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=
Classic presentation:
===Clinical Presentations of Breast Pathology===
*'''Abnormal/suspicious screening mammogram'''
**Suspicious microcalcifications and/or suspicious mass.
**Most common history on the specimen requisition
**May be accompanied by a [[BI-RADS]] score.
*Nipple discharge.
*Nipple discharge.
*Pain.
*Pain.
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*New nipple inversion.
*New nipple inversion.
*Skin changes, e.g. ''peau d'orange''.
*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===
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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 (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=
=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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