Neoplastic Flashcards
Neoplasm
• Not all neoplasms are malignant
• Malignant neoplasms(cancer) characteristics:
– Genetic disorder
– These genetic alterations are heritable
– The accumulation of mutations gives rise to a set of properties called the “hallmarks of cancer”
Nomenclature
• All tumors benign and malignant
– Parenchyma:
– Supporting stroma:
-transformed neoplastic cells
-connective tissue, blood vessels, and lymphatics
Benign Neoplasms (-oma)
• Classified according to the cell type of origin
• Suffix “-oma”
• classified on the basis of macroscopic or microscopic pattern of growth
Malignant Neoplasms
• Classified according to the cell type of origin (4)
– Carcinoma: arising from epithelial tissue
– Sarcoma: arising from mesenchymal tissue
– Lymphoma: arising from the lymphoreticular
system
– Leukemia: arising from hematopoietic elements
Exceptions are the Rule
• Melanoma • Seminoma • Hamartoma
Neoplasia = New Growth
Neoplasm
• Abnormal mass of tissue whose growth exceeds and is uncoordinated with that of the normal tissues
• Persists in an excessive manner after the cessation of the stimuli which evoked the change
• Obvious to normal control mechanisms of replication
Differentiation & Anaplasia
Differentiation:
Anaplasia:
- Differentiation: parenchymal cells of the neoplasm resemble comparable normal cells, both morphologically and functionally
- Anaplasia: lack of differentiation
Morphology of Anaplasia
• a lack of differentiation
• Cellular and nuclear pleomorphism
• Nuclear hyperchromasia
• Increased nuclear to cytoplasmic ratio
• Increased number of mitosis
• Loss of orientation of cells
• Formation of tumor giant cells
Dysplasia
• Disorderly but non-neoplastic growth
• in epithelial lesions
– loss of uniformity of cells
– Loss of architectural orientation
– The term dysplasia, without qualifications, does not indicate cancer
– do not necessarily progress to cancer
Differentiation and Anaplasia
- Benign tumors-
- Malignant tumors-
• Benign tumors- well-differentiated and resemble closely normal cells
• Malignant tumors- well differentiated to undifferentiated
Rate of Growth
- Benign tumors-
- Cancers-
• Benign neoplasia: grow slowly over a period of years*
• Cancers: grow rapidly or erratically*
• Many exceptions
• *the growth rate of tumors correlates with their level of differentiation
Local Invasion
- Benign tumors-
- Malignant tumors-
• Benign neoplasms -grow as cohesive expansile masses
– Capsule: derived largely from the stroma of the native tissue as the normal cells atrophy from pressure
• Malignant neoplasms- infiltrative growth with destruction of the surrounding tissue
Local Invasion
• Next to the development of metastasis, invasiveness is the most reliable feature of malignancy
Metastasis
•
identifies a neoplasm as malignant
Pathways of Spread
- Seeding of body cavities - ovary
* Lymphatic spread - carcinoma, breast
• Hematogenous spread - sarcoma
• Transplantation
Biology of Tumor Growth
- Neoplastic transformation of a cell
* Growth of the transformed cell
• Local invasion
• Distant metastasis
Factors Influencing Tumor Growth
• Kinetics of tumor cell growth
- how many cells in G1
• Tumor angiogenesis
• Tumor progression & heterogeneity
Kinetics of Tumor Growth
• Doubling time of tumor cells
– Because of defective controls (Rb, p53), easily triggered into cell cycle
– take longer to complete the cell cycle
- Fraction of tumor cells in replicative pool
– Depends on type of tumor - Rate of loss of cellsy (dying, differentiation)
Tumor Angiogenesis. **
- cannot enlarge beyond 1-2 mm in diameter or thickness unless they are vascularized
- Correlates with malignancy
- How do tumors develop a blood supply?
– Factors produced by tumor cells
– Factors produced by inflammatory cells
– The balance between angiogenesis factors and
inhibitors pushed to favor angiogenesis
Tumor Angiogenesis
• How do tumors develop a blood supply?
– Early in their growth—no angiogenesis
– months to years
– Then- “angiogenic switch”
–the change of some cells within the tumor to an angiogenic phenotype
Tumor Angiogenesis
- is controlled by a balance between pro- and anti- angiogenesis factors
- These controlling factors may be produced…
directly by the tumor cells themselves, or by inflammatory or stromal cells adjacent to the tumor
Tumor Angiogenesis
• Angiogenesis inducers:
– VEGF (vascular endothelial growth factor)
• (Early) tumors do not induce angiogenesis
• They remain small until the angiogenic switch terminates this phase
• Angiogenesis inhibitor: TSP-1(thrombospondin-1)
– P53 (a tumor suppressor gene) induces the synthesis of TSP-1
Tumor Angiogenesis
• The molecular basis of the angiogenic switch involves…
increased production of angiogenic factors and/or the loss of angiogenesis inhibitors
• Proteases elaborated by the tumor cells, or by stromal cells in response to the tumor affect the balance
Tumor Angiogenesis
• Proteases can
– Release
the angiogenic factor basic FGF (fibroblast growth factor)
– also release potent angiogenesis inhibitors
• Angiostatin
• Endostatin
• Vasculostatin
• Stromal fibroblasts can produce TSP-1
