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'''Non-invasive [[breast cancer]]''' is a common entity... since the introduction of radiologic breast screening.
'''Non-invasive breast carcinoma''' is a type of [[breast cancer]] and a common entity... since the introduction of radiologic breast screening.


It can neatly be divided into the discussion of two entities:  
Viewed simplistically, it can neatly be divided into the discussion of two entities:  
*Ductal carcinoma in situ, and,
#[[Ductal carcinoma in situ]] (DCIS).
*Lobular carcinoma in situ.
#[[Lobular carcinoma in situ]] (LCIS).


==Ductal carcinoma in situ==
Invasive breast cancer is dealt with in the article ''[[invasive breast cancer]]''. An introduction to the ''breast'' is found in the ''[[breast pathology]]'' article.
===General===
*Abbreviated ''DCIS''.
*Diagnosis based on nuclear abnormalities ''and'' architecture.
*It is typically picked-up during radiologic screening.


===Subtypes===
=Ductal neoplasia=
Subtypes are based on architecture:
==Overview==
*Solid.
This category includes:
**No spaces between cells.
#[[Atypical ductal hyperplasia]] (ADH).
*Cribriform.
#[[Ductal carcinoma in situ]] (DCIS).
**Honeycomb-like appearance: circular holes.
**"Cookie cutter" appearance/"punched-out" appearance/"Roman bridges" -- cells surround the circular holes.
*Papillary.
**Papillae with fibrovascular cores.
*Micropapillary.
**Small papillae without fibrovascular cores.
**Have "drum stick" shape.


NOTE: ''comedonecrosis'' - used to be considered a separate subtype -- essentially ''solid'' type DCIS with necrosis.
The difference between ADH and DCIS ''is'':
#The degree of '''nuclear atypia'''; high grade is DCIS.
#The '''extent'''; small lesions are ADH, large lesions (low-grade) DCIS.


===Histologic features===
==Is it ductal neoplasia?==
*Nuclear pleomorphism -- most important feature.  
===FEHUT versus ADH versus DCIS===
*Nuclear size - compared to RBCs to grade DCIS.
*Breast duct lumen with too many cells; this is common problem is breast pathology.<ref name=Ref_BP167-8>{{Ref BP|167-8}}</ref>  
**Compare sizes of nuclei if you cannot find RBCs.
**The general DDx for this scenario is: ''FEHUT'' versus ''ADH'' versus ''DCIS''.
***See ''[[Grading DCIS]]'' for details.
*+/-Mitoses.
*Cells cohesive.
**No spaces in between.
**Nuclei spaced equally.


===Size criteria for DCIS===
Notes:
DCIS must meet the following size criteria:<ref>Breast Pathology P.168.</ref>
*FEHUT = florid epithelial hyperplasia of the usual type, [[AKA]] ''epithelial hyperplasia'' (EH).
*2 membrane bound spaces -- OR -- 2 mm.
*ADH = [[atypical ductal hyperplasia]].
*If it isn't DCIS... it's atypical ductal hyperplasia (ADH).  
*DCIS = [[ductal carcinoma in situ]].


The treatment is similar; ADH and DCIS are both excised. 
====Tabular comparison - histomorphology====
 
Comparison of FEHUT, ADH and DCIS (memory device: ''CLEAN'' = cell spacing, luminal spaces, extent/size, arch., nuclei):
The differences are:
{| class="wikitable sortable"
*DCIS is cancer, i.e. this has life insurance implications.
! Morphology
*Radiation treatment - DCIS is irradiated; ADH does ''not'' get radiation.
! [[FEHUT]]
 
! [[ADH]]
===Grading DCIS===
! [[DCIS]]
Graded 1-3 (low-high)<ref>[http://surgpathcriteria.stanford.edu/breast/dcis/ http://surgpathcriteria.stanford.edu/breast/dcis/]</ref> - compare lesional nuclei to one another.
*Grade 1
**Nuclei 2-3x size of RBC.
**NO necrosis.
*Grade 2
**Nuclei 2-3x size of RBC.
**+/-Necrosis.
*Grade 3
**Nuclei >3x size of RBC.
**Necrosis usually present.
 
Notes:
*It is often hard to find RBCs when you want 'em. DCIS is pleomorphic.
*If no RBCs are present to compare with compare the nuclei to one another.
*If you see nuclei >3x larger than their neigbour you're ready to call DCIS Grade 3.
 
==FEHUT vs ADH vs DCIS==
*Breast duct lumen with too many cells.
*This is common problem is breast pathology.<ref>Breast Pathology PP. 167-8.</ref>
 
Definitions:
*EHUT = epithelial hyperplasia of the usual type, aka ''florid epithelial hyperplasia of the usual type'' (FEHUT).
*ADH = atypical ductal hyperplasia.
*DCIS = ductal carcinoma in situ.
 
*Mnemonic ''CLEAN'' = cell uniformity, luminal spaces, extent/size, arch., nuclei.
**CELLULAR COMPOSITION:
***EHUT = varied,
***ADH = focal uniformity,
***DCIS = uniform.
**LUMINA:
***EHUT = slits/irregular spaces,
***ADH = irregular spaces, no slits,
***DCIS = circular "punched-out".
**EXTENT:
***EHUT = usually lobulocentric,
***ADH = limited extent.
***DCIS = extensive.
**ARCHITECTURE:
***EHUT = irregular/swirling,
***ADH = DCIS-like,
***DCIS = DCIS architecture (solid, cribriform, comedo, papillary, micropapillary).
**NUCLEI:
***EHUT = variable,
***ADH = hyperchromatic + uniform,
***DCIS = evenly spaced.
 
===Tabular comparison===
Comparison of EHUT, ADH and DCIS:
{| class="wikitable"
| || '''EHUT''' || '''ADH''' || '''DCIS'''
|-
|-
| '''Cellular composition''' || varied || focal uniformity || uniform
| '''Cell spacing'''
| varied, streaming
| focal uniformity
| uniform
|-
|-
| '''Lumina''' || slits/irregular spaces || irregular spaces, no slits || circular "punched-out"
| '''Lumina'''
| slits/irregular spaces; <br>cells haphazardly <br>arranged around lumen
| irregular spaces, no slits
| circular "punched-out"; <br>cells side-by-side + <br>equally spaced @ interface
|-
|-
| '''Extent''' || usually lobulocentric || limited extent || extensive
| '''Extent'''
| usually lobulocentric
| limited extent
| extensive
|-
|-
| '''Architecture''' || irregular/swirling || DCIS-like || DCIS architecture (solid, cribriform, papillary, micropapillary)
| '''Architecture'''
| irregular/swirling
| DCIS-like
| DCIS architecture (solid, <br>cribriform, papillary, micropapillary)
|-
|-
| '''Nuclei''' || variable || hyperchromatic<br>& uniform || evenly spaced
| '''Nuclei'''
| variable, no nucleolus
| hyperchromatic<br>& uniform, usu. no nucleolus
| evenly spaced +/-nucleolus
|-
|-
|}
|}


Treatment - implications:
Treatment - implications:
*EHUT - nothing; EHUT is benign.
*[[FEHUT]] - nothing; FEHUT is benign.
*ADH - simple excision, i.e. lumpectomy.
*[[ADH]] - simple excision, i.e. lumpectomy.
*DCIS - excision (lumpectomy) + radiation.
*[[DCIS]] - excision (lumpectomy) + radiation.
*Invasive ductal carcinoma - excision with sentinel lymph node disection<ref>Sentinel Lymph Node Biopsy: What Breast Cancer Patients Need to Know. cancernews.com. URL: [http://www.cancernews.com/data/Article/202.asp http://www.cancernews.com/data/Article/202.asp]. Accessed on: 9 October 2009.</ref> and radiation.
*Invasive ductal carcinoma - excision with sentinel lymph node biopsy (for staging)<ref>Sentinel Lymph Node Biopsy: What Breast Cancer Patients Need to Know. cancernews.com. URL: [http://www.cancernews.com/data/Article/202.asp http://www.cancernews.com/data/Article/202.asp]. Accessed on: 9 October 2009.</ref> and radiation.
*Positive sentinel node - systemic chemotherapy. (???)
 
====IHC====
Usual ductal hyperplasia (AKA FEHUT) vs. [[ADH]]/[[DCIS]]:<ref>{{Cite journal  | last1 = Rabban | first1 = JT. | last2 = Koerner | first2 = FC. | last3 = Lerwill | first3 = MF. | title = Solid papillary ductal carcinoma in situ versus usual ductal hyperplasia in the breast: a potentially difficult distinction resolved by cytokeratin 5/6. | journal = Hum Pathol | volume = 37 | issue = 7 | pages = 787-93 | month = Jul | year = 2006 | doi = 10.1016/j.humpath.2006.02.016 | PMID = 16784976 }}</ref><ref name=pmid19675450>{{Cite journal  | last1 = Grin | first1 = A. | last2 = O'Malley | first2 = FP. | last3 = Mulligan | first3 = AM. | title = Cytokeratin 5 and estrogen receptor immunohistochemistry as a useful adjunct in identifying atypical papillary lesions on breast needle core biopsy. | journal = Am J Surg Pathol | volume = 33 | issue = 11 | pages = 1615-23 | month = Nov | year = 2009 | doi = 10.1097/PAS.0b013e3181aec446 | PMID = 19675450 }}</ref>
*FEHUT: ER-low/CK5-high profile.
*ADH/DCIS: ER-high/CK5-low.
 
Where:
*ER-high = diffuse strong staining in >90% of cells.
*CK5-high = mosaic pattern of staining in >20% of cells
*CK5-low = absent or staining in <20% of cells.
 
==Atypical ductal hyperplasia==
*Abbreviated ''ADH''.
{{Main|Atypical ductal hyperplasia}}
 
==Ductal carcinoma in situ==
*Abbreviated ''DCIS''.
{{Main|Ductal carcinoma in situ}}
 
=Lobular neoplasia=
==Overview==
Includes:
#Atypical lobular hyperplasia (ALH).
#Lobular carcinoma in situ (LCIS).
 
*These entities (ALH, LCIS) are near identical from a histomorphologic perspective.
*The difference is extent of involvement:
**ALH <50% of terminal duct lobular unit (TDLU) is involved.
**LCIS >=50% of TDLU is involved.
 
==Atypical lobular hyperplasia==
*Abbreviated ''ALH''.
{{Main|Atypical lobular hyperplasia}}


==Lobular carcinoma in situ==
==Lobular carcinoma in situ==
*Abbreviated ''LCIS''.
*Abbreviated ''LCIS''.
===General===
*Management is currently some matter of debate.
*Management is currently some matter of debate.
**''Association of Breast Surgery'' (UK) guidelines recommend excision of LCIS on biopsy,<ref name=pmid26492902/> as does a smaller (US) study.<ref name=pmid20637429>{{Cite journal  | last1 = O'Neil | first1 = M. | last2 = Madan | first2 = R. | last3 = Tawfik | first3 = OW. | last4 = Thomas | first4 = PA. | last5 = Fan | first5 = F. | title = Lobular carcinoma in situ/atypical lobular hyperplasia on breast needle biopsies: does it warrant surgical excisional biopsy? A study of 27 cases. | journal = Ann Diagn Pathol | volume = 14 | issue = 4 | pages = 251-5 | month = Aug | year = 2010 | doi = 10.1016/j.anndiagpath.2010.04.002 | PMID = 20637429 }}</ref>
**In the UK, most surgeons (~60%) excise LCIS seen on biopsy; however, a significant minority considers followup appropriate.<ref name=pmid26492902>{{Cite journal  | last1 = Chester | first1 = R. | last2 = Bokinni | first2 = O. | last3 = Ahmed | first3 = I. | last4 = Kasem | first4 = A. | title = UK national survey of management of breast lobular carcinoma in situ. | journal = Ann R Coll Surg Engl | volume = 97 | issue = 8 | pages = 574-7 | month = Nov | year = 2015 | doi = 10.1308/rcsann.2015.0037 | PMID = 26492902 }}</ref>
*Not detected radiologically - it is an incidental pathologic finding.
*Not detected radiologically - it is an incidental pathologic finding.
*The precursor to [[invasive ductal carcinoma of the breast]].
===Microscopic===
Features<ref name=Ref_TPoSP188>{{Ref TPoSP|188}}</ref><ref name=Ref_BP170>{{Ref BP|170}}</ref> - memory device ''ABCDEF'':
*'''A'''typia minimal - usually.
**Relatively small ~1-2x size lymphocyte.
*'''B'''orders of cells distinct/visible - ''dyscohesive''.
*'''C'''lear cytoplasm (focal).
**May have a signet ring cell-like appearance.
*'''D'''istend duct.
*'''E'''ccentric nucleus, usu. round.
*'''F'''illed ducts.
**'''No''' luminal spaces - '''key feature'''.
***Partially filled ducts are ''not'' LCIS.
DDx:
*[[Invasive ductal carcinoma of the breast|Invasive ductal carcinoma]].
*[[Atypical ductal hyperplasia]].
Images:
*[http://www.webpathology.com/image.asp?n=3&Case=291 LCIS (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=5&Case=291 LCIS (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=6&Case=291 LCIS - high mag. (webpathology.com)].
====Subclassification<ref name=Ref_BP170>{{Ref BP|170}}</ref>====
*Non-PLCIS.
**Type A.
***Nucleus 1-1.5x lymphocyte.
***No nucleolus.
**Type B.
***Nucleus ~2x lymphocyte.
***Nucleolus present.
*PLCIS (pleomorphic lobular carcinoma in situ).
DDx:
*Low-grade DCIS.
*High-grade DCIS for ''pleomorphic lobular carcinoma in situ''.
*[[Atypical lobular hyperplasia]].
===IHC===
*[[E-cadherin]] -ve ''or'' incomplete membrane staining.
*p120 catenin +ve cytoplasmic.<ref name="Sarrió-2004">{{Cite journal  | last1 = Sarrió | first1 = D. | last2 = Pérez-Mies | first2 = B. | last3 = Hardisson | first3 = D. | last4 = Moreno-Bueno | first4 = G. | last5 = Suárez | first5 = A. | last6 = Cano | first6 = A. | last7 = Martín-Pérez | first7 = J. | last8 = Gamallo | first8 = C. | last9 = Palacios | first9 = J. | title = Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions. | journal = Oncogene | volume = 23 | issue = 19 | pages = 3272-83 | month = Apr | year = 2004 | doi = 10.1038/sj.onc.1207439 | PMID = 15077190 }}</ref>
**Membranous staining in DCIS.


==See also==
=See also=
*[[Breast]]
*[[Breast]].
*[[Invasive breast cancer]]
*[[Invasive breast cancer]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Breast pathology]]
[[Category:Breast pathology]]
Michael
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