UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Paget disease of the breast

Authors
Michael S Sabel, MD
Donald L Weaver, MD
Section Editors
Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
Daniel F Hayes, MD
Lori J Pierce, MD
Deputy Editor
Wenliang Chen, MD, PhD

INTRODUCTION

In 1874, Sir James Paget described 15 women with chronic nipple ulceration who all went on to develop cancer of the involved breast within two years [1]. The ulceration was described as an eczema-like eruption on the nipple and areola with a copious clear yellowish exudate. Ultimately, this would become known as Paget disease of the breast (PDB) or mammary Paget disease. While Paget believed that the nipple changes were themselves benign, it was subsequently discovered that the characteristic cells within the epidermis of the nipple (Paget cells) were in fact malignant [2].

This topic review will discuss the clinical presentation, pathogenesis, pathology, diagnosis, and management of mammary Paget disease.

EPIDEMIOLOGY

PDB is much less common than other presentations of breast cancer, accounting for only 1 to 3 percent of new cases of female breast cancer that are diagnosed annually in the United States [3-7]. PDB can occur in men; however, this is an extremely rare finding. Although cases have been described in patients ranging in age from 26 to 88, the peak incidence is between 50 and 60 [8-11].

Histologic (subclinical) evidence of PDB may be more frequent. In a series of 3000 consecutive mastectomy specimens, the incidence of clinical Paget disease was 0.7 percent, but histologic evidence of the disease was present in 4.9 percent of the mastectomies [12].

At least some epidemiologic data suggest that the incidence of PDB is decreasing over time [13]. In a report of 1738 cases of PDB reported to the SEER database, the incidence of PDB decreased by 45 percent between 1988 and 2002, while the overall incidence of breast cancer increased over this same time period.

                    

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Sep 27 00:00:00 GMT 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Paget, J. On disease of the mammary areola preceding cancer of the mammary gland. St. Bartholomew's Hosp Rep 1874; 10:87.
  2. Thin, G. On the connection between disease of the nipple and areola and tumors of the breast. Trans Pathol Soc Lond 1881; 32:218.
  3. Ashikari R, Park K, Huvos AG, Urban JA. Paget's disease of the breast. Cancer 1970; 26:680.
  4. Dixon AR, Galea MH, Ellis IO, et al. Paget's disease of the nipple. Br J Surg 1991; 78:722.
  5. Nance FC, DeLoach DH, Welsh RA, Becker WF. Paget's disease of the breast. Ann Surg 1970; 171:864.
  6. Berg JW, Hutter RV. Breast cancer. Cancer 1995; 75:257.
  7. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61:212.
  8. Marshall JK, Griffith KA, Haffty BG, et al. Conservative management of Paget disease of the breast with radiotherapy: 10- and 15-year results. Cancer 2003; 97:2142.
  9. Chaudary MA, Millis RR, Lane EB, Miller NA. Paget's disease of the nipple: a ten year review including clinical, pathological, and immunohistochemical findings. Breast Cancer Res Treat 1986; 8:139.
  10. Kollmorgen DR, Varanasi JS, Edge SB, Carson WE 3rd. Paget's disease of the breast: a 33-year experience. J Am Coll Surg 1998; 187:171.
  11. Caliskan M, Gatti G, Sosnovskikh I, et al. Paget's disease of the breast: the experience of the European Institute of Oncology and review of the literature. Breast Cancer Res Treat 2008; 112:513.
  12. Lagios MD, Gates EA, Westdahl PR, et al. A guide to the frequency of nipple involvement in breast cancer. A study of 149 consecutive mastectomies using a serial subgross and correlated radiographic technique. Am J Surg 1979; 138:135.
  13. Chen CY, Sun LM, Anderson BO. Paget disease of the breast: changing patterns of incidence, clinical presentation, and treatment in the U.S. Cancer 2006; 107:1448.
  14. Franceschini G, Masetti R, D'Ugo D, et al. Synchronous bilateral Paget's disease of the nipple associated with bilateral breast carcinoma. Breast J 2005; 11:355.
  15. Ikeda DM, Helvie MA, Frank TS, et al. Paget disease of the nipple: radiologic-pathologic correlation. Radiology 1993; 189:89.
  16. Zakaria S, Pantvaidya G, Ghosh K, Degnim AC. Paget's disease of the breast: accuracy of preoperative assessment. Breast Cancer Res Treat 2007; 102:137.
  17. Vielh P, Validire P, Kheirallah S, et al. Paget's disease of the nipple without clinically and radiologically detectable breast tumor. Histochemical and immunohistochemical study of 44 cases. Pathol Res Pract 1993; 189:150.
  18. Lammie GA, Barnes DM, Millis RR, Gullick WJ. An immunohistochemical study of the presence of c-erbB-2 protein in Paget's disease of the nipple. Histopathology 1989; 15:505.
  19. Jamali FR, Ricci A Jr, Deckers PJ. Paget's disease of the nipple-areola complex. Surg Clin North Am 1996; 76:365.
  20. Miller L, Tyler W, Maroon M, Miller OF 3rd. Erosive adenomatosis of the nipple: a benign imitator of malignant breast disease. Cutis 1997; 59:91.
  21. Kobayashi TK, Ueda M, Nishino T, et al. Scrape cytology of pemphigus vulgaris of the nipple, a mimicker of Paget's disease. Diagn Cytopathol 1997; 16:156.
  22. Gupta RK, Simpson J, Dowle C. The role of cytology in the diagnosis of Paget's disease of the nipple. Pathology 1996; 28:248.
  23. Lucarotti ME, Dunn JM, Webb AJ. Scrape cytology in the diagnosis of Paget's disease of the breast. Cytopathology 1994; 5:301.
  24. Gillett CE, Bobrow LG, Millis RR. S100 protein in human mammary tissue--immunoreactivity in breast carcinoma, including Paget's disease of the nipple, and value as a marker of myoepithelial cells. J Pathol 1990; 160:19.
  25. Yao DX, Hoda SA, Chiu A, et al. Intraepidermal cytokeratin 7 immunoreactive cells in the non-neoplastic nipple may represent interepithelial extension of lactiferous duct cells. Histopathology 2002; 40:230.
  26. Lundquist K, Kohler S, Rouse RV. Intraepidermal cytokeratin 7 expression is not restricted to Paget cells but is also seen in Toker cells and Merkel cells. Am J Surg Pathol 1999; 23:212.
  27. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 2000; 13:962.
  28. van der Putte SC, Toonstra J, Hennipman A. Mammary Paget's disease confined to the areola and associated with multifocal Toker cell hyperplasia. Am J Dermatopathol 1995; 17:487.
  29. Kothari AS, Beechey-Newman N, Hamed H, et al. Paget disease of the nipple: a multifocal manifestation of higher-risk disease. Cancer 2002; 95:1.
  30. Zhao L, Yang X, Khan A, Kandil D. Diagnostic role of immunohistochemistry in the evaluation of breast pathology specimens. Arch Pathol Lab Med 2014; 138:16.
  31. Ceccherini AF, Evans AJ, Pinder SE, et al. Is ipsilateral mammography worthwhile in Paget's disease of the breast? Clin Radiol 1996; 51:35.
  32. Bijker N, Rutgers EJ, Duchateau L, et al. Breast-conserving therapy for Paget disease of the nipple: a prospective European Organization for Research and Treatment of Cancer study of 61 patients. Cancer 2001; 91:472.
  33. Yim JH, Wick MR, Philpott GW, et al. Underlying pathology in mammary Paget's disease. Ann Surg Oncol 1997; 4:287.
  34. Muttarak M, Siriya B, Kongmebhol P, et al. Paget's disease of the breast: clinical, imaging and pathologic findings: a review of 16 patients. Biomed Imaging Interv J 2011; 7:e16.
  35. Günhan-Bilgen I, Oktay A. Paget's disease of the breast: clinical, mammographic, sonographic and pathologic findings in 52 cases. Eur J Radiol 2006; 60:256.
  36. Kalima T, Sipponen J, Kivilaakso E, Sipponen P. Decreased prevalence of gallstones in gastric cancer. Am J Surg 1982; 144:531.
  37. Morrogh M, Morris EA, Liberman L, et al. MRI identifies otherwise occult disease in select patients with Paget disease of the nipple. J Am Coll Surg 2008; 206:316.
  38. Echevarria JJ, Lopez-Ruiz JA, Martin D, et al. Usefulness of MRI in detecting occult breast cancer associated with Paget's disease of the nipple-areolar complex. Br J Radiol 2004; 77:1036.
  39. Capobianco G, Spaliviero B, Dessole S, et al. Paget's disease of the nipple diagnosed by MRI. Arch Gynecol Obstet 2006; 274:316.
  40. Frei KA, Bonel HM, Pelte MF, et al. Paget disease of the breast: findings at magnetic resonance imaging and histopathologic correlation. Invest Radiol 2005; 40:363.
  41. Amano G, Yajima M, Moroboshi Y, et al. MRI accurately depicts underlying DCIS in a patient with Paget's disease of the breast without palpable mass and mammography findings. Jpn J Clin Oncol 2005; 35:149.
  42. Kim HS, Seok JH, Cha ES, et al. Significance of nipple enhancement of Paget's disease in contrast enhanced breast MRI. Arch Gynecol Obstet 2010; 282:157.
  43. Corsi F, Sartani A, Galli D, et al. Usefulness of Preoperative Diagnosis with Magnetic Resonance Imaging for Conservative Surgery in Paget's Disease of the Breast. Breast Care (Basel) 2010; 5:26.
  44. Fu W, Lobocki CA, Silberberg BK, et al. Molecular markers in Paget disease of the breast. J Surg Oncol 2001; 77:171.
  45. NEUBECKER RD, BRADSHAW RP. Mucin, melanin, and glycogen in Paget's disease of the breast. Am J Clin Pathol 1961; 36:49.
  46. Bussolati G, Pich A. Mammary and extramammary Paget's disease. An immunocytochemical study. Am J Pathol 1975; 80:117.
  47. Kirkham N, Berry N, Jones DB, Taylor-Papadimitriou J. Paget's disease of the nipple. Immunohistochemical localization of milk fat globule membrane antigens. Cancer 1985; 55:1510.
  48. Nadji M, Morales AR, Girtanner RE, et al. Paget's disease of the skin. A unifying concept of histogenesis. Cancer 1982; 50:2203.
  49. Vanstapel MJ, Gatter KC, De Wolf-Peeters C, et al. Immunohistochemical study of mammary and extra-mammary Paget's disease. Histopathology 1984; 8:1013.
  50. Meissner K, Rivière A, Haupt G, Löning T. Study of neu-protein expression in mammary Paget's disease with and without underlying breast carcinoma and in extramammary Paget's disease. Am J Pathol 1990; 137:1305.
  51. Anderson JM, Ariga R, Govil H, et al. Assessment of Her-2/Neu status by immunohistochemistry and fluorescence in situ hybridization in mammary Paget disease and underlying carcinoma. Appl Immunohistochem Mol Morphol 2003; 11:120.
  52. Schelfhout VR, Coene ED, Delaey B, et al. Pathogenesis of Paget's disease: epidermal heregulin-alpha, motility factor, and the HER receptor family. J Natl Cancer Inst 2000; 92:622.
  53. Sagebiel RW. Ultrastructural observations on epidermal cells in Paget's disease of the breast. Am J Pathol 1969; 57:49.
  54. Decaussin M, Laville M, Mathevet P, Frappart L. Paget's disease versus Toker cell hyperplasia in a supernumerary nipple. Virchows Arch 1998; 432:289.
  55. Sukumvanich P, Bentrem DJ, Cody HS 3rd, et al. The role of sentinel lymph node biopsy in Paget's disease of the breast. Ann Surg Oncol 2007; 14:1020.
  56. Paone JF, Baker RR. Pathogenesis and treatment of Paget's disease of the breast. Cancer 1981; 48:825.
  57. Fourquet A, Campana F, Vielh P, et al. Paget's disease of the nipple without detectable breast tumor: conservative management with radiation therapy. Int J Radiat Oncol Biol Phys 1987; 13:1463.
  58. Bulens P, Vanuytsel L, Rijnders A, van der Schueren E. Breast conserving treatment of Paget's disease. Radiother Oncol 1990; 17:305.
  59. Stockdale AD, Brierley JD, White WF, et al. Radiotherapy for Paget's disease of the nipple: a conservative alternative. Lancet 1989; 2:664.
  60. Rissanen PM, Holsti P. Paget's disease of the breast: the influence of the presence or absence of an underlying palpable tumor on the prognosis and on the choice of treatment. Oncology 1969; 23:209.
  61. Solin LJ, Kurtz J, Fourquet A, et al. Fifteen-year results of breast-conserving surgery and definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast. J Clin Oncol 1996; 14:754.
  62. Helme S, Harvey K, Agrawal A. Breast-conserving surgery in patients with Paget's disease. Br J Surg 2015; 102:1167.
  63. Kawase K, Dimaio DJ, Tucker SL, et al. Paget's disease of the breast: there is a role for breast-conserving therapy. Ann Surg Oncol 2005; 12:391.
  64. Singh A, Sutton RJ, Baker CB, Sacks NP. Is mastectomy overtreatment for Paget's disease of the nipple? Breast 1999; 8:191.
  65. Dalberg K, Hellborg H, Wärnberg F. Paget's disease of the nipple in a population based cohort. Breast Cancer Res Treat 2008; 111:313.
  66. Eusebio, RB, Deckers, PJ. Paget's disease of the nipple-areola complex: A plea for conservatism. Contemp Surg 1992; 40:13.
  67. Laronga C, Hasson D, Hoover S, et al. Paget's disease in the era of sentinel lymph node biopsy. Am J Surg 2006; 192:481.
  68. Lagios MD, Westdahl PR, Rose MR, Concannon S. Paget's disease of the nipple. Alternative management in cases without or with minimal extent of underlying breast carcinoma. Cancer 1984; 54:545.
  69. Polgár C, Orosz Z, Kovács T, Fodor J. Breast-conserving therapy for Paget disease of the nipple: a prospective European Organization for Research and Treatment of Cancer study of 61 patients. Cancer 2002; 94:1904.