In this article, the probability of finding malignancy on surgical excision after applying well-defined morphological criteria combined with immunohistochemical evaluation of cytokeratin 5/6 for the diagnosis of atypical ductal hyperplasia on core biopsies is examined. On the basis of morphology alone, the reviewers reclassified the diagnoses of 140 core biopsies as follows: atypical ductal hyperplasia (n = 64), ductal hyperplasia of usual type (n = 44), flat epithelial atypia (n = 11), and miscellaneous benign (n = 21). Cytokeratin 5/6 immunostain was negative in 85.7% of atypical ductal hyperplasia cases and positive in 77.8% of ductal hyperplasia of usual type cases. The probability of predicting malignancy in a surgical specimen following a core biopsy increased from 43.6% to 67.8% (P = .002) by adhering to defined criteria and using cytokeratin 5/6 immunostain. Expertise and adherence to defined criteria are required to establish an accurate diagnosis of atypical ductal hyperplasia. Cytokeratin 5/6 can be a useful adjunct in cases with ductal hyperplasia but not in columnar cell lesions, where it is universally negative.
Page DL, Dupont WDBenign breast disease: indicators of increased breast cancer risk. Cancer Detect Prev. 1992;16:93-97.
2.
Hartmann LC, Sellers TA, Frost MH, et al. Benign breast disease and the risk of breast cancer. N Engl J Med. 2005;353:229-237.
3.
Dupont WD, Page DLRisk factors for breast cancer in women with proliferative breast disease . N Engl J Med. 1985;312:146-151.
4.
London SJ, Connolly JL, Schnitt SJ, Colditz GAA prospective study of benign breast disease and the risk of breast cancer . JAMA. 1992;267:941-944.
5.
Santen RJ, Mansel R.Benign breast disorders. N Engl J Med. 2005 ;353:275-285.
6.
Liberman L., Dershaw DD, Glassman JR, et al. Analysis of cancers not diagnosed at stereotactic core breast biopsy. Radiology. 1997;203:151-157.
7.
Brown TA, Wall JW, Christensen ED, et al. Atypical hyperplasia in the era of stereotactic core needle biopsy. J Surg Oncol. 1998;67:168-173.
8.
Lin PH, Clyde JC, Bates DM, Garcia JM, Matsumoto GH, Girvin GWAccuracy of stereotactic core-needle breast biopsy in atypical ductal hyperplasia . Am J Surg. 1998;175:380-382.
9.
Brem RF, Behrndt VS, Sanow L., Gatewood OMAtypical ductal hyperplasia: histologic underestimation of carcinoma in tissue harvested from impalpable breast lesions using 11-gauge stereotactically guided directional vacuum-assisted biopsy. AJR Am J Roentgenol. 1999;172: 1405-1407.
10.
Bassett L., Winchester DP, Caplan RB, et al. Stereotactic core-needle biopsy of the breast: a report of the Joint Task Force of the American College of Radiology, American College of Surgeons, and College of American Pathologists. CA Cancer J Clin. 1997;47:171-190.
11.
Jackman RJ, Nowels KW, Shepard MJ, Finkelstein SI, Marzoni FA Jr.Stereotaxic large-core needle biopsy of 450 nonpalpable breast lesions with surgical correlation in lesions with cancer or atypical hyperplasia. Radiology. 1994;193:91-95.
12.
Liberman L., Cohen MA, Dershaw DD, Abramson AF, Hann LE, Rosen PPAtypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy. AJR Am J Roentgenol . 1995;164:1111-1113.
13.
Moore MM, Hargett CW III, Hanks JB,et al. Association of breast cancer with the finding of atypical ductal hyperplasia at core breast biopsy. Ann Surg. 1997;225:726-731.
14.
Schnitt SJ, Connolly JL, Tavassoli FA, et al. Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria. Am J Surg Pathol . 1992;16:1133-1143.
15.
van de Vijver MJ, Peterse H.The diagnosis and management of pre-invasive breast disease: pathological diagnosis- problems with existing classifications . Breast Cancer Res. 2003;5:269-275.
16.
Boecker W., Buerger H., Schmitz K., et al. Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high-molecular-weight cytokeratin expression patterns. J Pathol. 2001;195: 415-421.
17.
Boecker W., Moll R., Dervan P., et al. Usual ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal hyperplasia and ductal carcinoma in situ. J Pathol. 2002;198:458-467.
18.
Otterbach F. , Bankfalvi A., Bergner S., Decker T., Krech R., Boecker W.Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast. Histopathology. 2000;37:232-240.
19.
Going JJStages on the way to breast cancer. J Pathol. 2003;199:1-3.
20.
Lerwill MFCurrent practical applications of diagnostic immunohistochemistry in breast pathology. Am J Surg Pathol. 2004;28:1076-1091.
21.
Tavassoli FA, Devilee P.Tumours of the breast. In: Tavassoli FA, Devilee P, eds. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France: IARC Press; 2003: 64-68.
22.
Ellis IO, Humphreys S., Michell M., Pinder SE, Wells CA, Zakhour HDBest Practice No 179. Guidelines for breast needle core biopsy handling and reporting in breast screening assessment. J Clin Pathol. 2004;57: 897-902.
23.
MacGrogan G. , Arnould L., Mathoulin S., et al. CK 5/6 and E-cadherin and diagnostic agreement in proliferative breast lesions. Mod Pathol. 2005;18:41A.
24.
Douglas-Jones A., Shah V., Morgan J., Dallimore N., Rashid M.Observer variability in the histopathological reporting of core biopsies of papillary breast lesions is reduced by the use of immunohistochemistry for CK5/6, calponin and p63. Histopathology . 2005;47:202-208.
25.
Tan PH, Aw MY, Yip G., Bay BH, Sii LH, Murugaya S., Tse GMCytokeratins in papillary lesions of the breast: is there a role in distinguishing intraductal papilloma from papillary ductal carcinoma in situ? Am J Surg Pathol. 2005;29:625-632.
26.
Carlo VP, Fraser J., Pliss N., et al. Can absence of high molecular weight cytokeratin expression be used tas a marker of atypia in columnar cell lesions of the breast?Mod Pathol. 2003;16:24A.
27.
Simpson PT, Gale T., Reis-Filho JS, et al. Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis. Am J Surg Pathol. 2005;29:734-746.
28.
Lacroix-Triki M., Mery E., Voigt JJ, Istier L., Rochaix P.Value of cytokeratin 5/6 immunostaining using D5/16 B4 antibody in the spectrum of proliferative intraepithelial lesions of the breast. A comparative study with 34betaE12 antibody. Virchows Arch. 2003;442:548-554.
29.
Page DL, Simpson JF, Jensen RA, Carter BAAtypical ductal hyperplasia on core biopsy. Pathol Case Rev . 2003;8:245-248.
30.
National Comprehensive Cancer Network.Breast cancer screening and diagnosis. NCCN Practice Guidelines in Oncology. 2005;1:1-38.
