General pathology the growth and neoplasia

Pathology

1. NEOPLASIA
General Pathology
Dr: Ahmed Edrissi
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2. In these lectures you will understand the following:
Etiology (causes) of neoplasia. What evidence is there that neoplasia
is a genetic disorder? What is the role of the environment in
carcinogenesis?
Molecular Basis of neoplasia. Oncogenes and tumour suppressor
genes. Multistep carcinogenesis or tumour progression
environmental carcinogens and process of carcingenesis.
Mechanism of cancer spread. Types of cancer spread.
Tumour grading and staging
Effects of tumours on host: local effects, cancer cachexia,
paraneoplastic syndromes.
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3. INTRODUCTION
The term ‘neoplasia’ means new growth; the new growth produced is
called ‘neoplasm’ or ‘tumour’.
Abnormal mass of tissue
the growth of which exceeds and is uncoordinated with
that of normal tissue
and persists in the same excessive manner even after
removal of the cause.

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4. 4
Classification
Broadly classified based on clinical behaviors:
Benign localized lesion without spread to other sites
and amenable to surgical resection; the patient
typically survives.
Malignant called cancers, with aggressive behavior
including invasion and destruction of adjacent
tissues and capacity for spread to other sites
(metastasis).

5. SPECIAL CATEGORIES OF TUMOURS
1.Mixed tumours: Adenosquamous carcinoma
2. Teratomas
from the three germ cell layers— ectoderm, mesoderm and endoderm. (gonadal teratomas).
3. Blastomas (Embryomas)
arise from embryonal or partially differentiated cells which would normally form
blastema of the organs and tissue during embryogenesis. (neuroblastoma,
nephroblastoma )
4. Hamartoma
made of mature but disorganised cells of tissues indigenous to the particular organ
e.g. hamartoma of the lung consists of mature cartilage, mature smooth muscle and
epithelium.
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6. Nomenclature
✘According to:
?????? Histologic types: mesenchymal and epithelial
?????? Behavioral patterns: benign and malignant.
Benign the suffix -oma
Rhabdomyoma,fibroma and adenoma
Malignant:
• Carcinoma derived from epithelial cells
adenocarcinomas
• Sarcoma of mesenchymal cell origin
leiomyosarcomas
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7. TissueTissueBenignBenignMalignantMalignant
EpitheliumEpithelium
* * surfacesurfacePapillomaPapillomaCarcinomaCarcinoma
* * glandularglandularAdenomaAdenoma
AdenocarcinomAdenocarcinom
aa
Connective Connective
tissuestissues
~ ~omaoma ~ ~sarcomasarcoma
BloodBlood---- ---- leukemialeukemia
Germ cellsGerm cellsBenign Benign
teratomateratoma
seminomaseminoma
Neurons Neuroma Neuroma
Naming of some tumors
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8. Characteristics of Benign and Malignant Characteristics of Benign and Malignant
NeoplasmsNeoplasms
✘1. Differentiation & anaplasia
✘2. Rate of growth
✘3. Local invasion
✘4. Metastasis
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9. Grading and Staging of Cancers
✘Grading ✘Staging
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10. Tumours can effect the host in the Tumours can effect the host in the
following ways:following ways:
Local Effects
•Tumor Impingement on nearby structures
–Pituitary adenoma on normal gland,
Pancreatic carcinoma on bile duct,
Esophageal carcinoma on lumen
•Ulceration/bleeding
–Colon, Gastric, and Renal cell carcinomas.
Patient presents with anaemia.
•Infection (often due to obstruction)
–Pulmonary infections due to blocked bronchi
(lung carcinoma), Urinary infections due to
blocked ureters (cervical carcinoma)
•Rupture or Infarction
–Ovarian, Hepatocellular, and Adrenal cortical
carcinomas; Melano-carcinoma metastases
•Local Effects
•Cancer Cachexia
•Paraneoplastic Syndromes
–Endocrinopathies
–Neuromyopathies
–Osteochondral Disorders
–Vascular Phenomena
–Fever
–Nephrotic Syndrome
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11. Diagnosis of tumors
1.Clinical diagnosis:
2.Radiological diagnosis
3.Lab inv:
Routine: CBC, organ function tests, ...
Cytology: FNA
Histopathology: biopsy
IHC.
Biochemical : tumor markers
Cytogenetic /molecular biology techniques: PCR
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12. Management of tumors
✘Benign surgical removal.
✘Malignant:
-Surgical.
-Chemotherapy
-Radiotherapy
-Hormonal therapy
-Gene therapy
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13. How normal cell becomes malignant?????
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15. NORMAL CELL CYCLE
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16. Genetic evidence of carcinogenesis
1.Introduction of genes (activated oncogenes) in normal Cells in culture
make them transformed (lose contact Inhibition and divide
uncontrollably)
2.Transgenic mice/knock-out mice (mice with new onco-Genes Introduced
in cells at early embryological stages or Removing genes from them)
have a higher incidence of cancer
3.Patients with familial cancers have siblings with relatively Higher risk of
developing cancer. For example, mutation of BRCA-1 and BRCA-2
4.Patients with well known inherited cancer syndromes In which
inheritance of a single mutated gene have increased Risk of developing
tumours. A well known example is Familial Polyposis coli.
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17. Molecular basis of neoplasia
Basic principles
Four kinds of genes are targets for carcinogenic transformation:
1) proto-oncogenes promote cell growth and require the
alteration of only one allele ? to create out of control cellular
growth (cancer)
2) tumor suppressor genes inhibit cell growth and require the
alteration of both alleles to affect cell growth (recessive
oncogenes), DNA repair genes are similar
3) genes that regulate apoptosis may be dominant or recessive
but influence the ability of the cell to target itself for
destruction following cell damage
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18. The Good, the Bad, and the Ugly
✘Tumor suppressor genes prevent transformation [good]
✘Oncogenes cause transformation [bad]
✘Loss of genomic integrity [ugly]
-Inactivation of tumor suppressor genes
-Activation of oncogenes
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19. What are the sources of mutations?
✘Inherited germline mutations (rare)
✘Somatic (random mistakes)
-In structural genes
-In regulatory genes
✘Environmental:
-Infections (viral, bacterial)
-Chemicals (tobacco, food)
-Radiation (sun, X-ray, radioactive exposure)
✘Aging ( DNA repairing mechanism)
Chromosomal abn.
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20. Multi-steps mechanism
Initiation
Promotion
Progression
metastasis
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21. Chemical carcinogens
Direct:
Do not require metabolic activation such as
Alkylating agents and Acylating agents
Indirect: promoters( by metabolites)
✘Examples:
Polycyclic aromatic hydrocarbons
Aromatic amines and azo-dyes
Naturally-occurring products Afla toxin
Miscellaneous
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22. Infections
✘Viral (oncogenic viruses)
-HPV
-EBV
-HBV
-...
✘Bacterial: Helicobacter pylori
✘Parasites: schistosoma. Tv
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23. Radiation
✘Direct damage to DNA ...
OR
✘Indirect: by Free radical from water.
lead to
- Oncosupressor genes
-Error in DAN repair
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24. Thanks
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