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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>
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| *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>
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| **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>
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| Epidemiology:
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| *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>
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| ===Microscopic===
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| Features:
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| *Cytologic and architectural feature of low-grade DCIS.
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| **Cell spacing ~ equal.
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| **Lumina round.
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| **Architecture - classically ''cribriform'' or ''solid''; may be ''micropapillary'' or ''papillary''.
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| **Small nuclei.
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| ***Small indistinct nucleoli.
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| *Limited extent ([[diagnostic size cutoffs]]) - either:<ref>{{Ref DCHH|258}}</ref>
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| *#< Two complete ducts.
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| *#< 2 mm. ‡
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| DDx:
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| *Low-grade [[DCIS]].
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| *[[Florid epithelial hyperplasia of the usual type]] (FEHUT).
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| Notes:
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| *''High-grade DCIS'' is '''not''' in the [[DDx]] of ADH.
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| * ‡ 3 mm is used in papillary lesions.{{fact}}
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| ====Images====
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| <gallery>
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| Image:Atypical_ductal_hyperplasia_-_very_low_mag.jpg|ADH. Very low mag. (WC/Nephron)
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| Image:Atypical_ductal_hyperplasia_-_high_mag.jpg|ADH - high mag. (WC/Nephron)
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| </gallery>
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| ===IHC===
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| *CK5 <20% +ve.
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| *ER +ve - diffusely.
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| **Heterogenous in [[FEHUT]].
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| ==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.
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| **Low-grade DCIS does '''not''' have a malignant cytology.
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| *It is typically picked-up during radiologic screening.
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| ===Microscopic===
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| Features:
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| *Architectural changes:
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| **Equal spacing of cells - "cookie cutter" look.
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| **Cells line-up along lumen/glandular spaces - form "Roman briges".
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| **Architecture suggestive of DCIS - see ''[[Subtypes of DCIS]]''.
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| *Nuclear changes:
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| **Nuclear enlargement - at least 2-3x size of [[RBC]] - '''key feature'''.
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| ***Compared to RBCs to grade DCIS - see ''[[Grading DCIS]]''.
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| ****Compare sizes of nuclei if you cannot find RBCs.
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| **Nuclear pleomorphism - important feature.
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| *+/-Mitoses.
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| Note:
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| *Apocrine changes of cytoplasm -- several sets of criteria exist -- any of the following:
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| *#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>
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| *#Nuclear enlargement of 3x +/- nucleolar enlargement.<ref name=pmid18171412/>
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| *#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>
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| ====Subtypes of DCIS====
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| The subtypes are based on architecture.
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| Note:
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| *''Comedonecrosis'' used to be considered a separate subtype. [[Necrosis]] is seen most often in the context of ''solid ductal carcinoma in situ''.
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| =====Solid ductal carcinoma in situ=====
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| Features:
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| *Sheet of cells fills the duct
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| *No spaces between cells.
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| <gallery>
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| Image:Breast DCIS Solid IntermediateGrade SNP.jpg|Breast - Ductal carcinoma in situ - Solid variant- Intermediate grade - Medium power (SKB)
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| Image:Breast DCIS Solid SNP.jpg|Breast - Ductal carcinoma in situ - Solid variant- Intermediate grade - Low power (SKB)
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| Image:Breast DCIS Solid PA.JPG|Breast - Ductal carcinoma in situ - Solid variant - Medium power (SKB)
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| Image:Breast DCIS Comedonecrotic 2 PA.JPG|Breast - Ductal carcinoma in situ - Solid variant - Comedonecrosis (SKB)
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| Image:Breast DCIS Comedonecrosis MP PA.JPG|Breast - Ductal carcinoma in situ - Solid variant - Comedonecrosis (SKB)
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| </gallery>
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| DDx:
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| *[[LCIS]].
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| **May show dyscohesion
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| **More monomorphic population of cells
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| =====Cribriform ductal carcinoma in situ=====
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| Features:
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| *Honeycomb-like appearance: circular holes.
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| *"Cookie cutter" appearance/"punched-out" appearance/"Roman bridges" -- cells surround the circular holes.
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| <gallery>
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| Image:Breast DCIS Cribriform MP CTR.jpg|Breast - Ductal carcinoma in situ - cribriform varient - medium power (SKB)
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| Image:Breast DCIS Cribriform PA.JPG|Breast - Ductal carcinoma in situ - cribriform varient - medium power (SKB)
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| </gallery>
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| DDx:
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| *[[Collagenous spherulosis]].
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| *[[Adenoid cystic carcinoma of the breast]].
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| *Invasive cribriform carcinoma of the breast
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| =====Papillary ductal carcinoma in situ=====
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| Features:
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| *Papillae with fibrovascular cores.
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| *Papillae lack a myoepithelial layer
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| *Papillae are lined by atypical cells.
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| *Papillae within a ductal space lined by myoepithelial cells.
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| <gallery>
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| Image:Breast DCIS Papillary PA.JPG|Breast - Ductal carcinoma in situ - Papillary variant - Medium power (SKB)
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| </gallery>
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| DDX:
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| *[[Intraductal papilloma]]
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| *Ductal carcinoma in situ arising within an intraductal papilloma
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| *[[Intracystic papillary breast carcinoma]]
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| *[[Invasive papillary breast carcinoma]]
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| =====Micropapillary ductal carcinoma in situ=====
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| Features:
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| *Small papillae without fibrovascular cores.
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| *Have "drum stick" shape.
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| DDx:
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| *[[Gynecomastoid hyperplasia]].
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| <gallery>
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| Image:Breast DCIS MicropapillaryType MP CTR.jpg|Breast - Ductal carcinoma in situ - micropapillary variant - Medium power - (SKB)
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| Image:Breast DCIS Micropapillary SNP.jpg|Breast - Ductal carcinoma in situ - micropapillary variant - High power - (SKB)
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| Image:Breast DCIS Apocrine PA.JPG|Breast - Ductal carcinoma in situ - Micropapillary type with apocrine features - High power - (SKB)
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| </gallery>
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| ====Grading DCIS====
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| 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.
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| *Grade 1:
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| **Nuclei 2-3x size of [[RBC]].
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| **No necrosis.
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| *Grade 2:
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| **Nuclei 2-3x size of RBC.
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| **+/-[[Necrosis]].
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| *Grade 3:
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| **Nuclei >3x size of RBC.
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| **Necrosis usually present.
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| Notes:
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| *It is often hard to find RBCs when you want 'em. DCIS is pleomorphic.
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| *If no RBCs are present to compare with compare the nuclei to one another.
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| *If you see nuclei >3x larger than their neigbour you're ready to call DCIS Grade 3.
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| ====Size criteria for low-grade DCIS====
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| ADH is diagnosed if the lesion is small - specifically:<ref name=Ref_BP168>{{Ref BP|168}}</ref><ref>{{Ref DCHH|258}}</ref>
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| # < Two membrane-bound spaces.
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| # < 2 mm extent. ‡
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| The treatment is similar; ADH and DCIS are both excised.
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| The differences are:
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| *DCIS is cancer, i.e. this has life insurance implications.
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| *Radiation treatment - DCIS is irradiated; ADH does ''not'' get radiation.
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| Notes:
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| * ‡ 3 mm is used in papillary lesions.{{fact}}
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| ====Micrometastasis in DCIS====
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| 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>
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| =Lobular neoplasia= | | =Lobular neoplasia= |
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| ==Atypical lobular hyperplasia== | | ==Atypical lobular hyperplasia== |
| *Abbreviated ''ALH''. | | *Abbreviated ''ALH''. |
| | | {{Main|Atypical lobular hyperplasia}} |
| ===General===
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| *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>
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| **ALH with DIALH has a risk of developing breast cancer that is similar to [[LCIS]].
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| ===Microscopic===
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| Features:
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| *Extent criterium: <50% of terminal duct lobular unit (TDLU) is involved.
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| *See ''[[lobular carcinoma in situ]]'' for details.
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| DDx:
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| *[[Lobular carcinoma in situ]].
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| *[[Lobular carcinoma]].
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| ===IHC===
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| *E-cadherin -ve ''or'' incomplete membrane staining.
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| ==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. |