Difference between revisions of "Non-invasive breast carcinoma"

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Viewed simplistically, 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 (DCIS).
#[[Ductal carcinoma in situ]] (DCIS).
#Lobular carcinoma in situ (LCIS).
#[[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.
Invasive breast cancer is dealt with in the article ''[[invasive breast cancer]]''.  An introduction to the ''breast'' is found in the ''[[breast pathology]]'' article.
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====Tabular comparison - histomorphology====
====Tabular comparison - histomorphology====
Comparison of FEHUT, ADH and DCIS (memory device: ''CLEAN'' = cell spacing, luminal spaces, extent/size, arch., nuclei):
Comparison of FEHUT, ADH and DCIS (memory device: ''CLEAN'' = cell spacing, luminal spaces, extent/size, arch., nuclei):
{| class="wikitable"
{| class="wikitable sortable"
| || '''[[FEHUT]]''' || '''[[ADH]]''' || '''[[DCIS]]'''
! Morphology
! [[FEHUT]]
! [[ADH]]
! [[DCIS]]
|-
|-
| '''Cell spacing''' || varied, streaming || focal uniformity || uniform
| '''Cell spacing'''
| varied, streaming
| focal uniformity
| uniform
|-
|-
| '''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
| '''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, <br>cribriform, papillary, micropapillary)
| '''Architecture'''
| irregular/swirling
| DCIS-like
| DCIS architecture (solid, <br>cribriform, papillary, micropapillary)
|-
|-
| '''Nuclei''' || variable, no nucleolus || hyperchromatic<br>& uniform, usu. no nucleolus || evenly spaced +/-nucleolus
| '''Nuclei'''
| variable, no nucleolus
| hyperchromatic<br>& uniform, usu. no nucleolus
| evenly spaced +/-nucleolus
|-
|-
|}
|}
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==Atypical ductal hyperplasia==
==Atypical ductal hyperplasia==
*Abbreviated ''ADH''.
*Abbreviated ''ADH''.
===General===
{{Main|Atypical ductal hyperplasia}}
*Molecular studies have shown it is the same thing as low-grade DCIS; thus, some have called for abolition of the term.<ref>{{Cite journal  | last1 = Ghofrani | first1 = M. | last2 = Tapia | first2 = B. | last3 = Tavassoli | first3 = FA. | title = Discrepancies in the diagnosis of intraductal proliferative lesions of the breast and its management implications: results of a multinational survey. | journal = Virchows Arch | volume = 449 | issue = 6 | pages = 609-16 | month = Dec | year = 2006 | doi = 10.1007/s00428-006-0245-y | PMID = 17058097 }}</ref>
*ADH is considered an indication for a lumpectomy.<ref name=pmid7717215>{{cite journal |author=Liberman L, Cohen MA, Dershaw DD, Abramson AF, Hann LE, Rosen PP |title=Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy |journal=AJR Am J Roentgenol |volume=164 |issue=5 |pages=1111–3 |year=1995 |month=May |pmid=7717215 |doi= |url=http://www.ajronline.org/cgi/pmidlookup?view=long&pmid=7717215}}</ref>
**Two large studies suggest the conversion of an ADH on core biopsy to breast cancer on surgical excision, known as "up-grading", is approximately 30%.<ref name=pmid20619647>{{Cite journal  | last1 = Deshaies | first1 = I. | last2 = Provencher | first2 = L. | last3 = Jacob | first3 = S. | last4 = Côté | first4 = G. | last5 = Robert | first5 = J. | last6 = Desbiens | first6 = C. | last7 = Poirier | first7 = B. | last8 = Hogue | first8 = JC. | last9 = Vachon | first9 = E. | title = Factors associated with upgrading to malignancy at surgery of atypical ductal hyperplasia diagnosed on core biopsy. | journal = Breast | volume = 20 | issue = 1 | pages = 50-5 | month = Feb | year = 2011 | doi = 10.1016/j.breast.2010.06.004 | PMID = 20619647 }}</ref><ref name=pmid16978969>{{Cite journal  | last1 = Margenthaler | first1 = JA. | last2 = Duke | first2 = D. | last3 = Monsees | first3 = BS. | last4 = Barton | first4 = PT. | last5 = Clark | first5 = C. | last6 = Dietz | first6 = JR. | title = Correlation between core biopsy and excisional biopsy in breast high-risk lesions. | journal = Am J Surg | volume = 192 | issue = 4 | pages = 534-7 | month = Oct | year = 2006 | doi = 10.1016/j.amjsurg.2006.06.003 | PMID = 16978969 }}</ref>
 
Epidemiology:
*Relative risk of breast cancer, based on a median follow-up of 8 years, in a case control study of US registered nurses, is 3.7.<ref name=pmid1734106>{{Cite journal  | last1 = London | first1 = SJ. | last2 = Connolly | first2 = JL. | last3 = Schnitt | first3 = SJ. | last4 = Colditz | first4 = GA. | title = A prospective study of benign breast disease and the risk of breast cancer. | journal = JAMA | volume = 267 | issue = 7 | pages = 941-4 | month = Feb | year = 1992 | doi =  | PMID = 1734106 }}</ref>
 
===Microscopic===
Features:
*Cytologic and architectural feature of low-grade DCIS.
**Cell spacing ~ equal.
**Lumina round.
**Architecture - classically ''cribriform'' or ''solid''; may be ''micropapillary'' or ''papillary''.
**Small nuclei.
***Small indistinct nucleoli.
*Limited extent ([[diagnostic size cutoffs]]) - either:<ref>{{Ref DCHH|258}}</ref>
*#< Two complete ducts.
*#< 2 mm.
 
DDx:
*Low-grade [[DCIS]].
*[[Florid epithelial hyperplasia of the usual type]] (FEHUT).
 
Note:
*''High-grade DCIS'' is '''not''' in the [[DDx]] of ADH.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Atypical_ductal_hyperplasia_-_very_low_mag.jpg ADH - very low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Atypical_ductal_hyperplasia_-_high_mag.jpg ADH - high mag. (WC)].
 
===IHC===
*CK5 <20% +ve.
*ER +ve - diffusely.
**Heterogenous in [[FEHUT]].


==Ductal carcinoma in situ==
==Ductal carcinoma in situ==
*Abbreviated ''DCIS''.
*Abbreviated ''DCIS''.
===General===
{{Main|Ductal carcinoma in situ}}
*Diagnosis based on nuclear abnormalities ''and/or'' architecture.
**Low-grade DCIS does '''not''' have a malignant cytology.
*It is typically picked-up during radiologic screening.
 
===Microscopic===
Features:
*Architectural changes:
**Equal spacing of cells - "cookie cutter" look.
**Cells line-up along lumen/glandular spaces - form "Roman briges".
**Architecture suggestive of DCIS - see ''[[Subtypes of DCIS]]''.
*Nuclear changes:
**Nuclear enlargement - at least 2-3x size of RBC - '''key feature'''.
***Compared to RBCs to grade DCIS - see ''[[Grading DCIS]]''.
****Compare sizes of nuclei if you cannot find RBCs.
**Nuclear pleomorphism - important feature.
*+/-Mitoses.
 
Note:
*Apocrine changes of cytoplasm -- several sets of criteria exist -- any of the following:
*#Nuclei should be ~4x RBC for low grade, 5x RBC for high grade.<ref>URL: [http://surgpathcriteria.stanford.edu/breast/dcis/apocrinedcis.html http://surgpathcriteria.stanford.edu/breast/dcis/apocrinedcis.html]. Accessed on: 4 August 2011.</ref>
*#Nuclear enlargement of 3x +/- nucleolar enlargement.<ref name=pmid18171412/>
*#Multiple nucleoli + nuclear size variation.<ref name=pmid18171412>{{Cite journal  | last1 = O'Malley | first1 = FP. | last2 = Bane | first2 = A. | title = An update on apocrine lesions of the breast. | journal = Histopathology | volume = 52 | issue = 1 | pages = 3-10 | month = Jan | year = 2008 | doi = 10.1111/j.1365-2559.2007.02888.x | PMID = 18171412 }}</ref>
 
====Subtypes of DCIS====
The subtypes are based on architecture.
 
Note:
*''Comedonecrosis'' used to be considered a separate subtype.  [[Necrosis]] is seen most often in the context of ''solid ductal carcinoma in situ''.
=====Solid ductal carcinoma in situ=====
Features:
*No spaces between cells.
 
DDx:
*[[LCIS]].
=====Cribriform ductal carcinoma in situ=====
Features:
*Honeycomb-like appearance: circular holes.
*"Cookie cutter" appearance/"punched-out" appearance/"Roman bridges" -- cells surround the circular holes.
 
DDx:
*[[Collagenous spherulosis]].
*[[Adenoid cystic carcinoma of the breast]].
 
=====Papillary ductal carcinoma in situ=====
Features:
*Papillae with fibrovascular cores.
 
=====Micropapillary ductal carcinoma in situ=====
Features:
*Small papillae without fibrovascular cores.
*Have "drum stick" shape.
 
DDx:
*[[Gynecomastoid hyperplasia]].
 
====Grading DCIS====
Graded 1-3 (low-high)<ref>URL: [http://surgpathcriteria.stanford.edu/breast/dcis/ http://surgpathcriteria.stanford.edu/breast/dcis/]. Accessed on: 4 August 2011.</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.
 
====Size criteria for low-grade DCIS====
ADH is diagnosed if the lesion is small - specifically:<ref name=Ref_BP168>{{Ref BP|168}}</ref><ref>{{Ref DCHH|258}}</ref>
# < Two membrane-bound spaces.
# < 2 mm extent.
 
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.
 
====Micrometastasis in DCIS====
Micrometastasis in DCIS - not significant.<ref name=pmid14601079>{{Cite journal  | last1 = Lara | first1 = JF. | last2 = Young | first2 = SM. | last3 = Velilla | first3 = RE. | last4 = Santoro | first4 = EJ. | last5 = Templeton | first5 = SF. | title = The relevance of occult axillary micrometastasis in ductal carcinoma in situ: a clinicopathologic study with long-term follow-up. | journal = Cancer | volume = 98 | issue = 10 | pages = 2105-13 | month = Nov | year = 2003 | doi = 10.1002/cncr.11761 | PMID = 14601079 }}</ref><ref name=pmid16569492>{{Cite journal  | last1 = Broekhuizen | first1 = LN. | last2 = Wijsman | first2 = JH. | last3 = Peterse | first3 = JL. | last4 = Rutgers | first4 = EJ. | title = The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast. | journal = Eur J Surg Oncol | volume = 32 | issue = 5 | pages = 502-6 | month = Jun | year = 2006 | doi = 10.1016/j.ejso.2006.02.006 | PMID = 16569492 }}</ref>


=Lobular neoplasia=
=Lobular neoplasia=
Line 201: Line 100:
==Atypical lobular hyperplasia==
==Atypical lobular hyperplasia==
*Abbreviated ''ALH''.
*Abbreviated ''ALH''.
 
{{Main|Atypical lobular hyperplasia}}
===General===
*May occur with ''ductal involvement by cells of atypical lobular hyperplasia'' (abbreviated ''DIALH'').<ref name=pmid3343034>{{Cite journal  | last1 = Page | first1 = DL. | last2 = Dupont | first2 = WD. | last3 = Rogers | first3 = LW. | title = Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long-term follow-up study of cancer risk. | journal = Hum Pathol | volume = 19 | issue = 2 | pages = 201-7 | month = Feb | year = 1988 | doi =  | PMID = 3343034 }}</ref>
**ALH with DIALH has a risk of developing breast cancer that is similar to [[LCIS]].
 
===Microscopic===
Features:
*Extent criterium: <50% of terminal duct lobular unit (TDLU) is involved.
*See ''LCIS'' for details.
 
===IHC===
*E-cadherin -ve ''or'' incomplete membrane staining.


==Lobular carcinoma in situ==
==Lobular carcinoma in situ==
Line 218: Line 106:
===General===
===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===
===Microscopic===
Line 232: Line 123:
**'''No''' luminal spaces - '''key feature'''.
**'''No''' luminal spaces - '''key feature'''.
***Partially filled ducts are ''not'' LCIS.  
***Partially filled ducts are ''not'' LCIS.  
DDx:
*[[Invasive ductal carcinoma of the breast|Invasive ductal carcinoma]].
*[[Atypical ductal hyperplasia]].


Images:
Images:
Line 254: Line 149:


===IHC===
===IHC===
*E-cadherin -ve ''or'' incomplete membrane staining.
*[[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>
*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.
**Membranous staining in DCIS.

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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