How Do We Approach Benign Proliferative Lesions?
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Purpose of Review
The aim of this review is to summarize recently published literature addressing atypical ductal hyperplasia (ADH), lobular neoplasia (atypical lobular hyperplasia [ALH] and classic lobular carcinoma in situ [C-LCIS]), non-classic lobular carcinoma in situ (NC-LCIS), papillary lesions, and flat epithelial atypia (FEA).
While ADH, ALN, and C-LCIS are well-established markers of an increased risk of future breast cancers, the risk implications are less clear for papillary lesions and FEA. NC-LCIS is the least well-characterized lesion, with scant published literature on its natural history and surgical management when encountered on needle biopsy.
Recent data suggest that lobular neoplasia on core biopsy of a BI-RADS ≤ 4 concordant lesion does not require an excision, while ADH, atypical papillomas, and NC-LCIS should be excised. Evidence on FEA and papillomas without atypia suggests a low risk of upgrade on excision, and prospective studies on the upgrade of these lesions are ongoing.
KeywordsAtypical ductal hyperplasia (ADH) Lobular neoplasia (atypical lobular hyperplasia (ALH) and classic lobular carcinoma in situ (C-LCIS)) Non-classic lobular carcinoma in situ (NC-LCIS) Papillary breast lesions Flat epithelial atypia (FEA)
Compliance with Ethical Standards
Conflict of Interest
Faina Nakhlis declares that she has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Hoda SA, Brogi E, Koerner FC, Rosen PP, editors. Rosen’s breast pathology. 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2014.Google Scholar
- 5.Hartmann LC, Radisky DC, Frost MH, Santen RJ, Vierkant RA, Benetti LL, et al. Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study. Cancer Prev Res (Phila). 2014;7:211–7. https://doi.org/10.1158/1940-6207.CAPR-13-0222.CrossRefGoogle Scholar
- 7.Jackman RJ, Burbank F, Parker SH, Evans WP 3rd, Lechner MC, Richardson TR, et al. Atypical ductal hyperplasia diagnosed at stereotactic breast biopsy: improved reliability with 14-gauge, directional, vacuum-assisted biopsy. Radiology. 1997;204:485–8. https://doi.org/10.1148/radiology.204.2.9240540.CrossRefPubMedGoogle Scholar
- 8.Eby PR, Ochsner JE, DeMartini WB, Allison KH, Peacock S, Lehman CD. Frequency and upgrade rates of atypical ductal hyperplasia diagnosed at stereotactic vacuum-assisted breast biopsy: 9-versus 11-gauge. AJR Am J Roentgenol. 2009;192:229–34. https://doi.org/10.2214/AJR.08.1342.CrossRefPubMedGoogle Scholar
- 10.Kohr JR, Eby PR, Allison KH, DeMartini WB, Gutierrez RL, Peacock S, et al. Risk of upgrade of atypical ductal hyperplasia after stereotactic breast biopsy: effects of number of foci and complete removal of calcifications. Radiology. 2010;255:723–30. https://doi.org/10.1148/radiol.09091406.CrossRefPubMedGoogle Scholar
- 17.Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 2005;97:1652–62. https://doi.org/10.1093/jnci/dji372.CrossRefPubMedGoogle Scholar
- 18.Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res (Phila). 2010;3:696–706. https://doi.org/10.1158/1940-6207.CAPR-10-0076.CrossRefGoogle Scholar
- 20.Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014;383:1041–8. https://doi.org/10.1016/S0140-6736(13)62292-8.CrossRefPubMedGoogle Scholar
- 21.Bevers T, Ward JH, Arun B, Colditz G, Cowan KH, Daly M, et al. NCCN breast cancer risk reduction guidelines, version 1.2017: National Comprehensive Cancer Network; Available from: https://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf.
- 22.Rosen PP: Lobular carcinoma in situ and atypical lobular hyperplasia. In: Rosen’s breast pathology. 2nd ed. Philadelphia: Lippincott Williams and Wilkin; 2001. p. 581–618.Google Scholar
- 28.Renshaw AA, Cartagena N, Derhagopian RP, Gould EW. Lobular neoplasia in breast core needle biopsy specimens is not associated with an increased risk of ductal carcinoma in situ or invasive carcinoma. Am J Clin Pathol. 2002;117:797–9. https://doi.org/10.1309/T4XF-C61J-C95Y-VR4Q.CrossRefPubMedGoogle Scholar
- 32.Cangiarella J, Guth A, Axelrod D, Darvishian F, Singh B, Simsir A, et al. Is surgical excision necessary for the management of atypical lobular hyperplasia and lobular carcinoma in situ diagnosed on core needle biopsy? A report of 38 cases and review of the literature. Arch Pathol Lab Med. 2008;132:979–83. https://doi.org/10.1043/1543-2165(2008)132[979:ISENFT]2.0.CO;2.Google Scholar
- 35.• Nakhlis F, Gilmore L, Gelman R, Bedrosian I, Ludwig K, Hwang ES, et al. Incidence of adjacent synchronous invasive carcinoma and/or ductal carcinoma in-situ in patients with lobular neoplasia on core biopsy: results from a prospective multi-institutional registry (TBCRC 020). Ann Surg Oncol. 2016;23:722–8. https://doi.org/10.1245/s10434-015-4922-4. This is a prospective, multi-institutional, single arm trial of excisional biopsies for lobular neoplasia of core biopsy specifically designed to best estimate the upgrade rate to carcinoma. One of its other strengths is central pathology review. CrossRefPubMedGoogle Scholar
- 36.•• King TA, Pilewskie M, Muhsen S, Patil S, Mautner SK, Park A, et al. Lobular carcinoma in situ: a 29-year longitudinal experience evaluating clinicopathologic features and breast cancer risk. J Clin Oncol. 2015;33:3945–52. https://doi.org/10.1200/JCO.2015.61.4743. This study reports the largest series of patients with C-LCIS with the longest prospective follow-up to date, detailing the natural history of C-LCIS, including the future breast cancer risk magnitude. CrossRefPubMedCentralPubMedGoogle Scholar
- 38.Sneige N, Wang J, Baker BA, Krishnamurthy S, Middleton LP. Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases. Mod Pathol. 2002;15:1044–50. https://doi.org/10.1097/01.MP.0000027624.08159.19.CrossRefPubMedGoogle Scholar
- 39.Gomes DS, Porto SS, Balabram D, Gobbi H. Inter-observer variability between general pathologists and a specialist in breast pathology in the diagnosis of lobular neoplasia, columnar cell lesions, atypical ductal hyperplasia and ductal carcinoma in situ of the breast. Diagn Pathol. 2014;9:121. https://doi.org/10.1186/1746-1596-9-121.CrossRefPubMedCentralPubMedGoogle Scholar
- 43.Carder PJ, Shaaban A, Alizadeh Y, Kumarasuwamy V, Liston JC, Sharma N. Screen-detected pleomorphic lobular carcinoma in situ (PLCIS): risk of concurrent invasive malignancy following a core biopsy diagnosis. Histopathology. 2010;57:472–8. https://doi.org/10.1111/j.1365-2559.2010.03634.x.CrossRefPubMedGoogle Scholar
- 47.Nakhlis F, Harrison BT, Lester S, Hughes KS, Coopey SB, King TA. Evaluating the risk of upgrade to invasive breast cancer and/or DCIS on excision following a diagnosis of non-classic lobular carcinoma in situ. [Poster at San Antonio Breast Cancer Symposium, San Antonio, TX]. In press Dec 2017.Google Scholar
- 52.Rizzo M, Linebarger J, Lowe MC, Pan L, Gabram SG, Vasquez L, et al. Management of papillary breast lesions diagnosed on core-needle biopsy: clinical pathologic and radiologic analysis of 276 cases with surgical follow-up. J Am Coll Surg. 2012;214:280–7. https://doi.org/10.1016/j.jamcollsurg.2011.12.005.CrossRefPubMedGoogle Scholar
- 53.Khan S, Diaz A, Archer KJ, Lehman RR, Mullins T, Cardenosa G, et al. Papillary lesions of the breast: to excise or observe? Breast J 2017 Aug 27 [Epub ahead of print]. doi: https://doi.org/10.1111/tbj.12907.
- 56.Pareja F, Corben AD, Brennan SB, Murray MP, Bowser ZL, Jakate K, et al. Breast intraductal papillomas without atypia in radiologic-pathologic concordant core-needle biopsies: rate of upgrade to carcinoma at excision. Cancer. 2016;122:2819–27. https://doi.org/10.1002/cncr.30118.CrossRefPubMedCentralPubMedGoogle Scholar
- 57.Nayak A, Carkaci S, Gilcrease MZ, Liu P, Middleton LP, Bassett RL Jr, et al. Benign papillomas without atypia diagnosed on core needle biopsy: experience from a single institution and proposed criteria for excision. Clin Breast Cancer. 2013;13:439–49. https://doi.org/10.1016/j.clbc.2013.08.007.CrossRefPubMedCentralPubMedGoogle Scholar
- 59.Boufelli G, Giannotti MA, Ruiz CA, Barros N, Chala LF, Maesaka JY, et al. Papillomas of the breast: factors associated with underestimation. Eur J Cancer Prev. 2017. doi: https://doi.org/10.1097/CEJ.0000000000000343.
- 63.Shamonki J, Chung A, Huynh KT, Sim MS, Kinnaird M, Giuliano A. Management of papillary lesions of the breast: can larger core needle biopsy samples identify patients who may avoid surgical excision? Ann Surg Oncol. 2013;20:4137–44. https://doi.org/10.1245/s10434-013-3191-3.CrossRefPubMedGoogle Scholar
- 67.Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver M, editors. WHO classification of tumours, volume 4. 4th ed. Lyon: IARC; 2012.Google Scholar
- 72.Khoumais NA, Scaranelo AM, Moshonov H, Kulkarni SR, Miller N, McCready DR, et al. Incidence of breast cancer in patients with pure flat epithelial atypia diagnosed at core-needle biopsy of the breast. Ann Surg Oncol. 2013;20:133–8. https://doi.org/10.1245/s10434-012-2591-0.CrossRefPubMedGoogle Scholar
- 73.Bianchi S, Bendinelli B, Castellano I, Piubello Q, Renne G, Cattani MG, et al. Morphological parameters of flat epithelial atypia (FEA) in stereotactic vacuum-assisted needle core biopsies do not predict the presence of malignancy on subsequent surgical excision. Virchows Arch. 2012;461:405–17. https://doi.org/10.1007/s00428-012-1279-y.CrossRefPubMedGoogle Scholar
- 77.Bevers T, Helvie M, Bonaccio E, Calhoun KE, Daly M, Farrar W, et al. NCCN breast cancer screening and diagnosis guidelines, version 1.2017: National Comprehensive Cancer Network; Available from: https://www.nccn.org/professionals/physician_gls/PDF/breast-screening.pdf.