[[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]]''.

=Introduction=
==Overview of invasive breast cancer subtypes==
====Common epithelial subtypes====
Type and percentage of breast carcinomas:<ref name=Ref_PBoD1143>{{Ref PBoD|1143}}</ref>
*[[Invasive ductal carcinoma of the breast|Ductal]] - [[AKA]] no special type (NST) - 79%.
*[[invasive lobular carcinoma|Lobular]] - 10%.
*[[Tubular carcinoma of the breast|Cribriform / tubular]] - 6%.
*[[mucinous breast carcinoma|Mucinous]] (colloid) - 2%.
*[[medullary breast carcinoma|Medullary]] - 2%.
*Papillary - 1%.
*[[Metaplastic breast carcinoma|Metaplastic]] - <1%.

===Common stromal types===
*Malignant [[phyllodes tumour]].
*[[Angiosarcoma]] - post-radiation ~ 10 years.<ref>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html]. Accessed on: 28 November 2010.</ref>

===Good prognosis subtypes===
Three good prognosis subtypes:<ref>URL: [http://emedicine.medscape.com/article/1947145-overview http://emedicine.medscape.com/article/1947145-overview]. Accessed on: 24 August 2012.</ref>
*Tubular carcinoma.
*Mucinous carcinoma.
*Papillary carcinoma.

==Comprehensive list of invasive breast cancer subtypes==
====Epithelial====
Counterparts of in situ lesions:
*[[Invasive ductal carcinoma of the breast|Invasive ductal carinoma]], not otherwise specified.
*[[Invasive lobular carcinoma]].
*[[Invasive cribriform carcinoma of the breast|Invasive cribriform carcinoma]].
*[[Invasive papillary carcinoma of the breast|Invasive papillary carcinoma]].
*[[Invasive micropapillary carcinoma of the breast|Invasive micropapillary carcinoma]].

Other epithelial tumours:
*[[Tubular carcinoma of the breast|Tubular carcinoma]].
*[[Medullary breast carcinoma|Medullary carcinoma]].
*[[Mucinous breast carcinoma|Mucinous carinoma]].
*[[Metaplastic breast carcinoma|Metaplastic carcinoma]].
*[[Neuroendocrine tumour]].
*[[Apocrine carcinoma of the breast|Apocrine carcinoma]].
*Lipid-rich carcinoma.
*[[Secretory breast carcinoma|Secretory carcinoma]].
*Oncocytic carcinoma.
*[[Glycogen-rich clear cell carcinoma of the breast|Glycogen-rich clear cell carcinoma]].

Epithelial tumours seen in the [[salivary gland]]:
*[[Adenoid cystic carcinoma of the breast]].
*[[Acinic cell carcinoma]].
*[[Carcinoma ex pleomorphic adenoma]].

Seen in the skin:
*[[Sebaceous carcinoma]].

Clinically diagnosed:
*Inflammatory carcinoma.

In situ lesions:
*[[Ductal carcinoma in situ]].
*[[Lobular carcinoma in situ]].

Proliferative lesions:
*[[Usual ductal hyperplasia]].
*[[Flat epithelial atypia]].
*[[Atypical ductal hyperplasia]].

Non-specific:
*Microinvasive carcinoma.

Papillary:
*[[Intraductal papilloma|Papilloma]].
*Atypical papilloma.
*Intraductal papillary carcinoma.

Adenomas:
*Ductal adenoma.
*[[Tubular adenoma of the breast|Tubular adenoma]].
*[[Lactating adenoma]].
*Apocrine adenoma.
*[[Pleomorphic adenoma]].

====Myoepithelial====
*Myoepitheliosis.
*Adenomyoepithelial adenosis.
*[[Adenomyoepithelioma]].
*Malignant adenomyoepithelioma.

====Mesenchymal tumours====
:See: ''[[Soft tissue lesions]]''.

====Fibroepithelial tumours====
*[[Fibroadenoma]].
*[[Phyllodes tumour]].
*Periductal stromal sarcoma, low grade.
*[[Mammary hamartoma]].

====Nipple lesions====
*[[Nipple adenoma]].
*Syringomatous adenoma.
*[[Paget disease of the breast]].

====Other====
*[[Lymphoma]].
*[[Metastasis]].

==Familial breast cancer==
{{Main|Hereditary breast cancer}}

=Breast IHC=
==Molecular classification of ''invasive carcinoma''==
A molecular classification:<ref name=Ref_PCPBoD8_547>{{Ref PCPBoD8|547}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Type
! Percentage
! IHC
! Histology
! Prognosis/clinical
|-
| Luminal A
| ~45%
| ER+ PR+ HER2-
| well-differentiated
| good, chemo resistant
|-
| Luminal B
| 17%
| ER+ PR+ HER2+
| high grade
| poor, +/- chemo responsive
|-
| Normal breast-like
| ~8%
| ER+ PR+ (?) HER2-
| well-differentiated
| good
|-
| Basal-like
| ~20%
| ER- PR- HER2-
| poorly differentiated
| aggressive, may have good chemo response, classic for [[BRCA1]] mutation
|-
| HER2 positive
| ~10%
| ER- PR- (?) HER2+
| poorly differentiated
| poor
|}

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>

== Basal-like breast carcinoma==

*Overview:<ref>{{Cite journal | last1 = Badve | first1 = S. | last2 = Dabbs | first2 = DJ. | last3 = Schnitt | first3 = SJ. | last4 = Baehner | first4 = FL. | last5 = Decker | first5 = T. | last6 = Eusebi | first6 = V. | last7 = Fox | first7 = SB. | last8 = Ichihara | first8 = S. | last9 = Jacquemier | first9 = J. | title = Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. | journal = Mod Pathol | volume = 24 | issue = 2 | pages = 157-67 | month = Feb | year = 2011 | doi = 10.1038/modpathol.2010.200 | PMID = 21076464 }}
</ref>
**A category of breast carcinomas defined by gene expression profiling.
**''Not used'' in clinical practice.
**Somewhere between 15-30% of breast carcinomas.
**Can be roughly be identified by immunohistochemistry - basal markers (CK14, p63, calponin, SMA).
**Not derived from myoepithelial cells, merely express a phenotype more in keeping with basal cells than ductal cells.
**Most triple negative (ER, PgR, Her-2); therefore cannot be treated with the usual therapeutic agents.
**There is an association in young women between basal-like breast cancer and BRCA1 mutation.
**Discussions of BRCA1 associated tumors, TNBC and BLBC are typically muddied by the overlap.
**Increased incidence in some populations - African-Americans, young women
**Sporadic basal-like cancers do not have a BRCA1 mutation but may have a dysfunctional BRCA1 pathway.
**p53 mutations are frequent.

*This molecular group includes a variety of morphologic phenotypes including:
**High grade [[invasive ductal carcinoma]] of no special type.
**Medullary-like carcinoma (a carcinoma with some but not all the features of medullary carcinoma).
**[[Medullary breast carcinoma|Medullary carcinoma]]
**[[Metaplastic breast carcinoma|Metaplastic carcinoma]].
**[[Adenoid cystic carcinoma of the breast|Adenoid cystic carcinoma]].
**[[Secretory carcinoma]].

*Classic morphological clues of a basal type cancer usually refer to medullary carcinoma features:
**Relatively circumscribed.
**Geographic necrosis.
**Abundant mitoses.
**Pushing margins.
**Central fibrosis or necrosis.
**High histological grade.
**Exceptionally high mitotic rate.
**Pushing borders.
**Conspicuous lymphocytic infiltrate.

*Behaviour:
**Basal-like breast cancer is a heterogeneous group.
**The behaviour of basal-like breast cancer appears to fall into two groups:
***The tumours that are by nature low grade (ie adenoid cystic carcinoma) and/or do not metastasise have a better prognosis than other types of breast carcinoma.
***The tumours with early metastasis that may behave more aggressively
****Hematogenous spread -greater tendency to metastasise to visceral sites (notably lung and brain) instead of to nodes and bone.
**Many have a complete response to chemotherapy and survival rates similar to typical breast cancer
**Non-complete response to chemotherapy is associated with low survival at 5 years.

Other sources
Minireview: Basal-Like Breast Cancer: From Molecular Profiles to Targeted Therapies <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035993/>

== Triple Negative Breast Carcinoma ==
Features:<ref name=pmid21076464>{{Cite journal | last1 = Badve | first1 = S. | last2 = Dabbs | first2 = DJ. | last3 = Schnitt | first3 = SJ. | last4 = Baehner | first4 = FL. | last5 = Decker | first5 = T. | last6 = Eusebi | first6 = V. | last7 = Fox | first7 = SB. | last8 = Ichihara | first8 = S. | last9 = Jacquemier | first9 = J. | title = Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. | journal = Mod Pathol | volume = 24 | issue = 2 | pages = 157-67 | month = Feb | year = 2011 | doi = 10.1038/modpathol.2010.200 | PMID = 21076464 }}</ref>

**A category of breast carcinomas defined by immunohistochemical/FISH expression of ER, PR and HER2.
**''Important to identify'' in clinical practice.
**About 15% of breast carcinomas.
**Important group due to a lack of tailored therapies for this group
***Some triple negatives also express androgen receptor and have and [apocrine carcinoma] morphology.<ref>{{Cite journal | last1 = Niemeier | first1 = LA. | last2 = Dabbs | first2 = DJ. | last3 = Beriwal | first3 = S. | last4 = Striebel | first4 = JM. | last5 = Bhargava | first5 = R. | title = Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. | journal = Mod Pathol | volume = 23 | issue = 2 | pages = 205-12 | month = Feb | year = 2010 | doi = 10.1038/modpathol.2009.159 | PMID = 19898421 }}</ref>
****May respond to therapies targeting the androgen receptor.
***BCL11A overexpression recently identified as an oncogenic driver for some triple negatives <ref>{{Cite journal | last1 = Khaled | first1 = WT. | last2 = Choon Lee | first2 = S. | last3 = Stingl | first3 = J. | last4 = Chen | first4 = X. | last5 = Raza Ali | first5 = H. | last6 = Rueda | first6 = OM. | last7 = Hadi | first7 = F. | last8 = Wang | first8 = J. | last9 = Yu | first9 = Y. | title = BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells. | journal = Nat Commun | volume = 6 | issue = | pages = 5987 | month = | year = 2015 | doi = 10.1038/ncomms6987 | PMID = 25574598 }}</ref>
****Targeted therapies may include inhibitors of BCL11A.
**Triple-negative and basal-like phenotypes are not synonymous but overlap
***About 70% of triple-negative tumours are basal-like.
***About 70% of basal-like tumors are triple-negative tumours.
**Discussions of BRCA1 associated tumors, TNBC and BLBC are typically muddied by the overlap.
**Classic 'morphological clues' to a triple negative cancer usually refer to medullary carcinoma features.

==Immunostains for typing and diagnosis==
===DCIS versus LCIS===
Tabular comparison for DCIS versus LCIS:<ref name=Ref_BP275>{{Ref BP|275}}</ref><ref name=pmid18318578>{{cite journal |author=Yeh IT, Mies C |title=Application of immunohistochemistry to breast lesions |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=349-58 |year=2008 |month=March |pmid=18318578 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349}}</ref>
{| class="wikitable sortable"
!Disease
!E-cadherin
!Beta-catenin
!34betaE12
!CAM5.2 (CK8)
|-
|DCIS
| +ve
| +ve
| -ve
| +ve peripheral cytoplasm
|-
|LCIS
| -ve
| -ve
| +ve perinuclear
| +ve perinuclear
|}

===Invasive versus non-invasive===
Myoepithelial markers - typically lost in invasive carcinoma:<ref>{{Ref Lester3|88}}</ref>
{| class="wikitable sortable"
!Stain
!Location
!Notes
|-
| p63
| nuclear
| up to 10% of invasive tumours +ve<ref name=Ref_BP276>{{Ref BP|276}}</ref>
|-
| Smooth muscle actin (SMA)
| cytoplasmic
| stains myofibroblasts & blood vessels
|-
| Calponin
| cytoplasmic
| stains myofibroblasts & blood vessels
|-
| Smooth muscle myosin heavy chain (SMM-HC)
| cytoplasmic
| stains myofibroblasts & blood vessels
|}

===Usual ductal hyperplasia versus ductal carcinoma in situ===
Markers for UDH versus DCIS:<ref name=Ref_BP276>{{Ref BP|276}}</ref>
{| class="wikitable sortable"
!Disease
!CK5/6
!ER
|-
|UDH
| diffuse +ve
| patchy +ve
|-
|DCIS
| -ve
| diffuse +ve
|}

===Lymphovascular invasion===
{{Main|Lymphovascular invasion}}
*D2-40 - marks the lymphatic spaces.<ref>{{cite journal |author=Ordóñez NG |title=Podoplanin: a novel diagnostic immunohistochemical marker |journal=Adv Anat Pathol |volume=13 |issue=2 |pages=83-8 |year=2006 |month=March |pmid=16670463 |doi=10.1097/01.pap.0000213007.48479.94 |url=}}</ref><ref>{{cite journal |author=Kahn HJ, Marks A |title=A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors |journal=Lab. Invest. |volume=82 |issue=9 |pages=1255-7 |year=2002 |month=September |pmid=12218087 |doi= |url=}}</ref>
*CD31 - marks lymphovascular spaces.
*CD34 - marks lymphovascular spaces, less specific than CD31.

==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).
**Positive in most breast cancers; +ve in ~75-80%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
*PR (progesterone receptor).
**Positive in most breast cancers; +ve in ~65-70%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
*HER2/neu (HER2).
**Usually negative; -ve in 70-80%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
**Positivity associated with a worse prognosis.
**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:
*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>
===ER & PR scoring===
Nuclear staining:<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
*Give a percentage, i.e. 0-100%.
**Important cut points: 1% and 10%.
***0% = negative - not treated.
***<10% = low positivity - treated.

Notes:
*Normal breast epithelial cells have a patchy staining for ER and PR.
*Evaluated on the invasive component.
===HER2 scoring===
Immunohistochemical based testing:<ref name=pmid24382093>{{Cite journal | last1 = Rakha | first1 = EA. | last2 = Starczynski | first2 = J. | last3 = Lee | first3 = AH. | last4 = Ellis | first4 = IO. | title = The updated ASCO/CAP guideline recommendations for HER2 testing in the management of invasive breast cancer: a critical review of their implications for routine practice. | journal = Histopathology | volume = 64 | issue = 5 | pages = 609-15 | month = Apr | year = 2014 | doi = 10.1111/his.12357 | PMID = 24382093 }}</ref><ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf]. Accessed on: October 7, 2014.</ref>
{| class="wikitable sortable"
! Score
! Staining intensity
! Cells stained (%)
! Membrane staining
! Management
! Percentage of cases
|-
| '''0'''
| no staining/barely visible
| '''≤10%'''
| '''incomplete'''
| No HER2 blocker
| ~60%
|-
| '''1+'''
| minimal/barely visible
| '''>10%'''
| '''incomplete'''
| No HER2 blocker
| ~10%
|-
| '''2+'''
| weak-to-moderate
| '''>10%'''
| '''incomplete''' (circumferential)
| Needs [[SISH]] or [[FISH]]
| ~10% †
|-
| '''2+'''
| intense
| '''≤10%'''
| '''complete'''
| Needs [[SISH]] or [[FISH]]
| ~10% †
|-
| '''3+'''
| intense staining
| '''>10%''' ‡
| '''complete'''
| HER2 blocker
| ~20%
|}

Note for IHC:
*Normal breast epithelial cells do not stain with HER2.
*Evaluated on the invasive component.
*SISH = silver [[in situ hybridization]].
*FISH = fluorescence in situ hybridization.
*† Together approximately 10%.
*‡ The cut point was 10%, changed to 30% and then changed back to 10%.<ref name=pmid24382093/>

ISH based testing:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf]. Accessed on: October 7, 2014.</ref>
{| class="wikitable sortable"
! Result
! Ratio criteria
! Gene copy number criteria
|-
| Positive
| ≥2.0 HER2/CEP17
| ≥6.0 copies of HER2/cell
|-
| Equivocal
| <2.0 HER2/CEP17 (required)
| 4.0-6.0 copies of HER2/cell
|-
| Negative
| <2.0 HER2/CEP17
| <4.0 copies of HER2/cell
|}
Note for ISH:
*Can be called ''positive'' based on either ''ratio criteria'' or ''gene copy number criteria''.

===Clinical===
*ER & PR status determine whether a patient will get tamoxifen or other estrogen receptor modulators, such as raloxifene (Evista).
*HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.

=Characteristics of the subtypes=
==Invasive ductal carcinoma of the breast==
*[[AKA]] "NST" = No Specific Type.
*[[AKA]] ''invasive mammary carcinoma''.
{{Main|Invasive ductal carcinoma of the breast}}

==Invasive lobular carcinoma==
*Abbreviated ''ILC''.
*[[AKA]] ''lobular carcinoma''.
{{Main|Invasive lobular carcinoma}}

==Medullary breast carcinoma==
*[[AKA]] ''medullary carcinoma of the breast''.
{{Main|Medullary breast carcinoma}}

==Tubular carcinoma of the breast==
*[[AKA]] ''tubular carcinoma''.
{{Main|Tubular carcinoma of the breast}}

==Metaplastic breast carcinoma==
*[[AKA]] ''metaplastic carcinoma''.
{{Main|Metaplastic breast carcinoma}}

==Invasive micropapillary carcinoma of the breast==
*[[AKA]] ''micropapillary carcinoma''.
===General===
*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==
{{Main|Apocrine carcinoma of the breast}}

==Mucinous breast carcinoma==
*[[AKA]] ''mucinous carcinoma of the breast'', [[AKA]] ''colloid carcinoma of the breast''.
{{Main|Mucinous breast carcinoma}}

==Adenoid cystic carcinoma of the breast==
*[[AKA]] ''breast adenoid cystic carcinoma''.
{{Main|Adenoid cystic carcinoma of the breast}}

==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 cyst.
**May have a thick fibrous capsule
**The involved space is ''not'' lined by myoepithelial cells.
*The cyst contains an abnormal epithelial proliferation with cribriform, solid or papillary architecture.
**Loss of myoepithelial cells within the epithelial proliferation is a '''key feature'''.
**Scattered large cells with pale eosinophilic cytoplasm may be observed<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>.
***These cells are so-called globoid cells or clear cells and are immunoreactive for GCDFP-15.
***They should not be mistaken for myoepithelial cells.
**Neoplastic epithelial cells:
***[[Nuclear atypia]] - including: nucleoli, [[nuclear pleomorphism]].

IHC:
*Calponin/p63/SMA/CK5-6
**Loss of myoepithelial cells within the tumour.
**Loss of myoepithelial cells at the cyst wall.
*ER - Homogeneous staining of the epithelial proliferation.

Photos:
<gallery>
Image:Breast PapillaryCarcinomaEncysted 3 PA.JPG|Breast - Intracystic Papillary Carcinoma - Medium power (SKB)
Image:Breast PapillaryCarcinomaEncysted 2 PA.JPG|Breast - Intracystic Papillary Carcinoma - Medium power (SKB)
Image:Breast PapillaryCarcinomaEncysted PA.JPG|Breast - Intracystic Papillary Carcinoma - High power (SKB)
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|Breast - Intracystic papillary adenocarcinoma (top) with associated invasive ductal carcinoma (bottom) (SKB)
</gallery>
*WebPathology<http://www.webpathology.com/images/noimage.gif>
*WebPathology<http://www.webpathology.com/images/noimage.gif>
*WebPathology<http://www.webpathology.com/images/noimage.gif>

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.
***Myoepithelial markers (calponin/p63/SMA +ve)s hould be positive in a benign lesion.
*[[Papillary ductal carcinoma in situ]]
**Papillary DCIS shows myoepithelial cells (calponin/p63/SMA +ve) at the periphery of the involved spaces
**But papillary DCIS should be negative for myoepithelial cells within the focus of DCIS
**Papillary intracystic carcinoma does not show myoepithelial cells at the periphery of the involved spaces
*Invasive papillary carcinoma of the breast
**Similar architecture but no cystic space, frankly invasive.
**Very rare.
*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.
**Infiltrating carcinoma is usually of the 'no special type' variety.
*[[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
*Many potential pitfalls with papillary breast lesions on needle core biopsy.
**Complete excision is recommended<ref>{{Cite journal | last1 = Rizzo | first1 = M. | last2 = Linebarger | first2 = J. | last3 = Lowe | first3 = MC. | last4 = Pan | first4 = L. | last5 = Gabram | first5 = SG. | last6 = Vasquez | first6 = L. | last7 = Cohen | first7 = MA. | last8 = Mosunjac | first8 = M. | title = Management of papillary breast lesions diagnosed on core-needle biopsy: clinical pathologic and radiologic analysis of 276 cases with surgical follow-up. | journal = J Am Coll Surg | volume = 214 | issue = 3 | pages = 280-7 | month = Mar | year = 2012 | doi = 10.1016/j.jamcollsurg.2011.12.005 | PMID = 22244207 }}</ref>.
*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===
*Loss of myoepithelial markers within the lesion.

==Glycogen-rich clear cell carcinoma of the breast==
*Abbreviated ''GRCC''.
{{Main|Glycogen-rich clear cell carcinoma of the breast}}

==Secretory carcinoma of the breast==
*[[AKA]] ''secretory breast carcinoma'', abbreviated ''SBC''.
{{Main|Secretory carcinoma of the breast}}

==Invasive cribriform carcinoma of the breast==
{{Main|Invasive cribriform carcinoma of the breast}}

==Invasive papillary carcinoma of the breast==
*Rare
*Similar architecture to the encysted variant above but no cyst
*Frankly invasive
*The "solid" variant (papillae dramatically compressed together) can also occur
<gallery>
Image:Breast PapillaryCarcinoma Invasive LP SNP.jpg|Breast - Invasive Papillary Carcinoma - Low power (SKB)
Image:Breast PapillaryCarcinoma Invasive MP SNP.jpg|Breast - Invasive Papillary Carcinoma - Medium power (SKB)
Image:Breast PapillaryCarcinoma Invasive HP SNP.jpg|Breast - Invasive Papillary Carcinoma - High power (SKB)
Image:Breast PapillaryCarcinoma Invasive HP2 SNP.jpg|Breast - Invasive Papillary Carcinoma - High power (SKB)
Image:Breast PapillaryCarcinoma SolidVariant LP CTR.jpg|Breast - Invasive Papillary Carcinoma - Solid Variant - Low power (SKB)
Image:Breast PapillaryCarcinoma SolidVariant MP2 CTR.jpg|Breast - Invasive Papillary Carcinoma - Solid Variant - Medium power (SKB)
Image:Breast PapillaryCarcinoma SolidVariant MP CTR.jpg|Breast - Invasive Papillary Carcinoma - Solid Variant - Medium power (SKB)
Image:Breast PapillaryCarcinoma SolidVariant MP3 CTR.jpg|Breast - Invasive Papillary Carcinoma - Solid Variant - Medium power (SKB)
Image:Breast PapillaryCarcinoma SolidVariant HP CTR.jpg|Breast - Invasive Papillary Carcinoma - Solid Variant - High power (SKB)
</gallery>

=Grading breast cancer=
Most common system: ''Nottingham'' (aka Scarff-Bloom-Richardson) which is based on:
#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:
*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>

==Note about mitosis counting==
*One MUST adjust for the size of the field of view.

*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=
==Sentinel lymph node sampling in breast cancer==
{{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=
{{Main|Lymphovascular invasion}}
In the context of breast pathology, the Rosen criteria for LVI are widely excepted, and are as follows:<ref name=pmid6674861>{{Cite journal | last1 = Rosen | first1 = PP. | title = Tumor emboli in intramammary lymphatics in breast carcinoma: pathologic criteria for diagnosis and clinical significance. | journal = Pathol Annu | volume = 18 Pt 2 | issue = | pages = 215-32 | month = | year = 1983 | doi = | PMID = 6674861 }}</ref><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: 5 August 2011.</ref>
#Must be outside of the tumour proper.
#*LVI is usually very close -- typically within 0.1 cm.
#Contour of cells should differ from possible vessel wall.
#*DCIS with retraction artifact mimicing LVI has a contour that matches its surrounding fibrous tissue.
#Endothelium (usu. flat) should be visible.
#Lymphatics are found adjacent to [[blood vessels]] - vessels should be present in the vicinity.

Memory device ''LUBE-O'':
*'''L'''VI has a '''U'''nique contour, '''B'''lood vessels and '''E'''ndothelium in the vicinity, and is '''O'''utside of the tumour.

Note:
*LVI does not affect the stage.

=Other=
==Paget's disease==
{{Main|Paget disease of the breast}}
===General===
*Associated with underlying breast carcinoma.<ref name=emed_pagets>URL: [http://emedicine.medscape.com/article/1101235-diagnosis http://emedicine.medscape.com/article/1101235-diagnosis]</ref>

Notes:
*Unrelated to [[Paget disease of the bone]].

===Microscopic===
Features:<ref name=emed_pagets/>
*Cells in the epidermis:
**Epitheliod morphology (round/ovoid).
**Cells nested or single.
**Clear/pale cytoplasm '''key feature''' - may also be eosinophilic.
**Large nucleoli.

Images:
*[http://commons.wikimedia.org/wiki/File:Extramammary_Pagets_disease_low.jpg Paget's disease - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Extramammary_Pagets_disease_high.jpg Paget's disease - high mag. (WC)].

IHC & DDx:
*See ''[[Paget disease]]''.

==Trivia==
===Tumour size and lymph node metastases===
There is a paper<ref name=pmid18483831>{{Cite journal | last1 = Porembka | first1 = MR. | last2 = Abraham | first2 = RL. | last3 = Sefko | first3 = JA. | last4 = Deshpande | first4 = AD. | last5 = Jeffe | first5 = DB. | last6 = Margenthaler | first6 = JA. | title = Factors associated with lymph node assessment in ductal carcinoma in situ: analysis of 1988-2002 seer data. | journal = Ann Surg Oncol | volume = 15 | issue = 10 | pages = 2709-19 | month = Oct | year = 2008 | doi = 10.1245/s10434-008-9947-5 | PMID = 18483831 | url=http://onlinelibrary.wiley.com/doi/10.1002/cncr.24592/pdf}}</ref> that calculates the probability of [[lymph node]] mets based on tumour size. The developed formula is:

:<math>L_{To-Nodes}=1-exp(-Q_n D^Z)</math>

Where:
*<math>L_{To-Nodes}</math> = the probability of the lymph nodes being positive.
*D = the largest dimension of the tumour in millimetres.
*Z = 1.0041.
*<math>Q_n</math> = 0.019.

====Selected values====
{| class="wikitable"
| Tumour size (mm) || Probability
|-
| 5 || 9 %
|-
| 10 || 17 %
|-
| 15 || 25 %
|-
| 20 || 32 %
|-
| 25 || 38 %
|-
| 30 || 44 %
|-
| 35 || 49 %
|-
| 40 || 54 %
|-
| 45 || 58 %
|-
| 50 || 62 %
|}

===Natural history===
There is a theory that up to 22% of small (radiographically detected) breast tumours regress, based on an analysis in a large population.<ref name=pmid19029493>{{Cite journal | last1 = Zahl | first1 = PH. | last2 = Maehlen | first2 = J. | last3 = Welch | first3 = HG. | title = The natural history of invasive breast cancers detected by screening mammography. | journal = Arch Intern Med | volume = 168 | issue = 21 | pages = 2311-6 | month = Nov | year = 2008 | doi = 10.1001/archinte.168.21.2311 | PMID = 19029493 }}</ref> The study is supported by NCI's SEER data.<ref name=pmid19468099>{{Cite journal | last1 = Jatoi | first1 = I. | last2 = Anderson | first2 = WF. | title = Breast cancer overdiagnosis with screening mammography. | journal = Arch Intern Med | volume = 169 | issue = 10 | pages = 999-1000, author reply 1000-1 | month = May | year = 2009 | doi = 10.1001/archinternmed.2009.95 | PMID = 19468099 }}</ref> Also, it generated many comments.<ref name=pmid19029493/>

===Missed macrometastases===
The effect of missed macrometastases is small; this implies using [[IHC]] to look for isolated tumour cells is money that isn't well spent.<ref name=pmid21247310>{{Cite journal | last1 = Weaver | first1 = DL. | last2 = Ashikaga | first2 = T. | last3 = Krag | first3 = DN. | last4 = Skelly | first4 = JM. | last5 = Anderson | first5 = SJ. | last6 = Harlow | first6 = SP. | last7 = Julian | first7 = TB. | last8 = Mamounas | first8 = EP. | last9 = Wolmark | first9 = N. | title = Effect of occult metastases on survival in node-negative breast cancer. | journal = N Engl J Med | volume = 364 | issue = 5 | pages = 412-21 | month = Feb | year = 2011 | doi = 10.1056/NEJMoa1008108 | PMID = 21247310 }}</ref>

=See also=
*[[Breast]].
*[[Non-invasive breast cancer]].

=References=
{{reflist|2}}

=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)].

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

Intracystic papillary breast carcinoma

2015-04-28T10:58:16Z

Sarah: /* IHC */

==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 cyst.
**May have a thick fibrous capsule
**The involved space is ''not'' lined by myoepithelial cells.
*The cyst contains an abnormal epithelial proliferation with cribriform, solid or papillary architecture.
**Loss of myoepithelial cells within the epithelial proliferation is a '''key feature'''.
**Scattered large cells with pale eosinophilic cytoplasm may be observed<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>.
***These cells are so-called globoid cells or clear cells and are immunoreactive for GCDFP-15.
***They should not be mistaken for myoepithelial cells.
**Neoplastic epithelial cells:
***[[Nuclear atypia]] - including: nucleoli, [[nuclear pleomorphism]].

IHC:
*Calponin/p63/SMA/CK5-6
**Loss of myoepithelial cells within the tumour.
**Loss of myoepithelial cells at the cyst wall.
*ER - Homogeneous staining of the epithelial proliferation.

Photos:
<gallery>
Image:Breast PapillaryCarcinomaEncysted 3 PA.JPG|Breast - Intracystic Papillary Carcinoma - Medium power (SKB)
Image:Breast PapillaryCarcinomaEncysted 2 PA.JPG|Breast - Intracystic Papillary Carcinoma - Medium power (SKB)
Image:Breast PapillaryCarcinomaEncysted PA.JPG|Breast - Intracystic Papillary Carcinoma - High power (SKB)
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|Breast - Intracystic papillary adenocarcinoma (top) with associated invasive ductal carcinoma (bottom) (SKB)
</gallery>
*WebPathology<http://www.webpathology.com/images/noimage.gif>
*WebPathology<http://www.webpathology.com/images/noimage.gif>
*WebPathology<http://www.webpathology.com/images/noimage.gif>

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.
***Myoepithelial markers (calponin/p63/SMA +ve)s hould be positive in a benign lesion.
*[[Papillary ductal carcinoma in situ]]
**Papillary DCIS shows myoepithelial cells (calponin/p63/SMA +ve) at the periphery of the involved spaces
**But papillary DCIS should be negative for myoepithelial cells within the focus of DCIS
**Papillary intracystic carcinoma does not show myoepithelial cells at the periphery of the involved spaces
*Invasive papillary carcinoma of the breast
**Similar architecture but no cystic space, frankly invasive.
**Very rare.
*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.
**Infiltrating carcinoma is usually of the 'no special type' variety.
*[[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
*Many potential pitfalls with papillary breast lesions on needle core biopsy.
**Complete excision is recommended<ref>{{Cite journal | last1 = Rizzo | first1 = M. | last2 = Linebarger | first2 = J. | last3 = Lowe | first3 = MC. | last4 = Pan | first4 = L. | last5 = Gabram | first5 = SG. | last6 = Vasquez | first6 = L. | last7 = Cohen | first7 = MA. | last8 = Mosunjac | first8 = M. | title = Management of papillary breast lesions diagnosed on core-needle biopsy: clinical pathologic and radiologic analysis of 276 cases with surgical follow-up. | journal = J Am Coll Surg | volume = 214 | issue = 3 | pages = 280-7 | month = Mar | year = 2012 | doi = 10.1016/j.jamcollsurg.2011.12.005 | PMID = 22244207 }}</ref>.
*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===
*Loss of myoepithelial markers within the lesion.

===References===

2015-04-15T10:16:23Z

Sarah: /* Questions to Ask */

[[Image:Diagram showing the lobes and ducts of a breast CRUK 307.svg|thumb|250px|Diagram of the structure of breast. (CRUK/WC)]]
The '''breast''' is an important organ for the continuance of the species and one that [[pathologist]]s see quite often because it is often afflicted by [[breast cancer|cancer]]. Before women started [[smoking]] in large numbers, it was the number one cause of cancer death in women (in Canada).

Fortunately, breast cancer, these days, has a relatively good prognosis if it is detected early... and this is why there are week-ends to end breast cancer -- there are large numbers of breast cancer survivors that are well, wealthy and can advocate for better care and research into breast cancer.

=Clinical=
Classic presentation:
*Nipple discharge.
*Pain.
*Breast lump/mass.
*New nipple inversion.
*Skin changes, e.g. ''peau d'orange''.

Most common presentation:
*Abnormal/suspicious screening mammogram - suspicious microcalcifications and/or suspicious mass.

===Breast cancer screening===
Breast cancer screening, for normal risk individuals, starts at age 50 in Canada. In the USA, breast screening starts at age 40.

Radiologic screening is less effective in younger individual as:
# The breast is more dense and thus radiologically more difficult to interpret, and
# The incidence of breast cancer is lower.

===Breast radiology===
BI-RADS = Breast Imaging Reporting And Data System:<ref>URL: [http://breastcancer.about.com/od/diagnosis/a/birads.htm http://breastcancer.about.com/od/diagnosis/a/birads.htm]. Accessed on: 16 March 2011.</ref>

*0: Incomplete - come back for more imaging (radiologist ''cha-ching'').
*1: Negative.
*2: Benign finding(s).
*3: Probably benign -- often short follow-up.
*4: Suspicious abnormality -- needs biopsy.
*5: Highly suggestive of malignancy.
*6: [[Pathologist]] says there is a malignancy.

=Specimens=
Three major specimen types:
#Core needle biopsy (CNB).
#Lumpectomy.
#Modified radical mastectomy.

Note:
*Breast [[cytopathology]] is dealt with in the ''[[breast cytopathology]]'' article. Breast cytology is almost extinct unless you happen to be in Australia where for reasons unknown, the art is still taken seriously. Breast cytology is not sensitive or specific enough to justify forgoing a CNB.

===Core needle biopsy===
Work-up of CNBs is dependent on the clinical abnormality:<ref>MUA. 1 October 2010.</ref>
#Mass lesion - usu. obvious what is going on; typically 3 levels.
#Calcifications - abnormality may be very small; typically 10 levels.

===Lumpectomy===
Lumpectomies are usually oriented with short and long suture; '''s'''hort is typically '''s'''uperior (aspect) and '''l'''ong is typically '''l'''ateral (aspect).

===Modified radical mastectomy===
*Usually done with sentinel [[lymph node]] biopsy - as one cannot go back later to do this.

=Where to start=
{{Main|Short_power_list#Breast_pathology|Long_power_list#Breast_pathology}}
The following is a starting point for mentally framing routine breast pathology & some of the challenges in breast pathology:

The key to breast pathology is the myoepithelial cell.
**A benign gland has two cell layers - myoepithelial and epithelial.
**The luminal cell is epithelial
**The basal cells is myoepithelial
***The myoepithelial layer is hard to see at times.
***IHC can aid in visualizing the myoepithelial layer.
***The immunostains used in breast pathology for the myoepithelial layer include: CK5/6, SMA, p63, calponin

===Questions to Ask===
*Is it normal or close to normal?
**Are you familiar with normal/altered but benign/physiologic changes in the breast?
**Do the changes observed explain the biopsy (are you sure you are seeing the radiographic lesion)?
**Have you found the microcalcifications?

*Is it a neoplastic but benign?
**Are you familiar with the common benign breast neoplasms?
**Do you know the morphologic criteria for a benign breast gland?
**Do you know how to use IHC to confirm a benign process?

*Is it an in situ carcinoma?
**Are you familiar with DCIS and LCIS and their variants?
**Do you know the morphologic criteria for in situ carcinoma?
**Do you know how to use ICH to confirm an in situ carcinoma?
**Do you know how to report an in situ carcinoma?

*Is it invasive carcinoma?
**Do you know the morphologic criteria for an invasive gland?
**Do you know how to use IHC to confirm invasion?
**Do you know the morphologic features of typical invasive breast carcinoma?
**Do you know the subtypes?
**Do you understand the implications of some of the medullary/medullary-like subtype (especially in a young patient)?
**Do you know how to use IHC for prognostication?
**Do you understand the implications of triple negativity?
**Do you know how to report a breast carcinoma?

*Is it something stromal/spindled?

===Important Differential Diagnoses===

====Papillary Lesions====
*Nipple adenoma
*Intraductal papilloma
*Papillary ductal carcinoma in situ
*Intracystic papillary carcinoma
*Intracystic papillary carcinoma with an invasive component
*Invasive papillary carcinoma

====Basaloid Lesions====
*Adenoid Cystic Carcinoma of the Breast
*Intracystic Papillary Breast Carcinoma, Solid Variant
*Invasive Papillary Breast Carcinoma, Solid Variant
*Medullary Breast Carcinoma
*Medullary-like Breast Carcinoma
**Know when to start a discussion about BRCA mutations, triple negativity and the 'basal-like molecular phenotype'.

====Spindle Cell Lesions====
*Metaplastic Breast Carcinoma
*Treated Breast Carcinoma
*Mammary Myofibroblastoma
*Phyllodes Tumor - stromal component
*Desmoid Fibromatosis
*Nodular Fasciitis

=== Additional resources ===
*Breast Pathology Info [http://www.breastpathology.info/]
*Digital Atlas of Breast Pathology [http://www.hsc.stonybrook.edu/breast-atlas/]
*Pathology Outlines - Breast Nonmalignant [http://pathologyoutlines.com/breast.html]
*Pathology Outlines - Breast Malignant [http://pathologyoutlines.com/breastmalignant.html]
*WebPathology - Breast [http://www.webpathology.com/atlas_map.asp?section=9]

=Normal=
==Resting==
*Glands -- normally has two cell layers (like the [[prostate]]).
**Myoepithelial cells
***Frequently spindle-like, often hard to see.
**Secretory cells.
*Stroma:
**Not cellular.
**Not myxoid.

May be present:
*Calcification:
**Purple globs (with concentric rings) on H&E = calcium phosphate.
***Q. How to remember? A. '''P'''urple = '''P'''hosphate.
**Calcium oxalate visible with (light) polarization - not assoc. with malignancy.
**Often in the lumen of a gland, may be in the stroma.
**Calcific material typically has a well-demarcated border +/- "sharp corners".
**Radiologists can pick-up calcs (calcifications) that are approximately 100 micrometers; if "calcs" is on the requisition one needs to find calcs this size.<ref>MUA. 1 October 2010.</ref>
***The large calcs seen on radiology are approximately 1/5 - 1/6 the size of a HPF, if the field of view (FOV) is ~0.55 mm (as is the case with 22 mm-10x eye pieces and a 40x objective).

Image:
*[http://www.breastpathology.info/Images/calcs/FatNec1_700.jpg Breast with calcifications (breastpathology.info)].

Notes:
*The architecture is more important than the cytologic features in the diagnosis of malignancy in the breast;<ref>RS. 4 May 2010.</ref> low grade tumours have distorted architecture but normal/near normal cytology.

==Lactational changes==
*[[AKA]] secretory change, [[AKA]] lactational adenoma, [[AKA]] lactating adenoma <ref>URL: [Breast_pathology#Lactational_changes Breast_pathology#Lactational_changes. Accessed on: 3 October 2011.</ref>
===General===
*Lactational adenoma generally arises in during or in the few weeks after pregnancy.
*May be present focally in non-pregnant females.
*"Lactational adenoma"- circumscribed mass displacing the normal breast architecture (hyperplasia plus functional/physiologic change)
*"Lactational change"- normal breast tissue architecture preserved (functional/physiologic change).

ASIDE:
*Some believe ''lactational change'' and ''secretory change'' aren't the same...
**Lactational change = only in lactation.
**Secretory change = other times.
*This hair splitting is clinically irrelevant-- both are benign. Also, experts use the terms interchangeably.<ref name=pmid2879437>{{Cite journal | last1 = Tavassoli | first1 = FA. | last2 = Yeh | first2 = IT. | title = Lactational and clear cell changes of the breast in nonlactating, nonpregnant women. | journal = Am J Clin Pathol | volume = 87 | issue = 1 | pages = 23-9 | month = Jan | year = 1987 | doi = | PMID = 2879437 }}
</ref>

===Microscopic===
Features:<ref>URL: [http://flylib.com/books/en/2.953.1.9/1/ http://flylib.com/books/en/2.953.1.9/1/]. Accessed on: 6 August 2011.</ref>
*Glands dilated.
*Increased number of lobules.
**Relative decrease in intralobular and extralobular stroma.
*Luminal cells enlarged.
**Vacuolated cytoplasm.
**Hobnail morphology - hang into the lumen.
*Myoepithelial cells indistinct - after second trimester.
*Lactational "adenoma" may undergo infarction - Imagine what an infarcted lactational adenoma could look like in a FNA specimen!

DDx:
*[[Secretory carcinoma of the breast]].

====Images====
<gallery>
Image:Lactational_change_-_low_mag.jpg | Lactational change - low mag. (WC/Nephron)
Image:Lactational_change_-_high_mag.jpg | Lactational change - high mag. (WC/Nephron)
Image:Breast LactationalChange MP CTR.jpg|Breast - Lactational Change - medium power (SKB)
Image:Breast LactationalChange HP CTR.jpg|Breast - Lactational Change - high power (SKB)
Image:Breast LactationalAdenoma MP CTR.jpg|Breast - Lactational adenoma - medium power (SKB)
Image:Breast LactationalAdenoma HP CTR.jpg|Breast - Lactational adenoma - high power (SKB)
Image:Breast LactationalAdenoma LP SNP.jpg|Breast - Lactational adenoma - low power (SKB)
Image::Breast LactationalAdenoma MP SNP.jpg|Breast - Lactational adenoma - high power (SKB)
Image:Breast LactatingAdenoma (4) PA.JPG|Breast - Lactational adenoma - low power (SKB)
Image:Breast LactationalAdenoma MP SNP.jpg|Lactational adenoma - high power - in this example, the epithelium is flattened with clear bubbly cytoplasm (SKB)
Image:Breast LactatingAdenoma HP PA.JPG|Breast - Lactational adenoma - high power - shows snouting and decapitation secretion. (SKB)
</gallery>

www:
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=2&cat2=9&cat3=0&cat4=3&stype=n Lactational changes (gfmer.ch)].
*[http://www.webpathology.com/image.asp?case=320&n=7 Lactational changes in an angiosarcoma of the breast (webpathology.com)].
*[http://www.lab.anhb.uwa.edu.au/mb140/CorePages/FemaleRepro/femalerepro.htm#LabMamm Lactating breast (uwa.edu.au)].

==Major Pathologic Patterns==
===General classification===

{{familytree/start}}
{{familytree | | | | | | | | | | | A | | | | | | | | | | | |A='''Breast pathology'''}}
{{familytree | | | | |,|-|-|-|-|-|-|+|-|-|-|-|-|-|.| | | | | |}}
{{familytree | | | | B | | | | | X | | | | |C | | | | |B=Stromal pathology|X=Miscellaneous|C=Glandular pathology}}
{{familytree | |,|-|-|^|-|-|.| | | | | | |,|-|-|-|+|-|-|-|.| |}}
{{familytree | D | | | | E | | | | | F | | G | | H |D=Myxoid|E=Long slit-like spaces|F=Simple epithelium|G=Dilated|H=[[Breast pathology#Cellular lesions|Cellular lesions]]}}
{{familytree | |!| | | |,|-|^|-|.| | | | |!| | | |!| | | |!| |}}
{{familytree | I | | J | | K | | | L | | M | | N |I=[[Fibroadenoma]]|J=Malignant features|K=Benign features|L=[[Tubular carcinoma of the breast|Tubular carcinoma]]|M=[[FEA]], [[FCC]], [[Columnar cell change|CCC]]|N=[[FEHUT]], Neoplastic, Malignant}}
{{familytree | | | | | |!| | | |!| | | | | | | | | | | | | | |}}
{{familytree | | | | | O | | P | | | | | | | | | | | | | ||O=[[Phyllodes tumour|Malignant phyllodes]]|P=[[Phyllodes tumour|Benign phyllodes]]}}
{{familytree/end}}

Notes:
*The challenges in breast pathology are in: the ''Simple epithelium'' category and the ''Cellular lesions'' category.
*''Neoplastic'' includes: ADH and LDH.
*''Malignant'' includes: DCIS, LCIS, ductal carcinoma (DC) and lobular carcinoma (LC), some papillary lesions.
*''Lobular carcinoma'' (a '''pitfall''') may appear to be a stromal problem, i.e. the stroma looks too cellular.
*''Miscellaneous'' includes rare tumours of the breast that do not fit into another category, i.e. [[metastases]], [[lymphoma]]s, [[melanoma]], sarcomas. Skin-related pathology is dealt within the ''[[dermatologic neoplasms]]'' article. ''[[Paget disease of the breast]]'', which may be seen in the context of malignant breast lesions, is discussed in its own article.

===Cellular lesions===

{{familytree/start}}
{{familytree | | | | | | | | | | | | | C | | | | | | | | |C='''Cellular lesions (Glandular)'''}}
{{familytree | | | | | |,|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| |}}
{{familytree | | | | | SP | | SS | | DE | | SF | | FC |SP=Equal spacing, punched-out|SS=Streaming, periph. slit-like spaces.|DE=Discohesive cells, expanded gl.|SF=Single cells or single file|FC=Fibrovascular cores}}
{{familytree | | | | | |!| | | |!| | | |!| | | |!| | | |!| |}}
{{familytree | | | | | DL | | FEHUT | | LL | | LC | | PL |DL=Ductal lesion|FEHUT=[[FEHUT]]|LL=Lobular lesion|LC=[[Invasive lobular carcinoma|Lobular carcinoma]]|PL=[[Breast pathology#Papillary lesions|Papillary lesions]]}}
{{familytree | | | |,|-|^|-|.| | | |,|-|^|-|.| | | | | | | |}}
{{familytree | | | TL | | OL | | LTF | | GTF | | | | | | |TL=Two cell layers|OL=One cell layer|LTF=<50% of gl.|GTF=>50% of gl.}}
{{familytree | | | |!| | | |!| | | |!| | | |!| | | | | | | |}}
{{familytree | | | DNI | | DC | | ALH | | LCIS | | | | | | |DNI=Ductal non-inv. neoplasm|DC=[[Invasive ductal carcinoma of the breast|Ductal carcinoma]]|ALH=[[ALH]]|LCIS=[[LCIS]]}}
{{familytree | |,|-|^|-|.| | | | | | | | | | | | | | | | | |}}
{{familytree | LE | | SE | | | | | | | | | | | | | | | | |LE=Large extent|SE=Small extent}}
{{familytree | |!| | | |!| | | | | | | | | | | | | | | | | |}}
{{familytree | DCIS | | ADH | | | | | | | | | | | | | | | | |DCIS=[[DCIS]]|ADH=[[ADH]]}}
{{familytree/end}}
Notes:
*The largest challenge is: differentiating between the first two categories on level 2, i.e. ''equal spacing' vs. ''streaming''.
*The ''fibrovascular cores'' must arise from a tuft, i.e. if they are arising directly from the wall of glands only it is likely ''papillary DCIS''.

===Papillary lesions===

{{familytree/start}}
{{familytree | | | | | | | | | | | P | | | | | | |P='''Papillary lesions'''}}
{{familytree | | | | | |,|-|-|-|-|-|^|-|-|-|-|-|.| |}}
{{familytree | | | | | MP | | | | | | | | | |MA |MP=Myoepithelial cells '''present'''|MA=Myoepithelial cells '''absent'''}}
{{familytree | |,|-|-|-|^|-|-|-|.| | | | | | | |!| |}}
{{familytree | D | | | | | | E | | | | | | F |D=Unremarkable papillae|E=Atypia ''or'' arch. abnorm. ''or'' cellular proliferation|F=Neoplastic cells present}}
{{familytree | |!| | | |,|-|-|-|+|-|-|-|.| | | |!| |}}
{{familytree | G | | H | | I | | J | | K |G=[[intraductal papilloma|Benign intraductal papilloma]]|H=High grade atypia|I=Low grade atypia ''or'' abnorm. arch.|J=''Only'' cellular proliferation|K=[[Invasive papillary carcinoma of the breast|Intracystic (encapsulated) papillary ca.]]}}
{{familytree | | | | | |!| | | |!| | | |!| | | | | |}}
{{familytree | | | | | L | | |!| | | N | | | | |L=[[DCIS]] in papilloma|N=[[FEHUT]] in papilloma}}
{{familytree | | | | | | | |,|-|^|-|.| | | | | | | |}}
{{familytree | | | | | | | P | | Q | | | | | | |P=>3 mm extent|Q=<3 mm extent}}
{{familytree | | | | | | | |!| | | |!| | | | | | | |}}
{{familytree | | | | | | | R | | S | | | | | | |R=DCIS in papilloma|S=[[ADH]] in papilloma}}
{{familytree/end}}

Notes:
*Adapted from ''Mulligan & O'Malley''.<ref>{{cite journal |author=Mulligan AM, O'Malley FP |title=Papillary lesions of the breast: a review |journal=Adv Anat Pathol |volume=14 |issue=2 |pages=108–19 |year=2007 |month=March |pmid=17471117 |doi=10.1097/PAP.0b013e318032508d |url=}}</ref>
*The most important decision is the first one: myoepithelial cells present vs. absent.
*''abnorm. arch.'' = abnormal architecture present.
*''DCIS'' = ductal carcinoma in situ.
*''FEHUT'' = florid epithelial hyperplasia of the usual type.
*''extent'' refers to the size of the abnormal cell population within the papillary lesion.

=Malignant lesions=
==Non-invasive breast cancer==
{{main|Non-invasive breast cancer}}
This includes the ''in situ'' lesions - ''DCIS'' and ''LCIS''.

==Invasive breast cancer==
{{main|Invasive breast cancer}}
This is includes descriptions of the usual types... and the not so common ones.

=Common benign lesions=
The breast has lots of benign things. Unlike the prostate, the where benign is called ''benign'', everything has a name. It is more common among breast pathologists to sign-out things like: ''apocrine metaplasia'' (benign), ''columnar cell change'' (benign), and ''florid epithelial hyperplasia of the usual type (FEHUT)'' - instead of - ''benign breast tissue''.

==Mild epithelial hyperplasia==
===General===
*No increased risk of malignancy.
**Often ''not'' reported - as it has not clinical signficance.
*Has to be separated from ''[[moderate epithelial hyperplasia]]'' / ''[[florid epithelial hyperplasia]]''.

===Microscopic===
Features:<ref>{{Ref BP|159-160}}</ref>
*Breast glands with three ''or'' four cell layers above the basement membrane.
*Variable cells.

Note:
*No nuclear atypia.

DDx:
*[[Flat epithelial atypia]].
*[[Moderate epithelial hyperplasia]] / [[florid epithelial hyperplasia]].
*[[Atypical ductal hyperplasia]].

==Apocrine metaplasia==
===General===
*Benign/not significant. Can be considered to be pretty wallpaper in the house of breast pathology.

====Etiology====
*Increased number of mitochondria.
**In other body sites this has different names, e.g. ''[[Hurthle cell change]]'' (thyroid), ''[[oncocytoma|oncocytic]] change'' (kidney - [[oncocytoma]], thyroid).

===Microscopic===
Features:
*Eosinophilic cytoplasm - '''key feature'''.
*Voluminous pink cytoplasm.
*Apocrine snouts may be present.
**Small protrusiona at the apical aspect of the cell (composed of cytoplasm and plasma membrane).
*Central round nucleus
**Prominent nuclear membrane.
**Prominent, often single nucleolus.

Note:
*Apocrine changes, i.e. cytoplasmic eosinophilia, can appear in malignant tumours; eosinophilia doesn't make something benign.

====Images====
<gallery>
Image:Fibrocystic_change_-_very_high_mag.jpg | FCC with apocrine metaplasia (right bottom of image) - high mag. (WC/Nephron).
Image:Breast ApocrineChange HP CTR.jpg|Breast - Apocrine Change - high power (SKB)
</gallery>

==Duct ectasia==
*Dilation of large ducts secondary to luminal obstruction by inspissated secretions
*Presentation
**~age 40-50, possibly with cheesy nipple discharge
*Pathology
**Duct lumen dilated and containing foamy macrophages
**Necrosis/shedding of epithelium
**If duct rupture: chronic and granulomatous inflammation of periductal region
**Fibrotic thickening of duct wall
<gallery>
Image:Breast DuctEctasia LP PA.JPG|Breast - Duct Ectasia - low power (SKB)
Image:Breast DuctEctasia MP2 PA.JPG|Breast - Duct Ectasia - low power (SKB)
Image:Breast DuctEctasia MP PA.JPG|Breast - Duct Ectasia - medium power (SKB)
</gallery>

==Fibrocystic change==
*Abbreviated ''FCC''.
*[[AKA]] ''fibrocystic changes''.

===General===
*Really common.
*Benign.

===Microscopic===
Features:
*Dilated glands - '''key change'''.
**Glands normal: two cell layers present.
*Often seen together with ''apocrine metaplasia''.

====Images====
<gallery>
Image:Fibrocystic_change_-_intermed_mag.jpg | FCC - intermed. mag. (WC/Nephron)
Image:Fibrocystic_change_-_very_high_mag.jpg | FCC - high mag. (WC/Nephron)
Image:Phyllodes_tumour_-_very_low_mag.jpg | FCC - left of image - and a phyllodes tumour - very low mag. (WC/Nephron)
</gallery>

==Columnar cell change==
*Abbreviated ''[[CCC]]''.
*[[AKA]] ''blunt duct adenosis''.
===General===
*Columnar cell change is associated with (benign) calcification - '''key point'''.

===Microscopic===
Features:
*Secretory cells (line gland lumen) have columnar morphology.
*May have "apical snouts".
**Blebs or round balls eosinophilic material appear to be adjacent to the cell at their luminal surface.
**The snouts are attached to the cell-- appear as round ball only in the plane of section.
*Cytoplasm +/-eosinophilia.
*Often purple luminal calcifications

DDx:
*Flat epithelial atypia (>2 cell layers).{{Fact}}
**If the columnar cells shows low to intermediate grade atypia the process is termed "flat epithelial atypia"
**If higher grade atyia is present the lesion is termed "flat DCIS" (clinging carcinoma)

Image:
*[http://webpathology.com/image.asp?case=652&n=1 Columnar cell change (webpathology.com)].

==Gynecomastoid hyperplasia==
*[[AKA]] ''gynecomastia''.
{{Main|Gynecomastoid hyperplasia}}

=Lesions with increased risk of malignancy=

==Florid epithelial hyperplasia==
*[[AKA]] ''florid epithelial hyperplasia'', abbreviated ''FEH''.
*AKA ''florid epithelial hyperplasia of the usual type'', abbreviated ''FEHUT''.
*AKA ''epithelial hyperplasia'' - term should be avoid as it could lead to confusion with ''[[mild epithelial hyperplasia]]''.

===General===
*Mild increased risk of malignancy ~ 1.5-2x.<ref>{{Ref PCPBoD8|542}}</ref>
*Has to be separated from ''[[mild epithelial hyperplasia]]''.

Note:
*''Moderate epithelial hyperplasia'' redirects to this section.
**It is generally not separated from FEH, as the prognosis is thought to be the same.

===Microscopic===
Features:<ref>{{Ref BP|159-160}}</ref>
*Breast glands with ''more than'' four cell layers above the basement membrane - '''key feature'''.
*Irregular cell spacing; streaming.
*Slit-like lumina, esp. at the periphery of the duct.
*No [[DCIS]]-like architecture (not cribriform, not papillary, not micropapillary, not solid).
*No nuclear atypia - usually no [[nucleoli]].

Memory device ''CLEAN'':
*'''C'''ell spacing is irregular, '''L'''umina are slit-like, '''E'''xtent is less than 2 mm or 2 ducts, '''A'''rchitecture ''not'' DCIS-like, '''N'''uclear atypia ''not'' present.

DDx:
*[[Mild epithelial hyperplasia]].
*[[Atypical ductal hyperplasia]].
*Cribriform [[ductal carcinoma in situ]]

==Sclerosing adenosis==
===General===
*Can be scary... can look like [[ductal carcinoma]].
*Derived from ''sclerosing''<ref>URL: [http://dictionary.reference.com/browse/sclerosis http://dictionary.reference.com/browse/sclerosis]. Accessed on: 16 March 2011.</ref> (hardening) and ''adenosis'' (glandular enlargement).
**Think ''scaring'' + ''lotsa glands'' and you're pretty close.
*Management: follow-up, no further treatment.<ref>URL: [http://www.breastcancercare.org.uk/breast-cancer-information/breast-awareness/benign-breast-conditions/sclerosing-lesions http://www.breastcancercare.org.uk/breast-cancer-information/breast-awareness/benign-breast-conditions/sclerosing-lesions]. Accessed on: 30 April 2012.</ref>
===Microscopic===
Features:
*Acini are smaller than usual and there are more of them.
**Acini often slit-like.
*Fibrosis (scleroses) - pink on H&E surrounds the acini.
**Can mimic a [[desmoplastic reaction]].

Notes:
*The acini should:
**Be in lobular arrangements, i.e. in groups (benign appearance at low power) - '''key feature'''.
**Have two cell layers like well-behaved breast glands do.

DDx:
*Low-grade ductal carcinoma.
*[[Tubular adenoma of the breast]].
*[[Adenomyoepithelioma]].<ref name=chu>Chu et al. (2006). Adenomyoepithelioma of the Breast — A Case Report. Tzu Chi Med J. Vol. 18 No. 1. URL:URL: [http://www.tzuchi.com.tw/file/tcmj/95-1/2-8.pdf http://www.tzuchi.com.tw/file/tcmj/95-1/2-8.pdf]. Accessed on: 28 April 2012.</ref>

==Flat epithelial atypia==
===General===
Epidemiology:
*Associated with ADH & DCIS; may represent a non-obligate precursor lesion of ADH & DCIS.<ref name=pmid18384213>{{Cite journal | last1 = Lerwill | first1 = MF. | title = Flat epithelial atypia of the breast. | journal = Arch Pathol Lab Med | volume = 132 | issue = 4 | pages = 615-21 | month = Apr | year = 2008 | doi = 10.1043/1543-2165(2008)132[615:FEAOTB]2.0.CO;2 | PMID = 18384213 }}</ref>
*Low risk of progression to invasive malignancy.<ref name=pmid12927037>{{Cite journal | last1 = Schnitt | first1 = SJ. | title = The diagnosis and management of pre-invasive breast disease: flat epithelial atypia--classification, pathologic features and clinical significance. | journal = Breast Cancer Res | volume = 5 | issue = 5 | pages = 263-8 | month = | year = 2003 | doi = 10.1186/bcr625 | PMID = 12927037 }}</ref>

Management:
*Excision.

===Microscopic===
Features:
*"Flat" ~ three cells thick.
*Hypercellular gland -- several layers.
*Columnar cell morphology.
*+/-Apical snouts.

===Images===
<gallery>
Image:Breast FlatAtypia (3) PA.JPG|Breast - Flat Atypia (SKB)
</gallery>

DDx:
*[[Columnar cell change]].
*Columnar cell hyperplasia.
*[[ADH]].
*Flat [[DCIS]] (clinging carcinoma).
*Apocrine cyst - granular cytoplasm.
*[[Tubular carcinoma]] - should be considered due to the association.

===Molecular===
*Loss of 16q.
**Not used for [[diagnosis]].

==Complex sclerosing lesion==
*[[AKA]] ''radial scar''.
===General===
*The term ''radial scar'' is a misnomer. It isn't a ''scar''. It isn't associated with prior trauma or surgery.<ref name=Ref_PBoD8_1072>{{Ref PBoD8|1072}}</ref>
*May appear malignant on imaging.<ref name=pmid11167596>{{cite journal |author=Ung OA, Lee WB, Greenberg ML, Bilous M |title=Complex sclerosing lesion: the lesion is complex, the management is straightforward |journal=ANZ J Surg |volume=71 |issue=1 |pages=35–40 |year=2001 |month=January |pmid=11167596 |doi= |url=}}</ref>
*Associated with subsequent elevated risk of breast cancer.<ref>URL: [http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Radial_Scars.asp http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Radial_Scars.asp]. Accessed on: 4 May 2010.</ref>
*Management - usu. surgical excision.<ref name=pmid14514771>{{cite journal |author=Kennedy M, Masterson AV, Kerin M, Flanagan F |title=Pathology and clinical relevance of radial scars: a review |journal=J. Clin. Pathol. |volume=56 |issue=10 |pages=721–4 |year=2003 |month=October |pmid=14514771 |pmc=1770086 |doi= |url=}}</ref>
===Gross===
*Spiculated mass.
*Usually small - 3-7 mm.

====Image====
<gallery>
Image:Radial_scar.jpg | Radial scar - gross. (WC)
</gallery>
===Microscopic===
Features:<ref name=pmid14514771>{{cite journal |author=Kennedy M, Masterson AV, Kerin M, Flanagan F |title=Pathology and clinical relevance of radial scars: a review |journal=J. Clin. Pathol. |volume=56 |issue=10 |pages=721–4 |year=2003 |month=October |pmid=14514771 |pmc=1770086 |doi= |url=}}</ref><ref name=Ref_BP91>{{Ref BP|91}}</ref>
*Stellate appearance (low magnification).
*Center of lesion has "fibroelastosis" - stroma light pink (on H&E) - '''key feature'''.
**Scar like stroma with entrapped normal breast ducts and lobules.
**Glands appear to enlarge with distance from center of lesion.

Notes:
*Histomorphologic appearance may mimic a [[desmoplastic reaction]] of the stroma - leading to a misdiagnosis of malignancy.
*"[[Hyaline]] - pink stuff on H&E - is the key."

DDx:
*[[Invasive ductal carcinoma]] - should be considered if the lesion is asymmetrical ''or'' glands are dilated centrally.

====Images====
*[http://www.breastpathology.info/Images/Benign/Radial_scar/rs3a_700.jpg Radial scar (breastpathology.info)].

===IHC===
Features:
*p63 +ve.
*Calponin +ve.

Note:
*HMWK +ve/-ve. (???)

=Stromal lesions=
This section (below) covers stromal lesions of the breast, which vary from benign to malignant. The most common is (the benign) [[fibroadenoma]].

Non-breast stroma stromal lesions are covered in the ''[[soft tissue lesions]]'' article. [[Angiosarcoma]] (dealt with in the ''[[vascular tumours]]'' article) is the most common (non-breast stroma) sarcoma of the breast, and classically arises after treatment for a breast carcinoma.

==Fibroadenoma==
{{Main|Fibroadenoma}}

==Phyllodes tumour==
*Previously ''cystosarcoma phyllodes''.
{{Main|Phyllodes tumour}}

==Pseudoangiomatous stromal hyperplasia==
*Abbreviated ''PASH''.
*[[AKA]] ''nodular myofibroblastic stromal hyperplasia of the mammary gland''.<ref name=pmid12199757>{{Cite journal | last1 = Leon | first1 = ME. | last2 = Leon | first2 = MA. | last3 = Ahuja | first3 = J. | last4 = Garcia | first4 = FU. | title = Nodular myofibroblastic stromal hyperplasia of the mammary gland as an accurate name for pseudoangiomatous stromal hyperplasia of the mammary gland. | journal = Breast J | volume = 8 | issue = 5 | pages = 290-3 | month = | year = | doi = | PMID = 12199757 }}</ref>
{{Main|Pseudoangiomatous stromal hyperplasia}}

=Weird stuff=
Like in all niches of pathology... there is weird stuff.

==Mammary hamartoma==
*[[AKA]] ''breast hamartoma''.
{{Main|Mammary hamartoma}}

==Collagenous spherulosis==
*[[AKA]] ''mucinous spherulosis'', [[AKA]] ''spherulosis''.<ref name=stanford_collspher>URL: [http://surgpathcriteria.stanford.edu/breast/collspher/ http://surgpathcriteria.stanford.edu/breast/collspher/]. Accessed on: 4 September 2011.</ref>
{{Main|Collagenous spherulosis}}

==Nipple adenoma==
*[[AKA]] ''nipple duct adenoma''.
*[[AKA]] ''nipple adenoma of breast''.
*[[AKA]] ''adenoma of the nipple''.
*[[AKA]] ''florid papillomatosis of the nipple''.<ref name=pmid22342578>{{Cite journal | last1 = Boutayeb | first1 = S. | last2 = Benomar | first2 = S. | last3 = Sbitti | first3 = Y. | last4 = Harroudi | first4 = T. | last5 = Hassam | first5 = B. | last6 = Errihani | first6 = H. | title = Nipple adenoma in a man: An unusual case report. | journal = Int J Surg Case Rep | volume = 3 | issue = 5 | pages = 190-2 | month = | year = 2012 | doi = 10.1016/j.ijscr.2011.05.008 | PMID = 22342578 }}</ref>
{{Main|Nipple adenoma}}

==Intraductal papilloma==
*[[AKA]] ''papilloma''.
{{Main|Intraductal papilloma}}

==Lymphocytic mastitis==
*If the individual has [[diabetes mellitus]] it is ''[[diabetic mastopathy]]''.
{{Main|Lymphocytic mastitis}}

==Microglandular adenosis==
:'''''Not''' to be confused with [[microglandular hyperplasia]]''.
*Abbreviated ''MGA''.
{{Main|Microglandular adenosis}}

==Adenomyoepithelioma==
{{Main|Adenomyoepithelioma}}

==Mammary myofibroblastoma==
*[[AKA]] ''breast myofibroblastoma''.
*[[AKA]] ''myofibroblastoma of the breast''.
{{Main|Mammary myofibroblastoma}}

==Squamous metaplasia of lactiferous ducts==
*Abbreviated ''SMOLD''.
{{Main|Squamous metaplasia of lactiferous ducts}}

==Granular cell tumour of the breast==
{{Main|Granular cell tumour}}
===General===
*Uncommon.

===Gross===
*May be a spiculated mass and thus mimic malignancy radiologically.<ref name=pmid16615051>{{Cite journal | last1 = Yang | first1 = WT. | last2 = Edeiken-Monroe | first2 = B. | last3 = Sneige | first3 = N. | last4 = Fornage | first4 = BD. | title = Sonographic and mammographic appearances of granular cell tumors of the breast with pathological correlation. | journal = J Clin Ultrasound | volume = 34 | issue = 4 | pages = 153-60 | month = May | year = 2006 | doi = 10.1002/jcu.20227 | PMID = 16615051 }}</ref>

===Microscopic===
:See ''[[granular cell tumour]]''.

DDx:
*[[Invasive lobular carcinoma]].<ref name=pmid21398688>{{Cite journal | last1 = Tan | first1 = PH. | last2 = Harada | first2 = O. | last3 = Thike | first3 = AA. | last4 = Tse | first4 = GM. | title = Histiocytoid breast carcinoma: an enigmatic lobular entity. | journal = J Clin Pathol | volume = 64 | issue = 8 | pages = 654-9 | month = Aug | year = 2011 | doi = 10.1136/jcp.2011.088930 | PMID = 21398688 }}</ref>

=See also=
*[[Breast cytopathology]].
*[[Salivary gland]].
*[[Invasive breast cancer]].
*[[Non-invasive breast cancer]].

=References=
{{reflist|2}}

=External links=
*[http://www.breastpathology.info/Case_of_the_month/cotm_root.html A collection of breast pathology cases (breastpathology.info)].
*[http://www.webpathology.com/atlas_map.asp?section=9 Breast pathology (webpathology.com)].

[[Category:Breast pathology]]