3 Neoplasia
3 Neoplasia
3 Neoplasia
10 August 2023
Introduction
• “Tumor”
• Cardinal sign of inflammation
• Tumour=neoplasm
Introduction
• Neoplasm
• New growth.
• Genetic disorder of cell growth triggered by acquired or inherited
mutations affecting a single cell and its clonal progeny
• Oncology
• Study of tumours or neoplasms.
• More oriented towards treatment of neoplasia
Introduction
Benign Neoplasms
• Non-invasive and remains localised.
• Localised at site of origin – does not spread to other sites
• Slow growth rate.
• Close histological resemblance to parent tissue.
Clinical Features
• May occur in vulnerable locations – morbidity and mortality (Pressure on adjacent tissue (meningiomas → epilepsy).
• Obstruction of the flow of fluid.
• Production of hormone (benign thyroid tumour -thyrotoxicosis).
• Transformation into malignant neoplasm (adenomatous polyp to adenocarcinoma).
• Amenable to surgical removal
Introduction
Malignant Neoplasms
• Relatively rapid growth rate.
• Variable histological resemblance to the parent tissue.
• Poorly circumscribed.
• Invasive growth.
• Encroach on & destroy adjacent tissues.
• Central necrosis (outgrow blood supply).
• Metastasis.
Introduction
• Metastasis
• Pathways of Metastasis
• Lymphatic
• Carcinomas
• Lymph nodes become enlarged
• Haematogenous
• Sarcomas
• Some carcinomas
• Lung
• Liver
• Bone
• Brain
• Transcoloemic
• Peritoneal, pleural and pericardial cavities are common sites of this type of metastasis.
• This results in an effusion of fluid into the cavity.
• The fluid is rich in protein and may contain fibrin.
• Fluid also contains neoplastic cells causing the effusion.
Introduction
• Nomenclature
• Epithelial - Carcinoma
• Mesenchymal – Mesenchymal – Suffix = ‘oma
• Solid (sarcoma), blood (leukaemia/lymphoma
Introduction
• Tumour components
• Neoplastic parenchyma
• Reactive stroma
• Abundant collagenous stroma = desmoplasia
• Blood vessels, immune system cells
Introduction
Epithelial Neoplasms
Tissue of origin Benign Neoplasm Malignant Neoplasm
Stratified Squamous Squamous Papilloma Squamous Cell Carcinoma
Glandular Adenoma Adenocarcinoma
Renal Renal cell Adenoma Renal cell carcinoma
Hepatocyte Hepatocellular adenoma Hepatocellular carcinoma
Transitional Transitional cell papilloma Transitional cell carcinoma
Placental Hydatidiform mole Choriocarcinoma
Testicular Seminoma
Embryonal carcinoma
Melanocytes Nevus Malignant melanoma
Adenocarcinoma
Glandular epithelium Malignant epithelial neoplasm
Introduction
MESENCHYMAL NEOPLASMS
Introduction
Eye Retinoblastoma
Adrenal Neuroblastoma
Nephroblastoma
Kidney Malignant neoplasm of childhood
Introduction
• Hamartomas
• Disorganized mass composed of cells indigenous to the involved tissue
• Choristoma
• Heterotopic (misplaced) rest of cells.
Introduction
• Dysplasia
• Literally means “disordered growth.”
• High nuclear-to-cytoplasmic ratio
• Pleomorphism
• Loss of polarity
• In situ malignancy = Dysplasia of the whole epithelium without invasion
• Metaplasia
• Replacement of one type of cell with another
Introduction
• Differentiation
• Does the tumour resemble the tissue of origin by morphology and function?
• The extent or degree of resemblance – Undifferentiated, poor, moderate or well differentiated.
• Anaplasia
• Lack differentiation
• Pleomorphism
• Abnormal nucleus – colour, size
• Mitosis – bizarre
• Loss of polarity
• Necrosis
Introduction
Epidemiology of cancer
• 1 in 6 of all deaths – 2018
• 2030
• Cancer cases = 21.4 million, Cancer-related deaths = 13.2 million
Carcinogenesis
• “Creation of cancer”
• Process by which normal cells are transformed into neoplastic/cancer cells.
• Chronic inflammation
• Compensatory proliferation of cells to repair the damage.
• Increased pool of tissue stem cells – High risk of transformation.
• Activated immune cells
• ROS - damage DNA
• Inflammatory mediators - promote cell survival, even in the face of genomic
damage.
Carcinogenesis - Acquired Predisposing Conditions
• Precursor lesions
• Hyperplasia – Endometrium (hormonal stimulation)
• Metaplasia – Squamo-columnar junction of distal oesophagus
• Dysplasia – Cervix
• Immunodeficiency
• Deficits in T-cell immunity
Molecular basis of cancer
1. Initial mutation
2. Clonal expansion of a single
precursor
3. Four classes of genes that are
principal targets of cancer causing
mutations
4. Accumulation of complementary
mutations in a stepwise fashion over
time
5. Survival of the fittest
Molecular basis of cancer
Hallmarks of cancer
• Self-sufficiency in growth signals
• Grow without external stimuli
• Oncogenes – Growth factors or growth factor receptors
• Insensitivity to growth-inhibitory signals
• Inactivation of tumor suppressor genes - Knudson two hit hypothesis
• Altered cellular metabolism– Warburg effect
• Metabolic switch to aerobic glycolysis - synthesis of the macromolecules and organelles
required for rapid cell growth
Hallmarks of cancer
• Evasion of apoptosis
• Mutations in genes that result in resistance to apoptotic cell death
• Evasion of host immune response
• Limitless replicative potential (immortality)
• Evasion of senescence
• Evasion of mitotic crisis
• Cancer stem cells
• Sustained angiogenesis
• Invade and metastasis
Grading and Staging of Tumours
• Grading
• Differentiation.
• Poorly differentiated tumours = more aggressive behavior.
• Staging
• Determined by surgical exploration or imaging.
• Size, local and regional lymph node spread, and distant metastases.
• TNM
Laboratory Diagnosis of Cancers
• Cytologic Methods
• Fine Needle Aspiration (FNA)
• Cytologic Smears
• Histopathology
• Excision, biopsy
• Immunohistochemistry
• Flow Cytometry
• Molecular and Cytogenetic Diagnostics
• Tumour Markers
REFERENCES