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Underestimation of the Presence of Breast Carcinoma in Papillary Lesions Initially Diagnosed at Core-Needle Biopsy¹

¹ From the Department of Radiology, Medical College of Virginia, Box 980615, Richmond, VA 23298-0615. From the 2003 RSNA Annual Meeting. Received December 4, 2003; revision requested February 12, 2004; final revision received March 14, 2006; accepted March 22; final version accepted April 17. Supported by the Blanton-Sweeney Research Endowment MCV Foundation. Address correspondence to M.K.S. (e-mail: mksydnor{at}vcu.edu).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION References

 
Purpose: To retrospectively determine the degree of underestimation of breast carcinoma diagnosis in papillary lesions initially diagnosed at core-needle biopsy.

Materials and Methods: Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. Mammographic database review (1994–2003) revealed core biopsy diagnoses of benign papilloma (n = 38), atypical papilloma (n = 15), sclerotic papilloma (n = 6), and micropapilloma (n = 4) in 57 women (mean age, 57 years). Excisional or mammographic follow-up (2 years) findings were available. Patients with in situ or invasive cancer in the same breast or patients without follow-up were excluded. Findings were collected from mammography, ultrasonography, core technique, core biopsy, excision, and subsequent mammography. Reference standard was excisional findings or follow-up mammogram with no change at 2 years. Associations were examined with regression methods.

Results: In 38 of 63 lesions, surgical excision was performed; in 25 additional lesions (considered benign), follow-up mammography (24-month minimum) was performed, with no interval change. In 15 lesions, 14-gauge core needle was used; in 48, vacuum assistance (mean cores per lesion, 8.7). Carcinoma was found at excision in 14 of 38 lesions. Core pathologic findings associated with malignancy were benign papilloma (n = 1), sclerotic papilloma (n = 1), micropapilloma (n = 2), and atypical papilloma (n = 10). Frequency of malignancy was one (3%) of 38 benign papillomas, 10 (67%) of 15 atypical papillomas, two (50%) of four micropapillomas, and one (17%) of six sclerotic papillomas. Excisional findings included lobular carcinoma in situ (n = 2), ductal carcinoma in situ (n = 7), papillary carcinoma (n = 2), and invasive ductal carcinoma (n = 3). Low-risk group (micropapillomas and sclerotic and benign papillomas) was compared with high-risk atypical papilloma group. Core findings were associated with malignancy at excision for atypical papilloma (P = .006). Lesion location, mammographic finding, core number, or needle type were not associated (P > .05) with underestimation of malignancy at excision.

Conclusion: Benign papilloma diagnosed at core biopsy is infrequently (3%) associated with malignancy; mammographic follow-up is reasonable. Because of the high association with malignancy (67%), diagnosis of atypical papilloma at core biopsy should prompt excision for definitive diagnosis.

© RSNA, 2006

	INTRODUCTION

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Percutaneous breast biopsy has replaced surgical biopsy, in many instances, for the diagnosis of mammographically detected suspicious abnormalities. Such biopsy has evolved from fine-needle aspiration to automated core biopsy to vacuum-assisted biopsy. As this technology has advanced, so has the potential for percutaneous biopsy of more types of lesions.

Although percutaneous breast biopsy is a highly reliable method for the diagnosis of breast lesions, malignancy at subsequent surgical excision can be seen with certain pathologic conditions, particularly atypical hyperplasias (1–9) and radial scars (10,11). The term "histologic underestimate" has been used to describe occasions in which lesions are benign at biopsy but are malignant at excision (1). In these lesions, the pathologic findings may be heterogeneous, and excision of the complete lesion may be necessary to exclude malignancy in a portion that was not sampled with the percutaneous core-needle biopsy. Debate exists in regard to the possibility of underestimation of the presence of malignancy in papillomas diagnosed at percutaneous core-needle biopsy.

A papillary lesion of the breast may manifest as an asymptomatic mass or as a group of microcalcifications at mammography. Benign papillomas are intraductal epithelial proliferations on a frond-forming fibrovascular core. The intraductal epithelium has two components: (a) a basal myoepithelium, one cell layer thick, on which rests (b) a variably proliferative epithelium. Malignant papillary lesions lack all or most of the myoepithelial cell support layer and have architectural and/or cytologic features of ductal carcinoma in situ (DCIS) in the ductal epithelium found between fibrovascular fronds. Intermediate-grade lesions that can be classified somewhere between fully benign papillomas and malignant papillary carcinomas have a variably present supporting myoepithelial cell layer and less than complete DCIS-like changes in the epithelial component. Papillary proliferations with these intermediate features often are called atypical papillomas (12,13).

In some institutions, only papillomas called atypical at core biopsy undergo surgical excision, whereas benign papillomas are followed up mammographically. At other institutions, however, all papillary lesions undergo surgical excision to establish the definitive diagnosis (1). Thus the purpose of our study was to retrospectively determine the degree of underestimation of the diagnosis of breast carcinoma for papillary lesions initially diagnosed at core-needle biopsy.

	MATERIALS AND METHODS

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Patients
Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act–compliant study; informed consent was waived. We identified, through our mammographic database, 86 women (age range, 37–78 years) with 94 papillary lesions diagnosed at percutaneous core–needle biopsy from 1994 to 2003. The database was searched by using the terms "papilloma" and "papilloma with atypia." In all instances, medical charts and images were available. Either excisional pathologic findings or follow-up mammographic findings for at least 2 years were available for 57 women (mean age, 57 years; range, 37–74 years) with 63 papillary lesions in our study group. No patients reported nipple discharge as a complaint at presentation.

The 63 lesions were classified at core-needle biopsy as one of the following: benign papilloma (n = 38), sclerotic papilloma (n = 6), micropapilloma (n = 4), or atypical papilloma (n = 15). Excluded were patients with associated in situ or invasive cancer in the same breast, patients identified as having papillary carcinoma at core biopsy, or patients without follow-up mammographic or excisional results. In all patients, biopsy had been performed with stereotactic guidance or ultrasonographic (US) guidance. Automated core-needle devices were used for all US-guided procedures; vacuum-assisted probes or core-needle probes were used with stereotactic guidance.

Data Collection
We retrospectively reviewed the patients' mammograms, US images, and technical information about the biopsy procedure for each lesion. Two radiologists (M.K.S., E.S.S.d.P.) reviewed in consensus all mammograms and US images; data about biopsy technique were collected by one of them (M.K.S.). One radiologist had 21 years of experience in breast imaging (E.S.S.d.P.), and the other was a senior resident with 3 months of experience in breast imaging (M.K.S.).

In all instances, the mammographic findings were characterized as masses, microcalcifications, or ductal dilatation. Mass size and morphologic features (punctate, amorphous, pleomorphic) of microcalcifications were recorded. The lesions were further characterized according to the location in the breast (anterior, middle, or posterior third) and the presence or absence of a mass at US, if performed. Data about needle type (14-gauge core needle or 11- or 14-gauge needle with a breast biopsy system [Mammotome; Ethicon Endo-Surgery, Cincinnati, Ohio]) and number of cores were collected.

Follow-up
All of the atypical papillomas were surgically excised, and excisional pathologic results were collected from the reports (M.K.S.) and compared with core biopsy results. For the remaining three groups of nonatypical papillomas, mammographic follow-up or excisional biopsy was performed. In our practice, the nonatypical papillomas diagnosed at core biopsy were followed up prior to 2002, at which time we began recommending excision. All atypical papillomas were excised. All 63 lesions were either excised or followed up mammographically for at least 24 months.

For the lesions that were excised, the surgical pathology reports from the excision were reviewed (M.K.S.), and the lesions were classified in the following categories: (a) benign papilloma, (b) other benign lesion, (c) atypical papilloma, (d) papillary carcinoma, and (e) other malignancy. Lobular carcinoma in situ was included in the "other malignancy" category. Excisional pathologic findings or a follow-up mammogram with no change at 2 years was the reference standard. A lesion with no change at 2 years was considered benign.

Statistical Analysis
Associations between biopsy findings and the results of surgical excision were examined by using logistic regression methods (SAS for Windows, version 9.1.3; SAS, Cary, NC). Mammographic findings (presence of a mass, presence of microcalcifications, lesion location), number of cores obtained, and type of biopsy needle were included as covariates in the model. Generalized estimating equations were used to correct for five instances in which multiple lesions were included from the same patient (two lesions each in four patients and three lesions in one patient). A significant difference was determined with P < .05.

	RESULTS

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Benign and Malignant Lesions
Surgical excision was performed in 38 (60%) of 63 lesions; mammographic follow-up was a minimum of 24 months in 25 (40%). The mean follow-up was 34 months, and the range was 24–62 months. Of the 25 lesions that were followed up, 24 were benign papillomas at core biopsy and one was a sclerotic papilloma. None of these changed at follow-up mammography for at least 2 years. Consequently, they were considered benign.

Frequency of malignancy was one (3%) of 38 benign papillomas, 10 (67%) of 15 atypical papillomas, two (50%) of four micropapillomas, and one (17%) of six sclerotic papillomas. Malignancy was found for 14 of 38 lesions that were surgically excised. The frequency was as follows: one (8%) of 13 benign papillomas, two (50%) of four micropapillomas, one (17%) of six sclerotic papillomas, and 10 (67%) of 15 atypical papillomas. No malignancies were found in the additional 25 benign papillomas that were followed up for longer than 2 years. In one excised benign papilloma, a focus of lobular carcinoma in situ was found adjacent to the papilloma. The malignancy associated with a sclerotic papilloma was invasive ductal carcinoma with DCIS, which was thought to be an incidental finding immediately adjacent to the papilloma. Because of the small numbers of micropapillomas and sclerotic papillomas, these lesions were combined with benign papillomas into a low-risk group, which was compared with the high-risk atypical papilloma group. Core pathologic findings defined in this way were significantly associated with the presence of malignancy at excision for the atypical papilloma group (P = .006). The types of malignancy for the 14 of 38 lesions that were excised were papillary carcinoma (n = 2), DCIS (n = 7), invasive ductal carcinoma (n = 3), and lobular carcinoma in situ (n = 2).

Imaging Findings
Mammographic findings in the 63 lesions included 26 (41%) masses, 27 (43%) groups of microcalcifications, and 10 (16%) masses associated with microcalcifications. Of the 14 cancers at excision, four manifested as masses, nine were microcalcifications, and one was a mass with microcalcifications. Although microcalcifications were more frequent manifestations of malignancy, these mammographic findings were not significantly associated with the underestimation of malignancy (P = .48). Morphologic features of microcalcifications in the overall group of 37 lesions were as follows: punctuate, one (3%); amorphous, 27 (73%); and pleomorphic, nine (24%). For the 10 malignant lesions associated with microcalcifications, the morphologic features were most often amorphous (five lesions) or pleomorphic (five lesions). None of the malignancies manifested mammographically as ductal dilatation; however, eight benign lesions were characterized by this finding. US was performed in 23 lesions. Five of 14 malignancies were evaluated with US, and three manifested as solid masses.

In 63 lesions, the location of the lesions within the breast was as follows: 19 in the anterior third, 25 in the middle third, and 19 in the posterior third. In 14 malignancies, five were in the anterior third, four were in the middle third, and five were in the posterior third. There was no significant (P = .63) relationship between lesion location and the presence of malignancy at excision.

Needle Gauge and Number of Cores
Biopsy was performed in 15 of 63 lesions by using a 14-gauge automated core needle; in 48 lesions, biopsy was performed with an 11- or 14-gauge vacuum-assisted probe. The mean number of cores obtained per lesion was 8.7. There was no significant relationship between the type of needle (automated core or vacuum-assisted) (P = .51) or the number of cores (P = .18) obtained and the presence of malignancy at excision.

	DISCUSSION

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Papillomas may be found in either the major or minor lactiferous ducts of the breast. They are composed of a fibrovascular core, a myoepithelial layer, and an outer layer of cuboidal or columnar epithelium. Although papillomas usually are pedunculated, they occasionally may lack a stalk, appear to fully fill their duct of origin, and touch the duct or cyst wall on all sides. Papillomas typically are smaller than 1 cm and most often are found in women 30–50 years old. Occasionally, they may be identified only microscopically, in which case they may be termed micropapillomas or small ductal papillomas. Others may be extensively sclerotic and are referred to as sclerotic papillomas or ductal adenomas. Some demonstrate features of atypia, such as foci, similar to atypical ductal hyperplasia or low-grade DCIS (12), in which case they are termed either atypical papilloma or papillary carcinoma, depending on the extent of atypia. On the malignant end of the spectrum is invasive papillary carcinoma, which is an uncommon entity. Palpable masses are the features at presentation in 90% of papillary cancers. Invasive papillary carcinoma is a specialized type of ductal carcinoma, and it represents only 2% of all breast cancers (13).

Papillomas may be classified in a spectrum of lesions, which are not clearly malignant but may be associated with a slightly increased relative risk of subsequent invasive breast cancer. Lesions that are associated with a higher relative risk of cancers include atypical ductal hyperplasia, lobular carcinoma in situ, and atypical lobular hyperplasia (10). Although the treatment of atypical ductal hyperplasia diagnosed at core-needle biopsy has been extensively described (1–4,10) as requiring surgical excision for complete removal to exclude an underestimated cancer, the treatment of lobular neoplasia (5–9,14,15) and papillomas (14–17) diagnosed at core biopsy is more controversial.

Data obtained by Liberman et al (16) in 1999 included 19 cases of nonmalignant papillary lesions diagnosed by using core-needle biopsy. Nine of these lesions were described as benign and 10 were described as atypical with core biopsy pathologic findings. None of the benign papillomas were malignant at surgery or mammographic follow-up; three of 10 atypical lesions were malignant at surgery.

Philpotts et al (14) reported "borderline DCIS" in one (17%) of six papillary lesions with benign histologic findings at percutaneous breast biopsy. They concluded that surgical excision of lesions with benign histologic findings is warranted only if discordance between imaging findings and histologic findings exists.

Mercado et al (17) reviewed 18 nonmalignant papillary lesions, six of which were atypical, from core biopsy. None of the atypical lesions were malignant at excision. In the 12 benign papillomas, six were excised, and six were benign at mammographic follow-up. Of the six that were excised, five were benign. Findings in the sixth excised lesion were discordant with the mammographic findings, and the lesion was malignant at surgical excision. The conclusions of their study suggest that benign papillomas may not require surgical excision if the mammographic findings are concordant with the histopathologic results (17).

More recently, Mercado et al (18) published a study of papillary lesions diagnosed at core-needle biopsy and concluded that benign papillary lesions should be surgically excised. In this study of 43 lesions in 42 patients in whom 29 papillomas, eight sclerosing papillomas, and six other benign papillary lesions were found at core-needle biopsy, nine (21%) patients had atypical ductal hyperplasia or DCIS at excision.

Irfan and Brem (15) reviewed six papillomas diagnosed at core biopsy. One was atypical and demonstrated features of radial scar; it was excised. Two of the remaining five also were removed, and one of them demonstrated features of atypical ductal hyperplasia. Of the three that were not excised, one was stable mammographically at 6 months. The outcomes of the other two were not reported. In our study, the rate of malignancy upgrade was higher than rates reported in the aforementioned series. This difference may be related, in part, to case selection in that we included only papillomas and not other types of papillary lesions found at core biopsy. In addition, the number of patients included in our study was much larger than that reported in the other studies.

Limitations of our study may, in part, relate to the lack of a significant relationship between underestimation of carcinoma and some of the parameters studied. In a majority of the lesions, biopsy was performed by using an 11-gauge needle, so an assessment of the relationship between needle type and malignancy could not be performed. Because of the relatively low frequency of papillomas, in general, at core biopsy, statistical power could not be calculated prior to the study. The mean number of cores obtained was 8.7, although with our techniques, our goal, in general, is to acquire three to five samples with an automated core needle and 12 samples with vacuum assistance. Therefore, the needle type and number of cores are interrelated. In addition, the acquisition of a larger number of cores usually is prompted by lack of acquisition of the sample in the initial cores and does not necessarily reflect a larger volume of the actual lesion being sampled.

In our study, one of the 38 benign papillomas for which biopsy was performed was malignant at surgical excision. This malignancy was lobular carcinoma in situ, which most clinicians consider to be a high-risk lesion rather than a true cancer and which was most likely an incidental finding in the tissue specimen. The underestimation rate of 3% in benign papillomas suggests that mammographic follow-up rather than excision is reasonable. In atypical papillomas, however, the underestimation of malignancy is 67%. Because of the small numbers of micropapillomas and sclerotic papillomas, which are associated with underestimation rates of 50% and 17%, respectively, further study is needed. Unlike the findings of others about underestimation of carcinoma, we found no significant relationship between needle type or number of samples and the underestimation of disease. In the majority (48 of 63) of the lesions in this study, biopsy was performed with vacuum assistance, and use of this method may affect these results.

In conclusion, benign papilloma diagnosed at core biopsy is infrequently associated with malignancy at excision. We believe benign papillomas may be followed up mammographically if the mammographic findings are considered concordant with the pathologic findings; because of the high association with malignancy, the diagnosis of an atypical papilloma at core biopsy should prompt excision for definitive diagnosis. More study is needed of lesions identified at pathologic analysis as micropapillomas or sclerotic papillomas. We currently continue to recommend excision for these two subgroups.

	FOOTNOTES

 

Abbreviations: DCIS = ductal carcinoma in situ

Author contributions: Guarantors of integrity of entire study, M.K.S., E.S.S.d.P.; study concepts, M.K.S., E.S.S.d.P.; study design, M.K.S., E.S.S.d.P.; literature research, M.K.S., E.S.S.d.P.; clini-cal studies, M.K.S., E.S.S.d.P.; data acquisition, M.K.S., E.S.S.d.P.; data analysis/interpretation, M.K.S., E.S.S.d.P., J.D.W.; statistical analysis, M.K.S., E.S.S.d.P., J.D.W.; manuscript preparation, all authors; manuscript definition of intellectual content, M.K.S., E.S.S.d.P.; manuscript editing, all authors; manuscript revision/review, all authors; manuscript final version approval, E.S.S.d.P.

Authors stated no financial relationship to disclose.

	References

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This Article Abstract Full Text (PDF) All Versions of this Article: 2421031988v1 242/1/58    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sydnor, M. K. Articles by Shaw de Paredes, E. S. Search for Related Content PubMed PubMed Citation Articles by Sydnor, M. K. Articles by Shaw de Paredes, E. S.