specimens from 439 patients were retrieved from the pathology files. The cumulative diagnosis was determined that would have pertained after each level, and a comment was made as to the usefulness of each level. Standard histologic criteria for in situ lobular carcinoma and intraductal carcinoma were used. Lobular carcinoma in situ (LCIS) was defined as a lesion in which more than 50% of the acini of a terminal duct--lobular unit were dilated and completely filled by uniform, small, and dyscohesive cells with bland nuclei, uniform chromatin, and indistinct nucleoli, whereas ductal carcinoma in situ (DCIS) was characterized by a single cell population showing cytologic pleomorphism, presence of mitoses, or singlecell necrosis and an appropriate growth pattern in at least 2 duct spaces. Such defining characteristics of DCIS and LCIS are of particular importance because, in some core biopsy cases, not all of the diagnostic features of each are present on a single slide. For example, since some diagnostic features (ie, nuclear pleomorphism and/or mitosis) might be found in one level and other diagnostic features (ie, single-cell necrosis) could be seen on subsequent sections, the final diagnosis might be achieved by examining more than 1 level. Thus, both the reason for the usefulness of the levels and the final core biopsy diagnosis were recorded. All slides were reviewed by 1 of 3 dedicated breast pathologists.

RESULTS

During the study period, a total of 505 breast MRI-guided biopsies of lesions from 439 women were performed for a mass or abnormal enhancement detected by breast MRI examination (Table 1). The women's ages ranged from 18 to 84 years (mean, 54 years). The final diagnosis for the 505 cases was initially subdivided into 2 main categories: (1) lesions necessitating subsequent excision (Table 2) and (2) lesions that were not related to an indication for subsequent excision (Table 3). For the 174 cases included in the category of lesions necessitating excision, the most common diagnosis was DCIS in 54 cases (10.7%), followed by intraductal papilloma/radial scar in 49 cases (9.7%), and infiltrating carcinoma in 41 cases (8.1%). The invasive carcinoma category was represented by infiltrating ductal carcinoma in 20 cases (4%) (7 well differentiated, 7 well to moderately differentiated, and 6 poorly differentiated), infiltrating lobular carcinoma in 10 cases (2%), and infiltrating mixed ductal and lobular carcinoma in 11 cases (2.2%). Of the 54 patients for which DCIS was diagnosed, 39 (7.7%) had DCIS alone, 7 (1.4%) had mixed DCIS/LCIS, 6 (1.2%) had a concomitant intraductal papilloma/radial scar, 1 (0.2%) had DCIS and hamartoma, and 1 (0.2%) had DCIS arising in a background of atypical ductal hyperplasia (ADH) (Table 4). In the 26 cases in which ADH was the most advanced lesion, the ADH usually accompanied other lesions such as intraductal papilloma or mucocele (Table 5). A small number of patients (4, 0.8%) were given a diagnosis of perilobular capillary hemangioma alone (3 cases) or in association with intraductal papilloma/radial scar (1 case).

Most lesions not necessitating excision were represented by fibrocystic changes alone in 152 cases (30.1%), by fibrocystic changes associated with cysts lined by apocrine metaplastic cells in 54 cases (10.7%), and by fibroadenoma in 37 cases (7.3%). In the same category of lesions, atypical lobular hyperplasia/LCIS was diagnosed in 17 cases (3.4%). Other diagnostic categories (ie, fat necrosis, benign fibro-fatty tissue, fatty breast tissue with negative lymph node) were represented in 71 of the cases (15.1%) (Table 3).

Complete and accurate diagnosis was possible after examination of only the first slide (first histologic level) in 482 of the 505 specimens (95.4%). In 23 cases (4.6%), the diagnosis could be made on the first slide, but additional levels were deemed helpful (Table 6). Among those cases for which levels were helpful, 3 (0.6%) were associated with ADH, 17 (3.4%) with DCIS, 1 (0.2%) was associated with infiltrating ductal carcinoma, and 1 with a patient (0.2%) diagnosed with radial scar associated with LCIS. One of the 3 patients with ADH had microcalcifications in addition to ADH. For the patients with DCIS of the breast, DCIS alone was diagnosed in 8, DCIS associated with radial scar/intraductal papilloma was diagnosed in 4, DCIS and hamartoma were diagnosed in 1, and 4 patients had DCIS associated with LCIS. In all these cases, the diagnosis was suggested based on examination of the first slide, but some diagnostic features (pleomorphism, mitoses, or single-cell necrosis) were found at the subsequent histologic levels.

In the single patient for whom levels were needed to establish the final diagnosis, a diagnosis of florid ductal hyperplasia was made after the examination of the first slide. The next level revealed a small intraductal papilloma (0.15 cm microscopic measurement), which disappeared at the third and fourth levels. The diagnosis of intraductal papilloma for this patient was an incidental finding, which would have not changed the patient outcome anyway, since this lesion was so small (5 mm) and probably already entirely excised by core biopsy alone.

COMMENT

This study constitutes one of the largest series of the pathology of breast MRI-guided core biopsies reported to date; however, it additionally examines the amount of histologic sectioning necessary for the most accurate and complete diagnosis. Although prior studies (2,3) have examined the average amount of sectioning needed with respect to stereotactic core biopsies performed to evaluate radiologically identified calcifications and associated lesions (ie, atypical ductal hyperplasia and in situ or invasive carcinoma), to our knowledge, no study has specifically examined the amount of sectioning necessary with MRI-guided cores. In prostate biopsies, it has been shown (4) and confirmed (5-7) that only 3 sections are necessary to identify all significant foci, including atypical foci. For mammotome core biopsies performed for calcifications, a minimum of 3 levels are recommended, but many laboratories, (2,3) including our own, routinely examine these biopsy specimens in greater detail (4 to 6 levels) to maximize the chances of achieving a complete diagnosis in as short a time as possible. Additional levels are also useful in ultrasound-guided core biopsies, since both the tissue samples and the targeted lesions may be small.

These results indicate that routine examination of 1 level, with further levels only when deemed necessary, is sufficient for the assessment of needle core biopsies performed for MRI-detected abnormalities. A total of 95.4% of cases were accurately classified on the basis of the first slide. An additional 4.4% of cases were accurately classified after first-level examination in association with features revealed in the subsequent levels (without altering the first-level diagnosis). In only a single patient (0.2%), additional levels were required to make the diagnosis of intraductal papilloma, but even in this case the papilloma was so small (0.15 cm) that it disappeared on further sections, was probably an incidental finding, and thus did not warrant further treatment. (8)

In core biopsies performed for mammographic calcifications or sonographically for densities, the pathologist is usually able to confirm microscopically that the target has been hit, therefore achieving successful radiologic-pathologic correlation. Ultrasound and mammography target a mass and/or area of contrast, and the border, contour, solid and/or cystic nature of a mass, and patterns of calcifications are all static properties of a lesion that can be confirmed and translated by the pathologist at a histologic level. Multiple levels are often helpful and even vital (particularly in the evaluation of calcifications) in this pursuit. Magnetic resonance, however, measures a dynamic process of blood flow, and the target is not increased areas of vascularity, but increased vascular flow and permeability. This nonstatic property is impossible to specifically correlate with any particular static image on a histologic slide. Thus, in a benign biopsy, the pathologist has no method of confirming that the target has actually been sampled accurately and adequately. This study shows that additional levels do not appear to be helpful in this regard.

Routine examination of multiple levels can minimize diagnostic delay and maximize diagnostic accuracy at the expense of increased cost and workload. The need for both a timely and an accurate diagnosis must, however, be balanced against the increased workload both for the reporting pathologist and the laboratory staff preparing the sections. Individual departments should audit their own practice to establish the most appropriate process for their local breast screening service; however, it would appear that 1 section is sufficient for most MRI-guided breast core biopsies.

References

(1.) Floery D, Helbich TH. MRI-guided percutaneous biopsy of breast lesions: materials, techniques, success rates, and management in patients with suspected radiologic-pathologic mismatch. Magn Reson Imaging Clin N Am. 2006;14(3): 411-425.

(2.) Renshaw AA. Adequate histologic sampling of breast core needle biopsies. Arch Pathol Lab Med. 2001;125(8):1055-1057.

(3.) Kumaraswamy V, Carder PJ. Examination of breast needle core biopsy specimens performed for screen-detected microcalcification. J Clin Pathol. 2007;60: 681-684.

(4.) Renshaw AA. Adequate tissue sampling of prostate core needle biopsies. Am J Clin Pathol. 1997;107:26-29.

(5.) Reyes AO, Humphrey PA. Diagnostic effect of complete histologic sampling of prostate needle biopsies [abstract]. Mod Pathol. 1997;10:86A.

(6.) Brat DJ, Wills ML, Lecksell KL, Epstein JI. How often are diagnostic features missed with less extensive histologic sampling of prostate needle biopsy specimens? Am J Surg Pathol. 1999;23:257-262.

(7.) Lane RB, Lane CG, Mangold KA, Johnson MH, Allsbrook WC. Needle biopsies of the prostate: what constitutes adequate histologic sampling? Arch Pathol Lab Med. 1998;122:833-835.

(8.) Al Sarakbi W, Worku D, Escobar PF, Mokbel K. Breast papillomas: current management with a focus on a new diagnostic and therapeutic modality. Int Semin Surg Oncol. 2006;3:1.

Virgilius Cornea, MD; Shabnam Jaffer, MD; Ira J. Bleiweiss, MD; Chandandeep Nagi, MD

Accepted for publication February 20, 2009.

From the Department of Pathology, Mount Sinai School of Medicine, New York, New York (Drs Cornea and Nagi); and the Department of Pathology, Oncological Science, Mount Sinai Medical Center, New York, New York (Drs Jaffer and Bleiweiss). Dr Cornea is now with the Department of Pathology, University of Cincinnati, Cincinnati, Ohio.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Virgilius Cornea, MD, Department of Pathology, University of Cincinnati, 231 Albert B Sabin Way, Room 1358--MSB, Cincinnati, OH 45267-0529 (e-mail: virgilius_c@yahoo.com).
Table 1. Changes Detected by Breast Magnetic
Resonance Imaging (MRI) Examination in the 439
Patients in the Study

MRI Finding                               No. of Patients

Mass enhancement                                229
Linear/stippled enhancement                      19
Enhancement (not otherwise specified)           148
Others (a)                                       43

Total                                           439

(a) MRI findings not given; asymmetric tissue on MRI;
negative MRI but clinically suspicious lesion.

Table 2. Categories of Lesions Necessitating
Subsequent Surgical Excision

Lesions Necessitating Excision          No. (%) of Cases

Benign neoplastic lesions
  Intraductal papilloma/radial scar         49 (9.7)
  Hemangioma                                 4 (0.8)

Atypical/premalignant lesions
  ADH                                       26 (5.1)

Malignant/infiltrative lesions
  DCIS                                      54 (10.7)
  Invasive carcinoma                        41 (8.1)

Total                                      174 (34.5)

Abbreviations: ADH, atypical ductal hyperplasia; DCIS, ductal
carcinoma in situ.

Table 3. Categories of Lesions Not Necessitating
Subsequent Surgical Excision

Lesions Not Necessitating
Excision                         No. (%) of Cases

Benign nonneoplastic lesions
  FA                                 37 (7.3)
  FC                                152 (30.1)
  FC and apocrine cysts              54 (10.7)
  Others (a)                         71 (11.1)

ALH/LCIS
  ALH                                 5 (1.0)
  LCIS                               12 (2.4)

Total                               331 (65.5)

Abbreviations: ALH, atypical lobular hyperplasia; FA, fibroadenoma;
FC, fibrocystic changes; LCIS, lobular carcinoma in situ.

(a) Fat necrosis, benign fibro-fatty tissue, fatty breast tissue
with reactive lymph node, radiation-induced changes, and previous
biopsy site changes.

Table 4. Ductal Carcinoma In Situ (DCIS) and
Associated Lesions

Lesion             No. (%) of Cases

DCIS/LCIS               7 (1.4)
DCIS/IP/RS              6 (1.2)
DCIS/ADH                1 (0.2)
DCIS/hamartoma          1 (0.2)
DCIS alone             39 (7.7)
Total                  54 (10.7)

Abbreviations: ADH, atypical ductal hyperplasia; IP, intraductal
papilloma; LCIS, lobular carcinoma in situ; RS, radial scar.

Table 5. Atypical Ductal Hyperplasia (ADH) and
Associated Lesions

Lesion                     No. (%) of Cases

ADH and calcifications          1 (0.2)
ADH and mucocele                1 (0.2)
ADH and FA                      1 (0.2)
ADH and IP/RS                   8 (1.6)
ADH and RS/LCIS                 1 (0.2)
ADH alone                      14 (2.8)
Total                          26 (5.1)

Abbreviations: FA, fibroadenoma; IP, intraductal papilloma;
LCIS, lobular carcinoma in situ; RS, radial scar.

Table 6. Lesions for Which the Additional Levels
Were Deemed Helpful for the Diagnosis

                                      No. (%) of Cases     No. (%) of
                                      With Extra Levels      Cases
                                         Helpful but        Needing
Lesions Necessitating Excision           Not Needed       Extra Levels

Atypical/premalignant lesions
  ADH                                      3 (0.6)

Malignant lesions
  DCIS                                    17 (3.4)
  Invasive carcinoma                       1 (0.2)

Benign neoplastic lesions
  Intraductal papilloma/radial scar        1 (0.2)          1 (0.2)

Total                                     22 (4.4)          1 (0.2)

Abbreviations: ADH, atypical ductal hyperplasia; DCIS, ductal
carcinoma in situ.
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