Gen Path

1. My perceptions about cancer
• Be in a group of 4. Prepare ½ crosswise paper.
Select 1 (one) question and discuss your
perception.
Questions:
• How does it develop?
• How will it affect my patient?
• How is it diagnosed?
• How is it treated?

2. Neoplasia

3. Neoplasia
• “new growth”
• Neoplasm or tumor
• Refer to abnormal masses of tissue, the
growth of which is virtually autonomous and
exceeds that of normal tissues
• The growth persists after cessation of the
initiating stimulus

4. According to clinical behavior
• Benign
- localized lesion without spread to other
sites and amenable to surgical resection, the
patient typically survives although there are
exceptions
• Malignant
- aggressive behavior including invasion
and destruction of adjacent tissues and spread
to other sites

5. Components
• Clonal expansion of neoplastic cells
constituting the tumor parenchyma
• Supporting stroma composed of nonneoplastic connective tissue and blood
vessels, abundant collagenous stroma
(desmoplasia) and such tumors are rock hard
(scirrhous)

6. Benign tumors
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Adenomas
Cystadenomas
Papillomas
Polyps

7. Malignant tumors
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Carcinomas
Sarcomas
Mixed tumors
Teratomas

8. Characteristics
• Differentiation – refers to how closely tumor
cells histologically resemble their normal cell
counterparts
• Anaplasia – lack of differentiation
• Benign – well differentiated
• Malignant – well differentiated to
undifferentiated

9. • Pleomorphism – variation in the shape and
size of cells and/or nuclei
• Abnormal nuclear morphology
- hyperchromatism
- irregularly clumped chromatin
- prominent nucleoli
- increased nuclear to cytoplasmic ratios
• Abundant and/or atypical mitoses
• Loss of polarity

10. • Tumor giant cells
• Ischemic necrosis
• Dysplasia - loss of cellular uniformity and
architectural organization
- can occur next to a frank malignancy and
in many cases antedates the development
of cancer
- dysplasia do not equate to malignancy
and dysplastic cells do not necessarily
progress to cancer

11. - when dysplastic changes are marked and
involve the entire thickness of an
epithelium it is referred to as carcinomain-situ and this lesion can be a forerunner
to invasive carcinoma

12. Rates of Growth
• Fast growing tumors can have a high cell
turnover, that is rates of proliferation and
apoptosis are both high
• The portion of tumor cells that is actively
proliferating is called the growth fraction
• In general but not always, the growth rate of
tumors inversely correlates with the level of
differentiation; better differentiated tumors
grow more slowly

13. Cancer Stem Cells and Cancer Cell
Lineages
• A clinically detectable tumor is a
heterogenous population of cells originating
from the clonal expansion of a single cell
• Tumor stem cells can be derived by mutation
of normal stem cells or from differentiated
precursors that acquire the symmetric division
properties of stemness (the ability to sustain
persistent growth of the larger tumor

14. Local Invasion
• Most benign tumors grow as cohesive,
expnsile masses that develop a surrounding
rim of condensed connective tissue or capsule
• Malignant neoplasms are typically invasive
and infiltrative, destroying normal tissues

15. Metastasis
• Invsion of lymphatics, blood vessels or body
cavities by tumor followed by transport and
growth of secondary tumor masses
discontinuous from the primary tumor
• This is the single most important feature
distinguishing benign from malignant tumors

17. Pathways of Spread
• Seeding of body cavities and surfaces
• Lymphatic spread
• Hematogenous spread

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10 Causes of Death in the Philippines
(2009) -DOH
Diseases of the heart
Diseases of the vascular system
Malignant neoplasms
Pneumonia
Accidents
TB, all forms
Diabetes mellitus
Chronic lower respiratory disease
Nephritis, nephrotic and neoplasia
Certain conditions originating in the perinatal
area

19. 10 Causes of Cancer Deaths in the
Philippines (2010) - DOH
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Breast cancer
Lung cancer
Liver cancer
Cervical cancer
Colon cancer
Thyroid cancer
Rectal cancer
Ovarian cancer
Prostate cancer
Non-Hodgkin’s Lymphoma

20. Genetic Predisposition
• Inherited Cancer Syndromes (Autosomal
Dominant)
- Retinoblastoma, Li-Fraumeni syndrome,
Melanoma, Familial adenomatous polyposis
(colon cancer), Neurofibromatosis 1 and 2,
Breast and ovarian cancer, Multiple endocrine
neoplasia 1 and 2, Hereditary nonpolyposis
colon cancer, Nevoid basal cell carcinoma
syndrome, Cowden syndrome, Peutz-Jegher
syndrome, Renal cell carcinoma

21. • Inherited Autosomal Recessive Syndrome of
Defective DNA Repair
- Xeroderma pigmentosum, Ataxiatelangiectasia, Bloom syndrome, Fanconi
anemia
• Familial cancers
- Breast cancer, Ovarian cancer, Pancreatic
cancer

22. Nonhereditary Predisposing
Conditions
• Proliferation – regenerative, metaplastic,
hyperplastic or dysplastic – all increase the
risk of developing malignancy, since it is
proliferating cells that accumulate the genetic
lesions necessary for carcinogenesis

23. • Chronic Inflammation:
- increases the pool of stem cells that can
be subject to the effects of mutagens
- produces cytokines and growth factors to
drive cell survival and proliferation
- promotes genomic instability by the
production of reactive oxygen species
• Precancerous conditions

24. Molecular Basis of Cancer
• Non-lethal genetic damage underlies
carcinogenesis
• Tumors develop as clonal progeny of a single
genetically damaged progenitor cell
• Carcinogenesis is a multistep process
• Although tumors begin as monoclonal
proliferations by the time they are clinically
evident, they are extremely heterogenous

25. • Four classes of normal regulatory genes are
the targets of genetic damage:
- growth promoting proto-oncogenes
- growth inhibiting tumor suppressor
genes
- genes that regulate apoptosis
- genes that regulate DNA repair

26. Essential Alterations for Malignant
Transformation
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Self sufficiency in growth signals
Insensitivity to growth-inhibitory signals
Evasion of apoptosis
Defects in DNA repair
Limitless replicative potential
Sustained angiogenesis (nutrition and waste
removal)

27. • Ability to invade and metastasize
• Ability to escape immune recognition and
regulation
• Oncogenes – are genes that promote
autonomous cell growth in cancer
• Proto-oncogenes – unmutated normal
counterparts
• Oncoproteins – products of oncogenes

28. Proto-oncogenes, Oncogenes and
Oncoproteins
• Mutations convert proto-oncogenes into
constitutively active oncogenes that endow
the cell with growth self-sufficiently
• Growth factors
• Growth factor receptors
• Signal-transducing proteins

29. Oncogenes
• Growth factors
- PDGF-β-chain (astrocytoma,
osteosarcoma)
- Fibroblast growth factors (Stomach,
bladder, breast cancers and melanoma)
- TGF-α (astrocytoma, hepatocellular
cancer)
- HGF (thyroid)

30. • Growth factor receptors
- EGF-receptor family (squamous cell
carcinoma of the lungs, gliomas, breast
and ovarian cancers)
- CSF-1 receptor (Leukemia)
- receptor for neurotrophic factors
(Multiple endocrine neoplasia 2A and 2B),
familial meduallry thyroid cancer)
- PDGF receptor (Gliomas)
- Receptor for stem cell factor (GI and soft
tissue tumors)

31. • Proteins involved in signal transduction
- GTP-binding (RAS) (Colon, Lung,
Pancreatic, bladder and kidney tumors,
melanomas, hematologic)
- nonreceptor tyrosine kinase (chronic
myeloid and acute lymphoblastic
leukemia)
- RAS signal transduction (melanomas)
- WNT signal transduction
(hepatoblastomas and hepatocellular
carcinoma)

32. • Nuclear Regulatory Proteins
- Transcriptional activators (MYC) (Burkitt
lymphoma, neuroblastoma, small cell
carcinoma of lungs)
• Cell Cycle Regulators
- Cyclins (Mantle cell lymphoma, Breast
and esophageal cancers, Breast cancer
- Cyclin-dependent kinase (glioblastoma,
melanoma, sarcoma)

34. Carcinogenic Agents
• Chemical
- initiation (direct acting and indirect
acting agents)
- promotion
• Radiation (UV and ionizing)
• Oncogenic viruses and microbes (Heliobacter
pylori, HPV, EBV, Hepatitis B and C)

35. Host Defense Against Tumors
• Tumor antigens
• Antitumor Effector Mechanisms
• Immune Surveillance and Escape

36. Clinical Aspects of Neoplasia
• Location and impingement on adjacent
structures
• Functional activity (hormone production)
• Bleeding and infection
• Symptoms from tumor rupture or infarction
• Cachexia (wasting)

37. Grading and Staging
• Grading – based primarily on the degree of
differentiation (how well the tumor resembles
its normal counterpart), architectural features
or number of mitoses
• Staging – based on size of the primary tumor
and the extent of local and distant spread

38. Laboratory Diagnosis
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Histologic and cytologic method
Immunohistochemistry
Flow cytometry
Molecular diagnosis