Breast pathology

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:

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

Normal histology

• 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 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".

Image:

• Breast with calcifications (breastpathology.info).

Notes:

• 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.

Where to start...

The following entities are a starting point for understanding routinue breast pathology & some of challenges in breast pathology:

1. Apocrine change.
   • Pink benign cells.
2. Columnar cell change.
   • Columnar cells with blebs ("snouts") - often have calcifications (purple).
3. Fibroadenoma.
   • Abundant myxoid (light/blanched) stroma - very common.
4. EHUT (epithelial hyperplasia of the usual type).
   • Too many cells in a duct, cells overlap & form slit-like spaces.
5. DCIS (ductal carcinoma in situ).
   • 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.
6. Invasive ductal carcinoma.
   • Bread & butter cancer - in sheets or glands.
7. Lobular carcinoma.
   • Dyscohesive cells - can easily be missed.
8. 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.

Diagnoses overview

• Normal.
• Benign.
  • Columnar cell change.
    • Calcification often in lumen.
• Neoplastic.
  • Benign neoplastic:
    • Epithelial/myoepithelial - intraductal papilloma.
    • Stromal - fibroadenoma, benign phyllodes.
  • Malignant neoplastic:
    • Epithelial/myoepithelial - most common, e.g. ductal carcinoma.
    • Breast stroma - malignant phyllodes tumour.
    • Stromal, e.g. angiosarcoma - rare.

A tree diagram (overview)

General classifcation

Breast pathology

Stromal pathology

Glandular pathology

Myxoid

Long slit-like spaces

Simple epithelium

Dilated

Cellular lesion

Fibroadenoma

Malignant features

Benign features

Tubular carcinoma

FEA, FCC, CCC

EHUT, Neoplastic, Malignant

Malignant phyllodes

Benign phyllodes

Notes:

• Most of the problems in breast pathology are in: the Simple epithelium category and the Cellular lesion category.
• Neoplastic includes: ADH, and LDH.
• Malignant includes: DCIS, LCIS, ductal carcinoma (DC) and lobular carcinoma (LC), papillary lesions.
• Lobular carcinoma (a pitfall) may appear to be a stromal problem, i.e. the stroma looks too cellular.
• Sarcomas and lymphomas are not included here; both of these are very rare in the breast.

Cellular lesions

Cellular lesions

Equal spacing, punched-out

Streaming, periph. slit-like spaces.

Discohesive cells, expanded gl.

Single cells or single file

Fibrovascular cores

Ductal lesion

EHUT

Lobular lesion

Lobular carcinoma

Papillary lesions

Two cell layers

One cell layer

<50% of gl.

>50% of gl.

Ductal non-inv. neoplasm

Ductal carcinoma

LDH

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....

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

EHUT in papilloma

>3 mm extent

<3 mm extent

DCIS in papilloma

ADH in papilloma

Notes:

• 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.
• EHUT = epithelial hyperplasia of the usual type.
• extent refers to the size of the abnormal cell population within the papillary lesion.

Non-invasive breast cancer

Main article: Non-invasive breast cancer

This includes the in situ lesions - DCIS and LCIS.

Invasive breast cancer

Main article: Invasive breast cancer

This is includes descriptions of the usual types... and the not so common ones.

Benign

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 epithelial hyperplasia of the usual type (EHUT) - instead of - benign breast tissue.

Apocrine metaplasia

Histology

• Eosinophilic cytoplasm.

Note:

• Apocrine changes, i.e. cytoplasmic eosinophilia, can appear in malignant tumours; eosinophilia doesn't make it benign.

Etiology

• Increased number of mitochondria.
  • In other body sites this has different names, e.g. Hurthle cell change (thyroid), oncocytic change (kidney - oncocytoma, thyroid).

Significance

• Not significant. Can be considered to be pretty wallpaper in the house of breast pathology.

Columnar cell change

Histology

• 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 +/-eosinophilic.

DDx:

• Flat epithelial atypia (>2 cell layers)

Importance

• Columnar cell change is associated with (benign) calcification.

Flat epithelial atypia

Epidemology

• Associated with LCIS.

Microscopic

• Hypercellular gland -- several layers.
• Columnar cell morphology.
• +/-Apical snouts.

DDx

• Columnar cell change.

Sclerosing adenosis

General

• Can be scary... can look like ductal carcinoma.
• Derived from sclerosing (hardening) and adenosis (glandular enlargement)
  • Think scaring + lotsa glands and you're pretty close.

Histology

• Acini are smaller than usual and there are more of them.
  • Acini should be in lobular arrangements, i.e. in groups.
  • Acini should be round.
  • Acini should have two cell layers - like good breast glands do.
• Fibrosis (scleroses) - pink on H&E surrounds the acini.
  • Can mimic a dysmoplastic reaction.

Radial scar

• AKA complex sclerosing lesion.
• May appear malignant on imaging.
• Associated with subsequent elevated risk of breast cancer.

Microscopic

Feature:

• Hyaline is the key.
  • May mimic a desmoplastic reaction of stroma -- leading to a misdiagnosis of malignancy.

Fibroadenoma

General

• Very common benign finding.

Management

• Local excision.

Histology

• 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.

• Juvenile variant.
  • Typically younger patients.
  • "looks more malignant" - more mitoses, more atypical nuclei.

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.

Phyllodes tumour vs. fibroadenoma

Histo. 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.

Epi.:

• Phyllodes = older patients (usually)

Tx:

• Wide excision (vs. local excision for fibroadenoma)

Ref.:

Phyllodes tumour

Names comes from the word "leaf", with imagination it may look like one (the epithelial component = the veins of the leaf)

Clinical

• Wide excision -- this differs from fibroadenoma (just local excision)
• Approximately 6% are malignant

Gross

• Clefts, leaf-like structures - friable vis-a-vis a fibroadenoma.

Microscopic

• Large slit-like spaces.
• Cellular stroma that may be myxoid.
• +/-Mitoses.
• May have "malignant border" -- "pushing border" / "infiltrative border".

Malignant phyllodes?

Features of malignancy:

• Stromal cellular atypia.
• Mitotic activity in 10 HPFs.
• Stromal overgrowth -- epithelial elements absent in one low power field (x40).

A comparison between benign and malignant phyllodes - adapted from Taira et al.

	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

• Often abbreviated PASH.
• Benign lesion.
• Thought to arise due to myofibroblast abnormality - though not well understood.

Gross

Features:

• May form mass: grey-white & firm, with well circumscribed borders.

Microscopic

Features:

• Complex inter-anastomosing channels.
• May mimic angiosarcoma at low power; PASH may have the same architecture but lack nuclear atypia.

IHC

Findings:

• CD34 +ve.
• Vimentin +ve.
• Factor VIII -ve.

Breast radiology

BI-RADS = Breast Imaging Reporting And Data System

• 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.