Neoplasia Flashcards
What is neoplasia
New uncontrolled cell growth–> an abnormal tissue mass
Autonomous
Cells undergo neoplastic changes–> which is a result of genetic changes or mutation
In which cells do neoplasms usually occur
From cells that normally have proliferative capacity= Labile cells
What are stabile cells
Cells that stop dividing when growth stops
But can regenerate–> hence is injury occurs
E.g. liver cells, kidney, smooth muscle cells, vascular endothelium
What are permanent cells
Permanent cells–> don’t change throughout lifetime
Have varying differentation (well and poor differentiated)
Therefore no neoplasms
i.e. mature neurons, cardiac and skeletal myocytes
What are 2 types of neoplasia
Benign and Malignant
Both have 2 basic components:
1. Proliferating neoplastic cells–> their parenchyma
2. Supportive stroma–> connective tissue and BV’s
What is benign neoplasia
Cells growth that s localised–> encapsulated
Does not penetrate or invade
Does not metastisize (move)- cohesion
Usually well differentiated
What is malignant neoplasia
Cell growth invades adjacent tissue Erractic growth (asymmetrical) Slow to rapid mitotic growth Metastisize (move to different site)--> hence poor cohesion usually poor differentiation
What is the nomenclature for benign neoplasm
Tissue + ‘oma’
What are some harmfull effects of benigns
Create pressure on surrounding vital organs
Extra horonal secretion–> endocrine tumours= hyperpituitarism
Secondary complications becomes necrotic:
Can cause haemorrhage
Create ulceration
Create infection/inflammation
What are carcinomas
A type of malignant neoplasm
from epithelial cell origin–> any of the 3 germ layers
Tissues and organs develop from epiderm/sctoderm, mesoderm, endoderm
What are sarcomas
A type of malignant neoplasm
From mesenchymal cell origin==> the connective tissues, blood vessels, lymph
E.g. fibrosarcoma, liposarcoma
What does differentiation mean
degree to which tumour cells ‘cease to’ resemble, comparable to normal cells
both structurally and functionally
What does well differentiated mean
cells resembling mature normal cells of tissue of origin of neoplasm= easy diagnosis
What does poorly/undifferentiated mean
Primitive unspecialised cells–> hard diagnosis
What does anaplasia mean
the degree to which tumour cells function cease to resemble the comparable normal cell function
What does metastases mean
development of secondary malignant growths at a distance from primary site
the movement of a malignant neoplasms to a new site
hence tumour implants are discontinuous with primary site
Malignant
Majority cancers metastasize (except BCC)
Breast to bone is a common metastases
What is direct extension in metastases
Direct extension
By penetration creating fistulas
What is direct seeding in metastases
Across cavities
E.g. Pleural (lung), pericardial, thoracic, abdominal etc
Stomach cancee goes to ovary
What is lymphatics metastases
most common spread of cancer
follows natural drainage
Skip metastases, venous lymphatic anatomose, inflammation/radaition destroys lymphatics
Nodes enlarged in proximity of cancer
What is haematogenous in metastases
transfers via blood
Typical of sarcomas
Penetration of veins and arteries (more likely veins coz thinner walls?)
Venous drainage site of neoplasm
How do you determine grade of cancer
Grade is based on:
Differentiation of tumour cells
Number of mitosis within tumour both presumably correlate with aggressiveness of tumour
Differentiation may differ from one area to another as tumour evolves
Usually cancers become more undifferentiated as they progress
How do you determine stage of cancer
Based on:
Size of primary lesion
Extent of spread of regional lymph nodes
Presence or absence of blood borne metastases
The higher the stage the worse the prognosis
What are the 4 stages of growth and development of tumors
Transformation: malignant changes in a target cell
Growth of transformed cells
Local Invasion
Distant metastases
What are the 2 ways in which transformation of a cell can occur
Proto-oncogenes
Anti-oncogenes or Cancer suppressor genes
What is proto-oncogenes
It is a normal gene which when altered by mutation, becomes an oncogene
Activated by mutation or increased expression
Converted proto-oncogenes become/are oncogenes
Oncogenes promote extra or inappropriate cell proliferation
Only 15-20% human tumours contain activated oncogenes
What is anti-oncogene suppressor/cancer suppressor gene
Some cancers aarise not by activation of growth promoting genes, but by inactivation of genes
Normally suppressing cell proliferation
Influence only felt when absent
Growing evidence that loss of suppressor genes is the underlying mechanism to, malignant transformation
What are some factors that can cause the transformation in cells
Chemical carcinogens
Radiant Energy
Oncogenic viruses
Explain the effect of chemical carcinogens
Different chemicals affect different tissues
Complete carcinogens= ability to induce tumors without added factors
Incomplete carcinogens= only capable of initiation
DNA is the primary target for chemical carcinogens
Chemical carcinogens induce mutations in proto-oncogenes to become oncogenes to lead to abnormal growth and differentiation
Explain the effect of radiation carcinogenesis
Radiant energy–> U.V sunlight, ionizing electromagnetic (both produce neoplasms of all cell types)
Has a latency and cumulative effect
Possible additive and synergistic effects with other potential carcinogens
Action of radiant energy implicates damage to DNA
How do U.V. rays affect cells
Squamous Cell Carcinoma (S.C.C)/ Basal Cell Carsinoma (B.C.C)/ Melanocarcinoma of skin (melanoma)
Dependent on the dosages/exposure and melanin in skin
Effects on cell:
Inhibition of cell division
Inactivation of enzymes
Induction of mutations
Enough dosage kills cells
Hoe does ionizing radiation affect cells
X-rays and gamma rays
Is carcinogenic
Chromosomal breakages/translocations/point mutations (DNA injury)
Alters proteins
Inactivates enzymes
Injures membranes
Carcinogenicity correlates with its mutagenicity
Mutagenicity depends on:
Quantity/does of radiation
Quality (high v/s low)
does rate (divided does allows cellular recovery)
DNA repair
Host factors (immune status, hormonal influence, cell types, adults/embryonic)
What are soe examples of radiation induced cancers
- Leukaemias
- Cancer of thyroid
- Cancer of breast/lung/salivary glands
Skin/bone relatively resistant to radiation
Explain the effect of oncogenic carcinogens
transformation of cells
DNA and RNA oncogenic viruses–> some virues associated with cancer
One example of DNA oncogenic virus= HPV
Transmission of HPV= SCC of cervix in 90%; associated with sexual activity, also non-sexual transmission
Explain the growth of transformed cells
Feature of neoplasms: growth is uncontrolled and exceeds growth of normal tissue Cancers are generally- monoclonal= a transformed single cell 1 cell = 30 doublings= 10^9 Growth fraction (GF)= proportion of cells within tumor population that are in the proliferative pool, majority cells in clinically detectable tumour tumour growth= the imbalance between cell production and cell loss
What is the rate of tumour growth
Dependent on the growth fraction (GF) and the degree of imbalance b/c proliferation and loss Some neoplasms (leukaemia/lung Ca) have high growth fraction, t/f rapid clinical course Other neoplasms (breast cancer/colon) have low GF hence slower clinical course
Explain invasion of cells
In 3 steps:
- Attachment to basement membranes
- Secretion of preteolytic enzymes that locally degrade matrix components creating degradation
- Migration of tumor into degraded ECM zone
Cyclic repetition of these 3 steps leas to progressive invasion by advancing tumor cells
Explain distant metastases
Malignant cells less cohesive
Secretion of factors stimulating own mobility by autocrine mechanisms
Vascular dissemination
Homotypic adhesions of tumor cells only
Hetrotypic adhesions of tumur cells and platelets= enhanced survival and implantation
Explain the process of tumour spread
Transformation Growth/proliferation and angiogenesis Detachment Invasion Intravasation/release Survival (Host reactions) Arrest Extravasion/invasion Growth/angiogenesis (micrometastasis) Clinically important metastases
What is radial surgery
the removal of a tuor and a margin of normal tissue around tuour
What is a carcinoma in situ
Cancer confined to epithelial surface by basement membrane:
Lack of invasion hence metastasis
Cytological features of malignancy
Considered one step from cancer
time leads to penetration of basement membrane
What is cancer cachexia
A wasting symdrome–> advanced cancer
Survival is weeks/months
Range of etabolic, hormonal and cytokine-related abnormalities appear to be a result of interaction b/w metabolically active molecules produced by tumor and the host defense system
What are the effects of cancer cachexia
Progressive:
Decreased body fat–> increased anorexia
Decrease in lean mass
Increased weakness (asthenia)
Increased constipation
Increased anemia
Changes in carbohydrate and lipid metabolism
Usually ended by secondary infection
Some correlation b/w size/extent/severity
Pts have higher rates of whole body protein turnover and higer rate of metabolism of all nutrients than non cancer pts
Not caused by nutritional commands of tumor
Cancers rarely grow as fast as fetus–> yet mothers increases wt
What are some reasons for cachexia
Impaired immune system leads to secondary infections
Infections lead to debilitation and fever
Fever contributes to hypermetabolism
Ulcerative lesions from some anemia and weakness
Grief and depression from loss of appetite
What are common sites of secondary metastases to bone
BLT with ketchup and pickle B= Breast L= Lungs T= Thyroid Ketchup= Kidney Pickle= Prostate All the above metastases Spine is the main site for secondary's
