BREASTBREAST

LYMPHATIC DRAINAGE

AXILLARY (MOSTLY)

INTERNAL MAMMARY

SUPRACLAVICULAR

L

O

B

E

LOBULE

NORMAL lobule

One single

ACINUS(alveolus)

Epithelial cells

MYO-epithelial cells

Histology of the Normal Breast

Terminal duct

Lobular unit

Intralobular stroma

Interlobular stroma

Ductal CarcinomasArise Here

Lobular CarcinomasArise Here

Terminal Duct Lobular Unit

Epithelium

Myoepithelium

Immunostain for Smooth Muscle Actin

Epithelium

Myoepithelium

THREE NORMAL PHASES

• ACTIVE: about 50-50 Gland/Stroma ratio

• LACTATING: Mostly Glands (like

thyroid!!!), >>>50/50

• ATROPHIC: mostly stroma, <<<50/50

Pregnancy/Lactation

Prominent nucleoli

Lactational Change

post menopausal

QUIZ ???

BREAST PATHOLOGY

• DEVELOPMENTAL:• DEGENERATION:• INFLAMMATION:• NEOPLASM:

DEVELOPMENTAL

• MILKLINE REMNANTS• ACCESSORY (axillary) BREAST

TISSUE• NIPPLE INVERSION• MACROMASTIA

accessory nipples.

ACCESSORY

(axillary)

BREAST

TISSUE

Nipple retraction 1) CONGENITAL

2) ACQUIRED: CARCINOMA

3) ACQUIRED: PIERCING

Macromastia.

INFLAMMATION

• Acute Mastitis, staph most common• Duct-Ectaia, Periductal• Fat Necrosis, usually trauma• Lymphcytic, i.e., diabetic• Granulomatous, sarcoid, TB, etc., but

mostly idiopathic

ACUTE MASTITIS

Pap smear of nipple exudate

DUCTESIA

Ductesia CYSTS

Fat necrosis

FAT NECROSIS

FAT NECROSIS

FAT NECROSIS

LYMPHOYCYTIC MASTITISLYMPHOYCYTIC MASTITIS

(DIABETIC MASTOPATHY)(DIABETIC MASTOPATHY)

GRANULOMATOUS MASTITIS

GRANULOMATOUS MASTITIS

Fibrocystic Changes

Non-proliferative epithelium:

(cysts, fibrosis, adenosis). Proliferative (epithelial hyperplasia), without

atypia;• Mild epithelial hyperplasia,

• Moderate epithelial hyperplasia

• Florid epithelial hyperplasia Proliferative with atypia; (= CIS)

• Atypical epithelial hyperplasia.

Sclerosing adenosis.

CLINICAL PRESENTATIONS

•MASS,

palpable or mammographic

• NIPPLE DISCHARGE• PAIN

CYST

Blue dome cyst

FIBROSIS + CYSTS = FIBROCYSTIC DISEASE

FIBROCYSTIC DISEASE

CUBOIDAL

COLUMNARRED COLUMNAR

i.e. “APOCRINE”

ADENOSIS ↑ acini/lobule

CYST, GROSS

CYST, MICROSCOPIC

Duct hyperplasia & Periductal inflammation

Normal acinusNormal Duct

Intraductal Hyperplasia

• Definition: An increase above the normal, 2-cell layer thickness– Mild hyperplasia: 3-4 cell layers thick– Moderate hyperplasia: with epithelial

tufting and bridging– Severe (florid) hyperplasia: filling and

distending ducts

Proliferative Fibrocystic Change WITH Atypia

• Atypical Intraductal Hyperplasia• Atypical Lobular Hyperplasia

Epithelial Hyperplasia

papillary simple hyperplasia

(Ductal papillomatosis)

Moderate hyperplasia

Florid hyperplasia

FEATURES OF “ATYPIA”

• LOSS OF STROMA BETWEEN ACINI

• “SWISS CHEESE” HYPERPLASIA*

• CRIBRIFORMING**

• CELLULAR PLEOMORPHISM

• CELLULAR HYPERCHROMASIA

• INCREASED/ABNORMAL MITOSES*

• “ROMAN” BRIDGES***

• NECROSIS*** (“COMEDO-carcinoma”)

Ductal hyperplasia, Florid atypical

Epithelial Hyperplasia

Ductal hyperplasia

“SCLEROSING” ADENOSIS

Easy mistaken for ca.

SCLEROSING ADENOSIS

(RADIAL SCAR)

“SCLEROSING” ADENOSIS

NEOPLASIA

• Benign epithelial• Fibroadenoma• Intraductal papilloma

• Benign stromal• Benign Phyllodes tumor

• Premalignant• Malignant epithelial (adenocarcinomas )• Ductal, lobular• in-situ, infiltrating

• Malignant stromal• Malignant Phyllodes tumor (

Fibroadenoma

Homogeneous lesion with well circumscribed border

Fibroadenoma (Benign Biphasic Tumor)

Fibroadenomas will “shell out” at surgery

Fibroadenoma

Cleft

Fibroadenoma

FIBROADENOMA

Branching compressed ducts

Homogeneous stroma

Fibroadenoma

FIBROADENOMA

PAPILLOMA

Most papillomas arise in larger mammary ducts

Intraductal papilloma

Intraductal papilloma

Duct lining

Stalk

PAPILLOMA

PAPILLOMA

Relative Risk for Invasive Carcinoma Based on Histologic Evaluation of Breast Tissue Without Invasive Carcinoma

• NON-Proliferative Fibrocystic Changes (1X, No increased risk) – Small simple cysts, apocrine metaplasia, mild epithelial hyperplasia

• Proliferative Fibrocystic Changes (1.5-2X, Slight increased risk) – Moderate to florid hyperplasia– Sclerosing adenosis– Intraductal papilloma– Fibroadenoma

• Proliferative Fibrocystic Changes WITH ATYPIA (3-5X, Moderate increased risk)– Atypical ductal hyperplasia– Atypical lobular hyperplasia

• Carcinoma IN SITU (8-10X, HIGH RISK)– Ductal carcinoma in situ (DCIS)– Lobular carcinoma in situ (LCIS)

Atypical hyperplasia with family history or in a premenopausal woman has a risk of invasive carcinoma similar to DCIS

Relative Risk of Invasive Breast Carcinoma

Phyllodes Tumor

Note the size!

“Leaf-like” architecture

Increased mitotic activity

Malignant Phyllodes Tumor < 15%

6. Breast Cancer Pathology

In Situ CarcinomasInvasive CarcinomasSpecial Subtypes

FEATURES OF “ATYPIA”

• LOSS OF STROMA BETWEEN ACINI

• “SWISS CHEESE” HYPERPLASIA*

• CRIBRIFORMING**

• CELLULAR PLEOMORPHISM

• CELLULAR HYPERCHROMASIA

• INCREASED/ABNORMAL MITOSES*

• “ROMAN” BRIDGES***

• NECROSIS*** (“COMEDO-carcinoma”)

NORMAL DUCT NORMAL ACINUS

ATYPICAL HYPERPLASIA of DUCT ATYPICAL HYPERPLASIA, LOBULE

DCIS

Comedo type

DCIS

Cribriform type

DCIS

DCIS, microcalcifications

DCIS, microcalcifications

DCIS, ROMAN BRIDGES

NORMAL lobule

LCIS

5. Breast Pathology Specimens

Surgical Procedures to Sample Breast Lesions

Fine Needle Aspirate Biopsy of the Breast

• Analogy- predicting the picture of a completed puzzle by examining the unassembled pieces

• May be the initial evaluation of a palpable mass• Advantages over open biopsy:

– Fast– Cost effective– May eliminate an unnecessary procedure

• Disadvantages:– False negatives and false positives

Fine Needle Aspirate Biopsy of the Breast

• Benign Breast Cytology- – Cohesive groups of uniform ductal epithelial

cells without atypia

• Malignant Breast Cytology-– Poorly cohesive cells with atypia

(pleomorphism, enlarged nuclei, large nucleoli, mitotic activity)

– May see necrosis

• The “Triple Test”:– Clinical picture– Mammographic findings– Cytologic findings

Fine Needle Aspiration (FNA)

FNA Cytology Smear Specimen

Fine Needle Aspiration: Benign Ductal Epithelium Versus Breast Cancer

Needle Core Biopsy

Paget disease

Paget disease of the breast

Extramammary Paget disease

Invasive carcinoma

Invasive ductal carcinoma

Invasive lobular carcinoma

Tumor grade

• HISTOLOGY– Glands– Nuclei– Mitosis

• CYTOLOGY– Nuclei

• Size• Membrane• Chromatin• Nucleoli

Nuclear grade 1-3Good correlation with histologic grade