Pathology 10am - Angelfire



Pathology 10am and 11am Scribe fools: Eric Chan

Dr. Kaye and Joe Roman

Breasts

Scribe note: Dr. Kaye followed her notes very closely. She only lectured for an hour.

I. General comments

• The most important thing about breasts is the presentation of the breast mast and how to form a differential diagnosis of breast

• Abnormal mammogram can occur without a palpable lesion

• Being able to recognize the lesions grossly and microscopically, and the diagnostic techniques

II. Breast Anatomy

- Modified sweat gland covered by skin and subcutaneous tissue

- Resting mammary gland consists of 6-10 major duct systems which empty at the nipple and then are divided into lobules

- Each lobule consists 10 to 100s alveoli or acini

- The morphofunctional unit of the breast is composed of two units

- Terminal duct lobular unit (TDLU)

- consists lobule and smaller terminal ductules

- together empty into the segmental duct, then the lactiferous sinus, then the collecting duct

- (histological slide shown lobular unit, acini, terminal ductules)

- Large collecting ducts

- Most of the breast stroma consists a loose connective tissue, adipose tissue, elastic fibers that support the larger ducts (interlobular stroma)

- However each lobule is surrounded by the intralobular stroma (hormonal responsive stroma)

- Blood supply of the breast is predominantly from the internal mammary artery and lateral thoracic artery

- Lymphatic drainage is a valveless unidirectional flow from superficial to deep

- Majority of lymphatic drainage is to axillary nodes, 97%

- 3% going to internal mammary chain

III. Physiological changes in the female breast

o Growth related to puberty

o Changes associated in menstrual cycle

o Changes due to pregnancy and lactation

o Changes seen in old age

o At birth, breasts consists of primary mammary ducts clustered around the nipple

o With onset of puberty, there is enlargement (ages 9-13), proliferation and branching of the lactiferous ducts

o The hallmark of puberty is the development of the lobule

o With pregnancy, you see more proliferation of the duct structures and lobular development

o In 1st trimester, the breasts are largely under the influence of estrogen

▪ There is ducts sprouting and lobular development

o In 2nd trimester, more of a progesterone influence

▪ the corpus luteum is maintained and it secretes estrogen and progesterone

▪ the placenta secretes hcG

o 3rd trimester, colostrum is accumulating in the acini

o 4-5 days postpartum lactation begins with hypothalamus decreases its secretion of prolactin inhibitory factor

o Pituitary secretion of prolactin occurs which converts mammary epithelial cells to the secretory state

o During lactation the stromal to epithelial ratio is greatly reduced (not much of stroma, breasts consists mostly of lobules)

IV. Congenital anomalities

- Amastia- absence of one or both breasts (rare)

- Athelia- absence of the nipple (rare)

- Supernumerary breast- more than 2 breasts occurring on the milk line (most common)

- Supernumerary nipple- more than 2 nipples on the milk line

- Sometimes confused with a nevus

- Congenital inversion of the nipples

- Can be a problem in nursing

- Usually corrects from growth in pregnancy

- Virginal hypertrophy- one or both breast can be enlarged

- due to highly sensitivity to estrogen

- great amount of lobule formation and fibrous tissue sometimes requiring reduction

mammoplasty

- Gynecomastia- enlargement of the male breast

- can occur with a variety of dissimilar conditions

- most commonly seen in cirrhosis of liver because of decrease metabolism of

estrogen

- excisional biopsy is done to rule out carcinoma

- grossly it looks like a hockey puck

- microscopically there is proliferation of epithelium around the ducts (epithelial

hyperplasia) and increase stroma

- no lobules, just ducts

- also seen in Kleinfelter’s syndrome

- Axillary breast tissue

- Breast tissue can extend into the axilla and can enlarge during the menstrual cycle, lactation and pregnancy

- Can be mistaken for lymph node, lipoma, or carcinoma

- Often a biopsy is required to rule out carcinoma

- Important to a surgeon when removing breast tissue to make sure to remove any breast tissue that is present in the axillary also

V. Inflammatory Breast Processes (not common in general)

• Acute mastitus (most often see)

o associated with pregnancy (postpartum state) during lactation

o a cracked or fissured nipple allows bacteria to enter the breast tissue

o breast become swollen, painful, and red

o can have a single abscess or multiple

o usually unilateral

o Periductal mastitis

o painful subareolar mass

o keratinizing squamous epithelium extends down to abnormal depth into the lactiferous ducts causing a buildup of kertinatious debris

o it can later rupture causing inflammation

o it can be managed just by removing the duct

o 90% of women are smokers who have this condition

• Mammary duct ectasia

o occurs in older women, 5th or 6th decade, usually in multiparous woman

o painless periareolar mass with thick cheessy or bloody nipple secretion

o dilation of ducts with necrotic debris in the duct

o can lead to a mass, or a nipple retraction that can be confused with carcinoma

• Fat necrosis

o dimpling of the skin

o post traumatic (only 50% will tell you they remember they had trauma in the area)

o obese pendulous breasts are more prone to the trauma

o have to determine if carcinoma or fat necrosis because carcinoma can present with skin dimpling

o early signs are hemorrhage

o as the lesion heals on the mammogram, get calcifications around the rim and fibrosis

▪ can look like an egg shell

o the fat vacuoles coalesce to larger fat vacuoles

o it is trauma to the fat cells

o have macrophages that go in between fat cells and get rid of all the debris from necrotic fat

o classically, you see fat necrosis when a person has had an excisional biopsy of the breasts, they find out it is carcinoma

o opt to have mastectomy, after mastectomy, receive breast and see during the serial sections, you see a cavity with fat necrosis where the biopsy occurred

o fat necrosis occurs very often like this

VI. Fibrocystic changes (very common)

- not a disease

- defined as the pathological spectrum of alterations of the female breast thought to develop as a result of the cyclic changes in the menstrual cycle due to hormonal imbalances

- usually mulifocal, bilateral

- found in 59% of women in autopsy

- clinically it feels kind a cord-like, nodular

- microscopically, ducts are dilated, increase in stroma, some epithelium hyperplasia

- mild epithelial hyperplasia, no increase risk of development of carcinoma

- Robbins classify it as fibrosis, adenosis (increase in number of acini), and cyst formation

- moderate, florrid, or severe hyperplasia, there is a risk for developing carcinoma

- is not by definition fibrocystic changes

- this change is usually seen during reproductive years (when there are a lot of changes in the hormones)

- can be seen in a post-menopause women if she is taking hormone replacement therapy or she had fibrocystic change pre-menopause and the cyst persisted into the post-menopause years

- Gross photograph

- see large dilated cyst

- fibrosis is predominant

- sometimes get no symptoms unless of palpable lumps

- can produce mammographic density from calcifications and fibrosis

- The cysts are called blue domed cysts of Bloodgood (photo)

- usually contain a brown-greenish fluid

- Surrounding fibrosis is usually result from rupture of cyst with inflammation surrounding the cyst

- Microscopically you can see increase in fibrous tissue, dilation of ducts (duct dictasia), and adenosis (increase in number of acini)

- epithelial lining of cysts

- large polygonal cells with eosinophillic cytoplasm, round nuclei

- called apocrine metaplasia (hint that picture of it might be on test)

VII. Proliferative lesions

• Can be with or without fibrocystic changes

• Risk increases when classified as proliferative lesions

• The way the changes were identified was by large review studies of benign breast biopsies who later developed carcinoma

• Mild epithelial hyperplasia does not incur increase risk in developing carcinoma (risk of 1)

|Types |Risk |

|Moderate or Florid Epithelial Hyperplasia |1.5 to 2 times (slight increase in risk) |

|Sclerosing Adenosis |1.5 to 2 times (slight increase in risk) |

|Small Duct Papillomas |1.5 to 2 times (slight increase in risk) |

|Atypical Epithelial Hyperplasia (lobular or ductal) |4 to 5 times (moderate increase in risk) |

• hard to distinguish microscopically, even pathologists have hard time (don’t need to on test)

- Epithelial hyperplasia (slide shown)

- increase in number of cell layers in the duct

- proliferation of all duct epithelial cells

- it fills the space

- Dr. Kaye also pointed out fibrosis and duct atasia with fibrocystic change in background

- In the duct, you can have papillary hyperplasia (mild)

- Sclerosing adenosis

o can have a stellate shape or density in the mammogram (can be mistaken as a carcinoma)

o can be confused microscopically with carcinoma because the way acini and ducts are compressed in the fibrostroma especially in a frozen section (distorts the cells)

o have a double cell layer which is not very apparent, the lobule structure is maintained

o increases your risk slightly

- Small duct papilloma

- look like a large duct papilloma only they would be smaller and multiple throughout the breast

- usually clinically silent (no mass)

- increase risk of carcinoma slightly

VIII. Benign Tumors of the Breasts

• Three more common that will be covered are fibroadenoma, intraductal papilloma, and nipple adenoma

• Fibroadenoma

o Most common benign tumor of the female breast

o usually occurs in women of ages 20-35 years old

o well circumscribed

o usually in the upper outer quadrant

o usually non-painful, freely movable, no nipple discharge

o arises from the intralobular stroma

o slide with fibroadenoma

• have slit-like spaces (characteristic finding)

o well circumscribed

o usually around 2cm but can get as big as 15cm

o microscopically, fibroblastic stroma is the neoplastic part of the tumor

o thought the stroma is secreting something making the epithelium reactive

o looks like you have proliferation of the epithelium

o slide of tumor

o pointed out the compressed normal breast tissue

o also saw in a microscopic section of the slit-like spaces

• Intraductal papilloma

• usually solitary

• occur in the lactiferous ducts (big ducts that are near the nipple)

• picture of a dilated duct with a stalk connecting the papilloma to the duct

• usually very fragile, can break and become necrotic, bleeding into the duct

• have nipple discharge

• rarely more than 1cm

• usually occur in middle-age women, 48 years old

• don’t do a frozen section on this because it is so fragile and can distort the histology,

▪ making it hard to differentiate between a papillary carcinoma and intraductal papilloma

• slide shown

o know it is benign because of the double layer (myoepithelial and ductal epithelial cells)

• Nipple Adenoma

o Epithelial neoplasm

o Rare; tends to appear in the 4th or 5th decade of life

o Presents as a nodule beneath the nipple with bloody or serous discharge

o Histologically, nipple adenomas look similar to intraductal papillomas - the two are typically distinguished from one another by their location

o Surgical excision is curative

Stromal Lesions of the Breast

• Cystosarcoma Phyllodes

o Malignant tumor arising from intralobular stroma (similar to fibroadenoma)

o Relatively rare

o Range from low to high grade – low grade tumors can be cured by excision while high grade tumors often spread to the lungs, bone and CNS

o Usually metastasizes hematogenously – lymph node involvement is rare

o Gross slide of phyllodes tumor:

• In greek, the word phyllodes means “leaf-like” – when a gross specimen is cut, it is said to have a leaf-like appearance

• Phyllodes tumors often involve hemorrhage

o Microscopic slide of phyllodes tumor:

• Phyllodes tumors look similar to fibroadenoma in that both have proliferating stroma with slit-like spaces; however, phyllodes tumors have large, pleomorphic stromal cells with mitotic figures which are not seen in fibroadenoma

• Phyllodes tumors are not as well circumscribed as fibroadenoma

• Slide of Angiosarcoma of the right arm – A 72 y/o women who underwent a radical mastectomy (removal of breast, axillary nodes and skeletal muscles – not commonly used today) developed a chronically edematous arm. It was later discovered that this was a common complication in women who had this procedure and that the edematous arm often gave rise to angiosarcoma (the problem was named Stewart Trev’s Syndrome). Angiosarcoma has also been seen in the breast after radiation therapy.

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