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.
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.
- 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:
- The breast is more dense and thus radiologically more difficult to interpret, and
- The incidence of breast cancer is lower.
Three major specimen types:
- Core needle biopsy (CNB).
- Modified radical mastectomy.
- 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:
- Mass lesion - usu. obvious what is going on; typically 3 levels.
- 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.
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
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
- Nipple adenoma.
- Intraductal papilloma.
- Papillary ductal carcinoma in situ.
- Intracystic papillary carcinoma.
- Intracystic papillary carcinoma with an invasive component.
- Invasive papillary carcinoma.
- 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.
- Glands -- normally has two cell layers (like the prostate).
- Myoepithelial cells
- Frequently spindle-like, often hard to see.
- Secretory cells.
- Myoepithelial cells
- Not cellular.
- Not myxoid.
May be present:
- 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.
- 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).
- Purple globs (with concentric rings) on H&E = calcium phosphate.
- The architecture is more important than the cytologic features in the diagnosis of malignancy in the breast; low grade tumours have distorted architecture but normal/near normal cytology.
- 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).
- 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.
- 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.
- Lactational "adenoma" may undergo infarction - Imagine what an infarcted lactational adenoma could look like in a FNA specimen!
- Lactational changes (gfmer.ch).
- Lactational changes in an angiosarcoma of the breast (webpathology.com).
- Lactating breast (uwa.edu.au).
Major Pathologic Patterns
- 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.
|Streaming, periph. |
or single file
|Ductal lesion||FEHUT||Lobular lesion||Lobular carcinoma||Papillary lesions|
|Two cell layers||One cell layer||<50% of gl.||>50% of gl.|
|Large extent||Small extent|
- 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.
|Atypia or arch. abnorm.|
or cellular proliferation
|High grade atypia||Low grade atypia|
or abnorm. arch.
|>3 mm extent||<3 mm extent|
- Adapted from Mulligan & O'Malley.
- 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.
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
- No increased risk of malignancy.
- Often not reported - as it has no clinical signficance.
- Has to be separated from moderate epithelial hyperplasia / florid epithelial hyperplasia.
- Breast glands with three or four cell layers above the basement membrane.
- Variable cells.
- No nuclear atypia.
- Flat epithelial atypia.
- Moderate epithelial hyperplasia / florid epithelial hyperplasia.
- Atypical ductal hyperplasia.
- Dilation of large ducts secondary to luminal obstruction by inspissated secretions
- ~age 40-50, possibly with cheesy nipple discharge
- 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
- AKA fibrocystic changes (abbreviated FCC).
Columnar cell change
- AKA gynecomastia.
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.
Flat epithelial atypia
- Abbreviated FEA.
Complex sclerosing lesion
- AKA radial scar.
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.
- Previously cystosarcoma phyllodes.
Pseudoangiomatous stromal hyperplasia
Like in all niches of pathology... there is weird stuff.
- AKA breast hamartoma.
- AKA nipple duct adenoma.
- AKA nipple adenoma of breast.
- AKA adenoma of the nipple.
- AKA florid papillomatosis of the nipple.
- AKA papilloma.
- Not to be confused with microglandular hyperplasia.
- Abbreviated MGA.
Squamous metaplasia of lactiferous ducts
- Abbreviated SMOLD.
Granular cell tumour of the breast
- May be a spiculated mass and thus mimic malignancy radiologically.
- See granular cell tumour.
- 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.
- 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.
- URL: http://surgpathcriteria.stanford.edu/breast/collspher/. Accessed on: 4 September 2011.
- 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.
- 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.
- 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.