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Neoplasia I

Neoplasia I . Walter C. Bell, M.D. Definitions. Neoplasia = New growth Loss of responsiveness to normal growth controls Tumor – Swelling, clinically used interchangeably with “neoplasm” Oncology – Study of tumors Benign vs Malignant Clinical aggressiveness of neoplasm

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Neoplasia I

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  1. Neoplasia I Walter C. Bell, M.D.

  2. Definitions • Neoplasia = New growth • Loss of responsiveness to normal growth controls • Tumor – Swelling, clinically used interchangeably with “neoplasm” • Oncology – Study of tumors • Benign vs Malignant • Clinical aggressiveness of neoplasm • A cancer (L. crab) is a malignant neoplasm

  3. Nomenclature • Tumors are composed of • stroma (supporting connective tissue, blood supply) • parenchyma (the neoplastic cells which determines biologic behavior) • Tumor names are derived from the parenchymal component

  4. Nomenclature • Benign neoplasms end in the suffix “-oma” • Mesenchymal • Fibroma • Chondroma • Epithelial • Adenoma • Papilloma • Cystadenoma

  5. Nomenclature • Mesenchymal cancers are called sarcomas • Fibrosarcoma • Chondrosarcoma • Epithelial cancers are called carcinomas • Squamous cell carcinoma • Adenocarcinoma

  6. Neoplasia • Neoplasms are monoclonal (arise from a single cell which has undergone neoplastic transformation) • Stem cells may undergo divergent differentiation leading to heterogeneity • Mixed tumors • Pleomorphic adenoma • Teratoma • Fibroadenoma (appearance only)

  7. Confusing Terminology(Names that break the rules) • Lymphoma • Mesothelioma • Melanoma • Seminoma • Hepatoma – old terminology for HCC • Choristoma

  8. Benign vs Malignant • Most important clinical question for neoplasms • Determines appropriate therapy • Conservative vs wide excision • Evaluation of lymph nodes (staging) • Need for chemotherapy or radiation therapy

  9. Benign vs Malignant • Degree of differentiation • How closely do the parenchymal cells resemble normal cells of this type • Benign neoplasms are usually “well-differentiated” • Anaplasia = lack of differentiation (bizarre nuclei, atypical mitoses, loss of cell polarity) • Determined by microscopic examination

  10. Benign vs Malignant • Dysplasia – Pre neoplastic change usually in epithelia • May not progress to cancer

  11. Differentiation • In general, function correlates with differentiation • Unanticipated functions can emerge • Ectopic hormones • Fetal proteins

  12. Benign vs Malignant • Rate of growth • Most benign tumors grow slowly while most cancers grow fast • Many exceptions • Rate of growth for malignant tumors correlates with degree of differentiation • Despite rapid growth, cancers usually take years to become clinically apparent • Rapid growth may lead to necrosis

  13. Ki-67 in dysplasia Increased proliferation, disordered

  14. Benign vs Malignant • Local invasion • Benign neoplasms do not have the capacity to invade • Invasion is a characteristic of malignancy • Benign neoplasms often develop a fibrous capsule

  15. Benign vs Malignant • Metastasis • Metastases are secondary, remote implants of tumor • Metastatic spread is the most important hallmark of malignancy • Cancers differ in their ability to metastasize • Methods of metastasis: • Seeding • Lymphatic spread • Hematogenous spread

  16. Epidemiology • The study of the relationships of various factors determining the frequency and distribution of diseases in the human community • Contributes to understanding of risk factors and the origin of cancers • Smoking – Lung cancer • Fatty diets – Colon cancer

  17. Epidemiology • Geographic and environmental factors • Breast cancer – Death rates 4-5x higher in US and Europe than in Japan • Stomach cancer – Death rates 7x higher in Japan than in the US • Hepatocellular carcinoma – Uncommon in US, one of the most common and lethal cancers in some African populations • Most geographic patterns related to environmental exposures

  18. Epidemiology • Age • Frequency of cancer increases with age with peak between ages of 55 and 75 • Increased accumulation of somatic mutations • Heredity • 5-10% of cancers • Acquired preneoplastic disorders • Dysplasia, colonic adenoma

  19. Clinical Features of Malignancy • Cachexia • Decreased body fat, weakness, anorexia, anemia • Increased infections • Abnormalities of taste, increased metabolic rate • Correlates with size of tumor

  20. Clinical Features of Malignancy • Paraneoplastic Syndromes • 10-15% of cancer patients • Symptoms that can’t be explained by spread of the tumor or by indigenous hormones • Endocrinopathies (SIADH, Hypercalcemia) • Nerve and muscle disorders • Vascular and hematologic changes (thrombosis)

  21. Cancer Diagnosis • Biopsy • Fine-Needle aspiration (FNA) • Exfoliative cytology (pap smear) • Biochemical markers (PSA, CEA, Alpha-fetoprotein)

  22. Grading and Staging • Grade – Microscopic (degree of differentiation) • Stage – Pathologic and clinical findings describing the extend of disease • AJCC Stage – I-IV • Based on T – size and invasiveness of tumor, N – presence or absence of nodal metastases, M – presence or absence of distant metastases • Stage is a stronger predictor of prognosis than grade

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