Patho 2: test 1 Tissue Pathology of Cancer ppt

Tissue Pathology of Cancer

• Neoplasm/Tumor: The formation or presence of a new, abnormal growth of tissue
• Malignant: A tumor that tends to invade normal tissue or recur after removal; characterized by rapid growth, hemorrhage, necrosis, local invasiveness, and metastasis
• Benign: A slow-growing tumor that is non-invasive and does not metastasize; characterized by small size, well-demarcated borders, slow growth, non-invasiveness, and well-differentiated cells

Cancer Classification

• Based on:
  • Tissue and organ of origin
  • Extent of distribution (stages)
  • Microscopic appearance of the malignant tumor
  • Critical genetic changes in cancer cells

Benign Tumors

• Usually:
  • Encapsulated
  • Well demarcated
  • Well-organized stroma
  • Do not invade beyond their capsule
  • Do not spread to regional lymph nodes
• Named for the tissues where they arise with the suffix "-oma" (e.g., leiomyoma, lipoma)
• Can still cause symptoms if very large, block blood flow, or compress normal tissue
• Benign endocrine tumors can lead to overproduction of hormones

Malignant Tumors

• Characteristics:
  • Rapid cell growth rate (high mitotic activity)
  • Loss of differentiation (anaplasia)
  • Absence of normal tissue organization
  • Increased vascularity
  • Lack a capsule and can invade surrounding tissues
  • Can metastasize to regional lymph nodes
• Named according to the cell type from which they originate (e.g., carcinomas, adenocarcinomas, sarcomas, lymphomas, leukemias)

Progression to Malignancy

• Cancers develop incrementally as they accumulate genetic mutations
• Careful surveillance can detect atypical cells or abnormal growth before progression to malignancy
• Dysplasia:
  • A premalignant condition
  • Can range from mild to severe (low grade to high grade)
  • Histologic features:
    • Increased cell growth
    • Increased cellular atypia
  • Common sites: mouth mucosa, tongue, cervix, bladder, stomach, colon, breast, skin

Carcinoma In Situ (CIS)

• Preinvasive epithelial tumors of glandular or squamous cell origin
• Localized to the epithelium and have not penetrated the local basement membrane or invaded the surrounding stroma
• Histological features:
  • Altered cell growth
  • Cytologic atypia
  • Altered differentiation
• Common sites: cervix, skin, oral cavity, esophagus, and bronchus
• Ductal Carcinoma In Situ (DCIS): fills mammary ducts in breast, but no invasion
• Glandular CIS: stomach, endometrium, breast, large bowel
• 3 Fates:
  • Remain stable for a long time
  • Progress to invasion or metastasis
  • Regress or disappear

Genetics and Cancer

• Genomics: The study of functions and interactions of all the genes in the genome, including their interactions with environmental factors
• Genetics: Applies to mutations that can be inherited
• Genomics vs Genetics:
  • Genetics: mutations affecting an individual's germ cell
  • Genomics: includes germ cell mutations and somatic cell mutations, and interactions between genes and environment/viral/bacterial genes
• Critical Cancer Genes: Oncogenes and tumor suppressor genes regulate cell growth, division, differentiation, and death
• Sporadic vs Hereditary Cancers:
  • Sporadic: genetic changes in somatic cells, majority of cancer cases, generally occur at older ages, no family history, lower risks to other family members
  • Hereditary: strong cancer gene inherited through a germ cell line, high risks to other family members, often risks for other types of cancer too
  • Familial: multiple family members with the same cancer, unknown cause, moderate risk to other family members
• Hereditary Cancer "Clues":
  • Young ages of diagnosis (typically under 50)
  • Multiple family members with cancer
  • Multiple generations with cancer
  • Multiple cancers in the same person
  • Related cancers
  • Bilateral cancers
  • Rare cancers
  • Certain ancestries (Ashkenazi Jewish)
• Family Pedigree:
  • Allows us to look at the larger picture
  • Narrows down which gene to test for and whom to consider testing
  • Helps with test interpretation
• Interpreting a Pedigree Chart:
  • Remember Mendellian modes of inheritance
  • Determine if the pedigree chart shows an autosomal or X-linked disease
  • Determine whether the disorder is dominant or recessive

Cancer Syndromes

• Breast Cancer:
  • Most common cancer in women
  • 5-10% of breast cancer cases in the US are inherited
  • BRCA1 and BRCA2:
    • Autosomal dominant mutations
    • 50-80% lifetime risk of developing breast cancer
    • 20-50% lifetime risk of ovarian cancer and moderate risk of colon and prostate cancer
• Colorectal Cancer:
  • ~1 in 21 Americans will develop colorectal cancer
  • Family History:
    • The risk of colorectal cancer in people with one affected first-degree relative is 2-3 times higher than the general population
  • Hereditary Syndromes:
    • Familial Adenomatous Polyposis (FAP)
    • Hereditary Nonpolyposis Colorectal Cancer (HNPCC) (Lynch syndrome)
    • Hereditary Colorectal Cancer