Breast: Normal Histology Benign Disease Flashcards Preview

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Basic anatomy of breast + lymphatic drainage

  • The breast contains 6-10 major ductal systems.
  • Males have ducts but no acini (nor do girls before puberty)
  • Lymphatic drainage of the breast: axillary, supraclavicular & mediastinal lymph nodes  
  • Cancer is most common in the upper outer quadrant of the breast, which generally drains to the axillary nodes, which is why the axillary nodes are commonly the sentinel nodes for metastasis.


 What is the terminal duct-lobular unit, (TDLU)?



TDLU: terminal duct (smallest duct division) and the surrounding acini that drain into it. Functional unit of the breast.


Histology of epithelial components of breasts

  • Epithelial Components: 2 types of breast epithelium:
  • Keratinizing squamous epthielium
    • Most superficial layer which “dips into the orifices at the nipple”
    • Becomes the double-layer cubiodal epithelium
  • Double-layered cuboidal epithelium line the ducts (columnar)
    • 2 cell types:
      • Myoepithelial cells (MEC)
      • Luminal epithelial cells
    • more than two cell layers = abnormal.
    • Vacuolization of the cuboidal cells =  filling with milk.


Histology of stromal components of breasts

  • Stromal components: 2 types of breast stroma
  • Interlobular stroma → dense fibrous connective tissue admixed with adipose tissue
  • Intralobular stroma → envelopes acini of the lobules
  • Contain hormonally responsive fibroblast-like cells admixed with lymphocytes


Histologic appearance of resting breast

*as previously described*


Histologic appearance of breast during pregnancy/lactation

  • Maximum stimulation, epithelial
  •   vacuolization, secretion in lumina
  •  Pregnancy → ↑ terminal ducts
  •    (lobules)
  •  Lactation → ↑ acini draining to
  •   terminal ducts



Histologic appearance of post-emnopausal breast

Involution of TDLUs, acini atrophy Duct system remains

↑ interlobular fat & stroma

↓ intralobular fat & stroma



Basic breast-related changes throughout life

  • Puberty → stimulation by  E and P
  • Menstrual cycle → ↑ size/nodularity; luteal phase → ↑ tubules + acini
  • Pregnancy/lactation → maximum stimulation, epithelial vacuolization, secretion in lumina
  • Cessation of lactation → involution in 3 months
  • Post-lactation → ↓ lobules but overall there remains a permanent ↑ in size + number of lobules compared to pre-pregnancy


Congenital anomalies of breasts

  • supernumerary nipple / breasts
  • accessory breast tissue
  • congenital inversion of nipples



Characteristics of supernumerary nipples/breasts

  • Supernumerary (extra) nipple/breast = accessory breasts or nipples
  • During development human females get early breast development all the way down the sides of the anterior torso. These generally are reasorbed, but occasionally some of the tissue remains.
  • This can cause some worries → ie., a growing lump in the axilla during pregnancy.
  • Fine needle biopsy can distinguish ectopic breast tissue from cancer.
  • People with an inherited tendency towards breast cancer can get breast cancer in odd locations, as well.


Characteristics of congenital nipple retraction/inversion

Can be unilateral or bilateral, is generally normal.

Acquired nipple inversion, by contrast, is often a late sign of breast cancer.


Characteristics of hypertrophy of breast tissue

Juvenile hypertrophy (virginal hypertrophy): super-normal increase in size of the breasts, usually during puberty

Can be unilateral or bilateral.


Etiology unclear.

Often treated with breast reduction surgery.


Characteristics of gynecomastia

Gynecomastia → Enlargement of one or both breast in a male

Most common benign lesion in men

On histology you see large duct structures and lots of interlobular stroma.

Many cases idiopathic but can be due to an increase in estrogen.

Most often occurs at puberty and is self-limited; can be due to drug use.


Types of benign inflammatory breast lesions

  • acute mastitis and abscess
  • chronic mastitis
    • + mammary duct ectasia
    • + plasma cell mastitis
    • + granulomatous mastitis
  • periductal mastitis
  • fat necrosis


Characteristics of Acute mastitis/abscess

  • Acute inflammation of the breast, often with abscess. Often young women at onset of lactation
  • Painful, tender. Due to cracking of skin that allows entry of bacteria → Staph a.  
  • If untreated abscesses can cause fistulas with the skin.
  • Differential dx: inflammatory carcinoma
  • Rx: antibiotics, drainage of pus
  • If doesn’t respond to antibiotics get a biopsy


Characteristics of Chronic mastitis

  • Plugged ducts (which get distended) that become inflamed (it's sterile, however) → perimenopausal women
  • Uncommon
  • Fibrosis generally results post-inflammation → painless, firm, fixed mass, which mimics the findings of breast cancer
  • Not associated w/ bacterial infection
  • + MDE = Obstruction of the lactiferous ducts → Dilation of ducts
  • + PCM = Predominantly plasma cells
  • + GM = Inflammatory response that includes numerous foamy histiocytes & fibrosis


Characteristics of Periductal mastitis

  • Painful erythematous subareolar mass that looks like an infection → sometimes men too
  • 90% afflicted are smokers (Vitamin A deficiency??)
  • Not associated with lactation, reproductive history, age.
  • If recurrent → a fistula can develop and tunnel under smooth muscle of the nipple and open at the areolar edge
  • Inverted nipple common (due to underlying inflammation)


Characteristics of fat necrosis


Often follows trauma or ischemia to breast; causes necrosis → produces a PMN/macrophage/fibrosis process. Causes a hard, irregular mass that can be mistaken for cancer.


Characteristics of fibroadenoma


Solitary, discrete, well circumscribed, mobile benign mass of proliferating ducts (adenoma) in proliferating fibroblastic stroma (fibro)

Most common benign neoplasm of the breast.

Round, sharply demarcated, rubbery, mobile, 2-4 cm, usually solitary.

Usually found in young women; not associated with risk of malignancy.

They arise from the terminal duct-acini and are a mixture of stroma and ducts → ducts still have a 2-cell layer.

Growth ↑ during pregnancy.


Characteristics of lactating adenoma

A fibroadenoma with lots of ducts and not a lot of epithelium.

Generally occurs in lactating women

Doesn't seem to cause problems with lactation.

Probably not true neoplasms but exaggerated focal response to hormonal influences


Characteristics of intraductal papilloma


Growth inside a duct composed of fingerlike extensions (papillae) with fibrovascular core.

Benign (2 cell layers are intact), but can cause bloody nipple discharge

Bloody discharge can be confused with cancer → in papillomas, basal membrane is intact and there is no atypia, unlike papillary carcinomas


Characteristics of phyllodes tumor


Fibroadenoma-like tumors with way too much stroma

Often get very large, > 4 cm up to 16 cm and fleshy

"Leaflike" appearance on histology.

Mostly benign, sometimes malignant → larger or more mitotically active ones → can metastasize

Have to differentiate betw/ benign & malignant when describing the tumor



Characteristics of fibrocystic change

Fibrocystic change is related to cancer risk, so upon biopsy make sure you get to know exact type of change.

Can present in several ways: as single cyst, diffuse cysts, or diffuse cysts with a dominant lump

Fibrocystic change is the preferred terminology because not necessarily associated with disease


Characteristics of blue-dome cysts

Blue cysts (due to retained fluid) that develop from acinar structures in the TDLU. Usually unilobular.

Tends to be associated with fibrotic changes.

Generally asymptomatic, occasionally painful.

Fine-needle aspiration tends to resolve it.

Fairly common

Occasionally pre-malignant → associated with more than 2 cell layers of epithelium.


Characteristics of apocrine metaplasia

Essentially the secretory cells of the breast turn into sweat-secreting (apocrine) cells.

No specific gross features.

Most frequently in epithelial lining of cysts.

Abundant cytoplasm → indicative of benign

Protruding and granulated → “snouts” or “blebs”



Characteristics of sclerosing adenosis

Fibrosis without ducts; palpates as a firm, irregular mass that mimics cancer.

Histology: proliferation of ductular structures & stroma with distortion of the TDLU → this may look like cancer (compression of epithelium by fibrosis makes them look like solid cords of cells).

Multiple lobules may be seen.

See diffuse microcalcifications → also mimic cancer.

Slight risk of malignancy.


Proliferative vs. non-proliferative fibrocystic change

  • Both have cysts & fibrosis but only proliferative have hyperplasia
    • Proliferative (pre-malignant) has more than 2 epithelium cell layers (epithelial hyperplasia).
    • Common theme: an increase in the number of epithelial cell layers in the terminal ducts is almost always malignant.
    • Some fibrotic change is part of the normal aging process.
  • Non-proliferative
    • Identifying non-proliferative → look for two epithelial layers lining duct, in proliferative there are > 2.
    • Blue-dome cysts & apocrine metaplasia → non-proliferative
  • Proliferative: 2 kinds of hyperplasia: lobular & ductal 


Usual ductal hyperplasia vs. atypical hyperplasia

  • Spectrum of ductal hyperplasia changes: usual hyperplasia → atypical hyperplasia → carcinoma-in-situ
  • "Usual:" no atypia.
    • Mild hyperplasia  → minimal risk (1x)
    • Mod. hyperplasia → slightly ↑ risk (1.5-2x)
    • Florid hyperplasia  → slightly ↑ risk (1.5-2x)
  • Atypical: some (< 50% of ducts) atypia.
    • Mini-ducts form inside lumen.

    • Lots of acini filled with epithelium.

    • Nuclear/cytologic changes in cells.

  • Carcinoma in situ: lots (> 50% of ducts) of atypia.


Characteristics of atypical lobular hyperplasia

Lobular: ↑ cells within lobules → Atypical Lobular Hyperplasia (ALH) or Lobular Carcinoma In Situ (LCIS)

ALH = < 50% lobules filled & distended by epithelial proliferation → moderate risk (4-5x)

LCIS = > 50% lobules filled & distended by epithelial proliferation → high risk (8-10x)

LCIS is a marker for ↑ risk of developing invasive carcinoma.  Risk is equal for both breasts & subsequent carcinoma may be either ductal or lobular.