Neoplasia

Coordinator:Jill Pelling, Ph.D.

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Learning Objectives

Keywords

Clinical Topics
Conference

SUPPLEMENTAL IMAGE DATABASE

Benign vs. Malignant Neoplasms
Classification of Neoplasms

Benign tumors
Malignant tumors
- Squamous cell carcinoma, gross
- Squamous cell carcinoma, micro
- Ca epidermoide de células pequeńas y medianas, No queratinizante, No anaplásico, de tipo Transcisional
- Adenocarcinoma
- Ca de Mama Macro. Gran tumor.
- Ca de Mama Macro con invasion cutanea y necrosis
- Ca lobular de Mama micro con células en fila india
- Ca de Pene Macro
- Teratocarcinoma
- Melanoma, gross
- Burkitt Lymphoma
- Acute Myelogenous Leukemia, peripheral blood

Histologic diagnosis of malignancy

Benign tumors - growth by expansion
- Resemble parent tissues, histologically and cytologically
- Adenomatous polyp of colon, gross
- Adenomatous polyp of colon, micro
- Rabdomioma
- Lipoma, gross
- Lipoma, micro
Malignant tumors- growth by invasion
Electron Microscopy

Tumor cytology

Tumor markers

Cytokeratin stain

Invasion and Metastases

Patterns of Spread
- Direct extension
- Metastatic spread
- Hematogenous metastases
- Lymphatic metastases
Biology of Invasion and Metastasis
- Tumor heterogeneity
- Invasion
- Binding to ECM
- Degradation of ECM
- Movement through interstitial tissues
- Metastasis
- Invasion of the circulation
- Escape from the circulation
- Local growth
- angiogenesis
Target organs in metastatic disease

Grading and staging of tumors

Cancer grading
- Example: Grading of adenocarcinoma of the uterus
- Cancer staging
  - T= size of primary tumor
  - N = number and distribution of node metastases
  - M= presence and extent of distant metastases

The growth of cancers

cell cycle kinetics
doubling time
growth factors

The causes of cancer

Chemical carcinogenesis
- Initiation and promotion, multi-stage carcinogenesis
- Classes of chemical carcinogens
  - Polycyclic aromatic hydrocarbons (PAH)
  - Aflatoxin
  - Aromatic amines
  - Nitrosamines
  - Metals
Factors influencing chemical carcinogenesis
- Metabolism
- Sex and hormonal status
- Diet
Physical carcinogenesis
- Ultraviolet Radiation
- Gamma radiation
- Asbestos
- Foreign body
Viral carcinogenesis
DNA viruses
- Papilloma viruses
- Epstein Barr virus
- Hepatitis B virus
- Polyoma viruses (JC, BK)
RNA viruses
- Human T-cell leukemia viruses I and II (HTLV-I and II)

Role of Oncogenes in Cancer

Identification of oncogenes
Mechanisms of activation of oncogenes
- Point mutation - Ki-ras in pancreatic cancer
- gene amplification - HER-2/neu, erb-B in breast and ovarian cancer
  - homogenously staining regions (HSRs), double minutes
    - translocation - Philadelphia chromosome in chronic myelogenous leukemia (CML)
    - t(8,14) in Burkitt lymphoma
  - function of oncogene products
    - G proteins
    - Growth factors
    - Membrane receptors/tyrosine kinases
    - Nuclear regulatory proteins

Role of tumor suppressor genes in cancer

Retinoblastoma (Rb gene)
- Retinoblastoma (Rb) gene, patient photograph
- Retinoblastoma, histology
The p53 gene
Hereditary cancer
BrCa I in breast/ovarian cancer

Immunology of cancer

Immunologic defenses against cancer in animals
- Tumor antigens
Mechanisms of immunologic cytotoxicity
- T cell-mediated cytotoxicity
- Natural killer cell-mediated cytotoxicity
- Macrophage-mediated cytotoxicity
- Complement-mediated cytotoxicity
Immunologic defenses against cancer in humans

Systemic effects of cancer on the host

Paraneoplastic syndromes
Fever
Anorexia and weight loss
Endocrine syndromes
neurologic syndromes
skeletal muscle
hematologic syndromes
hypercoagulable state
gastrointestinal syndromes
renal syndromes
cutaneous syndromes
amyloidosis

Epidemiology of cancer

Incidence of cancer in the U.S.
Changing patterns of cancer incidence
Geographic and ethnic differences in cancer incidence