Difference between revisions of "Paget's disease of the breast"

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#redirect [[Paget_disease_of_the_breast]]
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Extramammary_Paget_disease_-_high_mag.jpg
| Width      =
| Caption    = Paget's disease. [[H&E stain]].
| Synonyms  =
| Micro      = large epithelioid cells - nested or single - in the epidermis, clear/pale cytoplasm (occasionally eosinophilic), large nucleoli
| Subtypes  =
| LMDDx      = benign Toker cell hyperplasia, [[malignant melanoma]], [[Bowen's disease]], [[apocrine carcinoma of the skin]]
| Stains    =
| IHC        = CK7 +ve, CEA +ve, S-100 -ve, [[CK5/6]] -ve, HER2 +ve
| EM        =
| Molecular  =
| IF        =
| Gross      = erythema, +/-weeping, +/-crusted
| Grossing  =
| Site      = [[breast]]
| Assdx      =
| Syndromes  =
| Clinicalhx =
| Signs      =
| Symptoms  =
| Prevalence =
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = usu. associated with invasive breast carcinoma
| Other      =
| ClinDDx    = [[nipple adenoma]], contact dermatitis
| Tx        =
}}
'''[[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'''.<ref name=pmid19919588>{{Cite journal  | last1 = Ellis | first1 = PE. | last2 = Maclean | first2 = AB. | last3 = Crow | first3 = JC. | last4 = Wong Te Fong | first4 = LF. | last5 = Rolfe | first5 = KJ. | last6 = Perrett | first6 = CW. | title = Expression of cyclin D1 and retinoblastoma protein in Paget's disease of the vulva and breast: an immunohistochemical study of 108 cases. | journal = Histopathology | volume = 55 | issue = 6 | pages = 709-15 | month = Dec | year = 2009 | doi = 10.1111/j.1365-2559.2009.03434.x | PMID = 19919588 }}</ref>
 
There is also a ''[[Paget's disease of the bone]]'' - just to make things confusing.  This is dealt with in [[Paget's disease of the bone|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:
#Mammary Paget's disease - dealt with in this article.
#[[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 [[invasive breast cancer|breast carcinoma]].<ref name=emed_pagets>URL: [http://emedicine.medscape.com/article/1101235-diagnosis http://emedicine.medscape.com/article/1101235-diagnosis]</ref>
 
Note:
*[[Extramammary Paget's disease]] is '''not''' usually associated with malignancy.
 
==Gross==
Features:<ref>{{Ref APBR|294 & 306 Q15}}</ref>
*Erythematous, i.e. red.
*+/-Crusted.
*+/-Weeping (wet).
 
DDx - clinical:
*[[Contact dermatitis]].<ref>URL: [http://www.danderm-pdv.is.kkh.dk/atlas/2-38.html http://www.danderm-pdv.is.kkh.dk/atlas/2-38.html]. Accessed on: 30 May 2012.</ref><ref name=pmid19882019>{{Cite journal  | last1 = Feroze | first1 = K. | last2 = Manoj | first2 = J. | last3 = Venkitakrishnan | first3 = S. | title = Allergic contact dermatitis mimicking mammary paget's disease. | journal = Indian J Dermatol | volume = 53 | issue = 3 | pages = 154-5 | month =  | year = 2008 | doi = 10.4103/0019-5154.43210 | PMID = 19882019 }}</ref>
 
Images:
*[http://www.sciencephoto.com/media/252126/enlarge Paget disease of the breast (sciencephoto.com)].
*[http://img.medscape.com/pi/emed/ckb/dermatology/1048885-1101235-864.jpg Paget disease of breast (medscape.com)].<ref>URL: [http://www.gfmer.ch/selected_images_v2/search_result_list.php?offset=15&param1=Paget%20disease%20of%20breast&param2=and 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.</ref>
 
==Microscopic==
Features:<ref name=emed_pagets/>
*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.<ref name=Ref_APBR306-7>{{Ref APBR|306-7 Q15}}</ref>
 
===DDx===
*Benign Toker cell hyperplasia.
*[[Malignant melanoma]].
*[[Bowen disease]].
*[[Nipple adenoma|Nipple (duct) adenoma]] (clinical DDx).
*[[Apocrine carcinoma of the skin]].<ref>URL: [http://derm101.com/searchResults.aspx?searchStr=apocrine+carcinoma&rootTerm=apocrine+carcinoma&searchType=2&rootID=12687 http://derm101.com/searchResults.aspx?searchStr=apocrine+carcinoma&rootTerm=apocrine+carcinoma&searchType=2&rootID=12687]. Accessed on: 9 September 2011.</ref>
**Images: [http://commons.wikimedia.org/wiki/File:Apocrine_carcinoma_-_intermed_mag.jpg apocrine carcinoma - intermed. mag. (WC)], [http://commons.wikimedia.org/wiki/File:Apocrine_carcinoma_-_high_mag.jpg apocrine carcinoma - high mag. (WC)].
 
===Images===
<gallery>
Image:Extramammary_Paget_disease_-_low_mag.jpg | Paget disease - low mag. (WC/Nephron)
Image:Extramammary_Paget_disease_-_high_mag.jpg | Paget disease - high mag. (WC/Nephron)
Image:Breast PagetDisease HP SNP.jpg|thumb|Breast Paget Disease - high power - (SKB)
Image:Breast PagetsDisease InvasiveDuctalCarcinoma PA.JPG|thumb|Breast Paget Disease - underlying invasive carcinoma - medium power - (SKB)
Image:Breast PagetsDisease HP PA.JPG|thumb|Breast Paget Disease - high power - (SKB)
Image:Breast PagetsDisease PA.JPG|thumb|Breast Paget Disease - high power - (SKB)
Image:Breast PagetDisease LP SNP.jpg|thumb|Breast Paget Disease - medium power - (SKB)
</gallery>
www:
*[http://path.upmc.edu/cases/case331.html Paget disease of the breast - several good pictures (upmc.edu)].
*[http://www.webpathology.com/image.asp?case=303&n=3 Paget disease of the nipple (webpathology.com)].
 
==IHC==
Panel:<ref name=emed_pagets/>
*S-100 -ve, HMB-45 -ve (both typically +ve in melanoma).
*CK7 +ve. (???)
**Toker cells CK7 +ve.<ref name=pmid19601945>{{Cite journal  | last1 = Nofech-Mozes | first1 = S. | last2 = Hanna | first2 = W. | title = Toker cells revisited. | journal = Breast J | volume = 15 | issue = 4 | pages = 394-8 | month =  | year =  | doi = 10.1111/j.1524-4741.2009.00743.x | PMID = 19601945 }}</ref>
*CEA +ve (-ve in Bowen's disease, -ve in Toker cells).
 
Additional:
*HER2/neu - usually +ve.
*[[CK5/6]] -ve.<ref>RS. May 2010.</ref>
**Usu. +ve in squamous cell carcinoma.<ref name=pmid19170169>{{Cite journal  | last1 = Khayyata | first1 = S. | last2 = Yun | first2 = S. | last3 = Pasha | first3 = T. | last4 = Jian | first4 = B. | last5 = McGrath | first5 = C. | last6 = Yu | first6 = G. | last7 = Gupta | first7 = P. | last8 = Baloch | first8 = Z. | title = Value of P63 and CK5/6 in distinguishing squamous cell carcinoma from adenocarcinoma in lung fine-needle aspiration specimens. | journal = Diagn Cytopathol | volume = 37 | issue = 3 | pages = 178-83 | month = Mar | year = 2009 | doi = 10.1002/dc.20975 | PMID = 19170169 }}</ref>
 
===Tabular comparison===
IHC features of Paget disease and its DDx:<ref>URL: [http://www.histopathology-india.net/EPD.htm http://www.histopathology-india.net/EPD.htm]. Accessed on: 4 December 2011.</ref><ref name=pmid12189500>{{Cite journal  | last1 = Marucci | first1 = G. | last2 = Betts | first2 = CM. | last3 = Golouh | first3 = R. | last4 = Peterse | first4 = JL. | last5 = Foschini | first5 = MP. | last6 = Eusebi | first6 = V. | title = Toker cells are probably precursors of Paget cell carcinoma: a morphological and ultrastructural description. | journal = Virchows Arch | volume = 441 | issue = 2 | pages = 117-23 | month = Aug | year = 2002 | doi = 10.1007/s00428-001-0581-x | PMID = 12189500 }}</ref>
{| class="wikitable sortable"
!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<ref name=pmid12680957>{{Cite journal  | last1 = Willman | first1 = JH. | last2 = Golitz | first2 = LE. | last3 = Fitzpatrick | first3 = JE. | title = Clear cells of Toker in accessory nipples. | journal = J Cutan Pathol | volume = 30 | issue = 4 | pages = 256-60 | month = Apr | year = 2003 | doi =  | PMID = 12680957 }}</ref>
|CEA '''-ve'''<ref name=pmid18758638/>
|HER2 -ve<ref name=pmid19601945>{{Cite journal  | last1 = Nofech-Mozes | first1 = S. | last2 = Hanna | first2 = W. | title = Toker cells revisited. | journal = Breast J | volume = 15 | issue = 4 | pages = 394-8 | month =  | year =  | doi = 10.1111/j.1524-4741.2009.00743.x | PMID = 19601945 }}</ref>
|S100 -ve<ref name=pmid18758638>{{Cite journal  | last1 = Fernandez-Flores | first1 = A. | title = Toker cell related to the folliculo-sebaceous-apocrine unit: a study of horizontal sections of the nipple. | journal = Rom J Morphol Embryol | volume = 49 | issue = 3 | pages = 339-43 | month =  | year = 2008 | doi =  | PMID = 18758638 }}</ref>
|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====
{| class="wikitable sortable"
!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
|-
|}
 
==Sign out==
<pre>
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.
</pre>
 
==See also==
*[[Breast]].
*[[Invasive breast cancer]].
*[[Paget disease]].
*[[Extramammary Paget disease]].
 
==References==
{{Reflist|2}}
 
[[Category:Breast pathology]]
[[Category:Diagnosis]]

Latest revision as of 15:49, 23 February 2023

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!

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

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

Sign out

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.