Breast pathology

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Diagram of the structure of breast. (CRUK/WC)

The breast is an important organ that pathologists see quite often because it is often afflicted by cancer. Before women started smoking in large numbers, it was a leading cause of cancer death in women.

Fortunately, breast cancer, in this day, has a relatively good prognosis if it is detected early.

Contents

Clinical

Clinical Presentations of Breast Pathology

  • Abnormal/suspicious screening mammogram
    • Suspicious microcalcifications and/or suspicious mass.
    • Most common history on the specimen requisition
    • May be accompanied by a BI-RADS score.
  • Nipple discharge.
  • Pain.
  • Breast lump/mass.
  • New nipple inversion.
  • Skin changes, e.g. peau d'orange.

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:

  1. The breast is more dense and thus radiologically more difficult to interpret, and
  2. The incidence of breast cancer is lower.

Breast radiology

Specimens

Three major specimen types:

  1. Core needle biopsy (CNB).
  2. Lumpectomy.
  3. Modified radical mastectomy.

Note:

  • Breast cytopathology is dealt with in the breast cytopathology article. Breast cytology is almost extinct unless you happen to be in Australia where for reasons unknown, the art is still taken seriously. Breast cytology is not sensitive or specific enough to justify forgoing a CNB.

Core needle biopsy

Work-up of CNBs is dependent on the clinical abnormality:[1]

  1. Mass lesion - usu. obvious what is going on; typically 3 levels.
  2. Calcifications - abnormality may be very small; typically 10 levels.

Note - if you have a high BI-RADS score on the biopsy requisition, and no correlating histologic findings, be sure to correlate with the specimen radiograph, consider leveling the specimen to exhaustion and/or note the lack of a correlating lesion on your report.

Lumpectomy

Lumpectomies are usually oriented with short and long suture; short is typically superior (aspect) and long is typically lateral (aspect).

Modified radical mastectomy

  • Usually done with sentinel lymph node biopsy - as one cannot go back later to do this.

Where to start

The following is a starting point for mentally framing routine breast pathology & some of the challenges in breast pathology:

The key to breast pathology is the myoepithelial cell.

    • A benign gland has two cell layers - myoepithelial and epithelial.
    • The luminal cell is epithelial
    • The basal cells is myoepithelial
      • The myoepithelial layer is hard to see at times.
      • IHC can aid in visualizing the myoepithelial layer.
      • The immunostains used in breast pathology for the myoepithelial layer include: CK5/6, SMA, p63 and calponin.

Questions to Ask

  • Is it normal or close to normal?
    • Are you familiar with normal/altered but benign/physiologic changes in the breast?
    • Do the changes observed explain the biopsy (are you sure you are seeing the radiographic lesion)?
    • Have you found the microcalcifications?
  • Is it a neoplastic but benign?
    • Are you familiar with the common benign breast neoplasms?
    • Do you know the morphologic criteria for a benign breast gland?
    • Do you know how to use IHC to confirm a benign process?
  • Is it an in situ carcinoma?
    • Are you familiar with DCIS and LCIS and their variants?
    • Do you know the morphologic criteria for in situ carcinoma?
    • Do you know how to use ICH to confirm an in situ carcinoma?
    • Do you know how to report an in situ breast carcinoma?
  • Is it invasive carcinoma?
    • Do you know the morphologic criteria for an invasive gland?
    • Do you know how to use IHC to confirm invasion?
    • Do you know the morphologic features of typical invasive breast carcinoma?
    • Do you know the subtypes?
    • Do you understand the implications of some of the medullary/medullary-like subtype (especially in a young patient)?
    • Do you know how to use IHC for prognostication?
    • Do you understand the implications of triple negativity?
    • Do you know how to report an invasive breast carcinoma?
  • Is it something stromal/spindled?

Important Differential Diagnoses

Papillary Lesions

  • Nipple adenoma.
  • Intraductal papilloma.
  • Papillary ductal carcinoma in situ.
  • Intracystic papillary carcinoma.
  • Intracystic papillary carcinoma with an invasive component.
  • Invasive papillary carcinoma.

Basaloid Lesions

  • Adenoid cystic carcinoma of the breast.
  • Intracystic papillary breast carcinoma, solid variant.
  • Invasive papillary breast carcinoma, solid variant.
  • Medullary breast carcinoma.
  • Medullary-like breast carcinoma.
    • Know when to start a discussion about BRCA mutations, triple negativity and the 'basal-like molecular phenotype'.

Spindle Cell Lesions

  • Metaplastic breast carcinoma.
  • Treated breast carcinoma.
  • Mammary myofibroblastoma.
  • Phyllodes Tumour - stromal component.
  • Desmoid fibromatosis.
  • Nodular fasciitis.

Additional resources

  • Breast Pathology Info [1]
  • Digital Atlas of Breast Pathology [2]
  • Pathology Outlines - Breast Nonmalignant [3]
  • Pathology Outlines - Breast Malignant [4]
  • WebPathology - Breast [5]

Normal breast

Resting breast

  • Glands -- normally has two cell layers (like the prostate).
    • Myoepithelial cells
      • Frequently spindle-like, often hard to see.
    • Secretory 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 associated 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 approximately 100 micrometers; if "calcs" is on the requisition one needs to find calcs this size.[2]
      • The large calcs seen on radiology are approximately 1/5 - 1/6 the size of a HPF, if the field of view (FOV) is ~0.55 mm (as is the case with 22 mm-10x eye pieces and a 40x objective).

Notes:

  • The architecture is more important than the cytologic features in the diagnosis of malignancy in the breast;[3] low grade tumours have distorted architecture but normal/near normal cytology.

Image

Lactational changes

  • AKA secretory change, AKA lactational adenoma, AKA lactating adenoma [4]

General

  • Lactational adenoma generally arises in during or in the few weeks after pregnancy.
  • May be present focally in non-pregnant females.
  • "Lactational adenoma"- circumscribed mass displacing the normal breast architecture (hyperplasia plus functional/physiologic change)
  • "Lactational change"- normal breast tissue architecture preserved (functional/physiologic change).

ASIDE:

  • Some believe lactational change and secretory change aren't the same...
    • Lactational change = only in lactation.
    • Secretory change = other times.
  • This hair splitting is clinically irrelevant-- both are benign. Also, experts use the terms interchangeably.[5]

Microscopic

Features:[6]

  • Glands dilated.
  • Increased number of lobules.
    • Relative decrease in intralobular and extralobular stroma.
  • Luminal cells enlarged.
  • Myoepithelial cells indistinct - after second trimester.
  • Lactational "adenoma" may undergo infarction - Imagine what an infarcted lactational adenoma could look like in a FNA specimen!

DDx:

Images

www:

Major Pathologic Patterns

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.[7]
  • 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

Microscopic

Features:[8]

  • Breast glands with three or four cell layers above the basement membrane.
  • Variable cells.

Note:

  • No nuclear atypia.

DDx:

Apocrine metaplasia

Duct ectasia

  • Dilation of large ducts secondary to luminal obstruction by inspissated secretions
  • Presentation
    • ~age 40-50, possibly with cheesy nipple discharge
  • Pathology
    • Duct lumen dilated and containing foamy macrophages
    • Necrosis/shedding of epithelium
    • If duct rupture: chronic and granulomatous inflammation of periductal region
    • Fibrotic thickening of duct wall

Fibrocystic change

  • AKA fibrocystic changes (abbreviated FCC).

Columnar cell change

Gynecomastoid hyperplasia

  • AKA gynecomastia.

Breast prostheses

Lesions with increased risk of malignancy

Florid epithelial hyperplasia

  • 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.
  • AKA usual ductal hyperplasia, abbreviated UDH.

Sclerosing adenosis

Flat epithelial atypia

  • Abbreviated FEA.

Complex sclerosing lesion

  • AKA radial scar.

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

Phyllodes tumour

  • Previously cystosarcoma phyllodes.

Pseudoangiomatous stromal hyperplasia

  • Abbreviated PASH.
  • AKA nodular myofibroblastic stromal hyperplasia of the mammary gland.[9]

Weird stuff

Like in all niches of pathology... there is weird stuff.

Mammary hamartoma

  • AKA breast hamartoma.

Collagenous spherulosis

Nipple adenoma

  • AKA nipple duct adenoma.
  • AKA nipple adenoma of breast.
  • AKA adenoma of the nipple.
  • AKA florid papillomatosis of the nipple.[11]

Intraductal papilloma

Lymphocytic mastitis

Microglandular adenosis

Not to be confused with microglandular hyperplasia.
  • Abbreviated MGA.

Adenomyoepithelioma

Mammary myofibroblastoma

  • AKA breast myofibroblastoma.
  • AKA myofibroblastoma of the breast.

Squamous metaplasia of lactiferous ducts

  • Abbreviated SMOLD.

Granular cell tumour of the breast

General

  • Uncommon.

Gross

  • May be a spiculated mass and thus mimic malignancy radiologically.[12]

Microscopic

See granular cell tumour.

DDx:

See also

References

  1. MUA. 1 October 2010.
  2. MUA. 1 October 2010.
  3. RS. 4 May 2010.
  4. URL: [Breast_pathology#Lactational_changes Breast_pathology#Lactational_changes. Accessed on: 3 October 2011.
  5. 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.
  6. URL: http://flylib.com/books/en/2.953.1.9/1/. Accessed on: 6 August 2011.
  7. 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.
  8. 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.
  9. 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.
  10. URL: http://surgpathcriteria.stanford.edu/breast/collspher/. Accessed on: 4 September 2011.
  11. Boutayeb, S.; Benomar, S.; Sbitti, Y.; Harroudi, T.; Hassam, B.; Errihani, H. (2012). "Nipple adenoma in a man: An unusual case report.". Int J Surg Case Rep 3 (5): 190-2. doi:10.1016/j.ijscr.2011.05.008. PMID 22342578.
  12. Yang, WT.; Edeiken-Monroe, B.; Sneige, N.; Fornage, BD. (May 2006). "Sonographic and mammographic appearances of granular cell tumors of the breast with pathological correlation.". J Clin Ultrasound 34 (4): 153-60. doi:10.1002/jcu.20227. PMID 16615051.
  13. Tan, PH.; Harada, O.; Thike, AA.; Tse, GM. (Aug 2011). "Histiocytoid breast carcinoma: an enigmatic lobular entity.". J Clin Pathol 64 (8): 654-9. doi:10.1136/jcp.2011.088930. PMID 21398688.

External links