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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).


Invasive breast cancer is dealt with in the article ''[[invasive breast cancer]]''.
Invasive breast cancer is dealt with in the article ''[[invasive breast cancer]]''.  An introduction to the ''breast'' is found in the ''[[breast pathology]]'' article.


==Ductal carcinoma in situ==
=Ductal neoplasia=
===General===
==Overview==
*Abbreviated ''DCIS''.
This category includes:
*Diagnosis based on nuclear abnormalities ''and'' architecture.
#[[Atypical ductal hyperplasia]] (ADH).
*It is typically picked-up during radiologic screening.
#[[Ductal carcinoma in situ]] (DCIS).
 
===Subtypes===
Subtypes are based on architecture:
*Solid.
**No spaces between cells.
*Cribriform.
**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.
 
===Histologic features===
*Nuclear pleomorphism -- most important feature. 
*Nuclear size - compared to RBCs to grade DCIS.
**Compare sizes of nuclei if you cannot find RBCs.
***See ''[[Grading DCIS]]'' for details.
*+/-Mitoses.
*Cells cohesive.
**No spaces in between.
**Nuclei spaced equally.
 
===Size criteria for DCIS===
DCIS must meet the following size criteria:<ref>Breast Pathology P.168.</ref>
*2 membrane bound spaces -- OR -- 2 mm.
*If it isn't DCIS... it's atypical ductal hyperplasia (ADH).  
 
The treatment is similar; ADH and DCIS are both excised. 
 
The differences are:
*DCIS is cancer, i.e. this has life insurance implications.
*Radiation treatment - DCIS is irradiated; ADH does ''not'' get radiation.
 
===Grading 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:  
The difference between ADH and DCIS ''is'':
*It is often hard to find RBCs when you want 'em. DCIS is pleomorphic.  
#The degree of '''nuclear atypia'''; high grade is DCIS.
*If no RBCs are present to compare with compare the nuclei to one another.
#The '''extent'''; small lesions are ADH, large lesions (low-grade) DCIS.
*If you see nuclei >3x larger than their neigbour you're ready to call DCIS Grade 3.


==FEHUT vs ADH vs DCIS==
==Is it ductal neoplasia?==
*Breast duct lumen with too many cells.
===FEHUT versus ADH versus DCIS===
*This is common problem is breast pathology.<ref>Breast Pathology PP. 167-8.</ref>
*Breast duct lumen with too many cells; this is common problem is breast pathology.<ref name=Ref_BP167-8>{{Ref BP|167-8}}</ref>
**The general DDx for this scenario is: ''FEHUT'' versus ''ADH'' versus ''DCIS''.


Definitions:
Notes:
*EHUT = epithelial hyperplasia of the usual type, aka ''florid epithelial hyperplasia of the usual type'' (FEHUT).
*FEHUT = florid epithelial hyperplasia of the usual type, [[AKA]] ''epithelial hyperplasia'' (EH).
*ADH = atypical ductal hyperplasia.
*ADH = [[atypical ductal hyperplasia]].
*DCIS = ductal carcinoma in situ.
*DCIS = [[ductal carcinoma in situ]].


*Mnemonic ''CLEAN'' = cell uniformity, luminal spaces, extent/size, arch., nuclei.
====Tabular comparison - histomorphology====
**CELLULAR COMPOSITION:
Comparison of FEHUT, ADH and DCIS (memory device: ''CLEAN'' = cell spacing, luminal spaces, extent/size, arch., nuclei):
***EHUT = varied,
{| class="wikitable sortable"
***ADH = focal uniformity,
! Morphology
***DCIS = uniform.
! [[FEHUT]]
**LUMINA:
! [[ADH]]
***EHUT = slits/irregular spaces,
! [[DCIS]]
***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]]

Latest revision as of 05:36, 23 January 2017

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

Viewed simplistically, it can neatly be divided into the discussion of two entities:

  1. Ductal carcinoma in situ (DCIS).
  2. Lobular carcinoma in situ (LCIS).

Invasive breast cancer is dealt with in the article invasive breast cancer. An introduction to the breast is found in the breast pathology article.

Ductal neoplasia

Overview

This category includes:

  1. Atypical ductal hyperplasia (ADH).
  2. Ductal carcinoma in situ (DCIS).

The difference between ADH and DCIS is:

  1. The degree of nuclear atypia; high grade is DCIS.
  2. The extent; small lesions are ADH, large lesions (low-grade) DCIS.

Is it ductal neoplasia?

FEHUT versus ADH versus DCIS

  • Breast duct lumen with too many cells; this is common problem is breast pathology.[1]
    • The general DDx for this scenario is: FEHUT versus ADH versus DCIS.

Notes:

Tabular comparison - histomorphology

Comparison of FEHUT, ADH and DCIS (memory device: CLEAN = cell spacing, luminal spaces, extent/size, arch., nuclei):

Morphology FEHUT ADH DCIS
Cell spacing varied, streaming focal uniformity uniform
Lumina slits/irregular spaces;
cells haphazardly
arranged around lumen 		irregular spaces, no slits circular "punched-out";
cells side-by-side +
equally spaced @ interface
Extent usually lobulocentric limited extent extensive
Architecture irregular/swirling DCIS-like DCIS architecture (solid,
cribriform, papillary, micropapillary)
Nuclei variable, no nucleolus hyperchromatic
& uniform, usu. no nucleolus 		evenly spaced +/-nucleolus

Treatment - implications:

  • FEHUT - nothing; FEHUT is benign.
  • ADH - simple excision, i.e. lumpectomy.
  • DCIS - excision (lumpectomy) + radiation.
  • Invasive ductal carcinoma - excision with sentinel lymph node biopsy (for staging)[2] and radiation.
  • Positive sentinel node - systemic chemotherapy. (???)

IHC

Usual ductal hyperplasia (AKA FEHUT) vs. ADH/DCIS:[3][4]

  • 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 article: Atypical ductal hyperplasia

Ductal carcinoma in situ

  • Abbreviated DCIS.
Main article: Ductal carcinoma in situ

Lobular neoplasia

Overview

Includes:

  1. Atypical lobular hyperplasia (ALH).
  2. 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 article: Atypical lobular hyperplasia

Lobular carcinoma in situ

  • Abbreviated LCIS.

General

  • Management is currently some matter of debate.
    • Association of Breast Surgery (UK) guidelines recommend excision of LCIS on biopsy,[5] as does a smaller (US) study.[6]
    • In the UK, most surgeons (~60%) excise LCIS seen on biopsy; however, a significant minority considers followup appropriate.[5]
  • Not detected radiologically - it is an incidental pathologic finding.
  • The precursor to invasive ductal carcinoma of the breast.

Microscopic

Features[7][8] - memory device ABCDEF:

  • Atypia minimal - usually.
    • Relatively small ~1-2x size lymphocyte.
  • Borders of cells distinct/visible - dyscohesive.
  • Clear cytoplasm (focal).
    • May have a signet ring cell-like appearance.
  • Distend duct.
  • Eccentric nucleus, usu. round.
  • Filled ducts.
    • No luminal spaces - key feature.
      • Partially filled ducts are not LCIS.

DDx:

Images:

Subclassification[8]

  • 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:

IHC

  • E-cadherin -ve or incomplete membrane staining.
  • p120 catenin +ve cytoplasmic.[9]
    • Membranous staining in DCIS.

See also

References

  1. ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 167-8. ISBN 978-0443066801.
  2. ↑ Sentinel Lymph Node Biopsy: What Breast Cancer Patients Need to Know. cancernews.com. URL: http://www.cancernews.com/data/Article/202.asp. Accessed on: 9 October 2009.
  3. ↑ Rabban, JT.; Koerner, FC.; Lerwill, MF. (Jul 2006). "Solid papillary ductal carcinoma in situ versus usual ductal hyperplasia in the breast: a potentially difficult distinction resolved by cytokeratin 5/6.". Hum Pathol 37 (7): 787-93. doi:10.1016/j.humpath.2006.02.016. PMID 16784976.
  4. ↑ Grin, A.; O'Malley, FP.; Mulligan, AM. (Nov 2009). "Cytokeratin 5 and estrogen receptor immunohistochemistry as a useful adjunct in identifying atypical papillary lesions on breast needle core biopsy.". Am J Surg Pathol 33 (11): 1615-23. doi:10.1097/PAS.0b013e3181aec446. PMID 19675450.
  5. ↑ 5.0 5.1 Chester, R.; Bokinni, O.; Ahmed, I.; Kasem, A. (Nov 2015). "UK national survey of management of breast lobular carcinoma in situ.". Ann R Coll Surg Engl 97 (8): 574-7. doi:10.1308/rcsann.2015.0037. PMID 26492902.
  6. ↑ O'Neil, M.; Madan, R.; Tawfik, OW.; Thomas, PA.; Fan, F. (Aug 2010). "Lobular carcinoma in situ/atypical lobular hyperplasia on breast needle biopsies: does it warrant surgical excisional biopsy? A study of 27 cases.". Ann Diagn Pathol 14 (4): 251-5. doi:10.1016/j.anndiagpath.2010.04.002. PMID 20637429.
  7. ↑ Weedman Molavi, Diana (2008). The Practice of Surgical Pathology: A Beginner's Guide to the Diagnostic Process (1st ed.). Springer. pp. 188. ISBN 978-0387744858.
  8. ↑ 8.0 8.1 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 170. ISBN 978-0443066801.
  9. ↑ Sarrió, D.; Pérez-Mies, B.; Hardisson, D.; Moreno-Bueno, G.; Suárez, A.; Cano, A.; Martín-Pérez, J.; Gamallo, C. et al. (Apr 2004). "Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions.". Oncogene 23 (19): 3272-83. doi:10.1038/sj.onc.1207439. PMID 15077190.
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