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.
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Note:
Note:
*Breast [[cytopathology]] is dealt with in the ''[[breast cytopathology]]'' article.  It is almost dead, as it is not as sensitive and specific as CNB.
*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===
===Core needle biopsy===
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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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*Usually done with sentinel [[lymph node]] biopsy - as one cannot go back later to do this.
*Usually done with sentinel [[lymph node]] biopsy - as one cannot go back later to do this.


=Normal=
=Where to start=
==Resting==
{{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 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==
*[[AKA]] secretory change, [[AKA]] lactational adenoma.<ref>URL: [Breast_pathology#Lactational_changes Breast_pathology#Lactational_changes. Accessed on: 3 October 2011.</ref>
*[[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===
===General===
*Lactational adenoma generally arises in during or in the few weeks after pregnancy.
*May be present focally in non-pregnant females.
*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:
ASIDE:
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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!


DDx:
DDx:
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Image:Lactational_change_-_low_mag.jpg | Lactational change - low mag. (WC/Nephron)
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: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>
</gallery>


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*[http://www.lab.anhb.uwa.edu.au/mb140/CorePages/FemaleRepro/femalerepro.htm#LabMamm Lactating breast (uwa.edu.au)].
*[http://www.lab.anhb.uwa.edu.au/mb140/CorePages/FemaleRepro/femalerepro.htm#LabMamm Lactating breast (uwa.edu.au)].


=Where to start=
==Major Pathologic Patterns==
{{Main|Short_power_list#Breast_pathology|Long_power_list#Breast_pathology}}
The following entities are a starting point for understanding routine breast pathology & some of challenges in breast pathology:
#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.
#[[Florid epithelial hyperplasia]].
#*Too many cells in a duct, cells overlap & form slit-like spaces.
#[[Ductal carcinoma in situ]] (DCIS).
#*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 of the breast|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.
 
==Common diagnoses - overview==
*Normal.
*Benign.
**Columnar cell change.
***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)==
===General classification===
===General classification===
<!--
<!--
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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=[[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}}
{{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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===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'''.
 
Note:
*Apocrine changes, i.e. cytoplasmic eosinophilia, can appear in malignant tumours; eosinophilia doesn't make something benign.
*Apocrine snouts may be present. (???)
**Small globules at the apical aspect of the cell (composed of cytoplasm and plasma membrane).


====Images====
==Duct ectasia==
*Dilation of large ducts secondary to luminal obstruction by inspissated secretions
*Presentation
**~age 40-50, possibly with cheesy nipple discharge
*Pathology
**Duct lumen dilated and containing foamy macrophages
**Necrosis/shedding of epithelium
**If duct rupture: chronic and granulomatous inflammation of periductal region
**Fibrotic thickening of duct wall
<gallery>
<gallery>
Image:Fibrocystic_change_-_very_high_mag.jpg | FCC with apocrine metaplasia (right bottom of image) - high mag. (WC/Nephron).
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>
</gallery>


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


===General===
==Breast prostheses==
*Benign enlargement of breasts in males.
{{Main|Breast prostheses}}
**Histologic changes may be seen in females.<ref name=stony03>URL: [http://www.hsc.stonybrook.edu/breast-atlas/XIII-03.htm http://www.hsc.stonybrook.edu/breast-atlas/XIII-03.htm]. Accessed on: 16 November 2011.</ref>
 
May be seen in the context of:
*[[Liver]] failure.
*[[Klinefelter syndrome]].
*Testicular estrogen-producing [[germ cell tumour]]. 
 
===Microscopic===
Features:<ref name=stony03>URL: [http://www.hsc.stonybrook.edu/breast-atlas/XIII-03.htm http://www.hsc.stonybrook.edu/breast-atlas/XIII-03.htm]. Accessed on: 16 November 2011.</ref>
*Moderate hyperplasia.
**Glands have more than 2 cell layers.
*"Budding" - individual cells jut into the lumen - '''key feature'''.
**Buds may be multicellular; however, narrower toward the centre of the lumen.
*Stromal palor.<ref>URL: [http://radiology.uchc.edu/eAtlas/Breast/1693.htm http://radiology.uchc.edu/eAtlas/Breast/1693.htm]. Accessed on: 16 November 2011.</ref>
 
DDx:
*[[Micropapillary DCIS]] - buds not narrower toward the centre of the lumen.
 
====Images====
<gallery>
Image:Gynecomastoid_hyperplasia_-_intermed_mag.jpg | Gynecomastoid hyperplasia - intermed. mag. (WC/Nephron)
Image:Gynecomastoid_hyperplasia_-_very_high_mag.jpg | Gynecomastoid hyperplasia - very high mag. (WC/Nephron)
Image:Gynecomastoid_hyperplasia_-2-_intermed_mag.jpg | Gynecomastoid hyperplasia - 2 - intermed. mag. (WC/Nephron)
</gallery>
www:
*[http://www.hsc.stonybrook.edu/breast-atlas/XIII-03.htm Gynecomastoid hyperplasia (stonybrook.edu)].
*[http://radiology.uchc.edu/eAtlas/Breast/1693.htm Gynecomastia (radiology.uchc.edu)].


=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.
 
DDx:
*[[Columnar cell change]].
*Columnar cell hyperplasia.
*[[ADH]].
*Low grade [[DCIS]].
*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:
*[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.
 
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."<ref>RS. May 2010.</ref>
 
DDx:
*[[Invasive ductal carcinoma]] - should be considered if the lesion is asymmetrical ''or'' glands are dilated centrally.
 
Image:
*[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=
Line 482: Line 361:


==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; there is [[no truth in names]] in pathology.
 
Management:
*Local excision -- without a large margin.
 
===Gross===
Features:<ref>{{Ref PCPBoD8|550}}</ref>
*Well-circumscribed.
*Rubbery - '''classic descriptor'''.
*Tan/white.
*+/-Lobulated appearance.
*+/-Slit-like spaces - short.
*+/-Calcification.
 
Images:
*[http://webpathology.com/image.asp?n=2&Case=276 Fibroadenoma - slit-like spaces (webpathology.com)].
*[http://webpathology.com/image.asp?case=276&n=3 Fibroadenoma - lobulated appearance (webpathology.com)].
*[http://www.surgical-tutor.org.uk/default-home.htm?tutorials/fibroadenoma.htm~right Fibroadenoma (surgical-tutor.org)].
 
===Microscopic===
Features:<ref name=Ref_BP110>{{Ref BP|110}}</ref>
*Abundant (intralobular) stroma - most '''key feature'''.
**Stroma is usually:
***White/pale, i.e. [[myxoid stroma|myxoid]], on H&E (normal stroma is pink).
****May be hyalinized (dark pink) if infarcted.
***Paucicellular - typical.
*Compression of glandular elements - very commonly seen.
**Glandular elements have at least two cell layers - epithelial and myoepithelial.
 
Notes:
#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.
#Do '''not''' comment on the margin - it is irrelevant.
 
DDx:
*[[Phyllodes tumour]] - long slit-like spaces (seen grossly), stroma is more cellular.
**+/-Mitoses,
**+/-"Stromal overgrowth" = large area where there is a 'loss of glands'.
*Sarcoma.
*[[Pseudoangiomatous stromal hyperplasia]].
**Small capillary-like structures in the stroma.
***Epithelial component often not compressed - as in fibroadenoma.
*[[Adenomyoepithelioma]] - for [[tubular adenoma of the breast]].
 
Images:
*[http://radiographics.rsna.org/content/27/suppl_1/S101/F40.expansion.html Infarcted fibroadenoma (rsna.org)].<ref name=pmid18180221>{{Cite journal  | last1 = Sabate | first1 = JM. | last2 = Clotet | first2 = M. | last3 = Torrubia | first3 = S. | last4 = Gomez | first4 = A. | last5 = Guerrero | first5 = R. | last6 = de las Heras | first6 = P. | last7 = Lerma | first7 = E. | title = Radiologic evaluation of breast disorders related to pregnancy and lactation. | journal = Radiographics | volume = 27 Suppl 1 | issue =  | pages = S101-24 | month = Oct | year = 2007 | doi = 10.1148/rg.27si075505 | PMID = 18180221 }}</ref>
*[http://www.imagingpathways.health.wa.gov.au/includes/images/image/fibroadenoma_he.jpg Fibroadenoma (gov.au)].<ref>URL: [http://www.imagingpathways.health.wa.gov.au/includes/dipmenu/image/image.html http://www.imagingpathways.health.wa.gov.au/includes/dipmenu/image/image.html]. Accessed on: 15 February 2012.</ref>
 
====Variants====
Four variants are described by the ''Washington Manual'':<ref name=Ref_WMSP262>{{Ref WMSP|262}}</ref>
#Juvenile.
#Complex.
#Myxoid.
#Cellular.
 
Considered a variant of fibroadenoma by many authorities:<ref name=Ref_BP116>{{Ref BP|116}}</ref>
*''[[Tubular adenoma of the breast]]''.
 
=====Juvenile fibroadenoma=====
*As the name suggests, is typically found in younger patients.
*Classic history: rapid growth.
 
Features (juvenile variant):<ref>URL: [http://www.breastpathology.info/fibro_variants.html#juvenile http://www.breastpathology.info/fibro_variants.html#juvenile]. Accessed on: 3 October 2011.</ref>
*Stromal and epithelial hyperplasia - '''key feature'''.
*+/-Tapering, thin micropapillae (''[[gynecomastoid hyperplasia]]'').<ref name=Ref_BP116>{{Ref BP|116}}</ref>
*Mitoses uncommon.
 
=====Myxoid fibroadenoma=====
*May be associated with ''[[Carney's complex]]''.
 
Features:
*[[Myxoid stroma]].
 
=====Cellular fibroadenoma=====
Features (cellular variant):
*Cellular.
*Mitoses.
 
=====Complex fibroadenoma=====
*Contain proliferative epithelium which outside and inside a fibroadenoma is associated with an increased risk of malignancy.
 
Features:<ref>URL: [http://www.breastpathology.info/fibro_variants.html#complex http://www.breastpathology.info/fibro_variants.html#complex]. Accessed on: 3 October 2011.</ref>
# [[Apocrine metaplasia]].
# Cysts > 3 mm.
# Calcification.
# [[Sclerosing adenosis]].
 
Memory devices:
*''FACS'': complex '''f'''ibroadenoma, '''a'''pocrine metaplasia, '''c'''alcs & '''c'''ysts, '''s'''clerosing adenosis.
*''CAMS'': '''c'''alcs, '''a'''pocrine metaplasia, '''m'''icrocysts, '''s'''clerosing adenosis.
 
=====Tubular adenoma of the breast=====
*Considered by many a variant of ''fibroadenoma''.
**[[IHC]] features of ''tubular adenoma of the breast'' and ''fibroadenoma'' are similar.<ref>{{Cite journal  | last1 = Maiorano | first1 = E. | last2 = Albrizio | first2 = M. | title = Tubular adenoma of the breast: an immunohistochemical study of ten cases. | journal = Pathol Res Pract | volume = 191 | issue = 12 | pages = 1222-30 | month = Dec | year = 1995 | doi =  | PMID = 8927570 }}</ref>
 
Features:<ref name=Ref_BP116>{{Ref BP|116}}</ref>
*Fibromyxoid stroma (like in a fibroadenoma).
*Small round glands.
 
Image:
*[http://www.webpathology.com/image.asp?case=277&n=1 Tubular adenoma of the breast (webpathology.com)].


==Phyllodes tumour==
==Phyllodes tumour==
*Previously ''cystosarcoma phyllodes''.
*Previously ''cystosarcoma phyllodes''.
 
{{Main|Phyllodes tumour}}
===General===
*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.
*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>
 
Notes:
*There are case reports of ''phyllodes tumours'' in the [[prostate gland]].<ref name=pmid20069045>{{Cite journal  | last1 = Bannowsky | first1 = A. | last2 = Probst | first2 = A. | last3 = Dunker | first3 = H. | last4 = Loch | first4 = T. | title = Rare and challenging tumor entity: phyllodes tumor of the prostate. | journal = J Oncol | volume = 2009 | issue =  | pages = 241270 | month =  | year = 2009 | doi = 10.1155/2009/241270 | PMID = 20069045 }}</ref>
* Outside of the breast a phyllodes-like histomorphology may represent an ''[[adenosarcoma]]''.<ref name=pmid20179434>{{Cite journal  | last1 = McCluggage | first1 = WG. | title = Mullerian adenosarcoma of the female genital tract. | journal = Adv Anat Pathol | volume = 17 | issue = 2 | pages = 122-9 | month = Mar | year = 2010 | doi = 10.1097/PAP.0b013e3181cfe732 | PMID = 20179434 }}</ref>
 
===Gross===
*Clefts/leaf-like structures.
*Friable - especially vis-à-vis a [[fibroadenoma]].
 
Image:
*[http://radiographics.rsna.org/content/29/3/907/F48.expansion.html Benign phyllodes tumour (rsna.org)].
 
===Microscopic===
Features - either 1, 2 or both of the following:
#Large slit-like spaces - '''key feature'''. †
#Cellular stroma  - '''key feature'''. †
#*May be [[myxoid stroma|myxoid]].
*+/-Infiltrative border.
*+/-Mitoses.
*+/-Nuclear atypia.
*+/-"Stromal overgrowth" ~ stroma fills microscopic field.
 
Notes:
* † Large slit-like spaces are required for a benign phyllodes tumour.
*# Slit-like spaces may absent in a borderline phyllodes ''or'' a malignant phyllodes.
*# A cellular tumour without features suggestive of malignancy and without slit-like spaces is a ''[[cellular fibroadenoma]]''.
*#*Some pathologists don't believe in ''cellular fibroadenoma'' - they call everything with stromal cellularity a ''phyllodes tumour''.<ref>URL: [http://www.breastpathologyconsults.com/blog/wp-content/uploads/2011/03/FEL_poster.pdf http://www.breastpathologyconsults.com/blog/wp-content/uploads/2011/03/FEL_poster.pdf]. Accessed on: 23 February 2012.</ref>
 
DDx:
*[[Fibroadenoma]].
*[[Metaplastic breast carcinoma]].
*Primary breast sarcoma.
*Other [[sarcoma]]s.
 
====Images====
<gallery>
Image:Phyllodes_tumour_-_very_low_mag.jpg | Phyllodes tumour - very low mag. (WC/Nephron)
Image:Phyllodes_tumour_-_low_mag.jpg | Phyllodes tumour - low mag. (WC/Nephron)
</gallery>
 
====Grading====
Phyllodes tumours are graded:
*Benign.
*Borderline.
*Malignant.
 
Grading phyllodes tumours - based on WMSP:<ref name=Ref_WMSP263>{{Ref WMSP|263}}</ref>
{| class="wikitable sortable"
! Feature
! Benign phyllodes
! Borderline phyllodes
! Malignant phyllodes
|-
| Circumscription
| Well
| Well
| Poor
|-
| Stromal overgrowth †
| none
| none
| may be present
|-
| Nuclear atypia
| mild
| mild-to-moderate
| moderate-to-marked
|-
| Mitoses per 10 [[HPF]]s ‡
| < 5
| 5-10
| >10
|-
| Heterologous elements
| +/- benign
| +/- benign
| +/- malignant
|-
| DDx
| [[fibroadenoma]]
| benign phyllodes, malignant phyllodes
| [[metaplastic breast carcinoma]], sarcoma
|-
|}
 
Notes:
* † Stromal overgrowth = epithelial elements absent in one low power field (LPF), defined as x40;<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> ''LPF'' is not adequately defined - see [[LPFitis]].
* ‡ ''HPF'' is not adequately defined - see [[HPFitis]].


==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===
*Benign lesion.
*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.
 
DDx:
*[[Angiosarcoma]].
*[[Fibroadenoma]].
 
====Images====
<gallery>
Image:Pseudoangiomatous_stromal_hyperplasia_-a-_low_mag.jpg | PASH - low mag. (WC/Nephron)
Image:Pseudoangiomatous_stromal_hyperplasia_-a-_intermed_mag.jpg | PASH - intermed. mag. (WC/Nephron)
Image:Pseudoangiomatous_stromal_hyperplasia_-_high_mag.jpg | PASH - high mag. (WC/Nephron)
</gallery>
www:
*[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===
Findings:<ref name=pmid7872425/>
*CD34 +ve.
*Vimentin +ve.
*Bcl-2 +ve.<ref name=pmid21843705/><ref>URL: [http://surgpathcriteria.stanford.edu/breast/pash/printable.html http://surgpathcriteria.stanford.edu/breast/pash/printable.html]. Accessed on: 28 April 2012.</ref>
*Factor VIII -ve.
*CD31 -ve.<ref name=pmid21843705>{{Cite journal  | last1 = Baker | first1 = M. | last2 = Chen | first2 = H. | last3 = Latchaw | first3 = L. | last4 = Memoli | first4 = V. | last5 = Ornvold | first5 = K. | title = Pseudoangiomatous stromal hyperplasia of the breast in a 10-year-old girl. | journal = J Pediatr Surg | volume = 46 | issue = 8 | pages = e27-31 | month = Aug | year = 2011 | doi = 10.1016/j.jpedsurg.2011.04.063 | PMID = 21843705 }}</ref>


=Weird stuff=
=Weird stuff=
Line 730: Line 377:
==Mammary hamartoma==
==Mammary hamartoma==
*[[AKA]] ''breast hamartoma''.
*[[AKA]] ''breast hamartoma''.
===General===
{{Main|Mammary hamartoma}}
*Benign.
*Disordered growth - see ''[[hamartoma]]''.
 
===Gross===
*Well-circumscribed - '''key feature'''.
 
===Microscopic===
Features:<ref name=Ref_BP117>{{Ref BP|117}}</ref>
*Disordered arrangement of ductal and lobular structures.
*Normal arrangement of cells with in the ductal structures, i.e. myoepithelium and epithelium present.
*Variable features:<ref name=surgpath_stan>URL: [http://surgpathcriteria.stanford.edu/breast/mammhamart/ http://surgpathcriteria.stanford.edu/breast/mammhamart/]. Accessed on: 4 October 2011.</ref>
*#Adipose tissue - predominant.
*#Dense fibrosis tissue - predominant.
*#Cystic glandular dilation.
 
Notes:
*If adipose tissue predominates; it may be labeled ''adenolipoma''.<ref name=surgpath_stan>URL: [http://surgpathcriteria.stanford.edu/breast/mammhamart/ http://surgpathcriteria.stanford.edu/breast/mammhamart/]. Accessed on: 4 October 2011.</ref>
 
DDx:
*[[Fibroadenoma]] - may have adipose tissue.
*[[Phyllodes tumour]] - may have adipose tissue.
*[[Pseudoangiomatous stromal hyperplasia]].
*[[Fibrocystic changes]].
 
Images:
*[http://www.breastpathology.info/sub-pages-iotw/2008/18.html Mammary hamartoma (breastpathology.info)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769817/figure/f2/ Mammary hamartoma (nih.gov)].<ref name=pmid12461066>{{Cite journal  | last1 = Tse | first1 = GM. | last2 = Law | first2 = BK. | last3 = Ma | first3 = TK. | last4 = Chan | first4 = AB. | last5 = Pang | first5 = LM. | last6 = Chu | first6 = WC. | last7 = Cheung | first7 = HS. | title = Hamartoma of the breast: a clinicopathological review. | journal = J Clin Pathol | volume = 55 | issue = 12 | pages = 951-4 | month = Dec | year = 2002 | doi =  | PMID = 12461066 | PMC = 1769817 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769817/}}</ref>
===IHC===
*None - it's a [[H&E]] diagnosis.


==Collagenous spherulosis==
==Collagenous spherulosis==
*[[AKA]] ''mucinous spherulosis'', [[AKA]] ''spherulosis''.<ref name=stanford_collspher>URL: [http://surgpathcriteria.stanford.edu/breast/collspher/ http://surgpathcriteria.stanford.edu/breast/collspher/]. Accessed on: 4 September 2011.</ref>
*[[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>
===General===
{{Main|Collagenous spherulosis}}
*Benign.
*Almost always an incidental finding.
*Can mimic [[ADH]], [[cribriform DCIS]], [[adenoid cystic carcinoma of the breast|adenoid cystic carcinoma]].<ref name=pmid16330938>{{Cite journal  | last1 = Resetkova | first1 = E. | last2 = Albarracin | first2 = C. | last3 = Sneige | first3 = N. | title = Collagenous spherulosis of breast: morphologic study of 59 cases and review of the literature. | journal = Am J Surg Pathol | volume = 30 | issue = 1 | pages = 20-7 | month = Jan | year = 2006 | doi =  | PMID = 16330938 }}</ref>
**Epidemiologically, it may be associated with [[LCIS]].<ref name=pmid16330938/>
 
===Microscopic===
Features:<ref name=stanford_collspher>URL: [http://surgpathcriteria.stanford.edu/breast/collspher/ http://surgpathcriteria.stanford.edu/breast/collspher/]. Accessed on: 4 September 2011.</ref><ref>URL: [http://www.hsc.stonybrook.edu/breast-atlas/V-33.htm http://www.hsc.stonybrook.edu/breast-atlas/V-33.htm]. Accessed on: 31 August 2011.</ref>
*Tubular/cribriform architecture.
*Intratubular eosinophilic material - '''key feature'''.
**Classical: Arranged like the spokes of a wheel ("radial spikes").
**Atypical: Granules ~ 1-2 micrometers.
*No mitotic activity.
*Two cells populations (epithelial & myoepithelial) - like a well-behaved breast gland.
 
Notes:
*Usually small lesions: < 50 spherules per lesion, <100 micrometers.
*May be multifocal.
*+/-Calcifications - may prompt biopsy.
 
DDx:
*[[Atypical ductal hyperplasia]].
*[[Cribriform DCIS]].
*[[Adenoid cystic carcinoma of the breast]].
 
====Images====
<gallery>
Image:Collagenous_spherulosis_-_intermed_mag.jpg | Collagenous spherulosis - intermed. mag. (WC/Nephron)
Image:Collagenous_spherulosis_-_very_high_mag.jpg | Collagenous spherulosis - very high mag. (WC/Nephron)
</gallery>
www:
*[http://www.hsc.stonybrook.edu/breast-atlas/V-33.htm Collagenous spherulosis (stonybrook.edu)].


==Nipple adenoma==
==Nipple adenoma==
Line 801: Line 388:
*[[AKA]] ''adenoma of the nipple''.
*[[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>
*[[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}}
===General===
*Rare.
*Reported in men.<ref name=pmid22342578/>
 
Clinical DDx:
*[[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>
 
===Microscopic===
Features:
*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>
 
Notes:
*Not encapsulated.<ref name=pmid2123505/>
*Lacks true fibrovascular cores.<ref>URL: [http://surgpathcriteria.stanford.edu/breast/nippleadenoma/printable.html http://surgpathcriteria.stanford.edu/breast/nippleadenoma/printable.html]. Accessed on: 6 August 2011.</ref>
*Focal necrosis may be present.<ref name=Ref_APBR307>{{Ref APBR|307 Q16}}</ref>
 
DDx:
*[[Intraductal papilloma]].
**Found within the duct '''not''' the stroma.
**Often deeper - one should '''not''' see skin in the histologic section.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Nipple_adenoma_-_low_mag.jpg Nipple adenoma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Nipple_adenoma_-_very_high_mag.jpg  Nipple adenoma - very high mag. (WC)].
*[http://www.breastpathology.info/sub-pages-benign-prolif/florid-papillomatosis-ex1-1.html Florid papillomatosis of the nipple - several images (breastpathology.info)].


==Intraductal papilloma==
==Intraductal papilloma==
*[[AKA]] ''papilloma''.
*[[AKA]] ''papilloma''.
===General===
{{Main|Intraductal papilloma of the breast}}
*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>
*Similar to ''[[papillary hidradenoma]]'' of the [[vulva]].
 
===Microscopic===
Features:
*True papillae - nipple-shaped structures with fibrovascular cores.
*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>
 
Notes:
*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>
*May degeneration and hyalinize to form a ''sclerosing papilloma''.
 
DDx:
*Intraductal papilloma with [[florid epithelial hyperplasia]].
*Intraductal papilloma with [[atypical ductal hyperplasia]]. †
*Intraductal papilloma with [[ductal carcinoma in situ]]. †
*[[Invasive papillary carcinoma of the breast]].
 
† Size criteria are different in papillomas.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Papillary_hidradenoma_-_low_mag.jpg Papillary hidradenoma - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Papillary_hidradenoma_-_very_high_mag.jpg Papillary hidradenoma - very high mag. (WC)].


==Lymphocytic mastitis==
==Lymphocytic mastitis==
===General===
*If the individual has [[diabetes mellitus]] it is ''[[diabetic mastopathy]]''.
*If the individual has [[diabetes mellitus]] (DM) it is called ''diabetic mastopathy''.<ref name=pmid12640102>{{Cite journal  | last1 = Valdez | first1 = R. | last2 = Thorson | first2 = J. | last3 = Finn | first3 = WG. | last4 = Schnitzer | first4 = B. | last5 = Kleer | first5 = CG. | title = Lymphocytic mastitis and diabetic mastopathy: a molecular, immunophenotypic, and clinicopathologic evaluation of 11 cases. | journal = Mod Pathol | volume = 16 | issue = 3 | pages = 223-8 | month = Mar | year = 2003 | doi = 10.1097/01.MP.0000056627.21128.74 | PMID = 12640102 }}</ref>
{{Main|Lymphocytic mastitis}}
*Rare.
 
===Microscopic===
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>
* Lymphocytic infiltrates - '''key feature''':
** Lobules.
** Perivascular.
* Enlarged stromal fibroblasts.
* Stromal collagen with keloid-like changes.
 
DDx:
*Diabetic mastopathy - if individual has diabetes.
*Primary [[lymphoma]] of the breast.
 
Images:
*[http://www.webpathology.com/image.asp?n=1&Case=655 Lymphocytic mastitis - low mag. (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=655&n=2 Lymphocytic mastitis - high mag. (webpathology.com)].
 
===IHC===
*B cell predominant (CD20 > CD3).<ref name=pmid12640102/>
**B cells CD43 -ve.
 
===Molecular===
*Negative clonality studies.


==Microglandular adenosis==
==Microglandular adenosis==
:'''''Not''' to be confused with [[microglandular hyperplasia]]''.
:'''''Not''' to be confused with [[microglandular hyperplasia]]''.
*Abbreviated ''MGA''.
*Abbreviated ''MGA''.
===General===
{{Main|Microglandular adenosis}}
*Controversial thingy.
 
Management:
*Excision.
 
===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>
*Round glands lined by a single layer of cells.
*May extend into fat.
*Lack of desmoplastic stroma.
 
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>
*[[Sclerosing adenosis]].
 
Images:
*[http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=1&s=20080802171452955&i=0&p=0 Microglandular adenosis (surgical pathologyatlas.com)].
*[http://webpathology.com/image.asp?n=1&Case=282 MGA - low mag. (webpathology.com)].
*[http://webpathology.com/image.asp?n=2&Case=282 MGA - high mag. (webpathology.com)].
*[http://www.breastpathology.info/Images/Benign/SclerAdenosis/mga1c_400.jpg MGA (breastpathology.info)].
*[http://www.breastpathology.info/sub-pages-iotw/2010/2.html MGA - several images (breastpathology.info)].
 
===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!
 
Others:
*EMA -ve.
**Tubular carcinoma usu. +ve.
*GCDFP-15 -ve.<ref>{{Ref APBR|296 Q20}}</ref>
*Ki-67 <3%.


==Adenomyoepithelioma==
==Adenomyoepithelioma==
===General===
{{Main|Adenomyoepithelioma}}
*Rare lesion consisting of epithelial and myoepithelial elements.
**May occur in other sites, e.g. tonsil.<ref name=pmid20356364>{{Cite journal  | last1 = Ren | first1 = J. | last2 = Song | first2 = L. | last3 = Dang | first3 = Q. | last4 = Zhang | first4 = X. | last5 = Jiang | first5 = SW. | last6 = Zhang | first6 = G. | last7 = Wang | first7 = N. | last8 = Liu | first8 = Z. | last9 = Wang | first9 = J. | title = Primary adenomyoepithelioma of tonsil. | journal = Head Neck Oncol | volume = 2 | issue =  | pages = 7 | month =  | year = 2010 | doi = 10.1186/1758-3284-2-7 | PMID = 20356364 }}</ref>
*May be benign or malignant.<ref name=pmid12591699>{{Cite journal  | last1 = Howlett | first1 = DC. | last2 = Mason | first2 = CH. | last3 = Biswas | first3 = S. | last4 = Sangle | first4 = PD. | last5 = Rubin | first5 = G. | last6 = Allan | first6 = SM. | title = Adenomyoepithelioma of the breast: spectrum of disease with associated imaging and pathology. | journal = AJR Am J Roentgenol | volume = 180 | issue = 3 | pages = 799-803 | month = Mar | year = 2003 | doi =  | PMID = 12591699 | url=http://www.ajronline.org/content/180/3/799.full}}</ref><ref name=pmid19480267>{{Cite journal  | last1 = Zizi-Sermpetzoglou | first1 = A. | last2 = Vasilakaki | first2 = T. | last3 = Grammatoglou | first3 = X. | last4 = Petrakopoulou | first4 = N. | last5 = Nikolaidou | first5 = ME. | last6 = Glava | first6 = C. | title = Malignant adenomyoepithelioma of the breast--case report. | journal = Eur J Gynaecol Oncol | volume = 30 | issue = 2 | pages = 234-6 | month =  | year = 2009 | doi =  | PMID = 19480267 }}</ref>
 
Note:
*Possibly the same tumour as [[epithelial-myoepithelial carcinoma]] of the [[salivary gland]].<ref name=pmid9769134>{{Cite journal  | last1 = Seifert | first1 = G. | title = Are adenomyoepithelioma of the breast and epithelial-myoepithelial carcinoma of the salivary glands identical tumours? | journal = Virchows Arch | volume = 433 | issue = 3 | pages = 285-8 | month = Sep | year = 1998 | doi =  | PMID = 9769134 }}</ref>
 
===Microscopic===
Features:<ref>URL: [http://www.webpathology.com/image.asp?n=1&Case=322 http://www.webpathology.com/image.asp?n=1&Case=322]. Accessed on: 16 August 2011.</ref>
*Well-circumscribed.
*Glandular architecture with:
**Easily identifiable myoepithelial cells - with clear cytoplasm - '''key feature'''.
**Eosinophilic cuboidal epithelial cells.
*Eosinophilic basement membrane material between glands.
 
DDx:
*[[Invasive ductal carcinoma of the breast]] (on core biopsy).
*Mammary pleomorphic adenoma.
*Ductal adenoma.
*[[Tubular adenoma of the breast]] - does not have a prominent (clear) myoepithelial component.
*[[Sclerosing adenosis]].<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>
 
====Images====
<gallery>
Image:Adenomyoepithelioma_-_low_mag.jpg | Adenomyoepithelioma - low mag. (WC/Nephron)
Image:Adenomyoepithelioma_-_high_mag.jpg | Adenomyoepithelioma - high mag. (WC/Nephron)
</gallery>
 
Webpathology.com:
*[http://www.webpathology.com/image.asp?n=1&Case=322 Adenomyoepithelioma - low mag. (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=4&Case=322 Adenomyoepithelioma - high mag. (webpathology.com)].


==Mammary myofibroblastoma==
==Mammary myofibroblastoma==
===General===
*[[AKA]] ''breast myofibroblastoma''.
*Rare.
*[[AKA]] ''myofibroblastoma of the breast''.
*Excision = cure.
{{Main|Mammary myofibroblastoma}}
*Postmenopausal females and older males.<ref name=pmid18723968>{{Cite journal  | last1 = Qureshi | first1 = A. | last2 = Kayani | first2 = N. | title = Myofibroblastoma of breast. | journal = Indian J Pathol Microbiol | volume = 51 | issue = 3 | pages = 395-6 | month =  | year =  | doi =  | PMID = 18723968 }}</ref><ref name=pmid22096693>{{Cite journal  | last1 = Mele | first1 = M. | last2 = Jensen | first2 = V. | last3 = Wronecki | first3 = A. | last4 = Lelkaitis | first4 = G. | title = Myofibroblastoma of the breast: Case report and literature review. | journal = Int J Surg Case Rep | volume = 2 | issue = 6 | pages = 93-6 | month =  | year = 2011 | doi = 10.1016/j.ijscr.2011.02.006 | PMID = 22096693 |    PMC = 3199680 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199680/?tool=pubmed}}</ref>
 
Note:
*In extra-mammary sites the tumour is known as a ''mammary-type myofibroblastoma'' may immunohistochemically and histomorphologically overlap with [[spindle cell lipoma]].<ref name=pmid11474286>{{Cite journal  | last1 = McMenamin | first1 = ME. | last2 = Fletcher | first2 = CD. | title = Mammary-type myofibroblastoma of soft tissue: a tumor closely related to spindle cell lipoma. | journal = Am J Surg Pathol | volume = 25 | issue = 8 | pages = 1022-9 | month = Aug | year = 2001 | doi =  | PMID = 11474286 }}</ref>
 
===Microscopic===
Features:<ref name=Ref_BP131>{{Ref BP|131}}</ref>
*Well-circumscribed lesion.
*Spindle cells without nuclear atypia arranged in fascicles.
*Interspersed thick bundles of collagen.
 
Notes:
*No calcifications.
*No necrosis.
*No hemorrhage.
 
DDx:
*[[Metaplastic breast carcinoma]].
*Fibromatosis.
*[[Leiomyoma]] of the breast.
*[[Nodular fasciitis]].
*[[Phyllodes tumour]].
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Mammary_myofibroblastoma_-_low_mag.jpg Mammary myofibroblastoma - low mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Mammary_myofibroblastoma_-_intermed_mag.jpg Mammary myofibroblastoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Mammary_myofibroblastoma_-_high_mag.jpg Mammary myofibroblastoma - high mag. (WC)].
*www:
**[http://path.upmc.edu/cases/case249.html Mammary myofibroblastoma - several images (upmc.edu)].
 
===IHC===
Features:<ref name=pmid22096693>{{Cite journal  | last1 = Mele | first1 = M. | last2 = Jensen | first2 = V. | last3 = Wronecki | first3 = A. | last4 = Lelkaitis | first4 = G. | title = Myofibroblastoma of the breast: Case report and literature review. | journal = Int J Surg Case Rep | volume = 2 | issue = 6 | pages = 93-6 | month =  | year = 2011 | doi = 10.1016/j.ijscr.2011.02.006 | PMID = 22096693 }}</ref>
*CD34 +ve.<ref name=pmid11474286/>
*Desmin +ve.<ref name=pmid11474286/>
*H-caldesmon +ve.
*Actin +ve.
*Vimentin +ve.
 
Other
*S100 -ve.
*Beta-catenin -ve. (???)


==Squamous metaplasia of lactiferous ducts==
==Squamous metaplasia of lactiferous ducts==
*Abbreviated ''SMOLD''.
*Abbreviated ''SMOLD''.
===General===
{{Main|Squamous metaplasia of lactiferous ducts}}
*Uncommon.<ref name=pmid22964367>{{Cite journal  | last1 = Lo | first1 = G. | last2 = Dessauvagie | first2 = B. | last3 = Sterrett | first3 = G. | last4 = Bourke | first4 = AG. | title = Squamous metaplasia of lactiferous ducts (SMOLD). | journal = Clin Radiol | volume = 67 | issue = 11 | pages = e42-6 | month = Nov | year = 2012 | doi = 10.1016/j.crad.2012.07.011 | PMID = 22964367 }}</ref>
*Associated with [[smoking]].<ref name=pmid22964367/>
*Post-menopausal women.
*May be associated with subareolar abscess.
 
===Gross===
*+/-Nipple inversion.<ref name=pmid887978/>
 
===Microscopic===
Features:
*Squamous epithelium - replaces (bilayered) lactiferous ducts - '''key feature'''.<ref name=pmid887978>{{Cite journal  | last1 = Powell | first1 = BC. | last2 = Maull | first2 = KI. | last3 = Sachatello | first3 = CR. | title = Recurrent subareolar abscess of the breast and squamous metaplasia of the lactiferous ducts: a clinical syndrome. | journal = South Med J | volume = 70 | issue = 8 | pages = 935-7 | month = Aug | year = 1977 | doi =  | PMID = 887978 }}</ref>
*Xanthomatous reaction.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Squamous_metaplasia_of_the_lactiferous_ducts_-_very_low_mag.jpg SMOLD - very low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Squamous_metaplasia_of_the_lactiferous_ducts_-_low_mag.jpg SMOLD - low mag. (WC)].


==Granular cell tumour of the breast==
==Granular cell tumour of the breast==
Line 1,032: Line 425:
===Microscopic===
===Microscopic===
:See ''[[granular cell tumour]]''.
:See ''[[granular cell tumour]]''.
DDx:
*[[Invasive lobular carcinoma]].<ref name=pmid21398688>{{Cite journal  | last1 = Tan | first1 = PH. | last2 = Harada | first2 = O. | last3 = Thike | first3 = AA. | last4 = Tse | first4 = GM. | title = Histiocytoid breast carcinoma: an enigmatic lobular entity. | journal = J Clin Pathol | volume = 64 | issue = 8 | pages = 654-9 | month = Aug | year = 2011 | doi = 10.1136/jcp.2011.088930 | PMID = 21398688 }}</ref>


=See also=
=See also=
Line 1,041: 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

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