Pathology Iii: Gyn Breast Lab Ii

Front 1

Fibrocystic Change

Back 1

Presentation: A 44-year-old female presents with bilateral, diffuse, irregular breast nodularity
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Front 2

Fibrocystic Change: What histologic changes may
you expect to see upon
reviewing the sections?

Back 2

Varying proportions of
fibrosis, cysts, epithelial
hyperplasia, apocrine
metaplasia and chronic
inflammation; not all need
be present.

Front 3

Fibrocystic Changes: Gross appearance- -carcinoma vs FCC

Back 3

Breast tissue with fibrocystic change. Cysts and fibrous tissue are evident. In contrast to the stroma seen in carcinoma, this fibrous tissue is shiny and homogenous. The quantity of collagen present in these areas is not nearly as much as in carcinoma, so that these masses typically feel rubbery (versus scirrhous and chalky in carcinoma).

Front 4

What histologic features in breast biopsy material may be associated
with INCREASE RISK of developing
breast carcinoma?

Back 4

Epithelial hyperplasia – moderate
to florid hyperplasia
-Sclerosing adenosis
-Small duct papillomas
-Atypical epithelial hyperplasia,
ductal or lobular

Front 5

What would you do if the
hyperplasia is atypical?

Back 5

Follow-up closely…unless: the
lesion is close to an inked margin
of resection, there is strong family
history of breast cancer, or
multiple recurrences of atypical
hyperplasia.

Front 6

Intraductal epithelial hyperplasia

Back 6

associated with slightly higher incidence of subsequent development of carcinoma of the breast). Small duct almost filled by proliferating cells.

Front 7

How do you tell histologically if ductal tissue is benign or malignant?

Back 7

To diagnose as benign, must identify two cell populations lining ducts: epithelial and myoepithelial layers. Absence of myoepithelial cells indicates invasive carcinoma. Immunohistochemical stains may be necessary to reveal the presence of myoepithelial cells.

Front 8

Distinguish epithelia from myoepithelia cells.

Back 8

Epithelial cells have rounded nuclei. Myoepithelial cells have flattened, spindly nuclei, with often vacuolated cytoplasm (halo).

Front 9

Fibroadenoma

Back 9

a. Most common benign breast tumor in women <35
b. Presentation: palpable, round, movable, rubbery mass
c. Gross: well circumscribed, tan, rubbery mass with small, cleftlikespaces
d. Micro: proliferation of benign stroma, ducts, and lobules

Front 10

Fibradenoma presentation on exam

Back 10

A 23-year-old female presents with a small 1.5 cm. freely moveable breast lump, located in the upper-outer quadrant of her right breast noted on self examination.

Front 11

Fibradenoma: Gross appearance compared to carcinoma

Back 11

“Shelled out” large, well-demarcated lesion. Notice that in contrast to breast carcinoma, this tumor has a very shiny, glistening appearance, has well defined, rounded borders, and no evidence of calcification within it.

Front 12

Phyllodes tumor

Back 12

a. Fibroadenoma variant usually involvesan older patient population (50s)
b. Micro: increased cellularity, stromal overgrowth, and irregular margins
c. May locally recur or rarely metastasize

Front 13

What is the most important microscopic feature in distinguishing
fibroadenoma from phyllodes tumor?

Back 13

Phyllodes tumors are distinguished from fibroadenoma based on
stromal cellularity, mitotic rate, nuclear pleomorphism, stromal
overgrowth, and infiltrative borders.

Front 14

Discuss the prognosis of fibroadenoma and phyllodes tumor.

Back 14

Fibroadenoma is a benign tumor.//

Low-grade phyllodes tumors may locally recur and rarely metastasize.//

High-grade phyllodes tumors behave even more aggressively.

Front 15

Paget Disease of the nipple

Back 15

a. Ulceration, oozing, crusting, and fissuring of the nipple and areola
b. Micro
i. Intraepidermal spread of tumor cells (Paget cells)
ii. Tumor cells occur singly or in groups
iii. Often have a clear halo surrounding the nucleus
c. Commonly associated with an underlying invasive or in situ ductal carcinoma

Front 16

Extramammary vs. mammary paget disease? What's the difference?

Back 16

In case of one in the nipple, there is underlying invasive or ductal carcinoma in situ

whereas extramammary Paget’s will have no underlying ductal carcinoma in situ (CIS)

Front 17

What is the Paget cell derived from?

Back 17

Underlying ductal carcinoma in situ cells (> 95% of cases).

Front 18

Differential diagnosis, based on the histology with Paget disease?

Back 18

Melanoma and squamous cell carcinoma in situ (Bowen’s disease).


Rule in melanoma if HMB-45 positive.

Front 19

Paget Dz Histo

Back 19

absence of intercellular bridges and a mitosis. The DCIS crawls up the epithelium to niple... disrupting juctions, resulting in leaking.

Front 20

Carcinoma of the breast: case history

Back 20

A healthy 42-year-old woman comes to you for a routine physical examination.
Her family history reveals that her mother died of breast cancer 5 years ago and that an older sister had a radical mastectomy for breast cancer 3 years ago.
A mammogram is performed and demonstrates a suspicious area in the upper outer quadrant of the left breast.
A breast biopsy is performed, and based upon the pathologic findings, estrogen/progesterone receptor analysis and Her-2/neu expression analysis are done.
Additionally, because of her family history, you request testing for alterations in BRCA-1 and BRCA-2 genes.

Front 21

Assume she has breast cancer. Why is age and family history important?

Back 21

Young age at presentation and significant family history suggests a
genetic predisposition.

Front 22

What percentage of breast cancers appear to be associated with an
inherited predisposition?

Back 22

5-10%

Front 23

Carcinoma of the breast: mammogram

Back 23

star-shaped mass or rounded mass with calcifications or architecturla distortions.

Front 24

At what age should yearly screening mammograms begin?

Back 24

At 40-50 years age.

Front 25

What is the most common area of origin for breast carcinoma?
Why is it important? Is primary tumor size important?

Back 25

Malignant tumors are most frequent in the upper outer quadrants of the breast. From this location they metastasize early to axillary lymph nodes.
Depending on primary tumor size and location, metastases may also involve internal mammary and supraclavicular nodes. The larger the primary, the more likely you are to find positive nodes.

Front 26

Why are the upper outer quadrants involved most frequently by
breast cancer?

Back 26

They contain a larger amount of breast tissue.

Front 27

Why were the estrogen/progesterone receptor analysis and Her-2/neu expression analysis performed?

Back 27

Tumors lacking estrogen or progesterone receptors are less likely to respond to hormonal manipulation. Breast carcinomas that overexpress Her-2/neu have a worse prognosis, may be less responsive to certain chemotherapeutic agents, yet may respond to therapy targeting this protein (Herceptin).

Front 28

What are implications of detecting BRCA1 or BRCA2 mutations?

Back 28

increased risk of breast and ovarian cancer esp. in women under age of 50.

Front 29

Role of BRCA1 and BRCA2 in men?

Back 29

BRCA1: increase prostate cancer.//

BRCA2: increased breast cancer

Front 30

What is inflammatory carcinoma?

Back 30

NOTHING TO DO WITH INFLAMMATION!//

It is a clinical diagnosis when the breast is reddened and warm (mastitis-like),
with diffuse, firm cutaneous edema producing an orange-skin appearance. Most have carcinomatosis of the dermal lymphatics, a poor prognostic sign. buzzword: 'Peau d'orange' (orange peel)

Front 31

Breast Carcinoma: Gross

Back 31

The tumor is not as shiny as the breast tissue secondary fibrous replacement of glandular tissue. This explains the firm, hard feeling of breast carcinomas on exam. The tumor has irregular, white finger-like projections extending out into the fat. This is why the tumors feel poorly demarcated.

Front 32

Breast Carcinoma: Histo

Back 32

monotonous, atypical and enlarged intraductal cells and central necrosis. Necrosis is often associated with microcalcifications. You may also see mitotic figures.

Front 33

Name three breast carcinoma types with a better prognosis than
breast carcinoma of no specific type (NOS).

Back 33

1. Medullary carcinoma

2. Colloid carcinoma

3. Tubular carcinoma

Front 34

Histo: Ductular vs. Lobular

Back 34

The presence of small ductular structures define this tumor as
ductal type (versus lobular).//

Lobular carcinomas invade in characteristic single cell rows (Indian-file type of infiltration).

Front 35

Leukoplakia (vulval)

Back 35

The white appearance of this vulvar lesion is caused by an increased number of cells and keratin.
Leukoplakia is a descriptive clinical term, is not a diagnosis.
Many lesions of the vulva may present as leukoplakia, so a biopsy is always necessary to establish the diagnosis of carcinoma in situ.

Front 36

What is the erythroplasia of Queyrat?

Back 36

Red-colored vulvar intraepithelial neoplasia (carcinoma in situ) lesions involving the nonkeratinized squamous epithelium of the vestibule.

Front 37

What is the bowenoid papulosis?

Back 37

Pigmented and papular or verrucoid vulvar intraepithelial neoplasia (carcinoma in situ) lesions involving the keratinized vulvar skin.

Front 38

Vulvar Intraepithelial Neoplasia: grading

Back 38

VIN 1 - immature cells, cellular disorganisation, mitotic activity in the lower one- third of the epithelium,
VIN 2 - immature cells with scanty cytoplasm and severe chromatinic alterations occupy most of the epithelium (changes of HPV info : perinuclear halos with displacement of the muclei by the intracytoplasmic viral protein, thickened cell borders, binucleation, multinucleation)
VIN 3 - unifocal or multifocal: small hyperpigmented lesions on the labia major,
(clinically: multiple small, pigmented papules less than 5 mm - 40% cases (bowenoid papulosis = dysplasia)

Front 39

histologic features of carcinoma in situ (VIN III).

Back 39

There is an increase in the thickness of the epithelium, with lack of maturation towards the surface.

lack of maturation towards the surface. There is dyskeratosis: individual cells are keratinizing before reaching the mucosal surface

mitotic figures extending close to the surface

Front 40

What is the evidence that suggests that HPV infection is involved in the pathogenesis of VIN III and is not just a secondary or unrelated event?

Back 40

Viral sequences are present within keratinocytes, are transcriptionally active and encode proteins which interfere with cell cycle control.
In vitro studies demonstrate that viral genes are capable of cellular
transformation.

Front 41

What HPV are involved?

Back 41

Only some HPV types, e.g. HPV 16/18, are associated with VIN III.
Others, e.g. HPV 6/11, are associated with vulval warts.

Front 42

Is vulvar squamous carcinoma always associated with HPV?

Back 42

no, also could be associated with lichen sclerosus and squamous hyperplasia

Front 43

Treatment of VIN

Back 43

Unifocal VIN III:
- local excision//


Multifocal VIN III:
- Patients should always have vulvoscopy and vulval mapping biopsies to determine the extent of the disease. Surgical excision or laser ablation can then be planned according to the distribution of the lesions.
- If very extensive, a conservative policy is often adopted. Patients are followed up carefully with regular vulvoscopy and biopsy and surgical intervention is reserved for the development of invasive disease.

Front 44

Abnormal Pap smear

Back 44

Pap smear with numerous koilocytes. The nuclei are somewhat enlarged, hyperchromatic, and wrinkled (raisinoid). There is a perinuclear halo void of cytoplasm (accumulation of virus particles), and the cytoplasm is condensed at the periphery of the cell.

Front 45

Which HPV types are considered high risk?

Back 45

HPV types 16, 18, 31, 33, 35

Front 46

Is there an association between HPV types and cervical
adenocarcinoma?

Back 46

Yes. HPV types 16, 18

Front 47

What the heck is SIL?

Back 47

CIN may progress to squamous intraepithelial lesion (SIL; condition that precedes cervical cancer) or to carcinoma in situ (cancer that does not extend beyond the epithelial membrane). SIL is also classified as low-grade or high-grade. High-grade SIL and carcinoma in situ may progress to invasive carcinoma

Front 48

Symptomology: Cervical carcinoma vs. endometrial cancer.

Back 48

Cervical carcinoma symptoms
Early: asymptomatic
Late: includes spotting or, more ominous, may be related to invasion of adjacent tissues and structures (bladder and rectum).//

Endometrial cancer symptoms
Early: bleeding

Front 49

Prognosis: Cervical vs. endometrial cancer

Back 49

Cervical carcinoma prognosis: stage dependent, i.e. screen-detected lesions are often microinvasive (stage Ia) and are curable by excision, hence similar to endometrial tumors prognostically. Symptomatic tumors present at a late stage, poorer prognosis
Endometrial cancer prognosis: good prognosis because it presents early: most tumors are stage I at diagnosis.

Front 50

CIN: Histo

Back 50

Most of the epithelial surface contains cells with enlarged hyperchromatic nuclei and irregular nuclear borders that do not become smaller towards the epithelial surface. There is a perinuclear halo.

Front 51

What evidence supports that most of
these high-grade SIL are neoplastic?

Back 51

They tend to be aneuploid, monoclonal,progressive, usually associated with the
oncogenic types of HPV (16, 18, 45, 56,38), and usually 1 type of HPV is identified in the lesion.

Front 52

CIN Progression

Back 52

takes about 10-15 years

CIN I (mild dysplasia)

. CIN II (moderate dysplasia)

. CIN III (severe dysplasia)

. CIS (carcinoma in situ)

. Invasive squamous-cell carcinoma