NEOPLASIA - PATHOLOGY - 2021 - EASYMEDNOTES
Neoplasia
Neoplasia is a new growth
It is an excessive an unregulated proliferation that eventually independent of physiologic growth stimuli.
cancer
Cancer is the common term for malignant tumours.
It is derived from the Latin word - crab.
clonality
A tumour is known to be clonal when the entire cells within a tumour arises from a single cell that has incurred genetic change.
A clonal neoplasm is therefore constituted by cells which carry the same genetic anomaly.
Two main components of all neoplasms
1) Tumour cells that have the parenchyma
2) Tumour stroma which is a supporting framework consisting of connective tissue and newly formed blood vessels.
Basic principles of carcinogenesis
1) Non-lethal
Genetic damage or mutation may be acquired by the action of environmental agents such as chemicals, radiation or viruses.
2) The classes of normal regulatory genes are:
I) The growth promoting proto-oncogenes
Activation of proto-oncogenes activation gives rise to oncogenes.
Proto- oncogenes are activated by
- Point mutation
- Chromosomal rearrangements translocation Inversion
- Gene amplification
II) Cancer suppressor genes - anti oncogenes
• Its physiologic role is to regulate cell growth, the inactivation of cancer suppressor genes is the key event in cancer genesis
• Examples of tumour suppressor genes - Rb, P53, APC and NF-1&2 genes
III) Genes that regulate apoptosis
- Genes that prevent or induce programmed cell death are also important variables in the cancer.
bcl-2 inhibits apoptosis
- others such as bax. Bad, and bcl-x5 favors programmed cell death.
IV) Genes that regulate DNA repair
• Inability to DNA repair can predispose to mutations in the genome - neoplastic transformations occurs.
Types of carcinogenesis:
There are three categories:
- Chemical carcinogenesis
- Radiation carcinogenesis
- Viral carcinogenesis
1. Chemical carcinogenesis
A variety of chemicals may induce tumours and this was observed by Sir Percival Pott’s.
The increased incidence of scrotal skin cancer in chimney sweeps to chronic exposure to soot.
Steps involved in chemical carcinogenesis
- the certain amount of dose of a chemical carcinogenic agents to a cell, results in the formation of initiation –promotion sequence
- Initiation causes permanent DNA damage which, is rapid and irreversible.
- However, initiation alone is not sufficient for tumour formation and thus, promoters can induce tumours in initiated cells, but they are non-tumour-ogenic by themselves.
- The effects of initiators, the cellular changes because of the application of promoters do not affect DNA directly and are reversible.
- Promoters render cells susceptible to additional mutations by causing cellular proliferation.
Examples of promoters include phorbol ester, hormones, phenols and drugs.
Chemical carcinogenic agents are two categories:
- Directly acting compound
-These are ultimate carcinogens.-They are highly reactive electrophiles, that can react with nucleophilic sites in the cell.
-This reaction is non-enzymatic and result in the formation of covalent addition products between the chemical carcinogen and a nucleotide in DNA.
-Electrophilic reactions may attack several electron-rich sites in the target cells including DNA, RNA, and proteins.
- Indirect acting compounds or pro-carcinogens
-Requires metabolic conversion to produce ultimate carcinogens capable of transforming cells.-Most known carcinogens are metabolized by cytochrome p-450 dependent monooxygenase.
-Examples of this group are: polycyclic and heterocyclic aromatic hydrocarbons, and aromatic amines etc.
-These chemical carcinogens lead to mutations in cells by affecting the functions of oncogenes, onco-suppressor genes and genes that regulate apoptosis.
2. Radiation carcinogenesis
Radiant energy like ultraviolet (UV) sun light or ionizing electromagnetic X rays and gamma rays and particulates (α,β, protons and neutrons) radiation can transform and induce neoplasm in both humans and experimental animals.
Two types of radiation injuries are recognized:
- Ultraviolet rays (UV light)
-UV rays are examples of non-ionizing radiation that cause vibration and rotation of atoms in biologic molecules.
-UV rays induce an increased incidence of squamous cell carcinoma, basal cell carcinoma and possibly malignant melanoma of skin.
Risk factors for developing UV rays related disorders depend on
- Type of UV rays – UV type B
- Intensity of exposure
- Quality of light absorbing “protective mantle” of melanin in the skin Ex. Australians (queen's land etc.)
- Ionizing radiation
Ionizing radiations are of short wave length and high frequency which can ionize biologic target molecules and eject electrons.
Electromagnetic and particulate radiations in forms of therapeutic, occupational or atomic bomb incidents can be carcinogenic
Occupational hazards include:
- Many of the pioneers in the development of roentegen rays develop skin cancers.
- Miners for radioactive elements -lung cancer
- Therapeutic irradiations have been documented to be carcinogenic.
- Thyroid cancer may result from childhood & infancy irradiation (9%), and by the same taken radiation therapy for spondylitis may lead to a possible acute leukemia year later.
- Hiroshima and Nagasaki initially principal cancers were acute and chronic myelogenous leukemias after a latent of about 7 years solid tumours such as breast, colon, thyroid and lung cancers increased in incidence.
- The skin, bone and gastrointestinal tract are relatively resistant to radiation-induced neoplasia.
3. Viral and bacterial carcinogenesis
Large groups of DNA and RNA viruses have proved to be oncogenic.
DNA oncogenic viruses:
- Human Papilloma Virus (HPV)
- Epstein Barr Virus (EBV)
- Hepatitis B Virus (HBV)
General feature of the oncogenic DNA virus
- Transforming DNA virus form stable associations with the host cell genome.
- The integrated virus is unable to complete its replicative cycle because the viral genes essential for completion of replication are interrupted during integration of viral DNA (E1/E2).
- Those viral genes that are transcribed early in the viral life cycle are expressed in the transformed cells.
RNA oncogenic viruses
- Human T cells leukemia/ lymphoma virus type 1 (HTLV-1) .
- HTLV-1 has tropism for CD4+T cells.
- HTLV-1 is also associated tropical spastic Para paresis.
Local invasion
Most cancers are accompanied by progressive infiltration and destruction of the surrounding tissue is known as local invasion.
Metastasis
Tumour implants discontinuous with the primary tumour, confirm the malignant nature of a tumour and are labelled metastases.
All cancers metastasize with a few exceptions like basal cell carcinoma (rodent ulcer) and gliomas of the central nervous system, which are locally invasive and rarely metastasize.
Pathways of Spread of the Tumours
1. Direct seeding of body cavities and surfaces:
- Penetration of a tumour into a natural open space, like pleural, pericardial, subarachnoid and synovial.
- Sometimes mucinous tumours of appendix and ovary both benign and malignant will fill the peritoneal cavity with a gelatinous neoplastic mass called ‘pseudomyxoma peritonei’.
2. Lymphatic spread
- There are number of inter-connections between lymphatic and vascular channels.
- Functional lymphatics are absent in tumours and lymphatic vessels located at the surface are sufficient for lymphatic spread.
- Lymphatic spread tends to follow natural routes of lymphatic drainage and is the usual route for dissemination of epithelial malignancies sarcomas may also use this route.
- Drainage of tumour cell debris and antigens may induce reactive hyperplasia and the spread of tumour cells to regional lymph nodes.
- A ‘sentinel’ lymph node is defined as the first node in the regional lymphatic chain to receive lymph flow from the primary tumour.
3. Hematogenous spread
- Typical of sarcomas but also seen in carcinomas.
- Arteries have thick walls, are less penetrable than veins.
- All portal blood flows to liver and all caval blood flows to lungs therefore, liver and lungs are the most frequently involved organs in hematogenous dissemination.
- Cancers in the vicinity of vertebral column like thyroid and prostate, metastasize to the vertebrae via paravertebral plexus.
Comments
Post a Comment