NEOPLASIA Dr G R Wright School of Pathology Division of Anatomical Pathology University of the Witwatersrand
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NEOPLASIA
NEOPLASIA
Dr G R Wright
School of Pathology
Division of Anatomical Pathology
University of the Witwatersrand
Neoplasia
Epithelial lesions
Connective tissue lesions
Tumours of childhood
Effects of tumours / Paraneoplastic syndromes
Pathology of Chemotherapy / Irradiation
Effects of Tumours
Effects of Tumours
Depends on the SITE, NATURE and SIZE of the individual tumour
LOCAL and GENERALISED effects
PARANEOPLASTIC SYNDROMES
Local effects
BENIGN TUMOURS:
Pressure / Obstruction
Functional Activity
Local Anatomical Complications
Torsion, infection, haemorrhage, ulceration
Malignant Transformation
Acoustic neurilemmoma deafness, RICP
Ble duct papilloma obstructive jaundice
5
Local Effects
MALIGNANT TUMOUS:
Pressure / Obstruction
Destruction of Tissue
Local Anatomical Complications
Ulceration, haemorrhage, infection
Pain
Ca Colon bowel obstruction
6
Generalised Effects
Starvation
Cachexia
Fever
Haematological Changes
Immunological Effects
Hormone production
More pronounced with malignant tumours
Paraneoplastic Syndromes
Paraneoplastic Syndromes
Collection of symptoms that can not be explained by the growth of the tumour
Clinical importance:
First manifestation of malignancy
Significant morbidity
Mimic metastatic disease
Paraneoplastic Syndromes
Divided into:
Endocrinopathies
Nerve and muscle syndromes
Dermatological disorders
Osseous, articular and soft tissue changes
Vascular and haematological changes
Endocrinopathies
Hormone / Hormone-like substance produced by cells that are not of endocrine origin
Cushing syndrome
Hypercalcaemia
Carcinoid syndrome
Polycythaemia
Hypoglycaemia
Cushing Syndrome
ACTH or ACTH-like substance
Small cell carcinoma of lung
Pancreatic carcinoma
Neural tumours
Carcinoid Syndrome
Excessive serotonin production
Neuroendocrine tumours
Clinical features:
Vasomotor disturbances (flushing)
Intestinal hypermotility (cramps, diarrhoea)
Bronchoconstriction
Systemic fibrosis
Myasthenia
? Immunological
Bronchogenic carcinomas
Weakness, autonomic dysfunction
Acanthosis Nigricans
? Epidermal growth factors from tumours
Gastric, lung & uterine carcinomas
Middle aged-elderly adults
Flexures
Acanthosis Nigricans
Velvety hyperpigmented
Acanthosis
Dermatomyositis
Immunological
Bronchogenic and breast carcinoma
Rashes & muscle weakness
Hypertrophic osteoarthropathy
Cause unknown
Bronchogenic carcinoma
Features:
Periosteal new bone formation
Arthritis of adjacent joints
Clubbing
Hypertrophic osteoarthropathy
Clubbing
Venous Thrombosis
Trousseau phenomenon
Pro-coagulatory products of tumours
Pancreatic & bronchogenic carcinoma
Nonbacterial Thrombotic Endocarditis
Hypercoagulability
Advanced mucin secreting adenocarcinoma
Bland small fibrinous vegetations on valves (L>R)
PATHOLOGY OF IRRADIATION
Radiation
Electromagnetic waves and particles
80% from natural sources UV light, cosmic radiation, radioisotopes
20% manufactured instruments, nuclear power plants
Effects dependant on dose and timing of exposure
Causes acute and chronic effects
Radiation
NON-IONISING RADIATION
Long wavelength, low frequency
Electricity, radio waves, microwaves, infrared, UV
IONISING RADIATION
Short wavelength, high frequency
Xrays, gamma rays, cosmic radiation
PARTICULATE alpha and beta particles, protone, mesons,deutrons
Radiation Effects
Dependant on:
Dose rate
Whole body vs focal & fractionated
Rapidly dividing cells are more radiosensitive than quiescent cells
Cells in G2 or Mitoses are most sensitive
Different cells have different repairative responses
Mechanisms of Cellular Damage
Ionization
Production of free radicals
DNA Damage
Strand breaks multiple double strand
Base alterations mutations
Cross-linking replication prevented
Tissue SensitivityDirectly proportional to rate of cell division:
HIGH
Haemopoietic tissue
Lymphoid tissue
Gonads
Intestinal mucosa
MEDIUM
Liver
Pancreas
Endocrine glands
Connective tissues
LOW
Heart muscle
Skeletal muscle
Nerve cells
Brain
Mature bone
Mature cartilage
Effects on Cells
Immediate death
Prevention of further division apoptosis
Change in genotype mutation
Repair
Blood vessels
Endothelial damage and loss
Exposure of collagen
Thrombosis and necrosis
Endothelial and intimal proliferation
Telangiectasis
Endarteritis obliterans
Bone Marrow
Suspends renewal of all 3 cell lines
Time to decrease in blood counts dependant on physiological survival of cells
Whole body marrow failure
Localised marrow fibrosis
Gastro-intestinal Mucosa
Nausea, vomiting, diarrhoea dehydration, electrolyte abnormalities
Ulceration
Haemorrhage
Secondary infection
Stricture, obstruction
Other tissues
Skin
Erythema, desquamation, ulceration dermal fibrosis
Gonads
Sterility
Germ cell mutation foetal abnormalities
Follicular cell damage in ovary artificial menopause
Lung
Rich blood supply
ARDS / DAD alveolar fibrosis
Kidney
Loss of parenchyma decreased renal function hypertension
Whole Body Irradiation
Effects depend on dose
Cerebral syndrome
Drowsiness, convulsions, coma
Hours post exposure
Gastro-intestinal syndrome
Vomiting, diarrhoea Ulceration, haemorrhage, infection
Days post exposure
Haemopoietic syndrome
Leucocytopaenia, thrombocytopaenia infection , haemorrhage
Weeks post exposure
Ultraviolet Radiation
Associated with squamous cell carcinoma, basal cell carcinoma, melanoma, etc
Three types
UVA
Inhibits DNA repair
UVB
Non-ionising DNA strand linkage
UVC
Filtered out by ozone layer
Very toxic
Radiotherapy
Some tumours more sensitive than others
Localised tumour cure
Disseminated disease palliative relief of symptoms eg pain and pressure effects
Used in combination with surgery / chemotherapy
Fractionation
Normal tissue - attempt repair between doses
More of tumour cells to enter cell cycle
PATHOLOGY OF CHEMOTHERAPEUTICS
Chemotherapy
Pathology depends on class of drug
Classes
DNA damaging free radicals, cross linking
DNA repair inhibitors
Antimetabolites
Antitubulin
Chemotherapy
Side effects:
Nausea, vomiting
Hair loss
Myelosuppression
Myositis
Organ specific toxicity (lung, heart, liver)
Sterility
Secondary malignancies
Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage
Diffuse alveolar infiltrate on CXR
ARDS = Clinical dx
DAD = Histological dx
Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage
Causes:
Infections eg. sepsis, TB
Physical / Injury eg trauma, drowning
Inhaled irritants eg smoke
Chemical injury eg chemotherapy - Bleomycin
Haematological conditions eg DIC
Pancreatitis
Ureamia
Hypersensitivity reactions
Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage
Bleomycin:
Antibiotic
Glycopeptide
Pulmonary toxicity dependant on
Age
Dose
Duration
Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage
ACUTE:
Heavy
Firm
Red / Congested
Boggy
Normal Lung
Airway
Vein
Alveoli
Inter-alveolar septum
Artery
Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage
Acute Phase
Congestion
Interstitial oedema
Intra-alveolar oedema, inflammation and fibrin deposition
Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage
Hyaline membranes
Pneumocyte type II proliferation and atypia
Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage
Chronic Phase
Organisation
Fibrosis
Thickening of inter- alveolar septae
Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage
Pathogenesis:
End result of alveolar injury due to different mechanisms
Damage to alveolar capillary endothelium or alveolar epithelium
Inflammatory process
Cardiotoxicity
NB Adriamycin (Doxorubicin)
Dilated cardiomyopathy - Progressive cardiac dilation and contractile dysfunction
Risk factors:
Age
Mediastinal D
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