Intro to Neoplasia Flashcards
Metaplasia
Exchange of normal (mature) epithelium for another type of epithelium, reversible
Dysplasia
A disordered growth and maturation of an epithelium, which is still reversible
Is the next step toward neoplasia.
Neoplasia
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
Characteristics for Malignant Neoplasms
Loss of differentiation Pleomorphism Abnormal nuclear morphology Mitosis, increased number and atypical Loss of polarity Ischemic necrosis Invasive Metastasis
Parenchyma vs. Stoma
Parenchyma: neoplastic cells
Stroma: connective tissue, supporting.
Benign tumors: cell type or tissue + “oma” fibroma, chondroma, adenoma, Exceptions : lymphoma mesothelioma melanoma seminoma
Carcinoma
arise in the epithelium : “carcinoma” squamous cell carcinoma Transitional carcinoma Adenocarcinoma Carcinoma – route of metastasis is lymph
Sarcomas
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
Benign vs. Malignant Characteristics
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
Lipoma
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)
Liposarcoma
Large bizarre lipoblasts
Sarcomas are best treated surgically, because most respond poorly to chemotherapy or radiation
Leiomyomas
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.
Osteosarcoma
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
Dx for Neoplasia
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
Abnormal Pap Smear
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
Tumor Grade
expression of tumor differentiation or anaplasia.
Grade 1 – well differentiated. (low grade)
Grade 2 – moderately differentiated.
Grade 3 – poorly differentiated/anaplastic (high grade)
Cancer Stage
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
Tumor Marker
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
Infiltrating Ductal Carcinoma
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.
Breast Cancer Biomarkers
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
Breast Cancer Treatment
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
HER 2
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
Ki67
nuclear antigen present in mid G1,S,G2 and the entire M phase
Biomarkers
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.
Immunohistochemistry
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
Estrogen Receptor
Tamoxifen (specific drug), interfere binding the estrogen receptor. The final result is the inhibition of transcription of genes that promote cancer progression
Activation of HER2 Pathway
Signaling pathway for the HER2 receptor, its activation ends in proliferation, cell cycle progression and survival of cells.
M1B1
nuclear antigen
Cyclin A
cell cycle late S, G2 and M phases
Cyclin E
G1 phase and entry into S phase more frequent in ER-
Cyclin D1
G1 phase
p27
Cdk inhibitor correlated with ER expression
BRCA1/2 mutated tumors are low p27
Sporadic Breast Cancer
Postmenopausal women
ER (estrogen receptor) +
Familial Breast Cancer
5-10% hereditary factors
Germ line mutations
Most are associated with inherited autosomal dominant mutations of either BRCA1 or BRCA2 genes
Penetrance (30-90%)
Breast Altered Genes
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
