1 / 57

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.

blade
Download Presentation

NEOPLASIA

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. NEOPLASIA Dr G R Wright School of Pathology Division of Anatomical Pathology University of the Witwatersrand

  2. Neoplasia Epithelial lesions Connective tissue lesions Tumours of childhood Effects of tumours / Paraneoplastic syndromes Pathology of Chemotherapy / Irradiation

  3. Effects of Tumours

  4. Effects of Tumours • Depends on the SITE, NATURE and SIZE of the individual tumour • LOCAL and GENERALISED effects • PARANEOPLASTIC SYNDROMES

  5. Local effects • BENIGN TUMOURS: • Pressure / Obstruction • Functional Activity • Local Anatomical Complications • Torsion, infection, haemorrhage, ulceration • Malignant Transformation

  6. Local Effects • MALIGNANT TUMOUS: • Pressure / Obstruction • Destruction of Tissue • Local Anatomical Complications • Ulceration, haemorrhage, infection • Pain

  7. Generalised Effects • Starvation • Cachexia • Fever • Haematological Changes • Immunological Effects • Hormone production More pronounced with malignant tumours

  8. Paraneoplastic Syndromes

  9. 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

  10. Paraneoplastic Syndromes • Divided into: • Endocrinopathies • Nerve and muscle syndromes • Dermatological disorders • Osseous, articular and soft tissue changes • Vascular and haematological changes

  11. Endocrinopathies • Hormone / Hormone-like substance produced by cells that are not of endocrine origin • Cushing syndrome • Hypercalcaemia • Carcinoid syndrome • Polycythaemia • Hypoglycaemia

  12. Cushing Syndrome • ACTH or ACTH-like substance • Small cell carcinoma of lung • Pancreatic carcinoma • Neural tumours

  13. Carcinoid Syndrome • Excessive serotonin production • Neuroendocrine tumours • Clinical features: • Vasomotor disturbances (flushing) • Intestinal hypermotility (cramps, diarrhoea) • Bronchoconstriction • Systemic fibrosis

  14. Myasthenia • ? Immunological • Bronchogenic carcinomas • Weakness, ± autonomic dysfunction

  15. AcanthosisNigricans • ? Epidermal growth factors from tumours • Gastric, lung & uterine carcinomas • Middle aged-elderly adults • Flexures

  16. AcanthosisNigricans Velvety hyperpigmented Acanthosis

  17. Dermatomyositis • Immunological • Bronchogenic and breast carcinoma • Rashes & muscle weakness

  18. Hypertrophic osteoarthropathy • Cause unknown • Bronchogenic carcinoma • Features: • Periosteal new bone formation • Arthritis of adjacent joints • Clubbing

  19. Hypertrophic osteoarthropathy Clubbing

  20. Venous Thrombosis • Trousseau phenomenon • Pro-coagulatory products of tumours • Pancreatic & bronchogenic carcinoma

  21. Nonbacterial Thrombotic Endocarditis • Hypercoagulability • Advanced mucin secreting adenocarcinoma • Bland small fibrinous vegetations on valves (L>R)

  22. PATHOLOGY OF IRRADIATION

  23. 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

  24. 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

  25. 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

  26. Mechanisms of Cellular Damage • Ionization • Production of free radicals • DNA Damage • Strand breaks – multiple double strand • Base alterations – mutations • Cross-linking – replication prevented

  27. 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

  28. Effects on Cells • Immediate death • Prevention of further division→ apoptosis • Change in genotype – mutation • Repair

  29. Blood vessels • Endothelial damage and loss • Exposure of collagen • Thrombosis and necrosis • Endothelial and intimal proliferation • Telangiectasis • Endarteritis obliterans

  30. 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

  31. Gastro-intestinal Mucosa • Nausea, vomiting, diarrhoea → dehydration, electrolyte abnormalities • Ulceration • Haemorrhage • Secondary infection • Stricture, obstruction

  32. 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

  33. 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

  34. 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

  35. 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

  36. PATHOLOGY OF CHEMOTHERAPEUTICS

  37. Chemotherapy • Pathology depends on class of drug • Classes • DNA damaging – free radicals, cross linking • DNA repair inhibitors • Antimetabolites • Antitubulin

  38. Chemotherapy • Side effects: • Nausea, vomiting • Hair loss • Myelosuppression • Myositis • Organ specific toxicity (lung, heart, liver) • Sterility • Secondary malignancies

  39. Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage ARDS = Clinical dx DAD = Histological dx Diffuse alveolar infiltrate on CXR

  40. 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

  41. Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage • Bleomycin: • Antibiotic • Glycopeptide • Pulmonary toxicity dependant on • Age • Dose • Duration

  42. Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage ACUTE: Heavy Firm Red / Congested Boggy

  43. Normal Lung Airway Vein Alveoli Inter-alveolar septum Artery

  44. Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage Acute Phase Congestion Interstitial oedema Intra-alveolar oedema, inflammation and fibrin deposition

  45. Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage Hyaline membranes Pneumocyte type II proliferation and atypia

  46. Adult Respiratory Distress Syndrome / Diffuse Alveolar Damage Chronic Phase Organisation → Fibrosis Thickening of inter- alveolar septae

  47. 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

  48. Cardiotoxicity • NB – Adriamycin (Doxorubicin) • Dilated cardiomyopathy - Progressive cardiac dilation and contractile dysfunction • Risk factors: • Age • Mediastinal DXT • Combination therapy • Pre-existing cardiac pathology • Dose intervals & total dose

  49. Dilated cardiomyopathy CXR Normal CXR

  50. Dilated Cardiomyopathy Thin wall

More Related