25 terms

Lecture 9 - Benign Breast

What are the normal histological features of the breast?
Duct and lobules lined by two cell types:
-lumincal epithelial cells: secretory function
-myoepithelial cells: structural support and contractile
-basement membrane: support
-dense fibrous tissue, adipose tissue, fibroblast, scatter lymphocytes
What cause the changes of the breast during and after puberty?
In prepubertal breast in males and females, the large duct system ends in terminal ducts with minimal lobule formation. Changes in breast are most dynamic and profound during reproductive age.

Cyclical estrogen and progesterone secretion induces growth of the ducts such that they elongate and acquire a thickened epithelium.

Differentiation of hormonally responsive periductal stroma occurs.

Lobules formation at the ends of terminal ducts.
What are the changes that take place during the menstrual cycle?
Effects of cyclic hormonal changes are manifested clinically by fluctuations in breast size and texture.

Follicular phase: stroma -dense and collagenized; epithelium - only one layer evident
Luteal phase: stromal edema; epithelium - 2 layers evident; luminal secretion; maximum size, nodularity, and sensitivity

Proliferative epithelial changes and stromal edema is greatest in the 2nd half of the cycle where it has its maximum size, nodularity, and sensitivity.

***Examine breasts during the 1st half of the cycle - proliferative/follicular b/c quiescent then
What are the changes that take place during pregnancy?
The breast is completely mature and functional upon onset.
-increase in size and number
-fully differentiation and functional activity
-marked lobular expansion, extensive secretory change
-More pronounced areolar pigmentation, dilation of superficial cutaneous veins

Regression and atrophy following cessation of lactation
-full regression to teh pre-pregnancy state does not occur, some increase in the number and size of lobules remains
What are the changes that take place during menopause?
•Ducts & lobules undergo atrophy & there is shrinkage of the interlobular & intralobular stroma, eventually lobules regress markedly
•Extent of lobular atrophy varies w/ available estrogen levels - regress w/ lack of estrogen
•***Dense interlobular stroma of young women is replaced by fat - therefore, increased sensitivity of the mammogram in older women so don't do it younger than 40 when cannot detect it well
Milk Line
Milk line:
-Bilaterally from the mid-axillae through the normal breasts then inferior to the medial groins.
-Embryological milk line goes complete atrophy accept for short segment at pectoral region to give rise to normal breast

Persistence of milk line:
-heterotopic breast tissue
-supernumerary nipples or breasts
Fat Necrosis
Mammogram reveal spiculated, poorly defined mass with calcifications - mimic cancer

-Localized necrosis of fat tissues
-Related to trauma, 32%
-Mimics cancer clinically
-Histologic features depend on stage; necrotic fat surrounded by foamy macrophages, giant cells, fibroblasts and fibrosis; +/- Ca2+
Duct Ectasia
Nonproliferative Breast Change
Dilated ducts with inspissated secretions; epithelial degeneration and periductal chronic lymphocytic reaction.

Clinically: intermittent nipple discharge: clear
Multiparous women, 40's to 50's
Clinically mimics cancer
Acute Mastitis
Infection or abscess of the breast that is a result of breast feeding
Periductal Mastitis
Recurrent subareolar abscess

SMOLD- squamous metaplasia of lactiferous ducts - Zuska disease; keratinizing squamous metaplasia of the nipple duct; intense Cl and granulomatous inflammation; secondary infection

Requires surgical intervention.
Lymphocytic mastopathy
Palpable mass; type 1 DM and autoimmune disease; collagenized stroma surround atrophic lobule with Cl
What are some Nonproliferative Breast Changes and whats is the associated risk for developing Breast cancer?
Duct ectasia
Cysts - can be filled with secretion
Apocrine metaplasia/change
Adenosis - A disease of a gland, especially one marked by the abnormal formation or enlargement of glandular tissue.
What are some Proliferative Diseases without atypia and whats is the associated risk for developing Breast cancer?
Usual hyperplasia
Sclerosing adenosis
What are some Proliferative Diseases with atypia and whats is the associated risk for developing Breast cancer?
Atypical ductal hyperplasia (ADH)
Atypical lobular hyperplasia (ALH)
Epithelial Hyperplasia Usual Type
More than 2 cell layer of epithelial cells
Heterogenous cells with irregular spaces
Usually incidental

•Affects ducts and/or lobules
•Usually not mass forming
•May be associated w/ cellular and/or architectural atypia
Proliferative Diseases without atypia
Fibrovascular cores extend into duct lumens, covered by epithelium.
Epithelium can have epithelial hyperplasia, apocrine metaplasia, sometimes have atypia or DCIS.
Nipple discharge.

•Branching papillae w/ fibrovascular cores covered by layers of epithelial & myoepithelial cells, dilated duct
•Distinct from small duct papillomas - solitary, involve lactiferous ducts, nipple discharge
•Probably no increased cancer risk
➢ May look very atypical - malignant counterpart usually arises de novo
•Age range 30-50
Sclerosing Adenosis
Increased number of acinar - distorted and compressed.
May be present with other follicular center cells or form a mass by itself.
Palpable mass, imaging density, calcificaiton or mass mimic invasive carcinoma

•Typical swirling pattern w/ some slightly dilated & some compressed glands
•Still myoepithelial cells - which help distinguish it from cancer
Radial Sclerosing Lesion/Complex Sclerosing Lesion
Radiographic show irregular central mass with LONG PROJECTIONS
CSL: sclerosing adenosis, papilloma, epithelial hyperplasia
Nonproliferative Breast Changes
•Increased number of acini in a lobule, dilated lumens
•Changes are often mixed, multifocal, bilateral, mass forming
•No increased risk for developing carcinoma
Small duct papillomas*
•Distinct from large duct papillomas
•Multiple - many areas in breast, many diff ducts can be affected
•Involve small ducts, no nipple discharge b/c ducts further away from nipple
•Fibrovascular cores extend into duct lumens, covered by epithelium
•Core composed of fibrous tissue & vessel
Atypical ductal hyperplasia
Proliferative Diseases with atypia
-Seen in 5-17% of biopsies for calcification.
-Cellular proliferation resembling DCIS but quantitative and qualitative insufficient.
-Monotonous cells forming complex architecture: cribiform, micropapillary, etc.
-Harbor acquired genetic loss or gain present in DCIS
Atypical lobular hyperplasia
Proliferative Diseases with atypia
Usually incidental, cytologic like Lobular Carcinoma In Situ but only partially involving a lobular unit.
Atypical vs. Non-atypical
Non Atypical
Non clonal proliferation
Architecture features:
- Irregular, peripheral fenestration
- Streaming or whirling

Cytological features:
- Heterogenous
- Variation in size and shape of the cells/nuclei
- Indistinct cell margins

ADH/DCIS is clonal
Architecture features:
- cribriform architecture with round and "punch out" spaces
- Ridged bars or arcades; roman bridge
- Solid

Cytological features:
- Monotonous: uniform nuclei,
evenly spaced
- distinct cell borders
-Most common benign tumor; age 20-30
-Hormonal responsive, increasing during pregnancy, can be complicated by infarction.
-Oval, white, rubbery, MOBILE mass.
-Well circumscribed, sharply demarcated from surrounding tissue.
-Hyalinized or myxoid stroma compress epithelium

-Arise from intralobular stroma of the TDLU involved (TDLU = Terminal duct, lobular unit)

Histology: stretched of ducts, can be shelled out - don't see any benign breast tissue so likely excised entirely
•Most common clinical & pathological abnormality of the male breast - newborns & adolescents

•Localized or diffuse, tender, asymmetric area of firmness & enlargement - unilateral or bilateral

•Associated w/ hyperestrogenism, meds, certain extramammary carcinomas

•Associated with high estrogen - chronic renal failure, meds, carcinomas such as lung cancer, testicular germ hormone producing tumors

•Histo: proliferation of epithelium in ducts w/ periductal edema (lighter area around duct) w/ some inflammation but lacking lobules/acini

•Can only develop ductal cancer in men, not lobular carcinoma b/c lack lobules