The role of immunohistochemistry in the differential diagnosis of papillary lesions of the breast

Papillary lesions of the breast represent a heterogeneous group with differing biological behaviour. Correct diagnosis is crucial but may be difficult, as many benign and malignant papillary lesions have similar appearances. Immunohistochemistry plays a useful role in their differentiation. Myoepithelial markers can help in differentiating papilloma from papillary carcinoma, as the former usually shows a continuous layer of myoepithelial cells. In intracystic papillary carcinoma, there is controversy as to the presence of a complete myoepithelial cell layer around these lesions. p63 is the marker of choice as the staining is nuclear, cross-reactivity is minimal, and sensitivity is high. Papilloma may frequently be complicated by superimposed different types of epithelial hyperplasia, which range from usual to atypical or even ductal carcinoma in situ, and they many be morphologically similar. Basal cytokeratins (CKs) are useful to differentiate these entities; as usual hyperplasia is positive for basal CKs with a mosaic staining pattern. CK5/6 is probably the best marker. Neuroendocrine markers (chromogranin A and synaptophysin) may be positive in papillary carcinoma, particularly in the solid type, and there may be some overlap with the ductal carcinoma in situ with spindle cells or endocrine ductal carcinoma in situ. A panel of CK5/6, p63 and neuroendocrine markers can be useful in the diagnostic investigation of problematic papillary lesions of the breast. As the experience with these markers remains rather limited, it is too early to recommend basing treatment choices on these marker studies alone. Complete removal of lesion is probably still the treatment of choice.

[1]  W. Wood,et al.  Surgical Follow-Up and Clinical Presentation of 142 Breast Papillary Lesions Diagnosed by Ultrasound-Guided Core-Needle Biopsy , 2008, Annals of Surgical Oncology.

[2]  L. Collins,et al.  Papillary lesions of the breast: selected diagnostic and management issues , 2007, Histopathology.

[3]  Yun Wu,et al.  Loss of myoepithelium is variable in solid papillary carcinoma of the breast , 2007, Histopathology.

[4]  H. Zaren,et al.  Papillary lesions of the breast discovered on percutaneous large core and vacuum-assisted biopsies: reliability of clinical and pathological parameters in identifying benign lesions. , 2007, American journal of surgery.

[5]  Masayuki Yoshida,et al.  Solid–papillary carcinoma of the breast: Clinicopathological study of 20 cases , 2007, Pathology international.

[6]  S. Krishnamurthy.  Solid Papillary Ductal Carcinoma In Situ Versus Usual Ductal Hyperplasia in the Breast: A Potentially Difficult Distinction Resolved by Cytokeratin 5/6 , 2007 .

[7]  S. Ichihara,et al.  Myoepithelial cells in solid variant of intraductal papillary carcinoma of the breast: a potential diagnostic pitfall and a proposal of an immunohistochemical panel in the differential diagnosis with intraductal papilloma with usual ductal hyperplasia , 2007, Virchows Archiv.

[8]  S. Ichihara,et al.  Double immunostaining with p63 and high‐molecular‐weight cytokeratins distinguishes borderline papillary lesions of the breast , 2007, Pathology international.

[9]  A. Mulligan,et al.  Papillary Lesions of the Breast: A Review , 2007, Advances in anatomic pathology.

[10]  A. Gown,et al.  Intracystic Papillary Carcinomas of the Breast: A Reevaluation Using a Panel of Myoepithelial Cell Markers , 2006, The American journal of surgical pathology.

[11]  J. Rabban,et al.  Solid papillary ductal carcinoma in situ versus usual ductal hyperplasia in the breast: a potentially difficult distinction resolved by cytokeratin 5/6. , 2006, Human pathology.

[12]  P. Tan,et al.  The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast , 2006, Journal of Clinical Pathology.

[13]  N. Dallimore,et al.  Immunohistochemistry increases the accuracy of diagnosis of benign papillary lesions in breast core needle biopsy specimens , 2006, Histopathology.

[14]  D. Visscher,et al.  Clinicopathologic Analysis of Solid Papillary Carcinoma of the Breast and Associated Invasive Carcinomas , 2006, The American journal of surgical pathology.

[15]  P. Tartter,et al.  Significance of Papillary Lesions at Percutaneous Breast Biopsy , 2006, Annals of Surgical Oncology.

[16]  N. Dallimore,et al.  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 , 2005, Histopathology.

[17]  P. Tan,et al.  Cytokeratins in Papillary Lesions of the Breast: Is There a Role in Distinguishing Intraductal Papilloma From Papillary Ductal Carcinoma In Situ? , 2005, The American journal of surgical pathology.

[18]  P. Tan,et al.  Ductal carcinoma in situ with spindle cells: a potential diagnostic pitfall in the evaluation of breast lesions , 2004, Histopathology.

[19]  M. Lacroix-Triki,et al.  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 34βE12 antibody , 2003, Virchows Archiv.

[20]  Horst Buerger,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 , 2002, The Journal of pathology.

[21]  P. V. van Diest,et al.  Ductal epithelial proliferations of the breast: a biological continuum? Comparative genomic hybridization and high‐molecular‐weight cytokeratin expression patterns , 2001, The Journal of pathology.

[22]  G. Farshid,et al.  Spindle cell ductal carcinoma in situ , 2001, Virchows Archiv.

[23]  A. Bankfalvi,et al.  Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast , 2000, Histopathology.

[24]  M. Vasei,et al.  Papillary Carcinoma of the Breast , 1999, Acta Cytologica.

[25]  R. Moll,et al.  Biological and prognostic significance of stratified epithelial cytokeratins in infiltrating ductal breast carcinomas , 1998, Virchows Archiv.

[26]  J. Chan,et al.  Endocrine ductal carcinoma in situ (E-DCIS) of the breast: a form of low-grade DCIS with distinctive clinicopathologic and biologic characteristics. , 1996, The American journal of surgical pathology.

[27]  W. Böcker,et al.  An immunohistochemical study of the breast using antibodies to basal and luminal keratins, alpha-smooth muscle actin, vimentin, collagen IV and laminin , 1992, Virchows Archiv A.

[28]  S. Morii,et al.  Keratin expression in the normal breast and in breast carcinoma , 1991, Histopathology.

[29]  R. Zarbo,et al.  Epitheliosis of the Breast An Immunohistochemical Characterization and Comparison to Malignant Intraductal Proliferations of the Breast , 1990, The American journal of surgical pathology.

[30]  R. Nagle,et al.  Characterization of breast carcinomas by two monoclonal antibodies distinguishing myoepithelial from luminal epithelial cells. , 1986, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[31]  F. Kraus,et al.  The differential diagnosis of papillary tumors of the breast , 1962, Cancer.

[32]  T. Hijaz,et al.  Underestimation of the presence of breast carcinoma in papillary lesions initially diagnosed at core-needle biopsy. , 2007, Radiology.

[33]  W. Böcker,et al.  An immunohistochemical study of the breast using antibodies to basal and luminal keratins, alpha-smooth muscle actin, vimentin, collagen IV and laminin , 2005, Virchows Archiv A.

[34]  J. Reichelt,et al.  Keratins: a structural scaffold with emerging functions , 2003, Cellular and Molecular Life Sciences CMLS.

[35]  G. Farshid,et al.  Spindle cell ductal carcinoma in situ. An unusual variant of ductal intra-epithelial neoplasia that simulates ductal hyperplasia or a myoepithelial proliferation. , 2001, Virchows Archiv : an international journal of pathology.

[36]  D. Cosgrove.  The breast , 1999, European Radiology.

[37]  E. Lane,et al.  Basal cell-specific and hyperproliferation-related keratins in human breast cancer. , 1991, The American journal of pathology.