Intro to Neoplasia

Question 1

Metaplasia

Answer 1

Exchange of normal (mature) epithelium for another type of epithelium, reversible

Question 2

Dysplasia

Answer 2

A disordered growth and maturation of an epithelium, which is still reversible
Is the next step toward neoplasia.

Question 3

Neoplasia

Answer 3

The entire epithelium is dysplastic, then it is now a neoplasia.
The BM can still be intact, and the carcinoma is confined
to the epithelium = “carcinoma in-situ”

Other times you cannot recognize the basement membrane because infiltration is deep, or tell the lamina propria from epithelium

Question 4

Characteristics for Malignant Neoplasms

Answer 4

Loss of differentiation
Pleomorphism 
Abnormal nuclear morphology
Mitosis, increased number and atypical
Loss of polarity
Ischemic necrosis
Invasive 
Metastasis

Question 5

Parenchyma vs. Stoma

Answer 5

Parenchyma: neoplastic cells
Stroma: connective tissue, supporting.

Benign tumors: cell type or tissue + “oma”
						fibroma, 
						chondroma, 
						adenoma, 
Exceptions : 	lymphoma
				mesothelioma
				melanoma
				seminoma

Question 6

Carcinoma

Answer 6

arise in the epithelium :  “carcinoma”
			squamous cell carcinoma
			Transitional carcinoma
			Adenocarcinoma
Carcinoma – route of metastasis is lymph

Question 7

Sarcomas

Answer 7

in mesenchymal tissues connective tissues : 			“sarcomas”
			striated muscle (rhabdomyosarcoma), 
			smooth muscle (leiomyosarcoma), 
			fat (liposarcoma), 
			blood vessels (angiosarcoma), 
			bone (osteosarcoma),
			cartilage (chondrosarcoma)
Sarcoma – route of metastasis is blood

Question 8

Benign vs. Malignant Characteristics

Answer 8

Benign: slow growth, low mitotic activity, no invasion, no metastases, circumscribed/encapsulated border, necrosis and ulceration is rare, often a exophytic growth pattern on the surface

Malignant: rapid growth, high mitotic activity, hyperchromatic/irregular/pleomorphic nuclei, invasion, metastases are frequent, borders are poorly defined/irregular, necrosis and ulceration are common, and often a endophytic growth pattern on the surface

Question 9

Lipoma

Answer 9

Lipoma It has the characteristics of a benign neoplasm:
it is well circumscribed, slow growing, and non-invasive
These neoplastic adipocytes are indistinguishable from normal adipocytes (well-differentiated)

Question 10

Liposarcoma

Answer 10

Large bizarre lipoblasts

Sarcomas are best treated surgically, because most respond poorly to chemotherapy or radiation

Question 11

Leiomyomas

Answer 11

Uterus, benign leiomyomas of varying size, all benign and well-circumscribed firm white masses
The cells do not vary greatly in size and shape and closely resemble normal smooth muscle cells.

Question 12

Osteosarcoma

Answer 12

Osteosarcoma of bone.
The large, bulky mass arises in the cortex of the bone and extends outward.

Composed of spindle cells. Osteoid formation is consistent with differentiation

Question 13

Dx for Neoplasia

Answer 13

Clinical information
Imaging techniques

Samples: 	
biopsy
Fine needle aspiration
Cytologic smears: Papanicolaou
Frozen section
H.E./ ICC/IHC

Flow cytometry: leukemias and lymphomas

Biochemical assays: PSA, hormones, circulating tumor markers CEA

Molecular diagnosis: PCR, FISH, DNA microarray

Question 14

Abnormal Pap Smear

Answer 14

A cervical Pap smear, dysplastic cells are present that have much larger and darker nuclei than the normal squamous cells with small nuclei and large amounts of cytoplasm

Question 15

Tumor Grade

Answer 15

expression of tumor differentiation or anaplasia.
Grade 1 – well differentiated. (low grade)
Grade 2 – moderately differentiated.
Grade 3 – poorly differentiated/anaplastic (high grade)

Question 16

Cancer Stage

Answer 16

A statement about cancer size and extent of spread.
American Joint Committee on Cancer (AJCC)
- T = tumor size (T 0 – 4)
- N = lymph node status (N 0 – 3)
- M = metastasis (M 0 -1)
Stage I – IV for most body sites. Criteria are body site specific

Question 17

Tumor Marker

Answer 17

is a molecular or tissue – based process that provides future behavior of a cancer but requires a special assay that is beyond routine clinical, radiographic, or pathologic examination.
can be measured at DNA, RNA, protein, cell and tissue levels

Question 18

Infiltrating Ductal Carcinoma

Answer 18

Infiltrating ductal carcinoma:
cords and nests of neoplastic cells with intervening collagen.
Microcalcification: dystrophic calcification

pleomorphic cells infiltrating through the stroma.
abundant pink collagen bands from desmoplasia.

Question 19

Breast Cancer Biomarkers

Answer 19

Estrogen receptor
75% of all breast cancer express ER +
ER + endocrine therapy Tamoxifen
ER – no benefit from endocrine therapy

Progesterone receptor
ER + PR+ greater benefit from adjuvant tamoxifen than ER+PR-

HER-2 Receptor
target for therapy Trastuzumab (Herceptin)

Treated via receptor antagonists

Question 20

Breast Cancer Treatment

Answer 20

Development of Trastuzumab - (Herceptin)
Testing for HER2 gene amplification by FISH or IHC

Shows how Anti Her2 monoclonal antibody inhibits the activation of the signaling via preventing the formation of the homodime

Question 21

HER 2

Answer 21

Over expression is indicative of aggressive phenotype

Is a critical target for at least two therapies: trastuzumab and lapatinib.

Gene amplification can be measured by many different assays, fluorescent or chromogenic in situ hybridization (FISH ) or by dot blot technology.

In primary or metastatic breast cancer tissue.

In blood, either as a soluble protein or expressed on circulating tumor cells.

HER2 protein overexpression can be quantify be WB, IHC, IF or ELISA

The circulating extracellular domain of HER2 can be detected in serum, plasma and saliva

Question 22

Ki67

Answer 22

nuclear antigen present in mid G1,S,G2 and the entire M phase

Question 23

Biomarkers

Answer 23

Biomarkers are proteins produced by the tumor cells that can be detected using IHC, FISH, etc. Biomarkers are important to determine the prognosis and to predict response to specific treatment, e.g. estrogen receptor – estrogen receptor antagonist.

Question 24

Immunohistochemistry

Answer 24

Step 1. The tissue section on the slide is represented with the protein (biomarker) of interest in orange

Step 2. The addition of the primary antibody that recognized specifically the protein of interest

Step 3. the secondary antibody binds only to the primary antibody, this secondary antibody is conjugated with chromogen which changes color in presence of specific substrates

Question 25

Estrogen Receptor

Answer 25

Tamoxifen (specific drug), interfere binding the estrogen receptor. The final result is the inhibition of transcription of genes that promote cancer progression

Question 26

Activation of HER2 Pathway

Answer 26

Signaling pathway for the HER2 receptor, its activation ends in proliferation, cell cycle progression and survival of cells.

Question 27

M1B1

Answer 27

nuclear antigen

Question 28

Cyclin A

Answer 28

cell cycle late S, G2 and M phases

Question 29

Cyclin E

Answer 29

G1 phase and entry into S phase more frequent in ER-

Question 30

Cyclin D1

Answer 30

G1 phase

Question 31

p27

Answer 31

Cdk inhibitor correlated with ER expression

BRCA1/2 mutated tumors are low p27

Question 32

Sporadic Breast Cancer

Answer 32

Postmenopausal women

ER (estrogen receptor) +

Question 33

Familial Breast Cancer

Answer 33

5-10% hereditary factors
Germ line mutations
Most are associated with inherited autosomal dominant mutations of either BRCA1 or BRCA2 genes
Penetrance (30-90%)

Question 34

Breast Altered Genes

Answer 34

HER2/neu/erb-B2
over expression is indicative of:
more aggressive phenotype,
lymph node metast. 
decreased overall survival

BRCA 1: majority of cancers attributable to single mutations . Penetrance 30 – 90%

BRCA 2

p53