Introduction to Neoplasia Major Topics for Discussion Definition of neoplasia Benign neoplasms Malignant neoplasms Spread of neoplastic cells (metastasis) Clinical evaluation: grading and staging Epidemiology Oncogenes and tumor suppressor genes

Neoplasia Clonal proliferation of cells Autonomous growth - uncoordinated Derived from cells with proliferative capacity (active cell cycle) Results from alterations in DNA Some resemblance to cell of origin

Classification Benign vs Malignant

Benign Neoplasms Grow slowly Do not invade adjacent tissues or metastasize (spread to distant sites) Often are encapsulated Closely resemble cell of origin (differentiated) Uncommonly cause patient death

Uterine Leiomyoma (benign smooth muscle cell tumor)

Benign Gastrointestinal Polyp

Benign Brain Tumor (Meningioma)

Malignant Neoplasms Grow more rapidly Invade adjacent tissues and have potential to metastasize Not encapsulated Less-closely resemble cell of origin More-likely to cause patient death

Adenocarcinoma of Colon

Adenocarcinoma of Uterus

Squamous Cell Carcinoma

Nomenclature General rules cell type + “oma” = benign neoplasm cell type + “carcinoma” = malignant neoplasm of epithelial origin cell type + “sarcoma” = malignant neoplasm of mesenchymal origin

Examples (Benign & Malignant) Chondroma & condrosarcoma Lipoma & liposarcoma Adenoma & adenocarcinoma (of breast) Papilloma & squamous cell carcinoma

These neoplasms have an “oma” suffix, but they are malignant. Exceptions to Rules Malignant tumors include: Teratoma Seminoma Lymphoma Melanoma These neoplasms have an “oma” suffix, but they are malignant.

Morphology of Neoplasms Differentiation – degree of resemblance to normal cell of origin Anaplasia – lack of differentiation Pleomorphism – variation in cell size and nuclear appearance Mitotic rate – reflects proliferative rate Necrosis – outgrow blood supply

Gross & Microscopic Features Benign Meningioma Malignant Melanoma

Benign Neoplasm of cartilage Normal Cartilage Benign Neoplasm of cartilage

Malignant Chondrosacrcoma

Squamous Cell Carcinoma (note the keratin “pearls”)

Spread of Neoplasms Carcinoma in situ Local invasion (no invasion of the basement membrane) Local invasion Seeding of body cavities (carcinomatosis) Distant metastasis Lymphatic spread Hematogenous spread

cervical biopsy shows carcinoma in-situ - CIS

Invasive Cervical Squamous Cell Carcinoma

Malignant Melanoma (radial growth phase)

Bone Metastases of Malignant Melanoma

Metastatic Liver Cancer

Peritoneal Carcinomatosis - Widely Disseminated Cancer

Hematogenous Spread

Lymphatic Spread

Mechanisms of Metastatis Altered Cell Adhesion Altered Cell Motility Hydrolytic enzymes Invasion

Grading and Staging Used to predict the behavior of neoplasms (prognosis) and determine appropriate therapy Grading – assessment of degree of differentiation and proliferative capacity Staging – assessment of tumor size and extent of spread locally and distantly

Epidemiology 20% of total mortality in the US Epithelial cancers (lung, colon, breast, prostate) are most common in adults Leukemia, lymphoma, CNS neoplasms are most common in children Geographic differences in incidence Environmental associations (carcinogens)

Cancer Incidence in US Males

Cancer Incidence US Females

Neoplasia is a Genetic Disease Oncogenes Tumor suppressor genes

Chromosomal Translocation and Neoplasia

Retinoblastoma and Rb Tumor Suppressor Gene Mutations

Path Key Words Adenocarcinoma Adenoma Carcinoma in situ Chondroma Chondrosarcoma Grading Hepatoma Leukemia Lipoma Melanoma Metastasis Peritoneal carcinomatosis Squamous cell carcinoma Staging Teratoma Transitional cell carcinoma