Breast pathology
The breast is an important organ for the continuance of the species and one that pathologists see quite often because it is often afflicted by cancer. Before women started smoking in large numbers, it was the number one cause of cancer death in women (in Canada).
Fortunately, breast cancer, these days, has a relatively good prognosis if it is detected early... and this is why there are week-ends to end breast cancer -- there are large numbers of breast cancer survivors that are well, wealthy and can advocate for better care and research into breast cancer.
The world of pathology can neatly be divided into two... those that like the breast and those that don't.
Clinical
Classic presentation:
- Nipple discharge.
- Pain.
- Breast lump/mass.
- New nipple inversion.
- Skin changes, e.g. peau d'orange.
Most common presentation:
- Abnormal/suspicious screening mammogram - suspicious microcalcifications and/or suspicious mass.
Breast cancer screening
Breast cancer screening, for normal risk individuals, starts at age 50 in Canada. In the USA, breast screening starts at age 40.
Radiologic screening is less effective in younger individual as:
- The breast is more dense and thus radiologically more difficult to interpret, and
- The incidence of breast cancer is lower.
Breast radiology
BI-RADS = Breast Imaging Reporting And Data System[1]
- 0: Incomplete - come back for more imaging (radiologist cha-ching).
- 1: Negative.
- 2: Benign finding(s).
- 3: Probably benign -- often short follow-up.
- 4: Suspicious abnormality -- needs biopsy.
- 5: Highly suggestive of malignancy.
- 6: Pathologist says there is a malignancy.
Specimens
Breast comes in three main flavours:
- Core needle biopsy (CNB).
- Lumpectomy.
- Radical mastectomy.
Lumpectomies are usually oriented with short and long suture; short is typically superior (aspect) and long is typically lateral (aspect).
Breast cytopathology is dealt with in the breast cytopathology article. It is almost dead, as it is not as sensitive and specific as CNB.
Work-up of CNBs is dependent on the clinical abnormality:[2]
- Mass lesion - usu. obvious what is going on; typically 3 levels.
- Calcifications - abnormality may be very small; typically 10 levels.
Normal
Resting
- Glands -- normally has two cell layers (like the prostate).
- Myoepithelial cells
- Frequently spindle-like, often hard to see.
- Secretory cells.
- Myoepithelial cells
- Stroma:
- Not cellular.
- Not myxoid.
May be present:
- Calcification:
- Purple globs (with concentric rings) on H&E = calcium phosphate.
- Q. How to remember? A. Purple = Phosphate.
- Calcium oxalate visible with (light) polarization - not assoc. with malignancy.
- Often in the lumen of a gland, may be in the stroma.
- Calcific material typically has a well-demarcated border +/- "sharp corners".
- Radiologists can pick-up calcs (calcifications) that are approx. 100 micrometers; if "calcs" is on the requisition one needs to find calcs this size.[3]
- Purple globs (with concentric rings) on H&E = calcium phosphate.
Image:
Notes:
- The architecture is more important than the cytologic features in the diagnosis of malignancy in the breast;[4] low grade tumours have distorted architecture but normal/near normal cytology.
Lactational changes
General
- May be present focally in non-pregnant females.
ASIDE:
- Some believe one ought lactational change and secretory change aren't the same...
- Lactationl change = only in lactation.
- Secretory change = other times.
- This hair splitting is clinically irrelevant-- both are benign. Also, experts use the terms interchangeably.[6]
Microscopic
Features:[7]
- Glands dilated.
- Increased number of lobules.
- Relative decrease in intralobular and extralobular stroma.
- Luminal cells enlarged.
- Vacuolated cytoplasm.
- Hobnail morphology - hang into the lumen.
- Myoepithelial cells indistinct - after second trimester.
Images:
- WC:
- www:
Where to start
The following entities are a starting point for understanding routine breast pathology & some of challenges in breast pathology:
- Apocrine change.
- Pink benign cells.
- Columnar cell change.
- Columnar cells with blebs ("snouts") - often have calcifications (purple).
- Fibroadenoma.
- Abundant myxoid (light/blanched) stroma - very common.
- Florid epithelial hyperplasia.
- Too many cells in a duct, cells overlap & form slit-like spaces.
- Ductal carcinoma in situ (DCIS).
- Too many cells in a duct, nuclei do not touch - "cells are spaced".
- Cells line-up around ovoid/circular spaces - "punch-out" appearance/"cookie cutter" look.
- Myoepithelial cells present.
- Invasive ductal carcinoma.
- Bread & butter cancer - in sheets or glands.
- Lobular carcinoma.
- Dyscohesive cells - can easily be missed.
- Tubular carcinoma.
- Glands have one cell layer... but near normal appearance.
The key to breast pathology is... seeing the two cell layers (at low power). The myoepithelial layer is hard to see at times and that is the challenge.
Common diagnoses - overview
- Normal.
- Benign.
- Columnar cell change.
- Calcification often in lumen.
- Columnar cell change.
- Neoplastic.
- Benign neoplastic:
- Epithelial/myoepithelial - intraductal papilloma.
- Stromal - fibroadenoma, benign phyllodes.
- Malignant neoplastic:
- Epithelial/myoepithelial - most common, e.g. ductal carcinoma, lobular carcinoma.
- Breast stroma - malignant phyllodes tumour.
- Stromal, e.g. angiosarcoma - quite rare.
- Benign neoplastic:
A tree diagram (overview)
General classification
Breast pathology | |||||||||||||||||||||||||||||||||||||||||||||||||
Stromal pathology | Miscellaneous | Glandular pathology | |||||||||||||||||||||||||||||||||||||||||||||||
Myxoid | Long slit-like spaces | Simple epithelium | Dilated | Cellular lesions | |||||||||||||||||||||||||||||||||||||||||||||
Fibroadenoma | Malignant features | Benign features | Tubular carcinoma | FEA, FCC, CCC | FEHUT, Neoplastic, Malignant | ||||||||||||||||||||||||||||||||||||||||||||
Malignant phyllodes | Benign phyllodes | ||||||||||||||||||||||||||||||||||||||||||||||||
Notes:
- The challenges in breast pathology are in: the Simple epithelium category and the Cellular lesions category.
- Neoplastic includes: ADH and LDH.
- Malignant includes: DCIS, LCIS, ductal carcinoma (DC) and lobular carcinoma (LC), some papillary lesions.
- Lobular carcinoma (a pitfall) may appear to be a stromal problem, i.e. the stroma looks too cellular.
- Miscellaneous includes rare tumours of the breast that do not fit into another category, i.e. metastases, lymphomas, melanoma, sarcomas. Skin-related pathology is dealt within the dermatologic neoplasms article. Paget disease of the breast, which may be seen in the context of malignant breast lesions, is discussed in its own article.
Cellular lesions
Cellular lesions (Glandular) | |||||||||||||||||||||||||||||||||||||||||||||||
Equal spacing, punched-out | Streaming, periph. slit-like spaces. | Discohesive cells, expanded gl. | Single cells or single file | Fibrovascular cores | |||||||||||||||||||||||||||||||||||||||||||
Ductal lesion | FEHUT | Lobular lesion | Lobular carcinoma | Papillary lesions | |||||||||||||||||||||||||||||||||||||||||||
Two cell layers | One cell layer | <50% of gl. | >50% of gl. | ||||||||||||||||||||||||||||||||||||||||||||
Ductal non-inv. neoplasm | Ductal carcinoma | ALH | LCIS | ||||||||||||||||||||||||||||||||||||||||||||
Large extent | Small extent | ||||||||||||||||||||||||||||||||||||||||||||||
DCIS | ADH | ||||||||||||||||||||||||||||||||||||||||||||||
Notes:
- The largest challenge is: differentiating between the first two categories on level 2, i.e. equal spacing' vs. streaming.
- The fibrovascular cores must arise from a tuft, i.e. if they are arising directly from the wall of glands only it is likely papillary DCIS.
Papillary lesions
Papillary lesions | |||||||||||||||||||||||||||||||||||||||
Myoepithelial cells present | Myoepithelial cells absent | ||||||||||||||||||||||||||||||||||||||
Unremarkable papillae | Atypia or arch. abnorm. or cellular proliferation | Neoplastic cells present | |||||||||||||||||||||||||||||||||||||
Benign intraductal papilloma | High grade atypia | Low grade atypia or abnorm. arch. | Only cellular proliferation | Intracystic (encapsulated) papillary ca. | |||||||||||||||||||||||||||||||||||
DCIS in papilloma | FEHUT in papilloma | ||||||||||||||||||||||||||||||||||||||
>3 mm extent | <3 mm extent | ||||||||||||||||||||||||||||||||||||||
DCIS in papilloma | ADH in papilloma | ||||||||||||||||||||||||||||||||||||||
Notes:
- Adapted from Mulligan & O'Malley.[8]
- The most important decision is the first one: myoepithelial cells present vs. absent.
- abnorm. arch. = abnormal architecture present.
- DCIS = ductal carcinoma in situ.
- FEHUT = florid epithelial hyperplasia of the usual type.
- extent refers to the size of the abnormal cell population within the papillary lesion.
Malignant lesions
Non-invasive breast cancer
This includes the in situ lesions - DCIS and LCIS.
Invasive breast cancer
This is includes descriptions of the usual types... and the not so common ones.
Common benign lesions
The breast has lots of benign things. Unlike the prostate, the where benign is called benign, everything has a name. It is more common among breast pathologists to sign-out things like: apocrine metaplasia (benign), columnar cell change (benign), and florid epithelial hyperplasia of the usual type (FEHUT) - instead of - benign breast tissue.
Mild epithelial hyperplasia
General
- No increased risk of malignancy.
- Often not reported - as it has not clinical signficance.
- Has to be separated from moderate epithelial hyperplasia / florid epithelial hyperplasia.
Microscopic
Features:[9]
- Breast glands with three or four cell layers above the basement membrane.
- Variable cells.
Note:
- No nuclear atypia.
DDx:
- Flat epithelial atypia.
- Moderate epithelial hyperplasia / florid epithelial hyperplasia.
- Atypical ductal hyperplasia.
Apocrine metaplasia
General
- Benign/not significant. Can be considered to be pretty wallpaper in the house of breast pathology.
Etiology
- Increased number of mitochondria.
- In other body sites this has different names, e.g. Hurthle cell change (thyroid), oncocytic change (kidney - oncocytoma, thyroid).
Microscopic
Features:
- Eosinophilic cytoplasm - key feature.
Note:
- Apocrine changes, i.e. cytoplasmic eosinophilia, can appear in malignant tumours; eosinophilia doesn't make something benign.
- Apocrine snouts may be present. (???)
- Small globules at the apical aspect of the cell (composed of cytoplasm and plasma membrane).
Image:
Fibrocystic change
- Abbreviated FCC.
- AKA fibrocystic changes.
General
- Really common.
- Benign.
Microscopic
Features:
- Dilated glands - key change.
- Glands normal: two cell layers present.
- Often seen together with apocrine metaplasia.
Image:
- WC:
Columnar cell change
General
- Columnar cell change is associated with (benign) calcification - key point.
Microscopic
Features:
- Secretory cells (line gland lumen) have columnar morphology.
- May have "apical snouts".
- Blebs or round balls eosinophilic material appear to be adjacent to the cell at their luminal surface.
- The snouts are attached to the cell-- appear as round ball only in the plane of section.
- Cytoplasm +/-eosinophilia.
DDx:
- Flat epithelial atypia (>2 cell layers).[citation needed]
Image:
Gynecomastoid hyperplasia
- AKA gynecomastia.
General
- Benign enlargement of breasts in males.
- Histologic changes may be seen in females.[10]
May be seen in the context of:
- Liver failure.
- Klinefelter syndrome.
- Testicular estrogen-producing germ cell tumour.
Microscopic
Features:[10]
- Moderate hyperplasia.
- Glands have more than 2 cell layers.
- "Budding" - individual cells jut into the lumen - key feature.
- Stromal palor.[11]
Images:
- www:
- WC:
Lesions with increased risk of malignancy
Florid epithelial hyperplasia
- AKA florid epithelial hyperplasia, abbreviated FEH.
- AKA florid epithelial hyperplasia of the usual type, abbreviated FEHUT.
- AKA epithelial hyperplasia - term should be avoid as it could lead to confusion with mild epithelial hyperplasia.
General
- Mild increased risk of malignancy ~ 1.5-2x.[12]
- Has to be separated from mild epithelial hyperplasia.
Note:
- Moderate epithelial hyperplasia redirects to this section.
- It is generally not separated from FEH, as the prognosis is thought to be the same.
Microscopic
Features:[13]
- Breast glands with more than four cell layers above the basement membrane - key feature.
- Irregular cell spacing; streaming.
- Slit-like lumina, esp. at the periphery of the duct.
- No DCIS-like architecture (not cribriform, not papillary, not micropapillary, not solid).
- No nuclear atypia - usu. not nucleoli.
Memory device CLEAN:
- Cell spacing is irregular, Lumina are slit-like, Extent is less than 2 mm or 2 ducts, Architecture not DCIS-like, Nuclear atypia not present.
DDx:
Sclerosing adenosis
General
- Can be scary... can look like ductal carcinoma.
- Derived from sclerosing[14] (hardening) and adenosis (glandular enlargement).
- Think scaring + lotsa glands and you're pretty close.
Microscopic
Features:
- Acini are smaller than usual and there are more of them.
- Acini often slit-like.
- Fibrosis (scleroses) - pink on H&E surrounds the acini.
- Can mimic a dysmoplastic reaction.
Notes:
- The acini should:
- Be in lobular arrangements, i.e. in groups (benign appearance at low power) - key feature.
- Have two cell layers like well-behaved breast glands do.
DDx:
- Low-grade ductal carcinoma.
Flat epithelial atypia
General
Epidemiology:
- Associated with ADH & DCIS; may represent a non-obligate precursor lesion of ADH & DCIS.[15]
- Low risk of progression to invasive malignancy.[16]
Microscopic
Features:
- "Flat" ~ three cells thick. (???)
- Hypercellular gland -- several layers.
- Columnar cell morphology.
- +/-Apical snouts.
DDx:
- Columnar cell change.
- ADH.
- Low grade DCIS.
Complex sclerosing lesion
- AKA radial scar.
General
- The term radial scar is a misnomer. It isn't a scar. It isn't associated with prior trauma or surgery.[17]
- May appear malignant on imaging.[18]
- Associated with subsequent elevated risk of breast cancer.[19]
- Management - usu. surgical excision.[20]
Gross
- Spiculated mass.
- Usually small - 3-7 mm.
Image:
Microscopic
- Stellate appearance (low magnification).
- Center of lesion has "fibroelastosis" - stroma light pink (on H&E) - key feature.
- Scar like stroma with entrapped normal breast ducts and lobules.
- Glands appear to enlarge with distance from center of lesion.
Image: Radial scar (breastpathology.info).
Notes:
- Histomorphologic appearance may mimic a desmoplastic reaction of stroma - leading to a misdiagnosis of malignancy.
- "Hyaline - pink stuff on H&E - is the key."[22]
Stromal lesions
This section (below) covers stromal lesions of the breast, which vary from benign to malignant. The most common is (the benign) fibroadenoma.
Non-breast stroma stromal lesions are covered in the soft tissue lesions article. Angiosarcoma (dealt with in the vascular tumours article) is the most common (non-breast stroma) sarcoma of the breast, and classically arises after treatment for a breast carcinoma.
Fibroadenoma
General
- Very common benign finding.
- The pathology is in the stroma; so, the lesion is really a misnomer by the naming rules.
- It ought to be called adenofibroma (as a few occasionally do)[23], as the glandular component is benign and the stromal component lesional.
Management:
- Local excision (without a large margin).
Microscopic
Features (fibroadenoma not otherwise specified):
- Myxoid stroma -- most important feature.
- Stroma is white/pale on H&E -- normal stroma is pink on H&E.
- Compression of glandular elements -- commonly seen.
DDx:
- Phyllodes tumour.
- Stroma is more cellular than in fibroadenoma.
- May have mitoses.
- "Stromal overgrowth" large area where there is a 'loss of glands'.
- Patients with phyllodes tumour are usually older than those with fibroadenoma.
- Sarcoma.
Notes:
- There is stuff about intracanalicular vs. pericanalicular.[24] It is irrelevant; there is no prognostic difference between the two.
- Do not comment on the margin - it is irrelevant.
Phyllodes tumour vs. fibroadenoma
Histology of phyllodes:
- More cellular.
- More mitoses.
- More nuclear pleomorphism.
- Stromal overgrowth - epithelial elements absent in one low power field (x40).
- Infiltrative borders.
- Long/large slit-like spaces - key feature.
- Small foci of long slit-like space may exist -- how much... no definition.
Epidemiology:
- Phyllodes = older patients (usually)
Tx:
- Wide excision for phyllodes vs. local excision for fibroadenoma.
Variants
Four variants are described by the Washington Manual:[25]
- Juvenile.
- Complex.
- Myxoid.
- Cellular.
Considered a variant of fibroadenoma by many authorities:[26]
Juvenile fibroadenoma
- As the name suggests, is typically found in younger patients.
- Classic history: rapid growth.
Features (juvenile variant):[27]
- Stromal and epithelial hyperplasia - key feature.
- Mitoses uncommon.
Myxoid fibroadenoma
- May be associated with Carney's complex.
Features:
Cellular fibroadenoma
Features (cellular variant):
- Cellular.
- Mitoses.
Complex fibroadenoma
- Contain proliferative epithelium which outside and inside a fibroadenoma is associated with an increased risk of malignancy.
Features:[28]
- Apocrine metaplasia.
- Cysts > 3 mm.
- Calcification.
- Sclerosing adenosis.
Memory devices:
- FACS: complex fibroadenoma, apocrine metaplasia, calcs & cysts, , sclerosing adenosis.
- CAMS: calcs, apocrine metaplasia, microcysts, sclerosing adenosis.
Tubular adenoma of the breast
- Considered by many a variant of fibroadenoma.
Features:[26]
- Fibromyxoid stroma (like in a fibroadenoma).
- Small round glands.
Image:
Phyllodes tumour
The name comes from the word "leaf"; with imagination or psychotropic drugs, it may look like one (the epithelial component = the veins of the leaf).
General
- Wide excision -- this differs from fibroadenoma (just local excision).
- Approximately 6% are malignant.[30]
Gross
- Clefts, leaf-like structures - friable vis-a-vis a fibroadenoma.
Microscopic
Features:
- Large slit-like spaces.
- Cellular stroma that may be myxoid.
- +/-Mitoses.
- May have "malignant border" -- "pushing border" / "infiltrative border".
Image:
Malignant phyllodes?
Features of malignancy:[31]
- Stromal cellular atypia.
- Mitotic activity in 10 HPFs.
- "HPF" is not adequately defined - see HPFitis. The authors should be spanked.
- Stromal overgrowth -- epithelial elements absent in one low power field (x40).[31]
- "LPF" is not adequately defined - see LPFitis. The authors should be spanked.
A comparison between benign and malignant phyllodes - adapted from Taira et al.[31]
Benign | Malignant | |
Stromal overgrowth | no | yes |
Mitoses | >4/10 HPF | >=10/10 HPF |
Atypia of stromal cells | <= moderate | marked |
See also: Phyllodes tumour vs. fibroadenoma.
Pseudoangiomatous stromal hyperplasia
General
- Benign lesion.
- Thought to arise due to myofibroblast abnormality - though not well understood.[33]
Gross
Features:[33]
- May form mass: grey-white & firm, with well circumscribed borders.
Microscopic
- Abundant breast stromal.
- Small, complex, inter-anastomosing (blood vessel/capillary-like) channels - key feature.
- Pseudoangiomatous = blood vessel-like.
Notes:
- May mimic angiosarcoma at low power; PASH may have the same architecture but lack nuclear atypia.
Images:
IHC
Findings:[33]
- CD34 +ve.
- Vimentin +ve.
- Factor VIII -ve.
Weird stuff
Like in all niches of pathology... there is weird stuff.
Mammary hamartoma
- AKA breast hamartoma.
General
- Benign.
- Disordered growth - see hamartoma.
Gross
- Well-circumscribed - key feature.
Microscopic
Features:[36]
- Disordered arrangement of ductal and lobular structures.
- Normal arrangement of cells with in the ductal structures, i.e. myoepithelium and epithelium present.
- Variable features:[37]
- Adipose tissue - predominant.
- Dense fibrosis tissue - predominant.
- Cystic glandular dilation.
Notes:
- If adipose tissue predominates; it may be labeled adenolipoma.[37]
DDx:
Images:
IHC
- None - it's a H&E diagnosis.
Collagenous spherulosis
General
- Benign.
- Almost always an incidental finding.
- Can mimic ADH, cribriform DCIS, adenoid cystic carcinoma.[40]
Microscopic
- Tubular/cribriform architecture.
- Intratubular eosinophilic material - key feature.
- Classical: Arranged like the spokes of a wheel ("radial spikes").
- Atypical: Granules ~ 1-2 micrometers.
- No mitotic activity.
- Two cells populations (epithelial & myoepithelial) - like a well-behaved breast gland.
Notes:
- Usually small lesions: < 50 spherules per lesion, <100 micrometers.
- May be multifocal.
- +/-Calcifications - may prompt biopsy.
Images:
- WC:
- www:
Nipple adenoma
- AKA nipple duct adenoma, nipple adenoma of breast, adenoma of the nipple.
General
- Rare.
Clinical DDx:
Microscopic
Features:
- Proliferation of epithelial and myoepithelial elements that extends into the breast stroma.[43]
Notes:
DDx:
Images:
Intraductal papilloma
General
- May cause nipple discharge.[45]
- Similar to papillary hidradenoma of the vulva.
Microscopic
Features:
- True papillae - nipple-shaped structures with fibrovascular cores.
- Intraductal proliferation of epithelial and myoepithelial elements.[43]
Notes:
- Lacks florid hyperplasia.[46]
- May degeneration and hyalinize to form a sclerosing papilloma.
Images:
Diabetic mastopathy
General
- Diabetes mellitus (DM).
- If DM is absent it is called lymphocytic mastitis.[47]
- Rare.
Microscopic
Features:[48]
- Stromal collagen with keloid-like changes.
- Lymphocytic infiltrates:
- Lobules.
- Perivascular.
- Enlarged stromal fibroblasts.
DDx:
- Primary lymphoma of the breast.
IHC
- B cell predominant (CD20 > CD3).[47]
- B cells CD43 -ve.
Molecular
- Negative clonality studies.
Microglandular adenosis
- Abbreviated MGA.
General
- Controversial thingy.
Microscopic
Features:[49]
- Round glands lined by a single layer of cells.
- May extend into fat.
DDx:
- Tubular carcinoma - has apical snouts, desmoplasia among other things; see page by Collins.[49]
- Sclerosing adenosis.
Images:
- Microglandular adenosis (surgical pathologyatlas.com).
- MGA - low mag. (webpathology.com).
- MGA - high mag. (webpathology.com).
- MGA (breastpathology.info).
- MGA - several images (breastpathology.info).
IHC
Features:[50]
- S100 +ve.
- 34BE12 +ve -- focal!
Adenomyoepithelioma
General
- Rare lesion consisting of epithelial and myoepithelial elements.
- May occur in other sites, e.g. tonsil.[51]
- May be benign or malignant.[52][53]
Note:
- Possibly the same tumour as epithelial-myoepithelial carcinoma of the salivary gland.[54]
Microscopic
Features:[55]
- Well-circumscribed.
- Glandular architecture with:
- Easily identifiable myoepithelial cells - with clear cytoplasm - key feature.
- Eosinophilic cuboidal epithelial cells.
- Eosinophilic basement membrane material between glands.
DDx:
- Invasive ductal carcinoma (on core biopsy).
- Mammary pleomorphic adenoma.
- Ductal adenoma.
Images:
- Webpathology.com:
- WC:
Mammary myofibroblastoma
General
- Rare.
- Excision = cure.
Note:
- In extra-mammary sites the tumour is known as a mammary-type myofibroblastoma may immunohistochemically and histomorphologically overlap with spindle cell lipoma.[56]
Microscopic
Features:[57]
- Well-circumscribed lesion.
- Spindle cells without nuclear atypia arranged in fascicles.
- Interspersed thick bundles of collagen.
Notes:
- No calcifications.
- No necrosis.
- No hemorrhage.
DDx:
- Fibromatosis.
- Metaplastic breast carcinoma.
- Leiomyoma of the breast.
Images:
- WC:
- www:
IHC
Features:[58]
Other
- S100 -ve.
Squamous metaplasia of lactiferous ducts
- Abbreviated SMOLD.
General
- Post-menopausal women.
- May be associated with subareolar abscess.
Microscopic
Features:
- Replacement of bilayer in lactiferous ducts with squamous epithelium.
- Xanthomatous reaction.
See also
References
- ↑ URL: http://breastcancer.about.com/od/diagnosis/a/birads.htm. Accessed on: 16 March 2011.
- ↑ MUA. 1 October 2010.
- ↑ MUA. 1 October 2010.
- ↑ RS. 4 May 2010.
- ↑ URL: [Breast_pathology#Lactational_changes Breast_pathology#Lactational_changes. Accessed on: 3 October 2011.
- ↑ Tavassoli, FA.; Yeh, IT. (Jan 1987). "Lactational and clear cell changes of the breast in nonlactating, nonpregnant women.". Am J Clin Pathol 87 (1): 23-9. PMID 2879437.
- ↑ URL: http://flylib.com/books/en/2.953.1.9/1/. Accessed on: 6 August 2011.
- ↑ Mulligan AM, O'Malley FP (March 2007). "Papillary lesions of the breast: a review". Adv Anat Pathol 14 (2): 108–19. doi:10.1097/PAP.0b013e318032508d. PMID 17471117.
- ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 159-160. ISBN 978-0443066801.
- ↑ 10.0 10.1 URL: http://www.hsc.stonybrook.edu/breast-atlas/XIII-03.htm. Accessed on: 16 November 2011.
- ↑ URL: http://radiology.uchc.edu/eAtlas/Breast/1693.htm. Accessed on: 16 November 2011.
- ↑ 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. 542. ISBN 978-1416054542.
- ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 159-160. ISBN 978-0443066801.
- ↑ URL: http://dictionary.reference.com/browse/sclerosis. Accessed on: 16 March 2011.
- ↑ Lerwill, MF. (Apr 2008). "Flat epithelial atypia of the breast.". Arch Pathol Lab Med 132 (4): 615-21. doi:10.1043/1543-2165(2008)132[615:FEAOTB]2.0.CO;2. PMID 18384213.
- ↑ Schnitt, SJ. (2003). "The diagnosis and management of pre-invasive breast disease: flat epithelial atypia--classification, pathologic features and clinical significance.". Breast Cancer Res 5 (5): 263-8. doi:10.1186/bcr625. PMID 12927037.
- ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1072. ISBN 978-1416031215.
- ↑ Ung OA, Lee WB, Greenberg ML, Bilous M (January 2001). "Complex sclerosing lesion: the lesion is complex, the management is straightforward". ANZ J Surg 71 (1): 35–40. PMID 11167596.
- ↑ URL: http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Radial_Scars.asp. Accessed on: 4 May 2010.
- ↑ 20.0 20.1 Kennedy M, Masterson AV, Kerin M, Flanagan F (October 2003). "Pathology and clinical relevance of radial scars: a review". J. Clin. Pathol. 56 (10): 721–4. PMC 1770086. PMID 14514771. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770086/.
- ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 91. ISBN 978-0443066801.
- ↑ RS. May 2010.
- ↑ Guinebretière, JM.; Menet, E.; Tardivon, A.; Cherel, P.; Vanel, D. (Apr 2005). "Normal and pathological breast, the histological basis.". Eur J Radiol 54 (1): 6-14. doi:10.1016/j.ejrad.2004.11.020. PMID 15797289.
- ↑ URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970216-9. Accessed on: 16 March 2011.
- ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 262. ISBN 978-0781765275.
- ↑ 26.0 26.1 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 116. ISBN 978-0443066801.
- ↑ URL: http://www.breastpathology.info/fibro_variants.html#juvenile. Accessed on: 3 October 2011.
- ↑ URL: http://www.breastpathology.info/fibro_variants.html#complex. Accessed on: 3 October 2011.
- ↑ Maiorano, E.; Albrizio, M. (Dec 1995). "Tubular adenoma of the breast: an immunohistochemical study of ten cases.". Pathol Res Pract 191 (12): 1222-30. PMID 8927570.
- ↑ Guerrero MA, Ballard BR, Grau AM (July 2003). "Malignant phyllodes tumor of the breast: review of the literature and case report of stromal overgrowth". Surg Oncol 12 (1): 27–37. PMID 12689668. http://linkinghub.elsevier.com/retrieve/pii/S0960740403000057.
- ↑ 31.0 31.1 31.2 Taira N, Takabatake D, Aogi K, et al (October 2007). "Phyllodes tumor of the breast: stromal overgrowth and histological classification are useful prognosis-predictive factors for local recurrence in patients with a positive surgical margin". Jpn. J. Clin. Oncol. 37 (10): 730-6. doi:10.1093/jjco/hym099. PMID 17932112. http://jjco.oxfordjournals.org/cgi/reprint/37/10/730.
- ↑ Leon, ME.; Leon, MA.; Ahuja, J.; Garcia, FU.. "Nodular myofibroblastic stromal hyperplasia of the mammary gland as an accurate name for pseudoangiomatous stromal hyperplasia of the mammary gland.". Breast J 8 (5): 290-3. PMID 12199757.
- ↑ 33.0 33.1 33.2 Powell CM, Cranor ML, Rosen PP (March 1995). "Pseudoangiomatous stromal hyperplasia (PASH). A mammary stromal tumor with myofibroblastic differentiation". Am. J. Surg. Pathol. 19 (3): 270–7. PMID 7872425.
- ↑ Vuitch MF, Rosen PP, Erlandson RA (February 1986). "Pseudoangiomatous hyperplasia of mammary stroma". Hum. Pathol. 17 (2): 185–91. PMID 3949338.
- ↑ 35.0 35.1 Ferreira, M.; Albarracin, CT.; Resetkova, E. (Feb 2008). "Pseudoangiomatous stromal hyperplasia tumor: a clinical, radiologic and pathologic study of 26 cases.". Mod Pathol 21 (2): 201-7. doi:10.1038/modpathol.3801003. PMID 18084246.
- ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 117. ISBN 978-0443066801.
- ↑ 37.0 37.1 URL: http://surgpathcriteria.stanford.edu/breast/mammhamart/. Accessed on: 4 October 2011.
- ↑ Tse, GM.; Law, BK.; Ma, TK.; Chan, AB.; Pang, LM.; Chu, WC.; Cheung, HS. (Dec 2002). "Hamartoma of the breast: a clinicopathological review.". J Clin Pathol 55 (12): 951-4. PMC 1769817. PMID 12461066. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769817/.
- ↑ 39.0 39.1 URL: http://surgpathcriteria.stanford.edu/breast/collspher/. Accessed on: 4 September 2011.
- ↑ 40.0 40.1 Resetkova, E.; Albarracin, C.; Sneige, N. (Jan 2006). "Collagenous spherulosis of breast: morphologic study of 59 cases and review of the literature.". Am J Surg Pathol 30 (1): 20-7. PMID 16330938.
- ↑ URL: http://www.hsc.stonybrook.edu/breast-atlas/V-33.htm. Accessed on: 31 August 2011.
- ↑ HANDLEY, RS.; THACKRAY, AC. (Jun 1962). "Adenoma of nipple.". Br J Cancer 16: 187-94. PMC 2070922. PMID 13904317. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2070922/?tool=pubmed.
- ↑ 43.0 43.1 43.2 "Adenoma of Nipple.". Br Med J 1 (5330): 563. Mar 1963. PMC 2123505. PMID 20789667. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2123505/?page=1.
- ↑ URL: http://surgpathcriteria.stanford.edu/breast/nippleadenoma/printable.html. Accessed on: 6 August 2011.
- ↑ Zervoudis, S.; Iatrakis, G.; Economides, P.; Polyzos, D.; Navrozoglou, I. (Jan 2010). "Nipple discharge screening.". Womens Health (Lond Engl) 6 (1): 135-51. doi:10.2217/whe.09.81. PMID 20050819.
- ↑ URL: http://surgpathcriteria.stanford.edu/breast/nippleadenoma/printable.html. Accessed on: 6 August 2011.
- ↑ 47.0 47.1 Valdez, R.; Thorson, J.; Finn, WG.; Schnitzer, B.; Kleer, CG. (Mar 2003). "Lymphocytic mastitis and diabetic mastopathy: a molecular, immunophenotypic, and clinicopathologic evaluation of 11 cases.". Mod Pathol 16 (3): 223-8. doi:10.1097/01.MP.0000056627.21128.74. PMID 12640102.
- ↑ URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_0707%20discussion.html. Accessed on: 28 November 2010.
- ↑ 49.0 49.1 URL: http://www.uscap.org/site~/iap2006/slides08-4v.htm. Accessed on: 18 May 2011.
- ↑ Joshi, MG.; Lee, AK.; Pedersen, CA.; Schnitt, S.; Camus, MG.; Hughes, KS. (Jan 1996). "The role of immunocytochemical markers in the differential diagnosis of proliferative and neoplastic lesions of the breast.". Mod Pathol 9 (1): 57-62. PMID 8821958.
- ↑ Ren, J.; Song, L.; Dang, Q.; Zhang, X.; Jiang, SW.; Zhang, G.; Wang, N.; Liu, Z. et al. (2010). "Primary adenomyoepithelioma of tonsil.". Head Neck Oncol 2: 7. doi:10.1186/1758-3284-2-7. PMID 20356364.
- ↑ Howlett, DC.; Mason, CH.; Biswas, S.; Sangle, PD.; Rubin, G.; Allan, SM. (Mar 2003). "Adenomyoepithelioma of the breast: spectrum of disease with associated imaging and pathology.". AJR Am J Roentgenol 180 (3): 799-803. PMID 12591699. http://www.ajronline.org/content/180/3/799.full.
- ↑ Zizi-Sermpetzoglou, A.; Vasilakaki, T.; Grammatoglou, X.; Petrakopoulou, N.; Nikolaidou, ME.; Glava, C. (2009). "Malignant adenomyoepithelioma of the breast--case report.". Eur J Gynaecol Oncol 30 (2): 234-6. PMID 19480267.
- ↑ Seifert, G. (Sep 1998). "Are adenomyoepithelioma of the breast and epithelial-myoepithelial carcinoma of the salivary glands identical tumours?". Virchows Arch 433 (3): 285-8. PMID 9769134.
- ↑ URL: http://www.webpathology.com/image.asp?n=1&Case=322. Accessed on: 16 August 2011.
- ↑ 56.0 56.1 56.2 McMenamin, ME.; Fletcher, CD. (Aug 2001). "Mammary-type myofibroblastoma of soft tissue: a tumor closely related to spindle cell lipoma.". Am J Surg Pathol 25 (8): 1022-9. PMID 11474286.
- ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 131. ISBN 978-0443066801.
- ↑ Mele, M.; Jensen, V.; Wronecki, A.; Lelkaitis, G. (2011). "Myofibroblastoma of the breast: Case report and literature review.". Int J Surg Case Rep 2 (6): 93-6. doi:10.1016/j.ijscr.2011.02.006. PMID 22096693.