Paget's disease of the breast

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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]

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

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!

General

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

Note:

Gross

Features:[3]

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

DDx - clinical:

Images:

Microscopic

Features:[2]

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

Note:

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

DDx

Images

  • Paget disease - low mag. (WC/Nephron)

  • Paget disease - high mag. (WC/Nephron)

  • Breast Paget Disease - high power - (SKB)

  • Breast Paget Disease - underlying invasive carcinoma - medium power - (SKB)

  • Breast Paget Disease - high power - (SKB)

  • Breast Paget Disease - high power - (SKB)

  • Breast Paget Disease - medium power - (SKB)

www:

IHC

Panel:[2]

  • 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).

Additional:

  • 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.

Comment:
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

References

  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: http://emedicine.medscape.com/article/1101235-diagnosis
  3. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 294 & 306 Q15. ISBN 978-1416025887.
  4. ↑ URL: http://www.danderm-pdv.is.kkh.dk/atlas/2-38.html. 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: http://www.gfmer.ch/selected_images_v2/search_result_list.php?offset=15&param1=Paget%20disease%20of%20breast&param2=and. 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: http://derm101.com/searchResults.aspx?searchStr=apocrine+carcinoma&rootTerm=apocrine+carcinoma&searchType=2&rootID=12687. 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: http://www.histopathology-india.net/EPD.htm. 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.
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