Paget's disease of the breast

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Paget's disease of the breast
Diagnosis in short

Paget's disease. H&E stain.

LM large epithelioid cells - nested or single - in the epidermis, clear/pale cytoplasm (occasionally eosinophilic), large nucleoli
LM DDx benign Toker cell hyperplasia, malignant melanoma, Bowen's disease, apocrine carcinoma of the skin
IHC CK7 +ve, CEA +ve, S-100 -ve, CK5/6 -ve, HER2 +ve
Gross erythema, +/-weeping, +/-crusted
Site breast

Prognosis usu. associated with invasive breast carcinoma
Clin. DDx nipple adenoma, contact dermatitis

Paget's disease of the breast, also Paget disease of the breast and Paget's disease of the nipple, is a lesion of the breast. It is abbreviated PDB.[1]

There is also a Paget's disease of the bone - just to make things confusing. This is dealt with in its own article and has nothing (from a pathologic perspective) to do with the Paget's disease discussed in this article; these two things just happened to be discovered by the same guy.

Non-bone Paget's disease is subdivided into:

  1. Mammary Paget's disease - dealt with in this article.
  2. Extramammary Paget's disease.

Histologically, i.e. under the microscope, the above are essentially identically; however, the associations (and prognosis) are quite different!


  • Cells in the epithelium, i.e. skin, that look like they don't belong.
  • Associated with underlying invasive breast carcinoma.[2]




  • Erythematous, i.e. red.
  • +/-Crusted.
  • +/-Weeping (wet).

DDx - clinical:




  • Epitheliod morphology (round/ovoid).
  • Cells nested or single.
  • Clear/pale cytoplasm key feature - may also be eosinophilic.
  • Large nucleoli.


  • The neoplastic cells of Paget's disease may contain melanin.[7]






  • S-100 -ve, HMB-45 -ve (both typically +ve in melanoma).
  • CK7 +ve. (???)
    • Toker cells CK7 +ve.[9]
  • CEA +ve (-ve in Bowen's disease, -ve in Toker cells).


  • HER2/neu - usually +ve.
  • CK5/6 -ve.[10]
    • Usu. +ve in squamous cell carcinoma.[11]

Tabular comparison

IHC features of Paget disease and its DDx:[12][13]

Entity CK5/6 CK7 CAM5.2 EMA CEA HER2 S100 HMB-45
Paget disease CK5/6 -ve CK7 +ve (?) CAM5.2 +ve EMA +ve CEA +ve HER2 +ve S100 -ve HMB-45 -ve
Bowen disease CK5/6 +ve CK7 -ve CAM5.2 -ve EMA -ve CEA -ve HER2 -ve (?) S100 -ve HMB-45 -ve
Toker cell hyperplasia CK5/6 ? CK7 +ve CAM5.2 ? EMA +ve/-ve[14] CEA -ve[15] HER2 -ve[9] S100 -ve[15] HMB-45 ?
Melanoma CK5/6 -ve CK7 -ve CAM5.2 -ve EMA -ve CEA -ve HER2 -ve S100 +ve HMB-45 +ve

Mini-table comparison

Entity CK7 CEA HER2
Paget disease CK7 +ve CEA +ve HER2 +ve
Toker cell hyperplasia CK7 +ve CEA -ve HER2 -ve
Bowen disease CK7 -ve CEA -ve HER2 -ve

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Right Nipple, Biopsy:
- Paget's disease.

The Paget-like cells stain as follows:
POSITIVE: CK7 (moderate, diffuse), HER2 (complete membranous, moderate/strong).
NEGATIVE: S-100, HMB-45, CK5, CEA-mono.

The morphologic and immunohistochemical findings are in keeping with Paget's disease of the breast.

The breast imaging findings are noted.

See also


  1. Ellis, PE.; Maclean, AB.; Crow, JC.; Wong Te Fong, LF.; Rolfe, KJ.; Perrett, CW. (Dec 2009). "Expression of cyclin D1 and retinoblastoma protein in Paget's disease of the vulva and breast: an immunohistochemical study of 108 cases.". Histopathology 55 (6): 709-15. doi:10.1111/j.1365-2559.2009.03434.x. PMID 19919588.
  2. 2.0 2.1 2.2 URL:
  3. Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 294 & 306 Q15. ISBN 978-1416025887.
  4. URL: Accessed on: 30 May 2012.
  5. Feroze, K.; Manoj, J.; Venkitakrishnan, S. (2008). "Allergic contact dermatitis mimicking mammary paget's disease.". Indian J Dermatol 53 (3): 154-5. doi:10.4103/0019-5154.43210. PMID 19882019.
  6. URL: Accessed on: 30 May 2012.
  7. Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 306-7 Q15. ISBN 978-1416025887.
  8. URL: Accessed on: 9 September 2011.
  9. 9.0 9.1 Nofech-Mozes, S.; Hanna, W.. "Toker cells revisited.". Breast J 15 (4): 394-8. doi:10.1111/j.1524-4741.2009.00743.x. PMID 19601945.
  10. RS. May 2010.
  11. Khayyata, S.; Yun, S.; Pasha, T.; Jian, B.; McGrath, C.; Yu, G.; Gupta, P.; Baloch, Z. (Mar 2009). "Value of P63 and CK5/6 in distinguishing squamous cell carcinoma from adenocarcinoma in lung fine-needle aspiration specimens.". Diagn Cytopathol 37 (3): 178-83. doi:10.1002/dc.20975. PMID 19170169.
  12. URL: Accessed on: 4 December 2011.
  13. Marucci, G.; Betts, CM.; Golouh, R.; Peterse, JL.; Foschini, MP.; Eusebi, V. (Aug 2002). "Toker cells are probably precursors of Paget cell carcinoma: a morphological and ultrastructural description.". Virchows Arch 441 (2): 117-23. doi:10.1007/s00428-001-0581-x. PMID 12189500.
  14. Willman, JH.; Golitz, LE.; Fitzpatrick, JE. (Apr 2003). "Clear cells of Toker in accessory nipples.". J Cutan Pathol 30 (4): 256-60. PMID 12680957.
  15. 15.0 15.1 Fernandez-Flores, A. (2008). "Toker cell related to the folliculo-sebaceous-apocrine unit: a study of horizontal sections of the nipple.". Rom J Morphol Embryol 49 (3): 339-43. PMID 18758638.