Pathology of Neoplasia

Neoplasia

  • Neoplasia: New formation, abnormal growth of tissues exceeding and un-coordinating with the evoking stimuli, loss of responsiveness to normal growth stimuli.
  • Neoplastic cells: Monoclonal, same origin from one transformed cell.
  • Nonneoplastic proliferations (reactions to inflammation): Polyclonal.
  • Neoplasia behaves as parasites, depending on the host nutrient, autonomy of growth, increases in size.
  • Some neoplasms behave as benign while others behave as malignant.
  • Malignant growth is not inhibited by contact with surrounding cells, discohesive, and transplantable, favoring invasion and metastasis.
  • Neoplastic cells bind to laminin and fibronectin in connective tissues, then secrete collagenases or proteases to invade the surrounding tissue.
  • Neoplastic cells may attain "immortality" or the ability to keep dividing indefinitely.
  • Nomenclature depends on parenchymal or mesenchymal origin, benign or malignant or borderline.
  • Parenchymal Cells: Functioning cells, like gland, epithelial, and hepatic cells.
  • Mesenchymal Cells: Supporting stroma, fibrous, muscle, and bone tissue (connective tissue).
  • Benign Tumors: add (oma) suffix to the end of the name of the tissue or cells from which they arise.
  • fibrous tissues - fibroma
  • cartilages – chondroma
  • glands - adenoma, etc.
  • Malignant Tumors: All malignant tumors are called cancer.
  • Arising from epithelial tissues - add carcinoma suffix to the tissue or cell of origin.
  • adenocarcinoma - glandular epithelium
  • squamous cell carcinoma - squamous epithelium, etc.
  • arising from mesenchymal (connective) tissue - suffix sarcoma at the end
  • fibrosarcoma - tumor from fibrous tissues,…etc.
  • Exceptions: Some malignant tumors are ended with the suffix (-oma). Seminoma, lymphoma, melanoma, teratoma, papilloma, polyp.
  • Cytological Features of Malignancy: Pleomorphism, hyperchromatism, coarse chromatin, abnormal mitotic figure, increased (Nuclear to Cytoplasmic) Ratio, presence of nucleoli.
  • Cellular Differentiation in Neoplasia: Degree of resemblance of neoplastic tissue to the original one.
  • Well Differentiated Tumors: High degree of resemblance to the normal tissue of origin.
  • Moderately Differentiated Tumor: Moderate degree of resemblance to the tissue of origin.
  • Poorly Differentiated Tumor: No resemblance to the tissue of origin, sometimes are called anaplastic tumors.
  • Anaplasia: Lack of differentiation, pleomorphism, abnormal cell morphology (atypia), abundant and/or atypical mitoses, and loss of polarity.
  • Benign tumors - well differentiated. Malignant tumors from well differentiated to undifferentiated.
  • Benign vs. Malignant Tumor
    • Benign tumors: Slowly growing mass, regular surface, capsulated, not attached to deep structures, noninvasive, no spread, well differentiated, no recurrence, no bleeding, -oma suffix
    • Malignant tumor: Rapidly growing mass, irregular surfaces, non-capsulated, attached to deep structures, invasive, spread and metastasis, poorly differentiated, recurrence, bleeding, sarcoma or carcinoma suffix
  • Hyperplasia: Increased cell number.
  • Metaplasia: Change from one cell type to another (reversible).
  • Dysplasia: Deranged cell growth resulting in cells that vary in size, shape, and organization.
  • Neoplasia: New, uncontrolled growth of cells that is not under physiologic control.
  • Dysplasia (Disordered Growth): Irreversible premalignant change affecting a focal area of epithelial tissues, without invading the basement membrane.
  • Grades of Dysplasia: Mild, mode rate, severe.
  • Invasion: Local spread when it breaches the basement membrane and invade the neighboring tissue.
  • Metastasis: Secondary spread of cancer in a remote area.
  • Invasion of Cancer: Local spread when it breaches the basement membrane and invade the neighboring tissue.
  • Local invasion occurs through a four-step process: Detachment, attachment, degradation, migration
  • Distant Spread; Metastasis of Cancer by blood, lymphatics, trans coelomic rout, through natural passages and by implantation and inoculation.
  • Staging of cancer describes the size of a tumour and how far it has spread from where it originated.
  • The grade describes the appearance of the cancerous cells; TNM system.
  • Grading schema are based upon the microscopic appearance of a neoplasm with H&E staining.
  • Diagnostic Methods for Neoplasia: History and physical examination, radiographic techniques, laboratory analyses, cytology, tissue biopsy and surgery, autopsy, serological markers, ancillary studies, flow cytometry.
  • Serological Markers Associated with Malignant Tumors:
    • hCG : choriocarcinoma
    • AFP: hepatocellular ca
    • calcitonin: thyroid medullary ca
    • prolactin: pituitary adenomas
    • CA 125: ovarian carcinoma
    • PSA: prostate carcinoma
    • chromogranin A: endocrine neoplasias
  • Etiology of Cancer: Chemical carcinogens, physical agents, ionizing radiation, oncogenic viruses.
  • Chemical Carcinogenesis: Multi-Step Process Involving numerous mutations involves initiation, promotion, progression, cancer
  • Ionizing Radiation includes: X-rays, gamma rays, particulate radiation.
  • Ultraviolet Light is Strongly epidemiologic relationship to squamous cell, basal cell, and melano-carcinoma in fair skinned people.
  • Asbestos fiber diameter is important. Thick fibers lodge in upper respiratory tract, thin fibers lodge in terminal alveoli.

Cancer Epidemiology

  • Cancer accounts for more than 20% of all deaths.
  • For most cancers, death rates in the United States have largely remained flat.
  • Carcinoma of the prostate incidence increases 30-fold from age 50 to 85.
  • Benign neoplasms have slow growth rate, are well-differentiated, and remain localized.
  • Malignant neoplasms have faster growth rate, may be well to poorly differentiated, invade surrounding tissues, and metastasize.
  • Prognosis of malignant tumors depends on size, location, cell type, degree of differentiation, rate of growth, stage, responsiveness to therapy, and general health of the patient.
  • Ten Hallmarks of Cancer 1. Growth signal autonomy- oncogenes 2. Insensitivity to growth inhibitory signals- Tumor suppressor genes 3. Evasion of PCD (apoptosis) 4. Evasion of cellular senescence- telomeres 5. Sustained angiogenesis 6. Tissue invasion and metastasis 7. Deregulated metabolic pathways 8. Evasion of the immune system 9. Chromosomal instability 10. Inflammation
  • Carcinogenic Agents
    • Chemical Carcinogens
    • Physical Agents
    • Ionizing Radiation
    • Oncogenic Viruses

Genetic Diseases

  • Genetic disease are common, 50% of spontaneous abortions during early gestation have a demonstrable genetic abnormality
  • Genetic Disorders can be categorized into monogenic, multi-factorial, chromosomal aberrations, mitochondrial disorders.
  • Mendelian Inheritance & Mutation Types: Dominant vs. Recessive Inheritance, Penetrance and Expressivity, De Novo Mutations vs. Inherited Mutations
  • Terminology in Genetics: Hereditary, Familial, Congenital, Genotype, Phenotype, Allele, Gene
  • HUNTINGTON DISEASE: Mutation in HTT gene (chromosome 4), CAG trinucleotide repeat expansion (>40 repeats), mutant huntingtin protein leads to neuronal toxicity.
  • Marfan Syndrome: Mutation in FBN1 gene (chromosome 15) defective fibrillin-1, a component of extracellular matrix, weak connective tissue due to abnormal fibrillin-1.
  • Neurofibromatosis Type 1 (NF1): Mutation in NF1 gene (chromosome 17), loss of neurofibromin, a tumor suppressor, Loss of RAS regulation, leading to increased cell proliferation.
  • ACHONDROPLASIA: caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene that results in its protein being overactive
  • CYSTIC FIBROSIS: Thickened mucus due to defective chloride and water transport, is targeted in the Nervous System.
  • PHENYLKETONURIA: Cortical atrophy, demyelination, neuronal loss, hypopigmentation, musty odor
  • SICKLE CELL ANEMIA (1/400 - 1/600): Mutation in HBB gene (chromosome 11), abnormal β-globin chain, HbS polymerizes under low oxygen, causing RBCs to sickle
  • TAY-SACHS DISEASE: Normal development to age 3-6 mos. Progressive loss of developmental milestones
  • GENETIC INSTABILITY IN CANCER: Gene, amplifications, chromosomal, translocations, retroviral insertions.
  • HAYFLICK LIMIT THEORY: average cell divide ~ 50 times before cell death telomeres on the end of the chromosome get smaller, telomeres will eventually no longer be present on the chromosome
  • Telomerase prevent cell division 15th or more times with the help of telomers.
  • Stages of Cancer TNM include Node involvement, tumor size and metastasis
  • Oncogene activation by retroviral insertions by promoter insertion and enhancer activation
  • Types and causes of numerical and structural chromosomal abnormalities
  • Amniocentesis Pros some immediate results uses amniotic fluid and fetal cells cons risky to fetus 1% complication rate done at 14-16 weeks gestation
  • Chorionic villus sampling/ test pros early test 8-10 weeks quick results cons doesn't test amniotic fluid not available everywhere 2% complication rate
  • Teratogens: Alcohol, teratoma, genetics and inherited traits affect a generation.
  • TORCH infections affect 1% to 5% of all liveborn infants in the United States
  • Agenesis is complete absence of an organ primordium lack of a specific cell type(s) in an organ Hypoplasia is reduced
  • Duchenne Muscular Dystrophy (DMD): X-linked recessive disorder caused by mutations in the DMD gene on the X chromosome.
  • Hemophilia B: X-linked recessive disorder caused by mutations in the F9 gene on the X chromosome.

Hemodynamic Disorders

  • The Starling Principle states that fluid movements between blood and tissues are determined by differences in hydrostatic and colloid osmotic (oncotic) pressures between plasma inside microvessels and fluid outside them.
  • Hydrostatic pressure arteriolar segments of capillaries is 32 mm Hg. -in the middle of the capillary, it is 20 mm Hg.
  • Normal and Aberrant chromosome segregation in meiosis by mitosis, mitosis and translocation.

Environmental Pathology

  • Environmental and occupational exposures contribute to human disease by many epidemiologic studies esablish the elevated severity of disease.
  • Fate of inspired pollutant particles depend on PM10, PM2.5 and PM0.1 particles in the terminal alveoli.
  • Gases Associated With Air Pollution: Sulfur Dioxide, Oxides of Nitrogen, Ozone, Carbon Monoxide
  • Passive Smoking health impact depends on the volume of the air in the room, number of active smokers, rate of air exchange, duration of exposure increase cardio vascular disease
  • Toxic metal exposures: Lead, mercury, arsenic.
  • Asbestos Diseases: Exposure Asbestosis and mesothelioma with Silicosis coal workers’ pneumoconiosis.
  • Lung Cancer Is Largely a Disease of Cigarette Smokers single most common cause of cancer death
  • Climate Change and heat stroke causes dehydration and renal and cardiovasculars issues
  • Lysergic Acid Diethylamide Morphologic Changes however acute effects are purely functional, involving transient changes in neuronal activity..