Difference between revisions of "Non-invasive breast carcinoma"

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Non-invasive breast carcinoma (view source)

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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).
 
Notes:
*''High-grade DCIS'' is '''not''' in the [[DDx]] of ADH.
* ‡ 3 mm is used in papillary lesions.{{fact}}
 
====Images====
<gallery>
Image:Atypical_ductal_hyperplasia_-_very_low_mag.jpg|ADH. Very low mag. (WC/Nephron)
Image:Atypical_ductal_hyperplasia_-_high_mag.jpg|ADH - high mag. (WC/Nephron)
</gallery>
===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:
*Sheet of cells fills the duct
*No spaces between cells.
 
<gallery>
Image:Breast DCIS Solid IntermediateGrade SNP.jpg|Breast - Ductal carcinoma in situ -  Solid variant-  Intermediate grade - Medium power (SKB)
Image:Breast DCIS Solid SNP.jpg|Breast - Ductal carcinoma in situ -  Solid variant-  Intermediate grade - Low power (SKB)
Image:Breast DCIS Solid PA.JPG|Breast - Ductal carcinoma in situ -  Solid variant - Medium power (SKB)
Image:Breast DCIS Comedonecrotic 2 PA.JPG|Breast - Ductal carcinoma in situ - Solid variant - Comedonecrosis (SKB)
Image:Breast DCIS Comedonecrosis MP PA.JPG|Breast - Ductal carcinoma in situ - Solid variant - Comedonecrosis (SKB)
</gallery>
 
DDx:
*[[LCIS]].
**May show dyscohesion
**More monomorphic population of cells
 
=====Cribriform ductal carcinoma in situ=====
Features:
*Honeycomb-like appearance: circular holes.
*"Cookie cutter" appearance/"punched-out" appearance/"Roman bridges" -- cells surround the circular holes.
 
<gallery>
Image:Breast DCIS Cribriform MP CTR.jpg|Breast - Ductal carcinoma in situ - cribriform varient  - medium power (SKB)
Image:Breast DCIS Cribriform PA.JPG|Breast - Ductal carcinoma in situ - cribriform varient  - medium power (SKB)
</gallery>
 
DDx:
*[[Collagenous spherulosis]].
*[[Adenoid cystic carcinoma of the breast]].
*Invasive cribriform carcinoma of the breast
 
=====Papillary ductal carcinoma in situ=====
Features:
*Papillae with fibrovascular cores.
 
<gallery>
Image:Breast DCIS Papillary PA.JPG|Breast - Ductal carcinoma in situ - Papillary variant - Medium power (SKB)
</gallery>
 
DDX:
 
*[[Intraductal papilloma]]
*Ductal carcinoma in situ arising within an intraductal papilloma
*[[Intracystic papillary breast carcinoma]]
*[[Invasive papillary breast carcinoma]]
 
=====Micropapillary ductal carcinoma in situ=====
Features:
*Small papillae without fibrovascular cores.
*Have "drum stick" shape.
 
DDx:
*[[Gynecomastoid hyperplasia]].
 
<gallery>
Image:Breast DCIS MicropapillaryType MP CTR.jpg|Breast - Ductal carcinoma in situ - micropapillary variant - Medium power - (SKB)
Image:Breast DCIS Micropapillary SNP.jpg|Breast - Ductal carcinoma in situ - micropapillary variant - High power - (SKB)
</gallery>
 
====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.
 
Notes:
* ‡ 3 mm is used in papillary lesions.{{fact}}
 
====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=
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==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 ''[[lobular carcinoma in situ]]'' for details.
 
DDx:
*[[Lobular carcinoma in situ]].
*[[Lobular carcinoma]].
 
===IHC===
*E-cadherin -ve ''or'' incomplete membrane staining.


==Lobular carcinoma in situ==
==Lobular carcinoma in situ==
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===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]].
*The precursor to [[invasive ductal carcinoma of the breast]].
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===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.
Michael
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