Difference between revisions of "Invasive breast cancer"

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Invasive breast cancer (view source)

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→‎Invasive versus non-invasive: added information from recent study on microinvasion
(→‎Invasive versus non-invasive: added information from recent study on microinvasion)
 
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[[Image:Breast_cancer.JPG|thumb|300px|Breast cancer at [[cut-up]]. (WC/John Hayman)]]
The article deals with '''invasive [[breast]] cancer''' and the evaluation of hormone receptor & HER2 status.  Non-invasive breast cancer is dealt with in ''[[non-invasive breast cancer]]''.
The article deals with '''invasive [[breast]] cancer''' and the evaluation of hormone receptor & HER2 status.  Non-invasive breast cancer is dealt with in ''[[non-invasive breast cancer]]''.


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*[[Invasive ductal carcinoma of the breast|Invasive ductal carinoma]], not otherwise specified.
*[[Invasive ductal carcinoma of the breast|Invasive ductal carinoma]], not otherwise specified.
*[[Invasive lobular carcinoma]].
*[[Invasive lobular carcinoma]].
*Invasive cribriform carcinoma.
*[[Invasive cribriform carcinoma of the breast|Invasive cribriform carcinoma]].
*[[Invasive papillary carcinoma of the breast|Invasive papillary carcinoma]].
*[[Invasive papillary carcinoma of the breast|Invasive papillary carcinoma]].
*[[Invasive micropapillary carcinoma of the breast|Invasive micropapillary carcinoma]].
*[[Invasive micropapillary carcinoma of the breast|Invasive micropapillary carcinoma]].
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Epithelial tumours seen in the [[salivary gland]]:
Epithelial tumours seen in the [[salivary gland]]:
*[[Adenoid cystic carcinoma]].
*[[Adenoid cystic carcinoma of the breast]].
*[[Acinic cell carcinoma]].
*[[Acinic cell carcinoma]].
*[[Carcinoma ex pleomorphic adenoma]].
*[[Carcinoma ex pleomorphic adenoma]].
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Papillary:
Papillary:
*[[Intraductal papilloma|Papilloma]].
*[[Intraductal papilloma of the breast|Papilloma]].
*Atypical papilloma.
*Atypical papilloma.
*Intraductal papillary carcinoma.
*Intraductal papillary carcinoma.
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|}
|}


The above is not applied clinically. A panel of [[immunostains]] (ER, PR, HER2, EGFR, CK5/6) can reproduce the molecular groupings; however, these groupings originate from gene expression profiling studies<ref name=pmid19704256>{{Cite journal  | last1 = Tang | first1 = P. | last2 = Skinner | first2 = KA. | last3 = Hicks | first3 = DG. | title = Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? | journal = Diagn Mol Pathol | volume = 18 | issue = 3 | pages = 125-32 | month = Sep | year = 2009 | doi = 10.1097/PDM.0b013e31818d107b | PMID = 19704256 }}</ref>
The above is not applied clinically. A panel of [[immunostains]] ([[ER]], PR, HER2, EGFR, [[CK5/6]]) can reproduce the molecular groupings; however, these groupings originate from gene expression profiling studies<ref name=pmid19704256>{{Cite journal  | last1 = Tang | first1 = P. | last2 = Skinner | first2 = KA. | last3 = Hicks | first3 = DG. | title = Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? | journal = Diagn Mol Pathol | volume = 18 | issue = 3 | pages = 125-32 | month = Sep | year = 2009 | doi = 10.1097/PDM.0b013e31818d107b | PMID = 19704256 }}</ref>


A newer classification outlines 10 subtypes based on molecular drivers identified by analysis of genomic and transcriptomic data from 2,000 breast tumors.<ref>{{Cite journal  | last1 = Curtis | first1 = C. | last2 = Shah | first2 = SP. | last3 = Chin | first3 = SF. | last4 = Turashvili | first4 = G. | last5 = Rueda | first5 = OM. | last6 = Dunning | first6 = MJ. | last7 = Speed | first7 = D. | last8 = Lynch | first8 = AG. | last9 = Samarajiwa | first9 = S. | title = The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. | journal = Nature | volume = 486 | issue = 7403 | pages = 346-52 | month = Jun | year = 2012 | doi = 10.1038/nature10983 | PMID = 22522925 }}</ref>
A newer classification outlines 10 subtypes based on molecular drivers identified by analysis of genomic and transcriptomic data from 2,000 breast tumors.<ref>{{Cite journal  | last1 = Curtis | first1 = C. | last2 = Shah | first2 = SP. | last3 = Chin | first3 = SF. | last4 = Turashvili | first4 = G. | last5 = Rueda | first5 = OM. | last6 = Dunning | first6 = MJ. | last7 = Speed | first7 = D. | last8 = Lynch | first8 = AG. | last9 = Samarajiwa | first9 = S. | title = The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. | journal = Nature | volume = 486 | issue = 7403 | pages = 346-52 | month = Jun | year = 2012 | doi = 10.1038/nature10983 | PMID = 22522925 }}</ref>


== Basal-like breast carcinoma==
== Basal-like breast carcinoma==
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| stains myofibroblasts & blood vessels
| stains myofibroblasts & blood vessels
|}
|}
Respecting findings that might indicate a more extensive search for microinvasion be undertaken in cases of pure ductal carcinoma in situ (DCIS), a recent study found 1) intermediate or high DCIS grade, 2) tumor thickness, and 3) diffuse peritumoral retraction clefts, but not such things as lymph node metastases, or HER2 score, independently increased the likelihood of finding a microinvasive component. <ref name=pmid28434924>{{cite journal |author=Mori K, Takeda M, Kodama Y, Kiyokawa H, Yasojima H, Mizutani M, Otani Y, Morikawa N, Masuda N, Mano M|title= Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ |journal=Human Pathology |volume=64 |issue= |pages=145-155 |year=2017 | pmid=28434924 |doi=10.1016/j.humpath.2017.04.004 }}</ref>


===Usual ductal hyperplasia versus ductal carcinoma in situ===
===Usual ductal hyperplasia versus ductal carcinoma in situ===
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{| class="wikitable sortable"  
{| class="wikitable sortable"  
!Disease  
!Disease  
!CK5/6
![[CK5/6]]
!ER
![[ER]]
|-
|-
|UDH
|UDH
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*CD31 - marks lymphovascular spaces.
*CD31 - marks lymphovascular spaces.
*CD34 - marks lymphovascular spaces, less specific than CD31.
*CD34 - marks lymphovascular spaces, less specific than CD31.
===Lymph node metastases===
Immunostaining of sentinel lymph nodes to look for [[isolated tumour cells]] and small [[lymph node metastases]] may be done.
*CAM5.2 may be used.
*'''Not''' done routinely.


==Treatment-related markers - overview==
==Treatment-related markers - overview==
*Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
**Sunnybrook uses ''CAM5.2''.
*ER (estrogen receptor).
*ER (estrogen receptor).
**Positive in most breast cancers; +ve in ~75-80%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
**Positive in most breast cancers; +ve in ~75-80%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
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**In the context of HER2 positivity, PTEN/PI3K/Akt/mTOR pathway dysregulation is a poor prognosticator.<ref name=pmid22454081>{{Cite journal  | last1 = Gallardo | first1 = A. | last2 = Lerma | first2 = E. | last3 = Escuin | first3 = D. | last4 = Tibau | first4 = A. | last5 = Muñoz | first5 = J. | last6 = Ojeda | first6 = B. | last7 = Barnadas | first7 = A. | last8 = Adrover | first8 = E. | last9 = Sánchez-Tejada | first9 = L. | title = Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. | journal = Br J Cancer | volume = 106 | issue = 8 | pages = 1367-73 | month = Apr | year = 2012 | doi = 10.1038/bjc.2012.85 | PMID = 22454081 }}</ref><ref name=pmid22172323>{{Cite journal  | last1 = Jensen | first1 = JD. | last2 = Knoop | first2 = A. | last3 = Laenkholm | first3 = AV. | last4 = Grauslund | first4 = M. | last5 = Jensen | first5 = MB. | last6 = Santoni-Rugiu | first6 = E. | last7 = Andersson | first7 = M. | last8 = Ewertz | first8 = M. | title = PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. | journal = Ann Oncol | volume =  | issue =  | pages =  | month = Dec | year = 2011 | doi = 10.1093/annonc/mdr546 | PMID = 22172323 }}</ref>  
**In the context of HER2 positivity, PTEN/PI3K/Akt/mTOR pathway dysregulation is a poor prognosticator.<ref name=pmid22454081>{{Cite journal  | last1 = Gallardo | first1 = A. | last2 = Lerma | first2 = E. | last3 = Escuin | first3 = D. | last4 = Tibau | first4 = A. | last5 = Muñoz | first5 = J. | last6 = Ojeda | first6 = B. | last7 = Barnadas | first7 = A. | last8 = Adrover | first8 = E. | last9 = Sánchez-Tejada | first9 = L. | title = Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. | journal = Br J Cancer | volume = 106 | issue = 8 | pages = 1367-73 | month = Apr | year = 2012 | doi = 10.1038/bjc.2012.85 | PMID = 22454081 }}</ref><ref name=pmid22172323>{{Cite journal  | last1 = Jensen | first1 = JD. | last2 = Knoop | first2 = A. | last3 = Laenkholm | first3 = AV. | last4 = Grauslund | first4 = M. | last5 = Jensen | first5 = MB. | last6 = Santoni-Rugiu | first6 = E. | last7 = Andersson | first7 = M. | last8 = Ewertz | first8 = M. | title = PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. | journal = Ann Oncol | volume =  | issue =  | pages =  | month = Dec | year = 2011 | doi = 10.1093/annonc/mdr546 | PMID = 22172323 }}</ref>  


Note:
Notes:
*Male breast cancer is usually hormone receptor positive (~97%), and HER2 positivity is quite rare (~6%).<ref name=pmid24080492>{{Cite journal  | last1 = Schildhaus | first1 = HU. | last2 = Schroeder | first2 = L. | last3 = Merkelbach-Bruse | first3 = S. | last4 = Binot | first4 = E. | last5 = Büttner | first5 = R. | last6 = Kuhn | first6 = W. | last7 = Rudlowski | first7 = C. | title = Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes. | journal = Breast | volume =  | issue =  | pages =  | month = Sep | year = 2013 | doi = 10.1016/j.breast.2013.08.008 | PMID = 24080492 }}</ref>  
*Male breast cancer is usually hormone receptor positive (~97%), and HER2 positivity is quite rare (~6%).<ref name=pmid24080492>{{Cite journal  | last1 = Schildhaus | first1 = HU. | last2 = Schroeder | first2 = L. | last3 = Merkelbach-Bruse | first3 = S. | last4 = Binot | first4 = E. | last5 = Büttner | first5 = R. | last6 = Kuhn | first6 = W. | last7 = Rudlowski | first7 = C. | title = Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes. | journal = Breast | volume =  | issue =  | pages =  | month = Sep | year = 2013 | doi = 10.1016/j.breast.2013.08.008 | PMID = 24080492 }}</ref>  
*ASCO/CAP guidelines recommend that cold ischemia time be <1 hour.<ref name=pmid22460807 >{{Cite journal  | last1 = Yildiz-Aktas | first1 = IZ. | last2 = Dabbs | first2 = DJ. | last3 = Bhargava | first3 = R. | title = The effect of cold ischemic time on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and HER2 expression in invasive breast carcinoma. | journal = Mod Pathol | volume = 25 | issue = 8 | pages = 1098-105 | month = Aug | year = 2012 | doi = 10.1038/modpathol.2012.59 | PMID = 22460807 }}</ref>
===ER & PR scoring===
===ER & PR scoring===
Nuclear staining:<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
Nuclear staining:<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
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==Invasive micropapillary carcinoma of the breast==
==Invasive micropapillary carcinoma of the breast==
*[[AKA]] ''micropapillary carcinoma''.
*[[AKA]] ''micropapillary carcinoma''.
===General===
{{Main|Invasive micropapillary carcinoma of the breast}}
*Poor prognosis.
*LVI common.<ref name=pmid20304650>{{Cite journal  | last1 = Yu | first1 = JI. | last2 = Choi | first2 = DH. | last3 = Park | first3 = W. | last4 = Huh | first4 = SJ. | last5 = Cho | first5 = EY. | last6 = Lim | first6 = YH. | last7 = Ahn | first7 = JS. | last8 = Yang | first8 = JH. | last9 = Nam | first9 = SJ. | title = Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: matched case-control study. | journal = Breast | volume = 19 | issue = 3 | pages = 231-7 | month = Jun | year = 2010 | doi = 10.1016/j.breast.2010.01.020 | PMID = 20304650 }}</ref>
 
===Microscopic===
Features:
*Clear spaces/clefting around (small) nests of tumour - '''diffuse/through-out the tumour''' - '''key feature'''.
**Described as "small clusters of tumour lying within dilated vascular channel-like spaces".<ref name=pmid20444748>{{Cite journal  | last1 = Yamaguchi | first1 = R. | last2 = Tanaka | first2 = M. | last3 = Kondo | first3 = K. | last4 = Yokoyama | first4 = T. | last5 = Kaneko | first5 = Y. | last6 = Yamaguchi | first6 = M. | last7 = Ogata | first7 = Y. | last8 = Nakashima | first8 = O. | last9 = Kage | first9 = M. | title = Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis. | journal = Jpn J Clin Oncol | volume = 40 | issue = 8 | pages = 781-7 | month = Aug | year = 2010 | doi = 10.1093/jjco/hyq056 | PMID = 20444748 | URL = http://jjco.oxfordjournals.org/content/40/8/781.long }}</ref>
 
Note:
*[[Invasive ductal carcinoma of the breast|Ductal carcinoma]] commonly has clefting... but it isn't diffuse.
 
Images:
*[http://www.flickr.com/photos/euthman/5300126397/ Invasive micropapillary carcinoma (flickr.com/euthman)].
*[http://www.breast-cancer.ca/images/invasive-micropapillary-breast-carcinoma-cells1.jpg Invasive micropapillary carcinoma - crappy image (breast-cancer.ca)].<ref>URL: [http://www.breast-cancer.ca/type/micropapillary-breast-carcinoma.htm http://www.breast-cancer.ca/type/micropapillary-breast-carcinoma.htm]. Accessed on: 30 May 2012.</ref>
 
===IHC===
*[[EMA]] +ve (periphery of nests); described as inside-out pattern.<ref name=pmid20444748>{{Cite journal  | last1 = Yamaguchi | first1 = R. | last2 = Tanaka | first2 = M. | last3 = Kondo | first3 = K. | last4 = Yokoyama | first4 = T. | last5 = Kaneko | first5 = Y. | last6 = Yamaguchi | first6 = M. | last7 = Ogata | first7 = Y. | last8 = Nakashima | first8 = O. | last9 = Kage | first9 = M. | title = Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis. | journal = Jpn J Clin Oncol | volume = 40 | issue = 8 | pages = 781-7 | month = Aug | year = 2010 | doi = 10.1093/jjco/hyq056 | PMID = 20444748 | URL = http://jjco.oxfordjournals.org/content/40/8/781.long }}</ref>
*E-cadherin +ve (centre of nests). (???)
*p63 +ve/-ve.


==Apocrine carcinoma of the breast==
==Apocrine carcinoma of the breast==
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==Adenoid cystic carcinoma of the breast==
==Adenoid cystic carcinoma of the breast==
*[[AKA]] ''breast adenoid cystic carcinoma''.
*[[AKA]] ''breast adenoid cystic carcinoma''.
===General===
{{Main|Adenoid cystic carcinoma of the breast}}
*Like tumour of the [[salivary gland]].
*Very rare <0.1% of breast malignancies.<ref name=pmid22154460/>
*Good prognosis.<ref name=pmid22154460>{{Cite journal  | last1 = Boujelbene | first1 = N. | last2 = Khabir | first2 = A. | last3 = Boujelbene | first3 = N. | last4 = Jeanneret Sozzi | first4 = W. | last5 = Mirimanoff | first5 = RO. | last6 = Khanfir | first6 = K. | title = Clinical review - Breast adenoid cystic carcinoma. | journal = Breast | volume =  | issue =  | pages =  | month = Dec | year = 2011 | doi = 10.1016/j.breast.2011.11.006 | PMID = 22154460 }}</ref>
 
===Microscopic===
:See: ''[[Adenoid cystic carcinoma]]'' article.
 
===IHC===
*One of the 'good prognosis' triple negative breast cancers - ER, PR and HER2 negative<ref>{{Cite journal  | last1 = Azoulay | first1 = S. | last2 = Laé | first2 = M. | last3 = Fréneaux | first3 = P. | last4 = Merle | first4 = S. | last5 = Al Ghuzlan | first5 = A. | last6 = Chnecker | first6 = C. | last7 = Rosty | first7 = C. | last8 = Klijanienko | first8 = J. | last9 = Sigal-Zafrani | first9 = B. | title = KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome. | journal = Mod Pathol | volume = 18 | issue = 12 | pages = 1623-31 | month = Dec | year = 2005 | doi = 10.1038/modpathol.3800483 | PMID = 16258515 }}</ref>
*Basal-like breast cancer - p63 and CK5/6 positive<ref>{{Cite journal  | last1 = Azoulay | first1 = S. | last2 = Laé | first2 = M. | last3 = Fréneaux | first3 = P. | last4 = Merle | first4 = S. | last5 = Al Ghuzlan | first5 = A. | last6 = Chnecker | first6 = C. | last7 = Rosty | first7 = C. | last8 = Klijanienko | first8 = J. | last9 = Sigal-Zafrani | first9 = B. | title = KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome. | journal = Mod Pathol | volume = 18 | issue = 12 | pages = 1623-31 | month = Dec | year = 2005 | doi = 10.1038/modpathol.3800483 | PMID = 16258515 }}</ref>
CD117 positive<ref>{{Cite journal  | last1 = Azoulay | first1 = S. | last2 = Laé | first2 = M. | last3 = Fréneaux | first3 = P. | last4 = Merle | first4 = S. | last5 = Al Ghuzlan | first5 = A. | last6 = Chnecker | first6 = C. | last7 = Rosty | first7 = C. | last8 = Klijanienko | first8 = J. | last9 = Sigal-Zafrani | first9 = B. | title = KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome. | journal = Mod Pathol | volume = 18 | issue = 12 | pages = 1623-31 | month = Dec | year = 2005 | doi = 10.1038/modpathol.3800483 | PMID = 16258515 }}</ref>
 
DDx:
*Cribriform [[DCIS]].
*Invasive cribriform carcinoma.
*[[Collagenous spherulosis]].
 
===Images===
*[http://path.upmc.edu/cases/case140.html Adenoid cystic carcinoma of the breast (upmc.edu)].>>
<gallery>
Image:Breast AdenoidCysticCarcinoma 2 LP CTR.jpg|Breast Adenoid Cystic Carcinoma - low power (SKB)
Image:Breast AdenoidCysticCarcinoma 2 MP CTR (3).jpg|Breast Adenoid Cystic Carcinoma - medium power (SKB)
Image:Breast AdenoidCysticCarcinoma 2 MP2 CTR.jpg|Breast Adenoid Cystic Carcinoma - medium power (SKB)
Image:Breast AdenoidCysticCarcinoma 2 MP2 CTR.jpg|Breast Adenoid Cystic Carcinoma - medium power (SKB)
Image:Breast AdenoidCysticCarcinoma 2 MP CTR.jpg|Breast Adenoid Cystic Carcinoma - medium power (SKB)
Image:Breast AdenoidCysticCarcinoma MP CTR.jpg|Breast Adenoid Cystic Carcinoma - medium power (SKB)
Image:Breast AdenoidCysticCarcinoma MP CTR (2).jpg|Breast Adenoid Cystic Carcinoma - medium power (SKB)
Image:Breast AdenoidCysticCarcinoma 2 HP CTR (2).jpg|Breast Adenoid Cystic Carcinoma - high power (SKB)
Image:Breast AdenoidCysticCarcinoma 2 HP CTR.jpg|Breast Adenoid Cystic Carcinoma - high power (SKB)
Image:Breast AdenoidCysticCarcinoma 2 HP3 CTR.jpg|Breast Adenoid Cystic Carcinoma - high power (SKB)
Image:Breast AdenoidCysticCarcinoma 2 HP2 CTR.jpg|Breast Adenoid Cystic Carcinoma - high power (SKB)
Image:Breast AdenoidCysticCarcinoma SolidType LP 14BR***.jpg|Breast - Adenoid Cystic Carcinoma -  Solid Type - Low power (SKB)
Image:Breast AdenoidCysticCarcinoma SolidType 14BR***.jpg|Breast - Adenoid Cystic Carcinoma -  Solid Type - medium power - Aggregates of basaloid cells without tubule or cyst formation.  (SKB)
Image:Breast AdenoidCysticCarcinoma SolidType HP 14BR***.jpg|Breast - Adenoid Cystic Carcinoma -  Solid Type - High power (SKB)
Image:Breast AdenoidCysticCarcinoma SolidType 2 14BR***.jpg|Breast Adenoid Cystic Carcinoma - Solid Type - high power (SKB)
</gallery>
 
===Other Resources===
Pathology Outlines [http://www.pathologyoutlines.com/topic/breastmalignantadenoidcystic.html]
 
==Intracystic papillary carcinoma of the breast==
*[[AKA]] ''encapsulated papillary carcinoma of the breast'', abbreviated ''EPC''.
===General===
*Very good prognosis<ref name=pmid21753694>{{Cite journal  | last1 = Rakha | first1 = EA. | last2 = Gandhi | first2 = N. | last3 = Climent | first3 = F. | last4 = van Deurzen | first4 = CH. | last5 = Haider | first5 = SA. | last6 = Dunk | first6 = L. | last7 = Lee | first7 = AH. | last8 = Macmillan | first8 = D. | last9 = Ellis | first9 = IO. | title = Encapsulated papillary carcinoma of the breast: an invasive tumor with excellent prognosis. | journal = Am J Surg Pathol | volume = 35 | issue = 8 | pages = 1093-103 | month = Aug | year = 2011 | doi = 10.1097/PAS.0b013e31821b3f65 | PMID = 21753694 }}</ref> - it is similar to [[DCIS]].
*Classical menopausal women.
*~30% present with bloody discharge.<ref name=pmid21057133>{{Cite journal  | last1 = Rodríguez | first1 = MC. | last2 = Secades | first2 = AL. | last3 = Angulo | first3 = JM. | title = Best cases from the AFIP: intracystic papillary carcinoma of the breast. | journal = Radiographics | volume = 30 | issue = 7 | pages = 2021-7 | month = Nov | year = 2010 | doi = 10.1148/rg.307105003 | PMID = 21057133 | URL = http://radiographics.rsnajnls.org/cgi/pmidlookup?view=long&pmid=21057133 }}</ref>
 
===Microscopic===
Features:
*Lesion confined to a duct (intraductal) ''or'' cyst (intracystic).
**May have a thick fibrous capsule = ''encapsulated papillary carcinoma''.<ref name=pmid21057133/>
*Loss of myoepithelial cells - '''key feature'''.
*Neoplastic epithelial cells:
**[[Nuclear atypia]] - including: nucleoli, [[nuclear pleomorphism]].
**Abnormal architecture - including cribriform, solid, micropapillary, papillary.
 
<gallery>
Image:Breast Carcinoma Papillary Intracystic SolidVariant LP CTR.jpg|Breast - Papillary Intracystic Carcinoma, Solid Variant - low power (SKB)
Image:Breast Carcinoma Papillary Intracystic SolidVariant MP2 CTR.jpg|Breast - Papillary Intracystic Carcinoma, Solid Variant - medium power (SKB)
Image:Breast Carcinoma Papillary Intracystic SolidVariant MP CTR.jpg|Breast - Papillary Intracystic Carcinoma, Solid Variant - medium power (SKB)
Image:Breast Carcinoma Papillary Intracystic SolidVariant HP2 CTR.jpg|Breast - Papillary Intracystic Carcinoma, Solid Variant - high power (SKB)
Image:Breast Carcinoma Papillary Intracystic SolidVariant HP CTR.jpg|Breast - Papillary Intracystic Carcinoma, Solid Variant - high power (SKB)
Image:Breast EncystedPapillaryCarcinoma InfiltratingDuctalCarcinoma PA.JPG|thumb|Breast - Intracystic papillary adenocarcinoma with associated invasive ductal carcinoma (SKB)
</gallery>
 
DDx<ref>{{Cite journal  | last1 = Collins | first1 = LC. | last2 = Schnitt | first2 = SJ. | title = Papillary lesions of the breast: selected diagnostic and management issues. | journal = Histopathology | volume = 52 | issue = 1 | pages = 20-9 | month = Jan | year = 2008 | doi = 10.1111/j.1365-2559.2007.02898.x | PMID = 18171414 }}
</ref><ref>{{Cite journal  | last1 = Pathmanathan | first1 = N. | last2 = Albertini | first2 = AF. | last3 = Provan | first3 = PJ. | last4 = Milliken | first4 = JS. | last5 = Salisbury | first5 = EL. | last6 = Bilous | first6 = AM. | last7 = Byth | first7 = K. | last8 = Balleine | first8 = RL. | title = Diagnostic evaluation of papillary lesions of the breast on core biopsy. | journal = Mod Pathol | volume = 23 | issue = 7 | pages = 1021-8 | month = Jul | year = 2010 | doi = 10.1038/modpathol.2010.81 | PMID = 20473278 }}</ref>:
*[[Intraductal papilloma]].
**Absent or scant stroma favors papillary carcinoma over papilloma.
**Is there a single cell or dual cell population in the lesion?
***ER staining will be heterologous in a benign lesion.
***If myoepithelial markers are negative within the lesion then malignancy is favoured. 
*[[Papillary ductal carcinoma in situ]]
**Papillary DCIS shows myoepithelial cells (calponin/p63/SMA +ve) at the periphery of the involved spaces
**Papillary intracystic carcinoma does not show myoepithelial cells at the periphery of the involved spaces
*Invasive carcinoma arising in association with papillary intracystic carcinoma
**Epithelial entrapment in the encysting fibrous tissue should not be interpreted as invasion. 
**Carcinoma must be seen in the breast tissue outside the encysting fibrous tissue.
*[[Adenoid cystic carcinoma of the breast]]
**The solid variant looks basaloid - solid adenoid cystic carcinoma or a 'basal-like' carcinoma should be considered in these cases.
 
Notes
*Adequately and carefully sample the specimen to exclude an invasive component.
*Report only the size of the invasive component (if present) to prevent over-estimation of tumor stage.


===IHC===
==Intracystic papillary breast carcinoma==
*Loss of myoepithelial markers within the lesion.
*[[AKA]] ''encapsulated or encysted papillary carcinoma of the breast'', abbreviated ''EPC''.
{{Main|Intracystic papillary breast carcinoma}}


==Glycogen-rich clear cell carcinoma of the breast==
==Glycogen-rich clear cell carcinoma of the breast==
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{{Main|Secretory carcinoma of the breast}}
{{Main|Secretory carcinoma of the breast}}


=Grading breast cancer=
==Invasive cribriform carcinoma of the breast==
Most common system: ''Nottingham'' (aka Scarff-Bloom-Richardson) which is based on:
{{Main|Invasive cribriform carcinoma of the breast}}
#Nuclear grade.
#*Small, regular (1.5-2x RBC dia.) = 1.
#*Moderated variability = 2.
#*Marked variation (>2.5x RBC dia.) = 3.
# Tubule formation.
#*Majority of tumour - tubules >75% = 1.
#*Moderate - 10% to 75% = 2.
#*Minimal <10% = 3.
# Mitotic rate.
#*0-5 mitosis/10 [[HPF]] (1.52 mm^2 --or-- 0.0152 mm^2 * 10) = 1.
#*6-10 mitosis/10 HPF (1.52 mm^2) = 2.
#*>11 mitosis/10 HPF (1.52 mm^2) = 3.
Mnemonic: ''TMN'' = tubule formation, mitotic rate, nuclear grade.


Notes:
==Invasive papillary carcinoma of the breast==
*Elston & Ellis devised the system that is used.<ref name=pmid12405945>{{cite journal |author=Elston CW, Ellis IO |title=Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19; 403-410 |journal=Histopathology |volume=41 |issue=3A |pages=151–2, discussion 152–3 |year=2002 |month=September |pmid=12405945 |doi= |url=}}</ref> They also wrote a follow-up article in 2002.<ref name=pmid1757079>{{cite journal |author=Elston CW, Ellis IO |title=Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up |journal=Histopathology |volume=19 |issue=5 |pages=403–10 |year=1991 |month=November |pmid=1757079 |doi= |url=}}</ref>
{{Main|Invasive papillary carcinoma of the breast}}
*Should '''not''' be confused with the indolent behaving [[intracystic papillary carcinoma of the breast]], also known as ''encapsulated papillary carcinoma of the breast''.


==Note about mitosis counting==
=Grading breast cancer=
*One MUST adjust for the size of the field of view.
{{Main|Breast cancer grading}}
 
*Most of the Resident scopes have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.
**Thus, on a resident scope (with a FOV of 0.2376 mm^2) one should sample 6 or 7 fields of view (FsOV).
***Calculation: 1.52 mm^2 (sampling area) / 0.2376 mm^2 (area / FOV ) = 6.40 FsOV.
 
*'''RANT''': Sampling 10 fields, where the field of view (FOV) is 0.152 mm^2, is ''not'' the same as sampling ten fields, where the FOV is 0.312 mm^2.  It surprises me that Elston & Ellis ignore the fact that "10 HPFs" on different microscopes represent different sample areas and that they do ''not'' standardize the sampling area.
 
==Calculating Nottingham score==
*Grade I = 3-5 points.
*Grade II = 6-7 points.
*Grade III = 8-9 points.
 
Notes:
*I've found most tumours are grade II. 
*The mitotic score is usually 1/3.
*The nuclear score is rarely 1/3 -- even in the tubular subtype.<ref>MUA. 20 January 2009.</ref>


=Staging breast cancer=
=Staging breast cancer=
==Sentinel lymph node sampling in breast cancer==
{{Main|Breast cancer staging}}
{{Main|Sentinel lymph node|Lymph node metastasis}}
===General===
*Selective sampling of lymph nodes.
*Used for staging.
*Positive LNs = poorer prognosis.
 
Notes:
*If there is no palpable disease, there is '''no''' mortality benefit from axillary lymph node dissection, i.e. positive axillary lymph nodes can be left in situ without affecting outcome.<ref>{{cite journal |author=Giuliano AE, Hunt KK, Ballman KV, ''et al.'' |title=Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial |journal=JAMA |volume=305 |issue=6 |pages=569–75 |year=2011 |month=February |pmid=21304082 |doi=10.1001/jama.2011.90 |url=}}</ref>
**This does not negate the fact that a positive sentinel LN biopsy (vs. negative sentinel LN biopsy) portends a poorer prognosis.
 
===Microscopic===
Features:
*Atypical cells.
**Nuclear changes of malignancy:
***Nuclear enlargement + variation in size.
***Variation in shape.
***Hyperchromasia and variation in staining.
**Usually in the subcapsular sinuses.
 
Pitfalls:
*Naevus cell rests.<ref>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_1107%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_1107%20discussion.html]. Accessed on: 28 November 2010.</ref>
 
===IHC===
Some hospitals use:
*CAM5.2 (LMWK) - to look for isolated tumour cells and small lymph node metstases.
 
==N stage==
Sampling usually selective, i.e. [[sentinel lymph nodes]] only.
===Indictionas for lymph node sampling===
Indications for lymph node sampling:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf]. Accessed on: 2 April 2012.</ref>
*Extensive [[DCIS]].
*Biopsy suspicious for invasion ''or'' with microinvasion.
*Clinical findings (large palable mass) or radiology findings (irregular features) suggestive of invasion.
*Planned mastectomy.
 
===Definitions===
Definitions:<ref name=acs_website>URL: [http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging]. Accessed on: 8 July 2010.</ref>
*Isolated tumour cells: <=0.2 mm ''or'' <=200 cells -- in a single cross-section. †
*Micrometastasis: <=0.2 cm ''and'' ( >0.2 mm ''or'' >200 cells ).
*Macrometastasis: >0.2 cm.
 
Notes:
* † The ''American Cancer Society'' web site says "or".<ref name=acs_website/>  The CAP protocol says "and/or" and notes it is all subjective.
*Isolated tumour cells are essentially ignored if the there is at least one macrometastasis.
 
===Details===
Lymph nodes:<ref>URL: [http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging]. Accessed on: 8 July 2010.</ref>
*pN0: nil.
**pN0(i+): <=0.2 mm ''and'' <200 cells.
*pN1: 1-3 axillary LNs ''or'' internal mammary LNs.
**pN1mi: <=0.2 cm ''and'' ( >0.2 mm ''or'' >=200 cells ).
**pN1a.
**pN1b.
**PN1c.
*pN2 4-9 positive LNs; internal mammary LNs ''or'' axillary LNs.
*pN3.
 
==T stage==
Tumour:<ref>URL: [http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging]. Accessed on: 8 July 2010.</ref><ref>URL: [http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging]. Accessed on: 9 July 2010.</ref>
*pT1: <= 20 mm.
**pT1mic <= 1 mm.
**pT1a > 1 mm ''and'' <= 5 mm.
**pT1b > 5 mm ''and'' <= 10 mm.
**pT1c > 10 mm ''and'' <= 20 mm.
*pT2: > 20 mm and <= 50 mm
*pT3: > 50 mm.
*pT4: chest wall or skin involvement.
 
Notes:
*Values should be rounded to the nearest millimetre.
**Therefore:
***1.4 mm would be ''pT1mic''.
***1.5 mm would be ''pT1a''.
 
==M stage==
Distant metastasis:
*cM0(i+) <=0.2 mm focus of tumour cells, without clinical signs and symptoms.
*pM1 focus of tumour cells > 0.2 mm.


=Lymphovascular invasion=
=Lymphovascular invasion=
Line 751: Line 550:


=External links=
=External links=
*[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees%2Fcancer%2Fcancer_protocols%2Fprotocols_index.html&_state=maximized&_pageLabel=cntvwr CAP protocols/checklists (cap.org)].
**[http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf Invasive breast cancer - checklist (cap.org)].
*[http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.html About breast cancer - molecular subtypes (komen.org)].
*[http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.html About breast cancer - molecular subtypes (komen.org)].


[[Category:Breast pathology]]
[[Category:Breast pathology]]
[[Category:Invasive breast cancer]]
[[Category:Invasive breast cancer]]
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