Difference between revisions of "Breast pathology"

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Breast pathology (view source)

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


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.
Fortunately, breast cancer, in this day, has a relatively good prognosis if it is detected early.


=Clinical=
=Clinical=
===Clinical Presentations of Breast Pathology===
===Clinical Presentations of Breast Pathology===
*'''Abnormal/suspicious screening mammogram''' - suspicious microcalcifications and/or suspicious mass.
*'''Abnormal/suspicious screening mammogram'''
**Suspicious microcalcifications and/or suspicious mass.
**Most common history on the specimen requisition
**Most common history on the specimen requisition
**May be accompanied by a BI-RADS score (see below)
**May be accompanied by a [[BI-RADS]] score.
*Nipple discharge.
*Nipple discharge.
*Pain.
*Pain.
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===Breast radiology===
===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>
{{Main|Breast imaging reporting and data system}}
 
*0: Incomplete - come back for more imaging.
*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.
 
Note - if you have a high BI-RADS score on the biopsy requisition, and no histologic findings, be sure to correlate with the specimen radiograph, level the specimen to exhaustion and note the lack of correlating lesion on your report.


=Specimens=
=Specimens=
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#Mass lesion - usu. obvious what is going on; typically 3 levels.
#Mass lesion - usu. obvious what is going on; typically 3 levels.
#Calcifications - abnormality may be very small; typically 10 levels.
#Calcifications - abnormality may be very small; typically 10 levels.
Note - if you have a high BI-RADS score on the biopsy requisition, and no correlating histologic findings, be sure to correlate with the specimen radiograph, consider leveling the specimen to exhaustion and/or note the lack of a correlating lesion on your report.


===Lumpectomy===
===Lumpectomy===
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***The myoepithelial layer is hard to see at times.
***The myoepithelial layer is hard to see at times.
***IHC can aid in visualizing the myoepithelial layer.
***IHC can aid in visualizing the myoepithelial layer.
***The immunostains used in breast pathology for the myoepithelial layer include: CK5/6, SMA, p63, calponin
***The immunostains used in breast pathology for the myoepithelial layer include: [[CK5/6]], SMA, [[p63]] and calponin.


===Questions to Ask===
===Questions to Ask===
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**Do you know the morphologic criteria for in situ carcinoma?
**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 use ICH to confirm an in situ carcinoma?
**Do you know how to report an in situ carcinoma?
**Do you know how to report an in situ breast carcinoma?


*Is it invasive carcinoma?
*Is it invasive carcinoma?
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**Do you know how to use IHC for prognostication?
**Do you know how to use IHC for prognostication?
**Do you understand the implications of triple negativity?
**Do you understand the implications of triple negativity?
**Do you know how to report a breast carcinoma?
**Do you know how to report an invasive breast carcinoma?


*Is it something stromal/spindled?
*Is it something stromal/spindled?
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====Papillary Lesions====
====Papillary Lesions====
*Nipple adenoma
*Nipple adenoma.
*Intraductal papilloma
*Intraductal papilloma.
*Papillary ductal carcinoma in situ
*Papillary ductal carcinoma in situ.
*Intracystic papillary carcinoma
*Intracystic papillary carcinoma.
*Intracystic papillary carcinoma with an invasive component
*Intracystic papillary carcinoma with an invasive component.
*Invasive papillary carcinoma
*Invasive papillary carcinoma.


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


====Spindle Cell Lesions====
====Spindle Cell Lesions====
*Metaplastic Breast Carcinoma
*Metaplastic breast carcinoma.
*Treated Breast Carcinoma
*Treated breast carcinoma.
*Mammary Myofibroblastoma
*Mammary myofibroblastoma.
*Phyllodes Tumor - stromal component
*Phyllodes Tumour - stromal component.
*Desmoid Fibromatosis
*Desmoid fibromatosis.
*Nodular Fasciitis
*Nodular fasciitis.


=== Additional resources ===
=== Additional resources ===
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*WebPathology - Breast [http://www.webpathology.com/atlas_map.asp?section=9]
*WebPathology - Breast [http://www.webpathology.com/atlas_map.asp?section=9]


=Normal=
=Normal breast=
==Resting==
==Resting breast==
*Glands -- normally has two cell layers (like the [[prostate]]).
*Glands -- normally has two cell layers (like the [[prostate]]).
**Myoepithelial cells
**Myoepithelial cells
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May be present:
May be present:
*Calcification:
*[[Breast calcifications|Calcification]]:
**Purple globs (with concentric rings) on H&E = calcium phosphate.
**Purple globs (with concentric rings) on H&E = calcium phosphate.
***Q. How to remember? A. '''P'''urple = '''P'''hosphate.
***Q. How to remember? A. '''P'''urple = '''P'''hosphate.
**Calcium oxalate visible with (light) polarization - not assoc. with malignancy.
**Calcium oxalate visible with (light) [[polarization]] - not associated with [[breast cancer|malignancy]].
**Often in the lumen of a gland, may be in the stroma.
**Often in the lumen of a gland, may be in the stroma.
**Calcific material typically has a well-demarcated border +/- "sharp corners".
**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>  
**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).
***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:
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.
*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.
===Image===
*[http://www.breastpathology.info/Images/calcs/FatNec1_700.jpg Breast with calcifications (breastpathology.info)].
*[http://www.wjso.com/content/7/1/70/figure/F3 Resting breast tissue (wjso.com)].


==Lactational changes==
==Lactational changes==
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*Luminal cells enlarged.
*Luminal cells enlarged.
**Vacuolated cytoplasm.
**Vacuolated cytoplasm.
**Hobnail morphology - hang into the lumen.
**[[Hobnail morphology]] - hang into the lumen.
*Myoepithelial cells indistinct - after second trimester.
*Myoepithelial cells indistinct - after second trimester.
*Lactational "adenoma" may undergo infarction - Imagine what an infarcted lactational adenoma could look like in a FNA specimen!
*Lactational "adenoma" may undergo infarction - Imagine what an infarcted lactational adenoma could look like in a FNA specimen!
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{{familytree | D | | | | | | E | | | | | | F |D=Unremarkable<br>papillae|E=Atypia ''or'' arch. abnorm.<br>''or'' cellular proliferation|F=Neoplastic cells<br>present}}
{{familytree | D | | | | | | E | | | | | | F |D=Unremarkable<br>papillae|E=Atypia ''or'' arch. abnorm.<br>''or'' cellular proliferation|F=Neoplastic cells<br>present}}
{{familytree | |!| | | |,|-|-|-|+|-|-|-|.| | | |!| |}}
{{familytree | |!| | | |,|-|-|-|+|-|-|-|.| | | |!| |}}
{{familytree | G | | H | | I | | J | | K |G=[[intraductal papilloma|Benign<br>intraductal<br>papilloma]]|H=High grade atypia|I=Low grade atypia<br>''or'' abnorm. arch.|J=''Only'' cellular<br>proliferation|K=[[Invasive papillary carcinoma of the breast|Intracystic<br> (encapsulated)<br>papillary ca.]]}}
{{familytree | G | | H | | I | | J | | K |G=[[intraductal papilloma of the breast|Benign<br>intraductal<br>papilloma]]|H=High grade atypia|I=Low grade atypia<br>''or'' abnorm. arch.|J=''Only'' cellular<br>proliferation|K=[[Encapsulated papillary carcinoma of the breast|Intracystic<br> (encapsulated)<br>papillary ca.]]}}
{{familytree | | | | | |!| | | |!| | | |!| | | | | |}}
{{familytree | | | | | |!| | | |!| | | |!| | | | | |}}
{{familytree | | | | | L | | |!| | | N | | | | |L=[[DCIS]] in<br>papilloma|N=[[FEHUT]] in<br>papilloma}}
{{familytree | | | | | L | | |!| | | N | | | | |L=[[DCIS]] in<br>papilloma|N=[[FEHUT]] in<br>papilloma}}
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===General===
===General===
*No increased risk of malignancy.
*No increased risk of malignancy.
**Often ''not'' reported - as it has not clinical signficance.
**Often ''not'' reported - as it has no clinical signficance.
*Has to be separated from ''[[moderate epithelial hyperplasia]]'' / ''[[florid epithelial hyperplasia]]''.
*Has to be separated from ''[[moderate epithelial hyperplasia]]'' / ''[[florid epithelial hyperplasia]]''.


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==Apocrine metaplasia==
==Apocrine metaplasia==
===General===
{{Main|Apocrine metaplasia of the breast}}
*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==
==Duct ectasia==
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==Fibrocystic change==
==Fibrocystic change==
*Abbreviated ''FCC''.
{{Main|Breast fibrocystic changes}}
*[[AKA]] ''fibrocystic changes''.
*[[AKA]] ''fibrocystic changes'' (abbreviated ''FCC'').
 
===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==
==Columnar cell change==
*Abbreviated ''[[CCC]]''.
{{Main|Columnar cell change of the breast}}
*[[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==
==Gynecomastoid hyperplasia==
*[[AKA]] ''gynecomastia''.
*[[AKA]] ''gynecomastia''.
{{Main|Gynecomastoid hyperplasia}}
{{Main|Gynecomastoid hyperplasia}}
==Breast prostheses==
{{Main|Breast prostheses}}


=Lesions with increased risk of malignancy=
=Lesions with increased risk of malignancy=


==Florid epithelial hyperplasia==
==Florid epithelial hyperplasia==
*[[AKA]] ''florid epithelial hyperplasia'', abbreviated ''FEH''.
*AKA ''florid epithelial hyperplasia of the usual type'', abbreviated ''FEHUT''.
*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]]''.
*AKA ''epithelial hyperplasia'' - term should be avoid as it could lead to confusion with ''[[mild epithelial hyperplasia]]''.
 
*AKA ''usual ductal hyperplasia'', abbreviated ''UDH''.
===General===
{{Main|Florid epithelial hyperplasia}}
*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==
==Sclerosing adenosis==
===General===
{{Main|Sclerosing adenosis of the breast}}
*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==
==Flat epithelial atypia==
===General===
*Abbreviated ''FEA''.
Epidemiology:
{{Main|Flat epithelial atypia}}
*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==
==Complex sclerosing lesion==
*[[AKA]] ''radial scar''.
*[[AKA]] ''radial scar''.
===General===
{{Main|Complex sclerosing lesion}}
*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=
=Stromal lesions=
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==Intraductal papilloma==
==Intraductal papilloma==
*[[AKA]] ''papilloma''.
*[[AKA]] ''papilloma''.
{{Main|Intraductal papilloma}}
{{Main|Intraductal papilloma of the breast}}


==Lymphocytic mastitis==
==Lymphocytic mastitis==
Michael
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