Difference between revisions of "Invasive breast cancer"
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===General=== | ===General=== | ||
*Very rare. | *Very rare. | ||
*Possibly a variant of [[apocrine carcinoma]].<ref name=pmid7611537>{{Cite journal | last1 = Hayes | first1 = MM. | last2 = Seidman | first2 = JD. | last3 = Ashton | first3 = MA. | title = Glycogen-rich clear cell carcinoma of the breast. A clinicopathologic study of 21 cases. | journal = Am J Surg Pathol | volume = 19 | issue = 8 | pages = 904-11 | month = Aug | year = 1995 | doi = | PMID = 7611537 }} | *Possibly a variant of [[apocrine carcinoma of the breast|apocrine carcinoma]].<ref name=pmid7611537>{{Cite journal | last1 = Hayes | first1 = MM. | last2 = Seidman | first2 = JD. | last3 = Ashton | first3 = MA. | title = Glycogen-rich clear cell carcinoma of the breast. A clinicopathologic study of 21 cases. | journal = Am J Surg Pathol | volume = 19 | issue = 8 | pages = 904-11 | month = Aug | year = 1995 | doi = | PMID = 7611537 }} | ||
</ref> | </ref> | ||
*Prognosis usu. poor. | *Prognosis usu. poor. |
Revision as of 18:18, 1 April 2012
The article deals with invasive breast cancer and the evaluation of hormone receptor & HER2 status. Non-invasive breast cancer is dealt with in non-invasive breast cancer.
Introduction
Overview of invasive breast cancer subtypes
Common epithelial subtypes
Type and percentage of breast carcinomas:[1]
- Ductal - AKA no special type (NST) - 79%.
- Lobular - 10%.
- Cribriform / tubular - 6%.
- Mucinous (colloid) - 2%.
- Medullary - 2%.
- Papillary - 1%.
- Metaplastic - <1%.
Common stromal types
- Malignant phyllodes tumour.
- Angiosarcoma - post-radiation ~ 10 years.[2]
Good prognosis subtypes
Three good prognosis subtypes:[3]
- Tubular carcinoma.
- Mucinous carcinoma.
- Papillary carcinoma.
Comprehensive list of invasive breast cancer subtypes
Epithelial
Counterparts of in situ lesions:
- Invasive ductal carinoma, not otherwise specified.
- Invasive lobular carcinoma.
- Invasive cribriform carcinoma.
- Invasive papillary carcinoma.
- Invasive micropapillary carcinoma.
Other epithelial tumours:
- Tubular carcinoma.
- Medullary carcinoma.
- Mucinous carinoma.
- Metaplastic carcinoma.
- Neuroendocrine tumour.
- Apocrine carcinoma.
- Lipid-rich carcinoma.
- Secretory carcinoma.
- Oncocytic carcinoma.
- Glycogen-rich clear cell carcinoma.
Epithelial tumours seen in the salivary gland:
Seen in the skin:
Clinically diagnosed:
- Inflammatory carcinoma.
In situ lesions:
Proliferative lesions:
Non-specific:
- Microinvasive carcinoma.
Papillary:
- Papilloma.
- Atypical papilloma.
- Intraductal papillary carcinoma.
Adenomas:
- Ductal adenoma.
- Tubular adenoma.
- Lactating adenoma.
- Apocrine adenoma.
- Pleomorphic adenoma.
Myoepithelial
- Myoepitheliosis.
- Adenomyoepithelial adenosis.
- Adenomyoepithelioma.
- Malignant adenomyoepithelioma.
Mesenchymal tumours
- See: Soft tissue lesions.
Fibroepithelial tumours
- Fibroadenoma.
- Phyllodes tumour.
- Periductal stromal sarcoma, low grade.
- Mammary hamartoma.
Nipple lesions
- Nipple adenoma.
- Syringomatous adenoma.
- Paget disease of the breast.
Other
Familial breast cancer
BRCA1 vs. BRCA2:[4]
Gene | Age | Histology | Other cancers |
BRCA1 | younger | worse types, e.g. triple negative breast ca. | uterine tube |
BRCA2 | older | sporadic types | stomach, melanoma, gallbladder, bile duct, pharynx |
Types of cancer assoc. with both BRCA1 and BRCA2:
- Ovarian, male breast, prostate, pancreas.
Breast IHC
Molecular classification of invasive carcinoma
A molecular classification:[5]
Type | Percentage | IHC | Histology | Prognosis/clinical |
---|---|---|---|---|
Luminal A | ~45% | ER+ PR+ HER2- | well-differentiated | good, chemo resistant |
Luminal B | 17% | ER+ PR+ HER2+ | high grade | poor, +/- chemo responsive |
Normal breast-like | ~8% | ER+ PR+ (?) HER2- | well-differentiated | good |
Basal-like | ~20% | ER- PR- HER2- | poorly differentiated | aggressive, may have good chemo response, classic for BRCA1 mutation |
HER2 positive | ~10% | ER- PR- (?) HER2+ | poorly differentiated | poor |
The above is not applied clinically. A panel of immunostains (ER, PR, HER2, EGFR, CK5/6) can reproduce the molecular groupings.[6]
Subtyping breast cancer
- DCIS vs LCIS:[7]
- E-cadherin (+ve DCIS, -ve LCIS).
- antibody 34betaE12 (+ve perinuclear LCIS, -ve DCIS).
- CAM5.2 (peripheral stain = DCIS, perinuclear stain = LCIS).
- CAM5.2 is against CK8.
- Beta-catenin (-LCIS, +DCIS).
- ADH and DCIS:[10]
- E-cadherin.
- Present in most epithelial cells.
- Lost in LCIS & invasive lobular carcinoma.
- SMMHC (smooth muscle cell myosin heavy chain).
- Marks myoepithelial cells.
- E-cadherin.
- Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
- Sunnybrook uses CAM5.2.
- ER (estrogen receptor).
- Positive in most breast cancers; +ve in ~75-80%.[11]
- PR (progesterone receptor).
- Positive in most breast cancers; +ve in ~65-70%.[11]
- HER2/neu.
- Usually negative; -ve in 70-80%.[11]
- Positivity association with a worse prognosis.
ER & PR scoring[11]
- Give a percentage, i.e. 0-100%.
- Important cut points: 1% and 10%.
- 0% = negative - not treated.
- <10% = low positivity - treated.
- Important cut points: 1% and 10%.
Notes:
- Normal breast epithelial cells have a patchy staining for ER and PR.
- Evaluated on the invasive component.
HER2 scoring
Immunohistochemical based testing:[11][12][13]
Score | Staining intensity | Cells stained (%) | Membrane staining | Management | Percentage of cases |
0 | nil | <10% | incomplete | No HER2 blocker | ~60% |
1+ | minimum | >10% | incomplete | No HER2 blocker | ~10% |
2+ | weak | >10% | complete | Needs SISH or FISH | ~10% |
3+ | uniform staining (used to be strong) | >30% (used to >10%) | complete | HER2 blocker | ~20% |
Notes 1:
- Normal breast epithelial cells do not stain with HER2.
- Evaluated on the invasive component.
- SISH = silver in situ hybridization.
- FISH = fluorescence in situ hybridization.
ISH based testing:[12]
Result | Ratio criteria | Gene copy number criteria |
Positive | >2.2 HER2/CEP17 | >6.0 copies of HER2/cell |
Equivocal | 1.8-2.2 HER2/CEP17 | 4.0-6.0 copies of HER2/cell |
Negative | <1.8 HER2/CEP17 | <4.0 copies of HER2/cell |
Notes 2:
- Can be called positive based on either ratio criteria or gene copy number criteria.
Clinical
- ER & PR status determine whether a patient will get tamoxifen or other estrogen receptor modulators, such as raloxifene (Evista).
- HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.
Characteristics of the subtypes
Invasive ductal carcinoma of the breast
General
- Most common type of invasive breast cancer.
Microscopic
Features:
- Atypical cells:
- Usually >2x RBC diameter.
- Nucleoli common.
- Forming ducts or sheets.
- +/-Mitoses.
- +/-Necrosis.
- Evidence of invasion:
- Atypical nucleus adjacent to adipocyte - diagnostic.
- "Infiltrative" pattern:
- Small glands of variable size within desmoplastic stroma.
- Glands lined by a single layer of cells.
DDx:
IHC
Myoepithelial markers - diagnostic for invasion:
- SMMS -ve.
- p63 -ve.
Prognostic markers - may be useful for metastates:
- ER +ve (diffuse).
- PR +ve (diffuse).
- HER2 -ve.
Invasive lobular carcinoma
- Abbreviated ILC.
- AKA lobular carcinoma.
General
Microscopic
Features:
- "Single file" - cell line-up in a row.
- Cell should not be cohesive -- lymphoma should briefly come to mind.
- primary lymphoma of the breast exists... but it is extremely rare.
- Cell should not be cohesive -- lymphoma should briefly come to mind.
- NO gland formation.
- If it forms glands... it is more likely NST.
- May have signet ring morphology.
- NO desmoplastic reaction, i.e. the stroma surrounding the tumour cells should look benign and undisturbed.
Note:
- commonly have low grade nuclear features
Images:
- Lobular carcinoma - low mag. (WC).
- Lobular carcinoma - high mag. (WC).
- Lobular carcinoma - 1 (WC).
- Lobular carcinoma - 2 (WC).
Subclassification:
- Classic lobular carcinoma.
- Low nuclear grade - NO significant variation of nucleus size.
- Pleomorphic lobular carcinoma.
- Significant nuclear atypia.
Note: Some pathologist grade lobular carcinoma like other types and avoid the term "pleomorphic lobular carcinoma."[15]
Medullary breast carcinoma
- AKA medullary carcinoma of the breast.
General
- Uncommon breast cancer subtype.
- Some pathologists don't believe this exists.
Epidemiology:
- Thought to have a better prognosis that no special type (NST).
- May be associated with a BRCA1 mutation.
Gross
- Well-circumscribed border.[16]
Aside - malignant well-circumscribed breast masses - radiologic DDx:[16]
- Medullary breast carcinoma.
- Mucinous breast carcinoma.
- Malignant phyllodes tumour.
- Invasive papillary carcinoma of the breast.
Microscopic
Features:
- Lesion has well-circumscribed border.
- Syncytial growth pattern = clumps of cells with poorly defined cell borders.
- Lymphocytic infiltrate.
- High nuclear grade (as per Nottingham grading system).
- No tubule formation.
IHC
Features - typical:[17]
- ER -ve.
- PR -ve.
- HER2 -ve.
Tubular carcinoma of the breast
- AKA tubular carcinoma.
General
Epidemiology:
- Typically excellent prognosis.
- Hormone receptors commonly present (ER +ve, PR +ve).
- Usually HER2 -ve.
- Classically seen in post-menopausal women.
Note:
- May be seen in association with lobular carcinoma in situ and columnar cell lesions - known as Rosen triad.[18]
- Memory device TLC = Tubular ca., LCIS, Columnar cell lesions.
Microscopic
- Well-formed tubules.
- Typically have angled ducts - "prows" - important feature (low power).
- Myoepithelial cells absent - diagnostic - may be have to appreciated without IHC.
- >70% of the tumour cells should be adjacent to lumen.[22]
- +/- Cribriform spaces.
- Apocrine snouts typical.
- +/-Calcification.
Notes:
- Prow = front of a ship.
- Looks benign to the uninitiated -- important.
DDx:
Image:
IHC
- ER +ve.
- PR +ve.
- HER2 -ve.
- HER2 positivity should prompt consideration of another diagnosis!
Metaplastic breast carcinoma
- AKA metaplastic carcinoma.
General
- May be difficult to diagnose.
- Prognosis - poor.
- Top of the differential diagnosis for spindle cell lesions of the breast.
Microscopic
Features - one of the following:[23][24]
- Malignant mesenchymal elements - either:
- Spindle cells.
- Osseous, chondroid or rhabdoid differentiation.
- Squamous component.
- Non-skin squamous cell carcinoma of the breast = metaplastic breast carcinoma.
Notes:
- Calcifications are uncommon.
- Cytology may be very bland, i.e. it may look very benign.
- May have minimal mitotic activity.
DDx:
- Fibromatosis.
- Malignant phyllodes tumour.
- Primary mammary sarcoma.
- Mammary myofibroblastoma.
- Nodular fasciitis.
Images:
- Metaplastic carcinoma (breastpathology.info).[23]
- Metaplastic carcinoma - case 1 - several images (upmc.edu).
- Metaplastic carcinoma - case 2 - several images (upmc.edu).
Subclassification
- There are various way to subclassify this subtype of breast cancer. This a consequence of physician automomy.
- There is a series of articles on the topic by Wargotz & Norris that is quite old... yet it is mentioned in Sterberg:[25]
- Matrix-producing carcinoma:[26]
- Features: cartilaginous and/or osseous stromal matrix; no osteoclastic giant cells.
- Spindle cell carcinoma:[27]
- Features: (non-malignant) spindle cells.
- Prognosis: better prognosis than other metaplastic carcinomas.
- Carcinosarcoma:[28]
- Features: malignant mesenchymal element.
- Prognosis: survival worse when compared to other metaplastic carcinomas.
- Squamous cell carcinoma of ductal origin:[29]
- Features: purely squamous; metastases are squamous cell carcinoma.
- Metaplastic carcinoma with osteoclastic giant cells:[30]
- Features: osteoclastic giant cells.
- The WHO subclassifies as follows:[31]
- Epithelial - includes: squamous cell carcinoma, adenocarcinoma with spindle cell differentiation, adenosquamous carcinoma.
- Mixed epithelial and mesenchymal - includes: carcinosarcoma, carcinoma with metaplasia (chondroid, osseous).
IHC
- S100 -ve (r/o melanoma).
- AE1/AE3 +ve (epithelial elements only).
- CK7 +ve (epithelial elements only).
- p63 +ve (epithelial elements only).
- Vimentin +ve.
- Desmin -ve.
- EMA -ve. (???)
Invasive micropapillary carcinoma of the breast
- AKA micropapillary carcinoma.
General
- Poor prognosis.
- LVI common.[32]
Microscopic
Features:
- Clear spaces/clefting around (small) nests of tumour - diffuse/through-out the tumour - key feature.
- Described as "small clusters of tumour lying within dilated vascular channel-like spaces".[33]
Note:
- Ductal carcinoma commonly has clefting... but it isn't diffuse.
IHC
- EMA +ve (periphery of nests); described as inside-out pattern.[33]
- E-cadherin +ve (centre of nests). (???)
- p63 +ve/-ve.
Apocrine carcinoma of the breast
General
- Need >=90% apocrine morphology.[34]
Microscopic
Features:[34]
- Prominent nucleoli.
- Often multiple.[35]
- Abundant granular eosinophilic cytoplasm.
- Architecture like invasive ductal carcinomas no special type.
Images:
IHC
Smaller tumours classically:[36]
- AR +ve.
- GCDFP-15 +ve.
Usually:[34]
- ER -ve.
- PR -ve.
Mucinous breast carcinoma
General
- Rare.
- Good prognosis.[37]
Microscopic
Features:
- Malignant mucin producing glands.
- Mucinous component must comprise >90% of the tumour - required for diagnosis.[38]
- Cells should float in the mucin - key feature.
- Glands typically have irregular edges.
- +/-Vessels within the mucin pools.
DDx:
- DCIS with a mucinous component.
- Mucin has a homogenous appearance, mucin lacks vascularization, mucin pools have a regular border.
Note:
- The amount of mucinous component to call mucinous carcinoma varies by anatomical site.
- All mucinous lesions should be excised.[39]
IHC
- ER +ve.
- PR +ve.
- HER2 -ve.
Adenoid cystic carcinoma of the breast
- AKA breast adenoid cystic carcinoma.
General
- Like tumour of the salivary gland.
- Very rare <0.1% of breast malignancies.[40]
- Good prognosis.[40]
Microscopic
- See: Adenoid cystic carcinoma article.
DDx:
- Cribriform DCIS.
- Collagenous spherulosis.
Images:
Invasive papillary carcinoma of the breast
- AKA intracystic papillary carcinoma of the breast, abbreviated IPC.
- AKA encapsulated papillary carcinoma of the breast, abbreviated EPC.
General
- Very good prognosis[41] - it is similar to DCIS.
- Classical menopausal women.
- ~30% present with bloody discharge.[42]
Microscopic
Features:
- Lesion confined to a duct (intraductal) or cyst (intracystic).
- May have a thick fibrous capsule = encapsulated papillary carcinoma.[42]
- Loss of myoepithelial cells - key feature.
- Neoplastic epithelial cells:
- Nuclear atypia - including: nucleoli, nuclear pleomorphism.
- Abnormal architecture - including cribriform, solid, micropapillary, papillary.
DDx:
IHC
- Loss of myoepithelial markers within the lesion.
Glycogen-rich clear cell carcinoma of the breast
- Abbreviated GRCC.
General
- Very rare.
- Possibly a variant of apocrine carcinoma.[43]
- Prognosis usu. poor.
Microscopic
Features:
- Groups of cells with abundant clear cytoplasm - need to comprise 90% of the tumour.[44]
- Various architectural arrangements: cords, trabeculae, clusters, cribriform.
- Minimal nuclear pleomorphism.
Notes:
- Histologic appearance may be similar to hyalinizing clear cell carcinoma.
DDx:
- Signet-ring carcinoma.
- Lipid-rich carcinoma.
- Apocrine carcinoma.
- Secretory carcinoma.
Image:
Stains
Features:[44]
- PAS +ve.
- PASD -ve.
Others:[44]
- Oil red O -ve.
- Lipid-rich carcinoma +ve.
IHC
Features:[44]
- BRST2 -ve.
- Apocrine carcinoma +ve.
Secretory carcinoma of the breast
- AKA secretory breast carcinoma, abbreviated SBC.
General
- Favourable prognosis.[45]
- Children and adults.
Microscopic
Features:[46]
- Abundant cytoplasm with fine vacuolation - clear/pale or amphophilic.
- Mitoses - uncommon.
- Nucleoli - rare.
- Architecture: solid, papillary, cribriform or microcystic.
DDx:
- Lactational change[47] - glandular architecture.
Images:
- Secretory breast carcinoma - low mag. (webpathology.com).
- Secretory breast carcinoma - high mag. (webpathology.com).
- Secretory breast carcinoma (nature.com).
IHC
Triple negative (ER -ve, PR -ve, HER2 -ve).[45]
Others:
- Alpha-lactalbumin +ve.
- S-100 protein +ve.
- Polyclonal CEA +ve.
Molecular pathology
Characteristic translocation:[45]
- t(12;15).
- ETV6-NTRK3.
Grading breast cancer
Most common system: Nottingham (aka Scarff-Bloom-Richardson) which is based on:
- Nuclear grade.
- Small, regular (1.5-2x RBC dia.) = 1.
- Moderated variability = 2.
- Marked variation (>2.5x RBC dia.) = 3.
- Tubule formation.
- Majority of tumour - tubules >75% = 1.
- Moderate - 10% to 75% = 2.
- Minimal <10% = 3.
- Mitotic rate.
- 0-5 mitosis/10 HPF (1.52 mm^2 --or-- 0.0152 mm^2 * 10) = 1.
- 6-10 mitosis/10 HPF (1.52 mm^2) = 2.
- >11 mitosis/10 HPF (1.52 mm^2) = 3.
Mnemonic: TMN = tubule formation, mitotic rate, nuclear grade.
Notes:
- Elston & Ellis devised the system that is used.[48] They also wrote a follow-up article in 2002.[49]
Note about mitosis counting
- One MUST adjust for the size of the field of view.
- Most of the Resident scopes have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.
- Thus, on a resident scope (with a FOV of 0.2376 mm^2) one should sample 6 or 7 fields of view (FsOV).
- Calculation: 1.52 mm^2 (sampling area) / 0.2376 mm^2 (area / FOV ) = 6.40 FsOV.
- Thus, on a resident scope (with a FOV of 0.2376 mm^2) one should sample 6 or 7 fields of view (FsOV).
- RANT: Sampling 10 fields, where the field of view (FOV) is 0.152 mm^2, is not the same as sampling ten fields, where the FOV is 0.312 mm^2. It surprises me that Elston & Ellis ignore the fact that "10 HPFs" on different microscopes represent different sample areas and that they do not standardize the sampling area.
Calculating Nottingham score
- Grade I = 3-5 points.
- Grade II = 6-7 points.
- Grade III = 8-9 points.
Notes:
- I've found most tumours are grade II.
- The mitotic score is usually 1/3.
- The nuclear score is rarely 1/3 -- even in the tubular subtype.[50]
Staging breast cancer
Definitions:[51]
- Isolated tumour cells: <=0.2 mm and <200 cells.
- Micrometastasis: <=0.2 cm and ( >0.2 mm or >=200 cells ).
- pT1: <= 2 cm.
- pT1mic <= 0.1 cm.
- pT1a > 0.1 cm and <= 0.5 cm.
- pT1b > 0.5 cm and <= 1.0 cm.
- pT1c > 1.0 cm and <= 2.0 cm.
- pT2: > 2 cm and <= 5 cm
- pT3: > 5 cm.
- pT4: chest wall or skin involvement.
Lymph nodes:[54]
- pN0: nil.
- pN0(i+): <=0.2 mm and <200 cells.
- pN1: 1-3 axillary LNs or internal mammary LNs.
- pN1mi: <=0.2 cm and ( >0.2 mm or >=200 cells ).
- pN1a.
- pN1b.
- PN1c.
- pN2 4-9 positive LNs; internal mammary LNs or axillary LNs.
- pN3.
Lymphovascular invasion
In the context of breast pathology, the Rosen criteria for LVI are widely excepted, and are as follows:[55][56]
- Must be outside of the tumour proper.
- LVI is usually very close -- typically within 0.1 cm.
- Contour of cells should differ from possible vessel wall.
- DCIS with retraction artifact mimicing LVI has a contour that matches its surrounding fibrous tissue.
- Endothelium (usu. flat) should be visible.
- Lymphatics are found adjacent to blood vessels - vessels should be present in the vicinity.
Memory device LUBE-O:
- LVI has a Unique contour, Blood vessels and Endothelium in the vicinity, and is Outside of the tumour.
Other
Paget's disease
General
- Associated with underlying breast carcinoma.[57]
Notes:
- Unrelated to Paget disease of the bone.
Microscopic
Features:[57]
- Cells in the epidermis:
- Epitheliod morphology (round/ovoid).
- Cells nested or single.
- Clear/pale cytoplasm key feature - may also be eosinophilic.
- Large nucleoli.
Images:
IHC & DDx:
- See Paget disease.
Sentinel lymph node biopsy
General
- Used for staging, positive LNs = poorer prognosis.
Notes:
- If there is no palpable disease, there is no mortality benefit from axillary lymph node dissection, i.e. positive axillary lymph nodes can be left in situ without affecting outcome.[58]
- This does not negate the fact that a positive sentinel LN biopsy (vs. negative sentinel LN biopsy) portends a poorer prognosis.
Microscopic
Features:
- Atypical cells.
- Nuclear changes of malignancy:
- Nuclear enlargement + variation in size.
- Variation in shape.
- Hyperchromasia and variation in staining.
- Usually in the subcapsular sinuses.
- Nuclear changes of malignancy:
Pitfalls:
- Naevus cell rests.[59]
IHC
Some hospitals use:
- CAM5.2 (LMWK) - to look for isolated tumour cells and small lymph node metstases.
Trivia
Tumour size and lymph node metastases
There is a paper[60] that calculates the probability of lymph node mets based on tumour size. The developed formula is:
Where:
- = the probability of the lymph nodes being positive.
- D = the largest dimension of the tumour in millimetres.
- Z = 1.0041.
- = 0.019.
Selected values
Tumour size (mm) | Probability |
5 | 9 % |
10 | 17 % |
15 | 25 % |
20 | 32 % |
25 | 38 % |
30 | 44 % |
35 | 49 % |
40 | 54 % |
45 | 58 % |
50 | 62 % |
Natural history
There is a theory that up to 22% of small (radiographically detected) breast tumours regress, based on an analysis in a large population.[61] The study is supported by NCI's SEER data.[62] Also, it generated many comments.[61]
Missed macrometastases
The effect of missed macrometastases is small; this implies using IHC to look for isolated tumour cells is money that isn't well spent.[63]
See also
References
- ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1143. ISBN 0-7216-0187-1.
- ↑ URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html. Accessed on: 28 November 2010.
- ↑ URL: http://emedicine.medscape.com/article/1947145-overview. Accessed on: 24 August 2012.
- ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1078. ISBN 978-1416031215.
- ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 547. ISBN 978-1416054542.
- ↑ Tang, P.; Skinner, KA.; Hicks, DG. (Sep 2009). "Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready?". Diagn Mol Pathol 18 (3): 125-32. doi:10.1097/PDM.0b013e31818d107b. PMID 19704256.
- ↑ Yeh IT, Mies C (March 2008). "Application of immunohistochemistry to breast lesions". Arch. Pathol. Lab. Med. 132 (3): 349-58. PMID 18318578. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349.
- ↑ Ordóñez NG (March 2006). "Podoplanin: a novel diagnostic immunohistochemical marker". Adv Anat Pathol 13 (2): 83-8. doi:10.1097/01.pap.0000213007.48479.94. PMID 16670463.
- ↑ Kahn HJ, Marks A (September 2002). "A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors". Lab. Invest. 82 (9): 1255-7. PMID 12218087.
- ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 122. ISBN 978-0443066450.
- ↑ 11.0 11.1 11.2 11.3 11.4 Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 241-2. ISBN 978-0443066450.
- ↑ 12.0 12.1 Lester, Susan Carole (2010). Manual of Surgical Pathology (3rd ed.). Saunders. pp. 87. ISBN 978-0-323-06516-0.
- ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 27 November 2011.
- ↑ URL: http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33006. Accessed on: 19 April 2011.
- ↑ MUA. Jan 22, 2009.
- ↑ 16.0 16.1 Yoo, JL.; Woo, OH.; Kim, YK.; Cho, KR.; Yong, HS.; Seo, BK.; Kim, A.; Kang, EY. (Oct 2010). "Can MR Imaging contribute in characterizing well-circumscribed breast carcinomas?". Radiographics 30 (6): 1689-702. doi:10.1148/rg.306105511. PMID 21071383.
- ↑ Matkovic, B.; Juretic, A.; Separovic, V.; Novosel, I.; Separovic, R.; Gamulin, M.; Kruslin, B.. "Immunohistochemical analysis of ER, PR, HER-2, CK 5/6, p63 and EGFR antigen expression in medullary breast cancer.". Tumori 94 (6): 838-44. PMID 19267102.
- ↑ Brandt, SM.; Young, GQ.; Hoda, SA. (May 2008). "The "Rosen Triad": tubular carcinoma, lobular carcinoma in situ, and columnar cell lesions.". Adv Anat Pathol 15 (3): 140-6. doi:10.1097/PAP.0b013e31816ff313. PMID 18434766.
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