Difference between revisions of "Breast pathology"

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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).   
[[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 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.
 
The world of pathology can neatly be divided into two... those that like the breast and those that don't.


=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=
Breast comes in three main flavours:
Three major specimen types:
#Core needle biopsy (CNB).
#Core needle biopsy (CNB).
#Lumpectomy.
#Lumpectomy.
#Radical mastectomy.
#Modified radical mastectomy.


Lumpectomies are usually oriented with short and long suture; '''s'''hort is typically '''s'''uperior (aspect) and '''l'''ong is typically '''l'''ateral (aspect).
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.
Breast [[cytopathology]] is dealt with in the ''[[breast cytopathology]]'' article.  It is almost dead, as it is not as sensitive and specific as CNB.


===Core needle biopsy===
Work-up of CNBs is dependent on the clinical abnormality:<ref>MUA. 1 October 2010.</ref>
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.
#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.


=Normal histology=
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===
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]] and 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 breast 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 an invasive 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 Tumour - 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 breast=
==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 approx. 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).


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


Notes:
ASIDE:
*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.
*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!


=Where to start=
DDx:
The following entities are a starting point for understanding routine breast pathology & some of challenges in breast pathology:
*[[Secretory carcinoma of the breast]].
#Apocrine change.
#*Pink benign cells.
#Columnar cell change.
#*Columnar cells with blebs ("snouts") - often have calcifications (purple).
#[[Fibroadenoma]].
#*Abundant myxoid (light/blanched) stroma - very common.
#EHUT (epithelial hyperplasia of the usual type).
#*Too many cells in a duct, cells overlap & form slit-like spaces.
#DCIS ([[ductal carcinoma in situ]]).
#*Too many cells in a duct, nuclei do not touch - "cells are spaced".
#*Cells line-up around ovoid/circular spaces - "punch-out" appearance/"cookie cutter" look.
#*Myoepithelial cells present.
#Invasive ductal carcinoma.
#*Bread & butter cancer - in sheets or glands.
#Lobular carcinoma.
#*Dyscohesive cells - can easily be missed.
#Tubular carcinoma.
#*Glands have one cell layer... but near normal appearance.


The key to breast pathology is... seeing the two cell layers (at low power). The myoepithelial layer is hard to see at times and that is the challenge.
====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>


==Common diagnoses - overview==
www:
*Normal.
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=2&cat2=9&cat3=0&cat4=3&stype=n Lactational changes (gfmer.ch)].
*Benign.
*[http://www.webpathology.com/image.asp?case=320&n=7 Lactational changes in an angiosarcoma of the breast (webpathology.com)].
**Columnar cell change.  
*[http://www.lab.anhb.uwa.edu.au/mb140/CorePages/FemaleRepro/femalerepro.htm#LabMamm Lactating breast (uwa.edu.au)].
***Calcification often in lumen.
*Neoplastic.
**Benign neoplastic:
***Epithelial/myoepithelial - [[intraductal papilloma]].
***Stromal - fibroadenoma, benign phyllodes.
**Malignant neoplastic:
***Epithelial/myoepithelial - most common, e.g. ductal carcinoma, lobular carcinoma.
***Breast stroma - malignant phyllodes tumour.
***Stromal, e.g. [[angiosarcoma]] - quite rare.


==A tree diagram (overview)==
==Major Pathologic Patterns==
===General classifcation===
===General classification===
<!--
<!--
BREAST PATHOLOGY - SIMPLE
BREAST PATHOLOGY - SIMPLE
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{{familytree | | | | B | | | | | X | | | | |C | | | | |B=Stromal<br>pathology|X=Miscellaneous|C=Glandular<br>pathology}}
{{familytree | | | | B | | | | | X | | | | |C | | | | |B=Stromal<br>pathology|X=Miscellaneous|C=Glandular<br>pathology}}
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{{familytree | D | | | | E | | | | | F | | G | | H |D=Myxoid|E=Long slit-like<br>spaces|F=Simple<br>epithelium|G=Dilated|H=Cellular lesions}}
{{familytree | D | | | | E | | | | | F | | G | | H |D=Myxoid|E=Long slit-like<br>spaces|F=Simple<br>epithelium|G=Dilated|H=[[Breast pathology#Cellular lesions|Cellular lesions]]}}
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{{familytree | I | | J | | K | | | L | | M | | N |I=[[Fibroadenoma]]|J=Malignant<br>features|K=Benign features|L=[[Tubular carcinoma of the breast|Tubular<br>carcinoma]]|M=[[FEA]], [[FCC]],<br>[[Columnar cell change|CCC]]|N=[[FEHUT]], Neoplastic,<br>Malignant}}
{{familytree | | | | | |!| | | |!| | | | | | | | | | | | | | |}}
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{{familytree | | | | | O | | P | | | | | | | | | | | | | ||O=Malignant<br>phyllodes|P=Benign phyllodes|}}
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{{familytree/end}}
{{familytree/end}}


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*''Malignant'' includes: DCIS, LCIS, ductal carcinoma (DC) and lobular carcinoma (LC), some papillary lesions.
*''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.
*''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.
*''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===
===Cellular lesions===
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{{familytree | | | | | SP | | SS | | DE | | SF | | FC |SP=Equal spacing,<br>punched-out|SS=Streaming, periph. <br>slit-like spaces.|DE=Discohesive cells,<br>expanded gl.|SF=Single cells<br>or single file|FC=Fibrovascular<br>cores}}
{{familytree | | | | | SP | | SS | | DE | | SF | | FC |SP=Equal spacing,<br>punched-out|SS=Streaming, periph. <br>slit-like spaces.|DE=Discohesive cells,<br>expanded gl.|SF=Single cells<br>or single file|FC=Fibrovascular<br>cores}}
{{familytree | | | | | |!| | | |!| | | |!| | | |!| | | |!| |}}
{{familytree | | | | | |!| | | |!| | | |!| | | |!| | | |!| |}}
{{familytree | | | | | DL | | EHUT | | LL | | LC | | PL |DL=Ductal lesion|EHUT=EHUT|LL=Lobular lesion|LC=Lobular carcinoma|PL=Papillary lesions}}
{{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 | | | |,|-|^|-|.| | | |,|-|^|-|.| | | | | | | |}}
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{{familytree | | | TL | | OL | | LTF | | GTF | | | | | | |TL=Two cell layers|OL=One cell layer|LTF=<50% of gl.|GTF=>50% of gl.}}
{{familytree | | | TL | | OL | | LTF | | GTF | | | | | | |TL=Two cell layers|OL=One cell layer|LTF=<50% of gl.|GTF=>50% of gl.}}
{{familytree | | | |!| | | |!| | | |!| | | |!| | | | | | | |}}
{{familytree | | | |!| | | |!| | | |!| | | |!| | | | | | | |}}
{{familytree | | | DNI | | DC | | LDH | | LCIS | | | | | | |DNI=Ductal non-inv.<br>neoplasm|DC=Ductal carcinoma|LDH=LDH|LCIS=LCIS}}
{{familytree | | | DNI | | DC | | ALH | | LCIS | | | | | | |DNI=Ductal non-inv.<br>neoplasm|DC=[[Invasive ductal carcinoma of the breast|Ductal carcinoma]]|ALH=[[ALH]]|LCIS=[[LCIS]]}}
{{familytree | |,|-|^|-|.| | | | | | | | | | | | | | | | | |}}
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{{familytree | LE | | SE | | | | | | | | | | | | | | | | |LE=Large extent|SE=Small extent}}
{{familytree | LE | | SE | | | | | | | | | | | | | | | | |LE=Large extent|SE=Small extent}}
{{familytree | |!| | | |!| | | | | | | | | | | | | | | | | |}}
{{familytree | |!| | | |!| | | | | | | | | | | | | | | | | |}}
{{familytree | DCIS | | ADH | | | | | | | | | | | | | | | | |DCIS=DCIS|ADH=ADH}}
{{familytree | DCIS | | ADH | | | | | | | | | | | | | | | | |DCIS=[[DCIS]]|ADH=[[ADH]]}}
{{familytree/end}}
{{familytree/end}}
Notes:
Notes:
*The largest challenge is: differentiating between the first two categories on level 2, i.e. ''equal spacing...' vs. ''streaming...''.
*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===
===Papillary lesions===
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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=Benign<br>intraductal<br>papilloma|H=High grade atypia|I=Low grade atypia<br>''or'' abnorm. arch.|J=''Only'' cellular<br>proliferation|K=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=EHUT in<br>papilloma}}
{{familytree | | | | | L | | |!| | | N | | | | |L=[[DCIS]] in<br>papilloma|N=[[FEHUT]] in<br>papilloma}}
{{familytree | | | | | | | |,|-|^|-|.| | | | | | | |}}
{{familytree | | | | | | | |,|-|^|-|.| | | | | | | |}}
{{familytree | | | | | | | P | | Q | | | | | | |P=>3 mm extent|Q=<3 mm extent}}
{{familytree | | | | | | | P | | Q | | | | | | |P=>3 mm extent|Q=<3 mm extent}}
{{familytree | | | | | | | |!| | | |!| | | | | | | |}}
{{familytree | | | | | | | |!| | | |!| | | | | | | |}}
{{familytree | | | | | | | R | | S | | | | | | |R=DCIS in<br>papilloma|S=ADH in<br>papilloma}}
{{familytree | | | | | | | R | | S | | | | | | |R=DCIS in<br>papilloma|S=[[ADH]] in<br>papilloma}}
{{familytree/end}}
{{familytree/end}}
Notes:  
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>
*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>
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*''abnorm. arch.'' = abnormal architecture present.
*''abnorm. arch.'' = abnormal architecture present.
*''DCIS'' = ductal carcinoma in situ.
*''DCIS'' = ductal carcinoma in situ.
*''EHUT'' = epithelial hyperplasia of the usual type.
*''FEHUT'' = florid epithelial hyperplasia of the usual type.
*''extent'' refers to the size of the abnormal cell population within the papillary lesion.
*''extent'' refers to the size of the abnormal cell population within the papillary lesion.


Line 192: Line 283:


=Common benign lesions=
=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 ''epithelial hyperplasia of the usual type (EHUT)'' - instead of - ''benign breast tissue''.
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''.


==Apocrine metaplasia==
==Mild epithelial hyperplasia==
===General===
===General===
*Benign/not significant.  Can be considered to be pretty wallpaper in the house of breast pathology.
*No increased risk of malignancy.
 
**Often ''not'' reported - as it has no clinical signficance.
===Etiology===
*Has to be separated from ''[[moderate epithelial hyperplasia]]'' / ''[[florid epithelial hyperplasia]]''.
*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===
===Microscopic===
Features:
Features:<ref>{{Ref BP|159-160}}</ref>
*Eosinophilic cytoplasm.
*Breast glands with three ''or'' four cell layers above the basement membrane.
*Variable cells.


Note:  
Note:
*Apocrine changes, i.e. cytoplasmic eosinophilia, can appear in malignant tumours; eosinophilia doesn't make it benign.
*No nuclear atypia.


==Fibrocystic change==
DDx:
*Abbreviated ''FCC''.
*[[Flat epithelial atypia]].
===General===
*[[Moderate epithelial hyperplasia]] / [[florid epithelial hyperplasia]].
*Really common.
*[[Atypical ductal hyperplasia]].
*Benign.
 
==Apocrine metaplasia==
{{Main|Apocrine metaplasia of the breast}}


===Microscopic===
==Duct ectasia==
Features:
*Dilation of large ducts secondary to luminal obstruction by inspissated secretions
*Dilated glands - '''key change'''.
*Presentation
**Glands normal: two cell layers present.
**~age 40-50, possibly with cheesy nipple discharge
*Often seen together with ''apocrine metaplasia''.
*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>


Image:
==Fibrocystic change==
*[http://commons.wikimedia.org/wiki/File:Phyllodes_tumour_-_very_low_mag.jpg FCC - left of image - and a phyllodes tumour - very low mag. (WC)].
{{Main|Breast fibrocystic changes}}
*[[AKA]] ''fibrocystic changes'' (abbreviated ''FCC'').


==Columnar cell change==
==Columnar cell change==
===Importance===
{{Main|Columnar cell change of the breast}}
*Columnar cell change is associated with (benign) calcification - '''key point'''.


===Microscopic===
==Gynecomastoid hyperplasia==
Features:
*[[AKA]] ''gynecomastia''.
*Secretory cells (line gland lumen) have columnar morphology.
{{Main|Gynecomastoid hyperplasia}}
*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 +/-eosinophilic.


DDx:
==Breast prostheses==
*Flat epithelial atypia (>2 cell layers).{{Fact}}
{{Main|Breast prostheses}}


==Sclerosing adenosis==
=Lesions with increased risk of malignancy=
===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.


===Microscopic===
==Florid epithelial hyperplasia==
Features:
*AKA ''florid epithelial hyperplasia of the usual type'', abbreviated ''FEHUT''.
*Acini are smaller than usual and there are more of them.
*AKA ''epithelial hyperplasia'' - term should be avoid as it could lead to confusion with ''[[mild epithelial hyperplasia]]''.
*Fibrosis (scleroses) - pink on H&E surrounds the acini.
*AKA ''usual ductal hyperplasia'', abbreviated ''UDH''.
**Can mimic a [[dysmoplastic reaction]].
{{Main|Florid epithelial hyperplasia}}


Notes:
==Sclerosing adenosis==
*The acini should be:
{{Main|Sclerosing adenosis of the breast}}
**In lobular arrangements, i.e. in groups.
**Round.
**Have two cell layers - like good breast glands do.


=Lesions with increased risk of malignancy=
==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>
 
===Microscopic===
Features:
*"Flat" ~ three cells thick. (???)
*Hypercellular gland -- several layers.
*Columnar cell morphology.
*+/-Apical snouts.
 
DDx:
*[[Columnar cell change]].
*[[ADH]].
*Low grade [[DCIS]].


==Complex sclerosing lesion==
==Complex sclerosing lesion==
===General===
*[[AKA]] ''radial scar''.
*[[AKA]] ''radial scar''.
**The term 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>
{{Main|Complex sclerosing lesion}}
*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.
 
Image: [http://commons.wikimedia.org/wiki/File:Radial_scar.jpg Radial scar - gross (WC)].
 
===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.
 
Image: [http://www.breastpathology.info/Images/Benign/Radial_scar/rs3a_700.jpg Radial scar (breastpathology.info)].
 
Notes:
*Histomorphologic appearance may mimic a desmoplastic reaction of stroma - leading to a misdiagnosis of malignancy.
*"Hyaline <nowiki>[pink stuff on H&E]</nowiki> is the key."<ref>RS. May 2010.</ref>


=Stromal lesions=
=Stromal lesions=
This section (below) covers stromal lesions of the breast, which vary from benign to malignant.  The most common is (the benign) fibroadenoma.   
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.
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==
==Fibroadenoma==
===General===
{{Main|Fibroadenoma}}
*Very common benign finding.
*The pathology is in the stroma; so, the lesion is really a misnomer by the naming rules.
**It ought to be called ''adenofibroma'' (as a few occasionally do)<ref name=pmid15797289>{{Cite journal  | last1 = Guinebretière | first1 = JM. | last2 = Menet | first2 = E. | last3 = Tardivon | first3 = A. | last4 = Cherel | first4 = P. | last5 = Vanel | first5 = D. | title = Normal and pathological breast, the histological basis. | journal = Eur J Radiol | volume = 54 | issue = 1 | pages = 6-14 | month = Apr | year = 2005 | doi = 10.1016/j.ejrad.2004.11.020 | PMID = 15797289 }}</ref>, as the glandular component is benign and the stromal component lesional.
 
Management:
*Local excision (without a large margin).
 
===Microscopic===
Features (fibroadenoma not otherwise specified):
*Myxoid stroma -- most '''important feature'''.
**Stroma is white/pale on H&E -- normal stroma is pink on H&E.
*Compression of glandular elements -- commonly seen.
 
DDx:
*Phyllodes tumour.
**Stroma is more cellular than in fibroadenoma.
**May have mitoses.
**"Stromal overgrowth" large area where there is a 'loss of glands'.
**Patients with phyllodes tumour are usually older than those with fibroadenoma.
*Sarcoma.
 
Note:
*There is stuff about ''intracanalicular'' vs. ''pericanalicular''.<ref>URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970216-9 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970216-9]. Accessed on: 16 March 2011.</ref>  It is irrelevant; there is no prognostic difference between the two.
 
====Juvenile variant====
Features (juvenile variant):
*"Looks more malignant":
**More mitoses.
**More atypical nuclei.
**More cellular.
 
Note:
*The ''juvenile variant'', as the name suggests, is typically found in younger patients.
 
====Phyllodes tumour vs. fibroadenoma====
Histology of phyllodes:
* More cellular.
* More mitoses.
* More nuclear pleomorphism.
* Stromal overgrowth - epithelial elements absent in one low power field (x40).
* Infiltrative borders.
* Long/large slit-like spaces - '''key feature'''.
** Small foci of long slit-like space may exist -- how much... no definition.
Epidemiology:
* Phyllodes = older patients (usually)
Tx:
* Wide excision for phyllodes vs. local excision for fibroadenoma.
Ref.: <ref>{{Ref PBoD|1150}}</ref>


==Phyllodes tumour==
==Phyllodes tumour==
The name comes from the word "leaf"; with imagination or psychotropic drugs, it may look like one (the epithelial component = the veins of the leaf).
*Previously ''cystosarcoma phyllodes''.
 
{{Main|Phyllodes tumour}}
===General===
*Wide excision -- this differs from fibroadenoma (just local excision).
*Approximately 6% are malignant.<ref name=pmid12689668>{{cite journal |author=Guerrero MA, Ballard BR, Grau AM |title=Malignant phyllodes tumor of the breast: review of the literature and case report of stromal overgrowth |journal=Surg Oncol |volume=12 |issue=1 |pages=27–37 |year=2003 |month=July |pmid=12689668 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0960740403000057}}</ref>
 
===Gross===
*Clefts, leaf-like structures - friable vis-a-vis a fibroadenoma.
 
===Microscopic===
Features:
*Large slit-like spaces.
*Cellular stroma that may be myxoid.
*+/-Mitoses.
*May have "malignant border" -- "pushing border" / "infiltrative border".
 
Image:
*[http://en.wikipedia.org/wiki/File:Phyllodes_tumour_-_very_low_mag.jpg Phyllodes tumour - very low mag. (WC)].
*[http://en.wikipedia.org/wiki/File:Phyllodes_tumour_-_low_mag.jpg Phyllodes tumour - low mag. (WC)].
 
====Malignant phyllodes?====
Features of malignancy:<ref name=pmid17932112>{{cite journal |author=Taira N, Takabatake D, Aogi K, ''et al'' |title=Phyllodes tumor of the breast: stromal overgrowth and histological classification are useful prognosis-predictive factors for local recurrence in patients with a positive surgical margin |journal=Jpn. J. Clin. Oncol. |volume=37 |issue=10 |pages=730-6 |year=2007 |month=October |pmid=17932112 |doi=10.1093/jjco/hym099 |url=http://jjco.oxfordjournals.org/cgi/reprint/37/10/730}}</ref>
*Stromal cellular atypia.
*Mitotic activity in 10 [[HPF]]s.
**"HPF" is not adequately defined - see [[HPFitis]]. The authors should be spanked.
*Stromal overgrowth -- epithelial elements absent in one low power field (x40).<ref name=pmid17932112/>
**"LPF" is not adequately defined - see [[LPFitis]]. The authors should be spanked.
 
 
A comparison between benign and malignant phyllodes - adapted from Taira et al.<ref name=pmid17932112/>
{| class="wikitable"
| || '''Benign''' || '''Malignant'''
|-
|Stromal overgrowth || no || yes
|-
|Mitoses || >4/10 [[HPF]] || >=10/10 HPF
|-
|Atypia of stromal cells || <= moderate || marked
|-
|}
 
See also: [[Phyllodes tumour vs. fibroadenoma]].


==Pseudoangiomatous stromal hyperplasia==
==Pseudoangiomatous stromal hyperplasia==
*Abbreviated ''PASH''.
*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>
*[[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}}


===General===
=Weird stuff=
*Benign lesion.
Like in all niches of pathology... there is weird stuff.
*Thought to arise due to myofibroblast abnormality - though not well understood.<ref name=pmid7872425>{{cite journal |author=Powell CM, Cranor ML, Rosen PP |title=Pseudoangiomatous stromal hyperplasia (PASH). A mammary stromal tumor with myofibroblastic differentiation |journal=Am. J. Surg. Pathol. |volume=19 |issue=3 |pages=270–7 |year=1995 |month=March |pmid=7872425 |doi= |url=}}</ref>
 
===Gross===
Features:<ref name=pmid7872425>{{cite journal |author=Powell CM, Cranor ML, Rosen PP |title=Pseudoangiomatous stromal hyperplasia (PASH). A mammary stromal tumor with myofibroblastic differentiation |journal=Am. J. Surg. Pathol. |volume=19 |issue=3 |pages=270–7 |year=1995 |month=March |pmid=7872425 |doi= |url=}}</ref>
*May form mass: grey-white & firm, with well circumscribed borders.
 
===Microscopic===
Features:<ref name=pmid3949338>{{cite journal |author=Vuitch MF, Rosen PP, Erlandson RA |title=Pseudoangiomatous hyperplasia of mammary stroma |journal=Hum. Pathol. |volume=17 |issue=2 |pages=185–91 |year=1986 |month=February |pmid=3949338 |doi= |url=}}</ref><ref name=pmid18084246>{{Cite journal  | last1 = Ferreira | first1 = M. | last2 = Albarracin | first2 = CT. | last3 = Resetkova | first3 = E. | title = Pseudoangiomatous stromal hyperplasia tumor: a clinical, radiologic and pathologic study of 26 cases. | journal = Mod Pathol | volume = 21 | issue = 2 | pages = 201-7 | month = Feb | year = 2008 | doi = 10.1038/modpathol.3801003 | PMID = 18084246 }}</ref>
*Abundant breast stromal.
*Small, complex, inter-anastomosing (blood vessel/capillary-like) channels - '''key feature'''.
**''Pseudoangiomatous'' = blood vessel-like.
 
Notes:
*May mimic angiosarcoma at low power; PASH may have the same architecture but lack nuclear atypia.


Images:
==Mammary hamartoma==
*[http://commons.wikimedia.org/wiki/File:Pseudoangiomatous_stromal_hyperplasia_-a-_low_mag.jpg PASH - low mag. (WC)].
*[[AKA]] ''breast hamartoma''.
*[http://commons.wikimedia.org/wiki/File:Pseudoangiomatous_stromal_hyperplasia_-a-_intermed_mag.jpg PASH - intermed. mag. (WC)].
{{Main|Mammary hamartoma}}
*[http://commons.wikimedia.org/wiki/File:Pseudoangiomatous_stromal_hyperplasia_-_high_mag.jpg PASH - high mag. (WC)].
*[http://www.nature.com/modpathol/journal/v21/n2/fig_tab/3801003f1.html#figure-title PASH (nature.com)].<ref name=pmid18084246>{{Cite journal  | last1 = Ferreira | first1 = M. | last2 = Albarracin | first2 = CT. | last3 = Resetkova | first3 = E. | title = Pseudoangiomatous stromal hyperplasia tumor: a clinical, radiologic and pathologic study of 26 cases. | journal = Mod Pathol | volume = 21 | issue = 2 | pages = 201-7 | month = Feb | year = 2008 | doi = 10.1038/modpathol.3801003 | PMID = 18084246 }}</ref>


===IHC===
==Collagenous spherulosis==
Findings:<ref name=pmid7872425/>
*[[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>
*CD34 +ve.
{{Main|Collagenous spherulosis}}
*Vimentin +ve.
*Factor VIII -ve.
 
=Weird stuff=
Like in all niches of pathology... there is weird stuff.


==Nipple adenoma==
==Nipple adenoma==
===General===
*[[AKA]] ''nipple duct adenoma''.
*Rare.
*[[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}}


Clinical DDx:
==Intraductal papilloma==
*[[Paget's disease of the breast]].<ref name=pmid13904317>{{Cite journal  | last1 = HANDLEY | first1 = RS. | last2 = THACKRAY | first2 = AC. | title = Adenoma of nipple. | journal = Br J Cancer | volume = 16 | issue =  | pages = 187-94 | month = Jun | year = 1962 | doi =  | PMID = 13904317 | PMC = 2070922 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2070922/?tool=pubmed  }}</ref>
*[[AKA]] ''papilloma''.
{{Main|Intraductal papilloma of the breast}}


===Microscopic===
==Lymphocytic mastitis==
Features:
*If the individual has [[diabetes mellitus]] it is ''[[diabetic mastopathy]]''.
*Proliferation of epithelial and myoepithelial elements that extends into the breast stroma.<ref name=pmid2123505>{{Cite journal  | title = Adenoma of Nipple. | journal = Br Med J | volume = 1 | issue = 5330 | pages = 563 | month = Mar | year = 1963 | doi =  | PMID = 20789667 | PMC = 2123505 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2123505/?page=1 }}</ref>
{{Main|Lymphocytic mastitis}}
**Not encapsulated.


Images:
==Microglandular adenosis==
*[http://commons.wikimedia.org/wiki/File:Nipple_adenoma_-_low_mag.jpg Nipple adenoma - low mag. (WC)].
:'''''Not''' to be confused with [[microglandular hyperplasia]]''.
*[http://commons.wikimedia.org/wiki/File:Nipple_adenoma_-_very_high_mag.jpg  Nipple adenoma - very high mag. (WC)].
*Abbreviated ''MGA''.
{{Main|Microglandular adenosis}}


==Intraductal papilloma==
==Adenomyoepithelioma==
===General===
{{Main|Adenomyoepithelioma}}
*May cause nipple discharge.<ref>{{Cite journal  | last1 = Zervoudis | first1 = S. | last2 = Iatrakis | first2 = G. | last3 = Economides | first3 = P. | last4 = Polyzos | first4 = D. | last5 = Navrozoglou | first5 = I. | title = Nipple discharge screening. | journal = Womens Health (Lond Engl) | volume = 6 | issue = 1 | pages = 135-51 | month = Jan | year = 2010 | doi = 10.2217/whe.09.81 | PMID = 20050819 }}</ref>


===Microscopic===
==Mammary myofibroblastoma==
Features:
*[[AKA]] ''breast myofibroblastoma''.
*Intraductal proliferation of epithelial and myoepithelial elements.<ref name=pmid2123505>{{Cite journal  | title = Adenoma of Nipple. | journal = Br Med J | volume = 1 | issue = 5330 | pages = 563 | month = Mar | year = 1963 | doi =  | PMID = 20789667 | PMC = 2123505 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2123505/?page=1 }}</ref>
*[[AKA]] ''myofibroblastoma of the breast''.
{{Main|Mammary myofibroblastoma}}


Notes:
==Squamous metaplasia of lactiferous ducts==
*Lacks florid hyperplasia.<ref>URL: [http://surgpathcriteria.stanford.edu/breast/nippleadenoma/printable.html http://surgpathcriteria.stanford.edu/breast/nippleadenoma/printable.html]. Accessed on: 6 August 2011.</ref>
*Abbreviated ''SMOLD''.
{{Main|Squamous metaplasia of lactiferous ducts}}


==Diabetic mastopathy==
==Granular cell tumour of the breast==
{{Main|Granular cell tumour}}
===General===
===General===
*Diabetes mellitus.
*Uncommon.


===Microscopic===
===Gross===
Features:<ref>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_0707%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_0707%20discussion.html]. Accessed on: 28 November 2010.</ref>
*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>
* Stromal collagen with keloid-like changes.
* Lymphocytic infiltrates:
** Lobules.
** Perivascular.
* Enlarged stromal fibroblasts.
 
==Microglandular adenosis==
===General===
*Controversial thingy.


===Microscopic===
===Microscopic===
Features:<ref name=uscap_mga>URL: [http://www.uscap.org/site~/iap2006/slides08-4v.htm http://www.uscap.org/site~/iap2006/slides08-4v.htm]. Accessed on: 18 May 2011.</ref>
:See ''[[granular cell tumour]]''.
*Round glands lined by a single layer of cells.
*May extend into fat.


DDx:
DDx:
*Tubular carcinoma - has apical snouts, desmoplasia among other things; see page by ''Collins''.<ref name=uscap_mga>URL: [http://www.uscap.org/site~/iap2006/slides08-4v.htm http://www.uscap.org/site~/iap2006/slides08-4v.htm]. Accessed on: 18 May 2011.</ref>
*[[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>
*Sclerosing adenosis.
 
Image:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=1&s=20080802171452955&i=0&p=0 Microglandular adenosis (surgical pathologyatlas.com)].
 
===IHC===
Features:<ref name=pmid8821958>{{Cite journal  | last1 = Joshi | first1 = MG. | last2 = Lee | first2 = AK. | last3 = Pedersen | first3 = CA. | last4 = Schnitt | first4 = S. | last5 = Camus | first5 = MG. | last6 = Hughes | first6 = KS. | title = The role of immunocytochemical markers in the differential diagnosis of proliferative and neoplastic lesions of the breast. | journal = Mod Pathol | volume = 9 | issue = 1 | pages = 57-62 | month = Jan | year = 1996 | doi = | PMID = 8821958 }}</ref>
*S100 +ve.
*34BE12 +ve -- focal!


=See also=
=See also=
Line 505: Line 437:
=References=
=References=
{{reflist|2}}
{{reflist|2}}
[[Category:Breast pathology]]


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

Latest revision as of 04:47, 1 July 2016

Diagram of the structure of breast. (CRUK/WC)

The breast is an important organ that pathologists see quite often because it is often afflicted by cancer. Before women started smoking in large numbers, it was a leading cause of cancer death in women.

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

Clinical

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.
  • Pain.
  • Breast lump/mass.
  • New nipple inversion.
  • Skin changes, e.g. peau d'orange.

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:

  1. The breast is more dense and thus radiologically more difficult to interpret, and
  2. The incidence of breast cancer is lower.

Breast radiology

Main article: Breast imaging reporting and data system

Specimens

Three major specimen types:

  1. Core needle biopsy (CNB).
  2. Lumpectomy.
  3. 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:[1]

  1. Mass lesion - usu. obvious what is going on; typically 3 levels.
  2. 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

Lumpectomies are usually oriented with short and long suture; short is typically superior (aspect) and long is typically lateral (aspect).

Modified radical mastectomy

  • Usually done with sentinel lymph node biopsy - as one cannot go back later to do this.

Where to start

Main articles: Short_power_list#Breast_pathology and 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 and 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 breast 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 an invasive 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 Tumour - stromal component.
  • Desmoid fibromatosis.
  • Nodular fasciitis.

Additional resources

  • Breast Pathology Info [1]
  • Digital Atlas of Breast Pathology [2]
  • Pathology Outlines - Breast Nonmalignant [3]
  • Pathology Outlines - Breast Malignant [4]
  • WebPathology - Breast [5]

Normal breast

Resting breast

  • 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. Purple = Phosphate.
    • Calcium oxalate visible with (light) polarization - not associated 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.[2]
      • 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).

Notes:

  • The architecture is more important than the cytologic features in the diagnosis of malignancy in the breast;[3] low grade tumours have distorted architecture but normal/near normal cytology.

Image

Lactational changes

  • AKA secretory change, AKA lactational adenoma, AKA lactating adenoma [4]

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.[5]

Microscopic

Features:[6]

  • Glands dilated.
  • Increased number of lobules.
    • Relative decrease in intralobular and extralobular stroma.
  • Luminal cells enlarged.
  • 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:

Images

  • Lactational change - low mag. (WC/Nephron)

  • Lactational change - high mag. (WC/Nephron)

  • Breast - Lactational Change - medium power (SKB)

  • Breast - Lactational Change - high power (SKB)

  • Breast - Lactational adenoma - medium power (SKB)

  • Breast - Lactational adenoma - high power (SKB)

  • Breast - Lactational adenoma - low power (SKB)

  • Breast - Lactational adenoma - low power (SKB)

  • Lactational adenoma - high power - in this example, the epithelium is flattened with clear bubbly cytoplasm (SKB)

  • Breast - Lactational adenoma - high power - shows snouting and decapitation secretion. (SKB)

www:

Major Pathologic Patterns

General classification

 
 
 
 
 
 
 
 
 
 
Breast pathology
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stromal
pathology
 
 
 
 
Miscellaneous
 
 
 
 
Glandular
pathology
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myxoid
 
 
 
Long slit-like
spaces
 
 
 
 
Simple
epithelium
 
Dilated
 
Cellular lesions
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fibroadenoma
 
Malignant
features
 
Benign features
 
 
Tubular
carcinoma
 
FEA, FCC,
CCC
 
FEHUT, Neoplastic,
Malignant
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malignant
phyllodes
 
Benign phyllodes
 
 
 
 
 
 
 
 
 
 
 
 
 

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, lymphomas, 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

 
 
 
 
 
 
 
 
 
 
 
 
Cellular lesions
(Glandular)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Equal spacing,
punched-out
 
Streaming, periph.
slit-like spaces.
 
Discohesive cells,
expanded gl.
 
Single cells
or single file
 
Fibrovascular
cores
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ductal lesion
 
FEHUT
 
Lobular lesion
 
Lobular carcinoma
 
Papillary lesions
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Two cell layers
 
One cell layer
 
<50% of gl.
 
>50% of gl.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ductal non-inv.
neoplasm
 
Ductal carcinoma
 
ALH
 
LCIS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Large extent
 
Small extent
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DCIS
 
ADH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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

 
 
 
 
 
 
 
 
 
 
Papillary lesions
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myoepithelial cells
present
 
 
 
 
 
 
 
 
 
Myoepithelial cells
absent
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unremarkable
papillae
 
 
 
 
 
Atypia or arch. abnorm.
or cellular proliferation
 
 
 
 
 
Neoplastic cells
present
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Benign
intraductal
papilloma
 
High grade atypia
 
Low grade atypia
or abnorm. arch.
 
Only cellular
proliferation
 
Intracystic
(encapsulated)
papillary ca.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DCIS in
papilloma
 
 
 
 
 
 
FEHUT in
papilloma
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
>3 mm extent
 
<3 mm extent
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DCIS in
papilloma
 
ADH in
papilloma
 
 
 
 
 
 

Notes:

  • Adapted from Mulligan & O'Malley.[7]
  • 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 article: Non-invasive breast cancer

This includes the in situ lesions - DCIS and LCIS.

Invasive breast cancer

Main article: 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

Microscopic

Features:[8]

  • Breast glands with three or four cell layers above the basement membrane.
  • Variable cells.

Note:

  • No nuclear atypia.

DDx:

Apocrine metaplasia

Main article: Apocrine metaplasia of the breast

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

  • Breast - Duct Ectasia - low power (SKB)

  • Breast - Duct Ectasia - low power (SKB)

  • Breast - Duct Ectasia - medium power (SKB)

Fibrocystic change

Main article: Breast fibrocystic changes
  • AKA fibrocystic changes (abbreviated FCC).

Columnar cell change

Main article: Columnar cell change of the breast

Gynecomastoid hyperplasia

  • AKA gynecomastia.
Main article: Gynecomastoid hyperplasia

Breast prostheses

Main article: Breast prostheses

Lesions with increased risk of malignancy

Florid epithelial hyperplasia

  • 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 usual ductal hyperplasia, abbreviated UDH.
Main article: Florid epithelial hyperplasia

Sclerosing adenosis

Main article: Sclerosing adenosis of the breast

Flat epithelial atypia

  • Abbreviated FEA.
Main article: Flat epithelial atypia

Complex sclerosing lesion

  • AKA radial scar.
Main article: Complex sclerosing lesion

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 article: Fibroadenoma

Phyllodes tumour

  • Previously cystosarcoma phyllodes.
Main article: Phyllodes tumour

Pseudoangiomatous stromal hyperplasia

  • Abbreviated PASH.
  • AKA nodular myofibroblastic stromal hyperplasia of the mammary gland.[9]
Main article: Pseudoangiomatous stromal hyperplasia

Weird stuff

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

Mammary hamartoma

  • AKA breast hamartoma.
Main article: Mammary hamartoma

Collagenous spherulosis

Main article: Collagenous spherulosis

Nipple adenoma

  • AKA nipple duct adenoma.
  • AKA nipple adenoma of breast.
  • AKA adenoma of the nipple.
  • AKA florid papillomatosis of the nipple.[11]
Main article: Nipple adenoma

Intraductal papilloma

Main article: Intraductal papilloma of the breast

Lymphocytic mastitis

Main article: Lymphocytic mastitis

Microglandular adenosis

Not to be confused with microglandular hyperplasia.
  • Abbreviated MGA.
Main article: Microglandular adenosis

Adenomyoepithelioma

Main article: Adenomyoepithelioma

Mammary myofibroblastoma

  • AKA breast myofibroblastoma.
  • AKA myofibroblastoma of the breast.
Main article: Mammary myofibroblastoma

Squamous metaplasia of lactiferous ducts

  • Abbreviated SMOLD.
Main article: Squamous metaplasia of lactiferous ducts

Granular cell tumour of the breast

Main article: Granular cell tumour

General

  • Uncommon.

Gross

  • May be a spiculated mass and thus mimic malignancy radiologically.[12]

Microscopic

See granular cell tumour.

DDx:

See also

References

  1. ↑ MUA. 1 October 2010.
  2. ↑ MUA. 1 October 2010.
  3. ↑ RS. 4 May 2010.
  4. ↑ URL: [Breast_pathology#Lactational_changes Breast_pathology#Lactational_changes. Accessed on: 3 October 2011.
  5. ↑ Tavassoli, FA.; Yeh, IT. (Jan 1987). "Lactational and clear cell changes of the breast in nonlactating, nonpregnant women.". Am J Clin Pathol 87 (1): 23-9. PMID 2879437.
  6. ↑ URL: http://flylib.com/books/en/2.953.1.9/1/. Accessed on: 6 August 2011.
  7. ↑ Mulligan AM, O'Malley FP (March 2007). "Papillary lesions of the breast: a review". Adv Anat Pathol 14 (2): 108–19. doi:10.1097/PAP.0b013e318032508d. PMID 17471117.
  8. ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 159-160. ISBN 978-0443066801.
  9. ↑ Leon, ME.; Leon, MA.; Ahuja, J.; Garcia, FU.. "Nodular myofibroblastic stromal hyperplasia of the mammary gland as an accurate name for pseudoangiomatous stromal hyperplasia of the mammary gland.". Breast J 8 (5): 290-3. PMID 12199757.
  10. ↑ URL: http://surgpathcriteria.stanford.edu/breast/collspher/. Accessed on: 4 September 2011.
  11. ↑ Boutayeb, S.; Benomar, S.; Sbitti, Y.; Harroudi, T.; Hassam, B.; Errihani, H. (2012). "Nipple adenoma in a man: An unusual case report.". Int J Surg Case Rep 3 (5): 190-2. doi:10.1016/j.ijscr.2011.05.008. PMID 22342578.
  12. ↑ Yang, WT.; Edeiken-Monroe, B.; Sneige, N.; Fornage, BD. (May 2006). "Sonographic and mammographic appearances of granular cell tumors of the breast with pathological correlation.". J Clin Ultrasound 34 (4): 153-60. doi:10.1002/jcu.20227. PMID 16615051.
  13. ↑ Tan, PH.; Harada, O.; Thike, AA.; Tse, GM. (Aug 2011). "Histiocytoid breast carcinoma: an enigmatic lobular entity.". J Clin Pathol 64 (8): 654-9. doi:10.1136/jcp.2011.088930. PMID 21398688.

External links

Retrieved from "https://librepathology.org/w/index.php?title=Breast_pathology&oldid=45259"