Revision as of 02:08, 1 May 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:

Epithelial tumours seen in the salivary gland:

Seen in the skin:

Sebaceous carcinoma.

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

Lymphoma.
Metastasis.

Familial breast cancer

Syndromes associated with breast cancer

Gene	Syndrome	Other cancers	Notes
BRCA1	-	male breast, ovarian, prostate, pancreas, fallopian tube	younger individual vis-à-vis BRCA2
BRCA2	-	male breast, ovarian, prostate, pancreas, stomach, melanoma, gallbladder, bile duct, pharynx	younger individual vis-à-vis BRCA2
TP53 (p53)	Li-Fraumeni syndrome (AKA SBLA syndrome)	sarcomas, brain cancer, larynx, lung, leukemia, adrenal cortical carcinoma	-
CHEK2	Li-Fraumeni syndrome (variant)	see p53	-
STK11	Peutz-Jeghers syndrome	breast cancer, GI cancer, Sertoli cell tumour, Granulosa cell tumour, SCTAT	-
PTEN	Cowden syndrome	breast, thyroid (PTC), endometrial, renal, colorectal	-
CDH1		invasive lobular carcinoma, gastric signet ring cell carcinoma	-

BRCA1 and BRCA2

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 associated 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]

Immunostains for typing and diagnosis

DCIS versus LCIS

Tabular comparison for DCIS versus LCIS:^[7]^[8]

Disease	E-cadherin	Beta-catenin	34betaE12	CAM5.2 (CK8)
DCIS	+ve	+ve	-ve	+ve peripheral cytoplasm
LCIS	-ve	-ve	+ve perinuclear	+ve perinuclear

Invasive versus non-invasive

Myoepithelial markers - typically lost in invasive carcinoma:^[9]

Stain	Notes
p63	up to 10% of invasive tumour +ve
Sommoth muscle actin (SMA)	stains myofibroblasts & blood vessels
Calponin	stains myofibroblasts & blood vessels
Smooth muscle myosin heavy chain (SMMS)	cytoplasmic stain of myoepithelial cells

Usual ductal hyperplasia versus ductal carcinoma in situ

Markers for UDH versus DCIS:^[9]

Disease	CK5/6	ER
UDH	diffuse +ve	patchy +ve
DCIS	-ve	diffuse +ve

Lymphovascular invasion

Main article: Lymphovascular invasion

D2-40 - marks the lymphatic spaces.^[10]^[11]
CD31 - marks lymphovascular spaces.
CD34 - marks lymphovascular spaces, less specific than CD31.

Treatment-related markers - overview

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%.^[12]
PR (progesterone receptor).
- Positive in most breast cancers; +ve in ~65-70%.^[12]
HER2/neu.
- Usually negative; -ve in 70-80%.^[12]
- Positivity association with a worse prognosis.

ER & PR scoring^[12]

Give a percentage, i.e. 0-100%.
- Important cut points: 1% and 10%.
  - 0% = negative - not treated.
  - <10% = low positivity - treated.

Notes:

Normal breast epithelial cells have a patchy staining for ER and PR.
Evaluated on the invasive component.

HER2 scoring

Immunohistochemical based testing:^[12]^[13]^[14]

Score	Staining intensity	Cells stained (%)	Membrane staining	Management	Percentage of cases
0	nil	<=10%	incomplete	No HER2 blocker	~60%
1+	minimal-to-weak	>10%	incomplete	No HER2 blocker	~10%
2+	weak-to-moderate or intense	>10% weak-to-moderate or <=30% intense	complete	Needs SISH or FISH	~10%
3+	intense & uniform staining (used to be strong)	>30% (used to >10%)	complete	HER2 blocker	~20%

Note for IHC:

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:^[13]

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

Note for ISH:

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

AKA "NST" = No Specific Type.
AKA invasive mammary carcinoma.

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

May be associated with a CDH1 mutation - seen in diffuse type gastric cancer.^[15]^[16]

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.
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:

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."^[17]

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.^[18]

Aside - malignant well-circumscribed breast masses - radiologic DDx:^[18]

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:^[19]

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.^[20]
- Memory device TLC = Tubular ca., LCIS, Columnar cell lesions.

Microscopic

Features:^[21]^[22]^[23]

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.^[24]
+/- Cribriform spaces.
Apocrine snouts typical.
+/-Calcification.

Notes:

Prow = front of a ship.
Looks benign to the uninitiated -- important.

DDx:

Image:

Tubular carcinoma - (uchc.edu).

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:^[25]^[26]

Malignant mesenchymal elements - either:
1. Spindle cells.
2. 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:

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:^[27]
1. Matrix-producing carcinoma:^[28]
  - Features: cartilaginous and/or osseous stromal matrix; no osteoclastic giant cells.
2. Spindle cell carcinoma:^[29]
  - Features: (non-malignant) spindle cells.
  - Prognosis: better prognosis than other metaplastic carcinomas.
3. Carcinosarcoma:^[30]
  - Features: malignant mesenchymal element.
  - Prognosis: survival worse when compared to other metaplastic carcinomas.
4. Squamous cell carcinoma of ductal origin:^[31]
  - Features: purely squamous; metastases are squamous cell carcinoma.
5. Metaplastic carcinoma with osteoclastic giant cells:^[32]
  - Features: osteoclastic giant cells.
- The WHO subclassifies as follows:^[33]
1. Epithelial - includes: squamous cell carcinoma, adenocarcinoma with spindle cell differentiation, adenosquamous carcinoma.
2. 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.^[34]

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".^[35]

Note:

Ductal carcinoma commonly has clefting... but it isn't diffuse.

IHC

EMA +ve (periphery of nests); described as inside-out pattern.^[35]
E-cadherin +ve (centre of nests). (???)
p63 +ve/-ve.

Apocrine carcinoma of the breast

General

Need >=90% apocrine morphology.^[36]

Microscopic

Features:^[36]

Prominent nucleoli.
- Often multiple.^[37]
Abundant granular eosinophilic cytoplasm.
Architecture like invasive ductal carcinomas no special type.

Images:

Apocrine carcinoma (upmc.edu).

IHC

Smaller tumours classically:^[38]

AR +ve.
GCDFP-15 +ve.

Usually:^[36]

ER -ve.
PR -ve.

Mucinous breast carcinoma

AKA mucinous carcinoma of the breast, AKA colloid carcinoma of the breast.

General

Rare.
Good prognosis.^[39]

Microscopic

Features:

Malignant mucin producing glands.
- Mucinous component must comprise >90% of the tumour - required for diagnosis.^[40]
- 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.^[41]

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.^[42]
Good prognosis.^[42]

Microscopic

See: Adenoid cystic carcinoma article.

DDx:

Cribriform DCIS.
Collagenous spherulosis.

Images:

Adenoid cystic carcinoma of the breast (upmc.edu).

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^[43] - it is similar to DCIS.
Classical menopausal women.
~30% present with bloody discharge.^[44]

Microscopic

Features:

Lesion confined to a duct (intraductal) or cyst (intracystic).
- May have a thick fibrous capsule = encapsulated papillary carcinoma.^[44]
Loss of myoepithelial cells - key feature.
Neoplastic epithelial cells:
- Nuclear atypia - including: nucleoli, nuclear pleomorphism.
- Abnormal architecture - including cribriform, solid, micropapillary, papillary.

DDx:

Intraductal papilloma.

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.^[45]
Prognosis usu. poor.

Microscopic

Features:

Groups of cells with abundant clear cytoplasm - need to comprise 90% of the tumour.^[46]
- 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:

GRCC (ijpmonline.org).^[46]

Stains

Features:^[46]

PAS +ve.
PASD -ve.

Others:^[46]

Oil red O -ve.
- Lipid-rich carcinoma +ve.

IHC

Features:^[46]

BRST2 -ve.
- Apocrine carcinoma +ve.

Secretory carcinoma of the breast

AKA secretory breast carcinoma, abbreviated SBC.

General

Favourable prognosis.^[47]
Children and adults.

Microscopic

Features:^[48]

Abundant cytoplasm with fine vacuolation - clear/pale or amphophilic.
Mitoses - uncommon.
Nucleoli - rare.
Architecture: solid, papillary, cribriform or microcystic.

DDx:

Lactational change^[49] - glandular architecture.

Images:

IHC

Triple negative (ER -ve, PR -ve, HER2 -ve).^[47]

Others:

Alpha-lactalbumin +ve.
S-100 protein +ve.
Polyclonal CEA +ve.

Molecular pathology

Characteristic translocation:^[47]

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.^[50] They also wrote a follow-up article in 2002.^[51]

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.

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.^[52]

Staging breast cancer

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.^[53]
- 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.

Pitfalls:

Naevus cell rests.^[54]

IHC

Some hospitals use:

CAM5.2 (LMWK) - to look for isolated tumour cells and small lymph node metstases.

N stage

Indictionas for lymph node sampling

Indications for lymph node sampling:^[55]

Extensive DCIS.
Biopsy suspicious for invasion or with microinvasion.
Clinical findings (large palable mass) or radiology findings (irregular features) suggestive of invasion.
Planned mastectomy.

Definitions

Definitions:^[56]

Isolated tumour cells: <=0.2 mm or <=200 cells -- in a single cross-section. †
Micrometastasis: <=0.2 cm and ( >0.2 mm or >200 cells ).
Macrometastasis: >0.2 cm.

Notes:

† The American Cancer Society web site says "or".^[56] The CAP protocol says "and/or" and notes it is all subjective.
Isolated tumour cells are essentially ignored if the there is at least one macrometastasis.

Details

Lymph nodes:^[57]

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.

T stage

Tumour:^[58]^[59]

pT1: <= 20 mm.
- pT1mic <= 1 mm.
- pT1a > 1 mm and <= 5 mm.
- pT1b > 5 mm and <= 10 mm.
- pT1c > 10 mm and <= 20 mm.
pT2: > 20 mm and <= 50 mm
pT3: > 50 mm.
pT4: chest wall or skin involvement.

Notes:

Values should be rounded to the nearest millimetre.
- Therefore:
  - 1.4 mm would be pT1mic.
  - 1.5 mm would be pT1a.

M stage

Distant metastasis:

cM0(i+) <=0.2 mm focus of tumour cells, without clinical signs and symptoms.
pM1 focus of tumour cells > 0.2 mm.

Lymphovascular invasion

Main article: Lymphovascular invasion

In the context of breast pathology, the Rosen criteria for LVI are widely excepted, and are as follows:^[60]^[61]

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.

Note:

LVI does not affect the stage.

Other

Paget's disease

Main article: Paget disease of the breast

General

Associated with underlying breast carcinoma.^[62]

Notes:

Unrelated to Paget disease of the bone.

Microscopic

Features:^[62]

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.

Trivia

Tumour size and lymph node metastases

There is a paper^[63] that calculates the probability of lymph node mets based on tumour size. The developed formula is:

L_{To-Nodes}=1-exp(-Q_{n}D^{Z})

Where:

$L_{To-Nodes}$ = the probability of the lymph nodes being positive.
D = the largest dimension of the tumour in millimetres.
Z = 1.0041.
$Q_{n}$ = 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.^[64] The study is supported by NCI's SEER data.^[65] Also, it generated many comments.^[64]

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.^[66]

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.
↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 275. ISBN 978-0443066801.
↑ 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.
↑ ^9.0 ^9.1 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 276. ISBN 978-0443066801.
↑ 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.
↑ ^12.0 ^12.1 ^12.2 ^12.3 ^12.4 Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 241-2. ISBN 978-0443066450.
↑ ^13.0 ^13.1 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.
↑ Online 'Mendelian Inheritance in Man' (OMIM) 192090
↑ MUA. Jan 22, 2009.
↑ ^18.0 ^18.1 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.
↑ 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. 1146. ISBN 0-7216-0187-1.
↑ URL: http://www.bweems.com/nsj3mp2.jpg.
↑ URL: http://surgpathcriteria.stanford.edu/breast/tubularcabr/.
↑ Stalsberg, H.; Hartmann, WH. (May 2000). "The delimitation of tubular carcinoma of the breast.". Hum Pathol 31 (5): 601-7. PMID 10836300.
↑ ^25.0 ^25.1 URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html. Accessed on: 28 November 2010.
↑ Barnes, PJ.; Boutilier, R.; Chiasson, D.; Rayson, D. (May 2005). "Metaplastic breast carcinoma: clinical-pathologic characteristics and HER2/neu expression.". Breast Cancer Res Treat 91 (2): 173-8. doi:10.1007/s10549-004-7260-y. PMID 15868445.
↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 328. ISBN 978-0781779425.
↑ Wargotz, ES.; Norris, HJ. (Jul 1989). "Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma.". Hum Pathol 20 (7): 628-35. PMID 2544506.
↑ Wargotz, ES.; Deos, PH.; Norris, HJ. (Aug 1989). "Metaplastic carcinomas of the breast. II. Spindle cell carcinoma.". Hum Pathol 20 (8): 732-40. PMID 2473024.
↑ Wargotz, ES.; Norris, HJ. (Oct 1989). "Metaplastic carcinomas of the breast. III. Carcinosarcoma.". Cancer 64 (7): 1490-9. PMID 2776108.
↑ Wargotz, ES.; Norris, HJ. (Jan 1990). "Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin.". Cancer 65 (2): 272-6. PMID 2153044.
↑ Wargotz, ES.; Norris, HJ. (Nov 1990). "Metaplastic carcinomas of the breast: V. Metaplastic carcinoma with osteoclastic giant cells.". Hum Pathol 21 (11): 1142-50. PMID 2227922.
↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 214. ISBN 978-0443066801.
↑ Yu, JI.; Choi, DH.; Park, W.; Huh, SJ.; Cho, EY.; Lim, YH.; Ahn, JS.; Yang, JH. et al. (Jun 2010). "Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: matched case-control study.". Breast 19 (3): 231-7. doi:10.1016/j.breast.2010.01.020. PMID 20304650.
↑ ^35.0 ^35.1 Yamaguchi, R.; Tanaka, M.; Kondo, K.; Yokoyama, T.; Kaneko, Y.; Yamaguchi, M.; Ogata, Y.; Nakashima, O. et al. (Aug 2010). "Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis.". Jpn J Clin Oncol 40 (8): 781-7. doi:10.1093/jjco/hyq056. PMID 20444748.
↑ ^36.0 ^36.1 ^36.2 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 217. ISBN 978-0443066801.
↑ O'Malley, FP.; Bane, A. (Jan 2008). "An update on apocrine lesions of the breast.". Histopathology 52 (1): 3-10. doi:10.1111/j.1365-2559.2007.02888.x. PMID 18171412.
↑ Honma, N.; Takubo, K.; Akiyama, F.; Sawabe, M.; Arai, T.; Younes, M.; Kasumi, F.; Sakamoto, G. (Aug 2005). "Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast.". Histopathology 47 (2): 195-201. doi:10.1111/j.1365-2559.2005.02181.x. PMID 16045781.
↑ Barkley, CR.; Ligibel, JA.; Wong, JS.; Lipsitz, S.; Smith, BL.; Golshan, M. (Oct 2008). "Mucinous breast carcinoma: a large contemporary series.". Am J Surg 196 (4): 549-51. doi:10.1016/j.amjsurg.2008.06.013. PMID 18809061.
↑ Dogan, E.; Aksoy, S.; Dizdar, O.; Arslan, C.; Dede, DS.; Ozisik, Y.; Altundag, K.. "Pure mucinous carcinoma of the breast: a single center experience.". J BUON 16 (3): 565-7. PMID 22006768.
↑ Jacobs, TW.; Connolly, JL.; Schnitt, SJ. (Sep 2002). "Nonmalignant lesions in breast core needle biopsies: to excise or not to excise?". Am J Surg Pathol 26 (9): 1095-110. PMID 12218567.
↑ ^42.0 ^42.1 Boujelbene, N.; Khabir, A.; Boujelbene, N.; Jeanneret Sozzi, W.; Mirimanoff, RO.; Khanfir, K. (Dec 2011). "Clinical review - Breast adenoid cystic carcinoma.". Breast. doi:10.1016/j.breast.2011.11.006. PMID 22154460.
↑ Rakha, EA.; Gandhi, N.; Climent, F.; van Deurzen, CH.; Haider, SA.; Dunk, L.; Lee, AH.; Macmillan, D. et al. (Aug 2011). "Encapsulated papillary carcinoma of the breast: an invasive tumor with excellent prognosis.". Am J Surg Pathol 35 (8): 1093-103. doi:10.1097/PAS.0b013e31821b3f65. PMID 21753694.
↑ ^44.0 ^44.1 Rodríguez, MC.; Secades, AL.; Angulo, JM. (Nov 2010). "Best cases from the AFIP: intracystic papillary carcinoma of the breast.". Radiographics 30 (7): 2021-7. doi:10.1148/rg.307105003. PMID 21057133.
↑ Hayes, MM.; Seidman, JD.; Ashton, MA. (Aug 1995). "Glycogen-rich clear cell carcinoma of the breast. A clinicopathologic study of 21 cases.". Am J Surg Pathol 19 (8): 904-11. PMID 7611537.
↑ ^46.0 ^46.1 ^46.2 ^46.3 ^46.4 Thondavadi, SR.; Krishnamurthy, J.; Gubbanna, VM.. "A case report of glycogen-rich clear cell carcinoma of breast.". Indian J Pathol Microbiol 53 (2): 374-5. doi:10.4103/0377-4929.64289. PMID 20551566.
↑ ^47.0 ^47.1 ^47.2 Vasudev, P.; Onuma, K. (Dec 2011). "Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression.". Arch Pathol Lab Med 135 (12): 1606-10. doi:10.5858/arpa.2010-0351-RS. PMID 22129193.
↑ Laé, M.; Fréneaux, P.; Sastre-Garau, X.; Chouchane, O.; Sigal-Zafrani, B.; Vincent-Salomon, A. (Feb 2009). "Secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the basal-like carcinoma spectrum.". Mod Pathol 22 (2): 291-8. doi:10.1038/modpathol.2008.184. PMID 19011601.
↑ Vesoulis, Z.; Kashkari, S.. "Fine needle aspiration of secretory breast carcinoma resembling lactational changes. A case report.". Acta Cytol 42 (4): 1032-6. PMID 9684599.
↑ Elston CW, Ellis IO (September 2002). "Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19; 403-410". Histopathology 41 (3A): 151–2, discussion 152–3. PMID 12405945.
↑ Elston CW, Ellis IO (November 1991). "Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up". Histopathology 19 (5): 403–10. PMID 1757079.
↑ MUA. 20 January 2009.
↑ Giuliano AE, Hunt KK, Ballman KV, et al. (February 2011). "Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial". JAMA 305 (6): 569–75. doi:10.1001/jama.2011.90. PMID 21304082.
↑ URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1107%20discussion.html. Accessed on: 28 November 2010.
↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 2 April 2012.
↑ ^56.0 ^56.1 URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
↑ URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
↑ URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
↑ URL: http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging. Accessed on: 9 July 2010.
↑ Rosen, PP. (1983). "Tumor emboli in intramammary lymphatics in breast carcinoma: pathologic criteria for diagnosis and clinical significance.". Pathol Annu 18 Pt 2: 215-32. PMID 6674861.
↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 5 August 2011.
↑ ^62.0 ^62.1 URL: http://emedicine.medscape.com/article/1101235-diagnosis
↑ Porembka, MR.; Abraham, RL.; Sefko, JA.; Deshpande, AD.; Jeffe, DB.; Margenthaler, JA. (Oct 2008). "Factors associated with lymph node assessment in ductal carcinoma in situ: analysis of 1988-2002 seer data.". Ann Surg Oncol 15 (10): 2709-19. doi:10.1245/s10434-008-9947-5. PMID 18483831. http://onlinelibrary.wiley.com/doi/10.1002/cncr.24592/pdf.
↑ ^64.0 ^64.1 Zahl, PH.; Maehlen, J.; Welch, HG. (Nov 2008). "The natural history of invasive breast cancers detected by screening mammography.". Arch Intern Med 168 (21): 2311-6. doi:10.1001/archinte.168.21.2311. PMID 19029493.
↑ Jatoi, I.; Anderson, WF. (May 2009). "Breast cancer overdiagnosis with screening mammography.". Arch Intern Med 169 (10): 999-1000, author reply 1000-1. doi:10.1001/archinternmed.2009.95. PMID 19468099.
↑ Weaver, DL.; Ashikaga, T.; Krag, DN.; Skelly, JM.; Anderson, SJ.; Harlow, SP.; Julian, TB.; Mamounas, EP. et al. (Feb 2011). "Effect of occult metastases on survival in node-negative breast cancer.". N Engl J Med 364 (5): 412-21. doi:10.1056/NEJMoa1008108. PMID 21247310.

External links

CAP protocols/checklists (cap.org).
- Invasive breast cancer - checklist (cap.org).

[Ref_PBoD1143-1] 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.

[2] URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html. Accessed on: 28 November 2010.

[3] URL: http://emedicine.medscape.com/article/1947145-overview. Accessed on: 24 August 2012.

[Ref_PBoD8_1078-4] 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.

[Ref_PCPBoD8_547-5] 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.

[pmid19704256-6] 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.

[Ref_BP275-7] O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 275. ISBN 978-0443066801.

[pmid18318578-8] 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.

[Ref_BP276-9] 9.0 ^9.1 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 276. ISBN 978-0443066801.

[10] 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.

[11] 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.

[Ref_Lester241-2-12] 12.0 ^12.1 ^12.2 ^12.3 ^12.4 Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 241-2. ISBN 978-0443066450.

[Lester3_87-13] 13.0 ^13.1 Lester, Susan Carole (2010). Manual of Surgical Pathology (3rd ed.). Saunders. pp. 87. ISBN 978-0-323-06516-0.

[14] URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 27 November 2011.

[15] URL: http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33006. Accessed on: 19 April 2011.

[omim192090-16] Online 'Mendelian Inheritance in Man' (OMIM) 192090

[17] MUA. Jan 22, 2009.

[pmid21071383-18] 18.0 ^18.1 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.

[19] 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.

[pmid18434766-20] 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.

[Ref_PBoD1146-21] 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. 1146. ISBN 0-7216-0187-1.

[22] URL: http://www.bweems.com/nsj3mp2.jpg.

[23] URL: http://surgpathcriteria.stanford.edu/breast/tubularcabr/.

[pmid10836300-24] Stalsberg, H.; Hartmann, WH. (May 2000). "The delimitation of tubular carcinoma of the breast.". Hum Pathol 31 (5): 601-7. PMID 10836300.

[metaplastic-25] 25.0 ^25.1 URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html. Accessed on: 28 November 2010.

[pmid15868445-26] Barnes, PJ.; Boutilier, R.; Chiasson, D.; Rayson, D. (May 2005). "Metaplastic breast carcinoma: clinical-pathologic characteristics and HER2/neu expression.". Breast Cancer Res Treat 91 (2): 173-8. doi:10.1007/s10549-004-7260-y. PMID 15868445.

[27] Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 328. ISBN 978-0781779425.

[28] Wargotz, ES.; Norris, HJ. (Jul 1989). "Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma.". Hum Pathol 20 (7): 628-35. PMID 2544506.

[29] Wargotz, ES.; Deos, PH.; Norris, HJ. (Aug 1989). "Metaplastic carcinomas of the breast. II. Spindle cell carcinoma.". Hum Pathol 20 (8): 732-40. PMID 2473024.

[30] Wargotz, ES.; Norris, HJ. (Oct 1989). "Metaplastic carcinomas of the breast. III. Carcinosarcoma.". Cancer 64 (7): 1490-9. PMID 2776108.

[31] Wargotz, ES.; Norris, HJ. (Jan 1990). "Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin.". Cancer 65 (2): 272-6. PMID 2153044.

[32] Wargotz, ES.; Norris, HJ. (Nov 1990). "Metaplastic carcinomas of the breast: V. Metaplastic carcinoma with osteoclastic giant cells.". Hum Pathol 21 (11): 1142-50. PMID 2227922.

[33] O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 214. ISBN 978-0443066801.

[pmid20304650-34] Yu, JI.; Choi, DH.; Park, W.; Huh, SJ.; Cho, EY.; Lim, YH.; Ahn, JS.; Yang, JH. et al. (Jun 2010). "Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: matched case-control study.". Breast 19 (3): 231-7. doi:10.1016/j.breast.2010.01.020. PMID 20304650.

[pmid20444748-35] 35.0 ^35.1 Yamaguchi, R.; Tanaka, M.; Kondo, K.; Yokoyama, T.; Kaneko, Y.; Yamaguchi, M.; Ogata, Y.; Nakashima, O. et al. (Aug 2010). "Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis.". Jpn J Clin Oncol 40 (8): 781-7. doi:10.1093/jjco/hyq056. PMID 20444748.

[Ref_BP217-36] 36.0 ^36.1 ^36.2 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 217. ISBN 978-0443066801.

[37] O'Malley, FP.; Bane, A. (Jan 2008). "An update on apocrine lesions of the breast.". Histopathology 52 (1): 3-10. doi:10.1111/j.1365-2559.2007.02888.x. PMID 18171412.

[pmid16045781-38] Honma, N.; Takubo, K.; Akiyama, F.; Sawabe, M.; Arai, T.; Younes, M.; Kasumi, F.; Sakamoto, G. (Aug 2005). "Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast.". Histopathology 47 (2): 195-201. doi:10.1111/j.1365-2559.2005.02181.x. PMID 16045781.

[pmid18809061-39] Barkley, CR.; Ligibel, JA.; Wong, JS.; Lipsitz, S.; Smith, BL.; Golshan, M. (Oct 2008). "Mucinous breast carcinoma: a large contemporary series.". Am J Surg 196 (4): 549-51. doi:10.1016/j.amjsurg.2008.06.013. PMID 18809061.

[pmid22006768-40] Dogan, E.; Aksoy, S.; Dizdar, O.; Arslan, C.; Dede, DS.; Ozisik, Y.; Altundag, K.. "Pure mucinous carcinoma of the breast: a single center experience.". J BUON 16 (3): 565-7. PMID 22006768.

[pmid12218567-41] Jacobs, TW.; Connolly, JL.; Schnitt, SJ. (Sep 2002). "Nonmalignant lesions in breast core needle biopsies: to excise or not to excise?". Am J Surg Pathol 26 (9): 1095-110. PMID 12218567.

[pmid22154460-42] 42.0 ^42.1 Boujelbene, N.; Khabir, A.; Boujelbene, N.; Jeanneret Sozzi, W.; Mirimanoff, RO.; Khanfir, K. (Dec 2011). "Clinical review - Breast adenoid cystic carcinoma.". Breast. doi:10.1016/j.breast.2011.11.006. PMID 22154460.

[pmid21753694-43] Rakha, EA.; Gandhi, N.; Climent, F.; van Deurzen, CH.; Haider, SA.; Dunk, L.; Lee, AH.; Macmillan, D. et al. (Aug 2011). "Encapsulated papillary carcinoma of the breast: an invasive tumor with excellent prognosis.". Am J Surg Pathol 35 (8): 1093-103. doi:10.1097/PAS.0b013e31821b3f65. PMID 21753694.

[pmid21057133-44] 44.0 ^44.1 Rodríguez, MC.; Secades, AL.; Angulo, JM. (Nov 2010). "Best cases from the AFIP: intracystic papillary carcinoma of the breast.". Radiographics 30 (7): 2021-7. doi:10.1148/rg.307105003. PMID 21057133.

[pmid7611537-45] Hayes, MM.; Seidman, JD.; Ashton, MA. (Aug 1995). "Glycogen-rich clear cell carcinoma of the breast. A clinicopathologic study of 21 cases.". Am J Surg Pathol 19 (8): 904-11. PMID 7611537.

[pmid20551566-46] 46.0 ^46.1 ^46.2 ^46.3 ^46.4 Thondavadi, SR.; Krishnamurthy, J.; Gubbanna, VM.. "A case report of glycogen-rich clear cell carcinoma of breast.". Indian J Pathol Microbiol 53 (2): 374-5. doi:10.4103/0377-4929.64289. PMID 20551566.

[pmid22129193-47] 47.0 ^47.1 ^47.2 Vasudev, P.; Onuma, K. (Dec 2011). "Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression.". Arch Pathol Lab Med 135 (12): 1606-10. doi:10.5858/arpa.2010-0351-RS. PMID 22129193.

[pmid19011601-48] Laé, M.; Fréneaux, P.; Sastre-Garau, X.; Chouchane, O.; Sigal-Zafrani, B.; Vincent-Salomon, A. (Feb 2009). "Secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the basal-like carcinoma spectrum.". Mod Pathol 22 (2): 291-8. doi:10.1038/modpathol.2008.184. PMID 19011601.

[pmid9684599-49] Vesoulis, Z.; Kashkari, S.. "Fine needle aspiration of secretory breast carcinoma resembling lactational changes. A case report.". Acta Cytol 42 (4): 1032-6. PMID 9684599.

[pmid12405945-50] Elston CW, Ellis IO (September 2002). "Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19; 403-410". Histopathology 41 (3A): 151–2, discussion 152–3. PMID 12405945.

[pmid1757079-51] Elston CW, Ellis IO (November 1991). "Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up". Histopathology 19 (5): 403–10. PMID 1757079.

[52] MUA. 20 January 2009.

[53] Giuliano AE, Hunt KK, Ballman KV, et al. (February 2011). "Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial". JAMA 305 (6): 569–75. doi:10.1001/jama.2011.90. PMID 21304082.

[54] URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1107%20discussion.html. Accessed on: 28 November 2010.

[55] URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 2 April 2012.

[acs_website-56] 56.0 ^56.1 URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.

[57] URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.

[58] URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.

[59] URL: http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging. Accessed on: 9 July 2010.

[pmid6674861-60] Rosen, PP. (1983). "Tumor emboli in intramammary lymphatics in breast carcinoma: pathologic criteria for diagnosis and clinical significance.". Pathol Annu 18 Pt 2: 215-32. PMID 6674861.

[61] URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 5 August 2011.

[emed_pagets-62] 62.0 ^62.1 URL: http://emedicine.medscape.com/article/1101235-diagnosis

[pmid18483831-63] Porembka, MR.; Abraham, RL.; Sefko, JA.; Deshpande, AD.; Jeffe, DB.; Margenthaler, JA. (Oct 2008). "Factors associated with lymph node assessment in ductal carcinoma in situ: analysis of 1988-2002 seer data.". Ann Surg Oncol 15 (10): 2709-19. doi:10.1245/s10434-008-9947-5. PMID 18483831. http://onlinelibrary.wiley.com/doi/10.1002/cncr.24592/pdf.

[pmid19029493-64] 64.0 ^64.1 Zahl, PH.; Maehlen, J.; Welch, HG. (Nov 2008). "The natural history of invasive breast cancers detected by screening mammography.". Arch Intern Med 168 (21): 2311-6. doi:10.1001/archinte.168.21.2311. PMID 19029493.

[pmid19468099-65] Jatoi, I.; Anderson, WF. (May 2009). "Breast cancer overdiagnosis with screening mammography.". Arch Intern Med 169 (10): 999-1000, author reply 1000-1. doi:10.1001/archinternmed.2009.95. PMID 19468099.

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@@ Line 213: / Line 213: @@
 The above is not applied clinically. A panel of [[immunostains]] (ER, PR, HER2, EGFR, CK5/6) can reproduce the molecular groupings.<ref name=pmid19704256>{{Cite journal  | last1 = Tang | first1 = P. | last2 = Skinner | first2 = KA. | last3 = Hicks | first3 = DG. | title = Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? | journal = Diagn Mol Pathol | volume = 18 | issue = 3 | pages = 125-32 | month = Sep | year = 2009 | doi = 10.1097/PDM.0b013e31818d107b | PMID = 19704256 }}</ref>
-==Subtyping breast cancer==
+==Immunostains for typing and diagnosis==
 ===DCIS versus LCIS===
 Tabular comparison for DCIS versus LCIS:<ref name=Ref_BP275>{{Ref BP|275}}</ref><ref name=pmid18318578>{{cite journal |author=Yeh IT, Mies C |title=Application of immunohistochemistry to breast lesions |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=349-58 |year=2008 |month=March |pmid=18318578 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349}}</ref>
@@ Line 253: / Line 253: @@
 | Smooth muscle myosin <br>heavy chain (SMMS)
 | cytoplasmic stain of myoepithelial cells
+|}
+===Usual ductal hyperplasia versus ductal carcinoma in situ===
+Markers for UDH versus DCIS:<ref name=Ref_BP276>{{Ref BP|276}}</ref>
+{| class="wikitable sortable"
+!Disease
+!CK5/6
+!ER
+|-
+|UDH
+| diffuse +ve
+| patchy +ve
+|-
+|DCIS
+| -ve
+| diffuse +ve
 |}
@@ Line 258: / Line 274: @@
 {{Main|Lymphovascular invasion}}
 *D2-40 - marks the lymphatic spaces.<ref>{{cite journal |author=Ordóñez NG |title=Podoplanin: a novel diagnostic immunohistochemical marker |journal=Adv Anat Pathol |volume=13 |issue=2 |pages=83-8 |year=2006 |month=March |pmid=16670463 |doi=10.1097/01.pap.0000213007.48479.94 |url=}}</ref><ref>{{cite journal |author=Kahn HJ, Marks A |title=A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors |journal=Lab. Invest. |volume=82 |issue=9 |pages=1255-7 |year=2002 |month=September |pmid=12218087 |doi= |url=}}</ref>
+*CD31 - marks lymphovascular spaces.
+*CD34 - marks lymphovascular spaces, less specific than CD31.
 ==Treatment-related markers - overview==

Difference between revisions of "Invasive breast cancer"

Revision as of 02:08, 1 May 2012

Introduction

Overview of invasive breast cancer subtypes

Common epithelial subtypes

Common stromal types

Good prognosis subtypes

Comprehensive list of invasive breast cancer subtypes

Epithelial

Myoepithelial

Mesenchymal tumours

Fibroepithelial tumours

Nipple lesions

Other

Familial breast cancer

Syndromes associated with breast cancer

BRCA1 and BRCA2

Breast IHC

Molecular classification of invasive carcinoma

Immunostains for typing and diagnosis

DCIS versus LCIS

Invasive versus non-invasive

Usual ductal hyperplasia versus ductal carcinoma in situ

Lymphovascular invasion

Treatment-related markers - overview

ER & PR scoring[12]

HER2 scoring

Clinical

Characteristics of the subtypes

Invasive ductal carcinoma of the breast

General

Microscopic

IHC

Invasive lobular carcinoma

General

Microscopic

Medullary breast carcinoma

General

Gross

Microscopic

IHC

Tubular carcinoma of the breast

General

Microscopic

IHC

Metaplastic breast carcinoma

General

Microscopic

Subclassification

IHC

Invasive micropapillary carcinoma of the breast

General

Microscopic

IHC

Apocrine carcinoma of the breast

General

Microscopic

IHC

Mucinous breast carcinoma

General

Microscopic

IHC

Adenoid cystic carcinoma of the breast

General

Microscopic

Invasive papillary carcinoma of the breast

General

Microscopic

IHC

Glycogen-rich clear cell carcinoma of the breast

General

Microscopic

Stains

IHC

Secretory carcinoma of the breast

General

Microscopic

IHC

Molecular pathology

Grading breast cancer

ER & PR scoring^[12]