Neoplasia

Flashcard Set 1: Neoplasia Basics (Based on PATH3610 07 Neoplasia Foster Presentation.pdf)

• Front: What does ASCUS stand for in a Pap smear? Back: Atypical squamous cells of uncertain significance.

• Front: What is the normal progression in cervical cancer? Back: Normal ➔ Cell changes (dysplasia) ➔ ASCUS: Mild cell changes ➔ LSIL: Moderate cell changes ➔ HSIL: Serious cell changes ➔ Cancer ➔ Carcinoma in situ (CIN) ➔ Invasive carcinoma.

• Front: What does LSIL stand for? Back: Low grade squamous intraepithelial lesion.

• Front: List some risk factors for cervical carcinoma. Back: Early age at first intercourse, Multiple sexual partners, Male partner with multiple previous sexual partners, High risk male sexual partners, Smoking, Sexually transmitted diseases, Human Papillomavirus (HPV) infection.

• Front: What percentage of dysplasia, carcinoma in situ, and carcinomas have HPV DNA? Back: >99.7%.

• Front: Persistent infection with oncogenic types of HPV may cause cancer in which regions? Back: Oropharynx and anogenital regions.

• Front: Name some high-risk types of HPV associated with cervical carcinoma. Back: HPV 16 (50%), HPV 18 (25%), HPV 6, and HPV 11 are high-risk types.

• Front: What is Gardasil®9 protective against? Back: HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58.

• Front: Describe the continuous spectrum of neoplasia. Back: Normal ➔ premalignant (field cancerization) ➔ neoplasia. This can also involve stages like hyperplasia ➔ metaplasia ➔ dysplasia ➔ neoplasia.

• Front: Define metaplasia. Back: Change from one cell type to another.

• Front: Define dysplasia. Back: Bad growth.

• Front: List the components of a neoplasm. Back: Neoplastic cells, stroma and blood vessels, other cells (dendritic cells, lymphocytes).

• Front: Name the two main theories of neoplasia. Back: Somatic mutation theory and Tissue organization field theory.

• Front: Outline the multistep process in the Somatic Mutation Theory of neoplasia. Back: Initiation ➔ promotion ➔ progression.

• Front: List some hallmarks of neoplasia. Back: Sustain proliferative signaling, evade growth suppressors, resist cell death, enable replicative immortality, induce angiogenesis, activate invasion and metastasis, reprogramming energy metabolism, evading immune destruction.

• Front: What is the role of tumor suppressor genes? Back: Control cell cycle, apoptosis, and DNA repair.

• Front: What are oncogenes derived from? Back: Proto-oncogenes.

• Front: What is the suffix for a benign neoplasm? Back: -oma.

• Front: What suffixes indicate a malignant neoplasm? Back: -carcinoma and -sarcoma.

• Front: What are some local and hormonal effects of neoplasia on the host? Back: Lymph node obstruction.

• Front: What mediates cancer cachexia? Back: Cachexin – TNFα.

• Front: What is currently the best method for prognosis of neoplasia? Back: Phenotype. Biopsy is the method to determine the phenotype.

• Front: What tests are done on samples from a neoplasm or body fluids? Back: Cytology, Histology, and liquid biopsy.

• Front: What does the grade of a neoplasm refer to? Back: Histological assessment of mass linked to outcome.

• Front: What does the stage of a neoplasm refer to? Back: Spread to other tissues.

• Front: List the staging criteria for neoplasms. Back: Local invasion, Vascular invasion, Lymph node metastases, Distant metastases.

• Front: What can cytology be used for in the context of staging? Back: Detection of metastases in lymph nodes.

• Front: Define biopsy. Back: Taking samples and looking at them. bios = life, opsis = to look.

• Front: What is histology on tissue called? Back: Histopathology.

• Front: What is cytology on cells called? Back: Fine needle aspiration.

• Front: List some components evaluated in a liquid biopsy. Back: Circulating tumor cells, cell free DNA – circulating tumor DNA, microRNA.

• Front: What is grading of a neoplasm based on? Back: Histological features, features of ‘malignancy’, degree of dysplasia, cell division - proliferation (mitotic count), apoptotic rate.

• Front: Name the pathways of metastasis. Back: Haematogenous (angiosarcoma), Lymphatic (mammary adenocarcinoma), Surfaces and cavities (mesothelioma).

• Front: List some ways to express prognosis statistically. Back: Death rate, Median survival, Survival ‘curve’, Survival rate (1 year, 2 year, 5 year, 10 year, 15 year).

• Front: What are some local disease therapies for neoplasia? Back: Surgical excision, Cytoreduce + Radiation therapy + treat as metastatic disease.

• Front: What are some therapies for metastatic disease? Back: Chemotherapy (cytotoxic, directed/targeted), Immune modulation.

• Front: Name an important tumor suppressor gene. Back: P53.

Flashcard Set 2: General Pathology and Neoplasia (Based on PATH3610 Course Materials Required reading Course Notes (1).pdf)

• Front: Define disease. Back: ‘dis-’ meaning ‘from’, and ‘ease’ form the term ‘disease’. It is the failure of the adaptive mechanisms of the body, an imbalance of homeostasis.

• Front: What is pathology? Back: The study of suffering (pathos meaning ‘suffering’, ‘-ology’ is 'the study of'). It brings together the cause (aetiology), mechanisms of development (pathogenesis), structural alterations (lesions), and functional consequences (clinical significance) of a disease process.

• Front: What is incidence of a disease? Back: The number of new cases of a disease each year.

• Front: What is prevalence of a disease? Back: The number of occurrences of the disease in a year and is the total number affected.

• Front: Outline Koch's postulates. Back: i. The suspected organism must always be present in the lesions, ii. It must be grown in a pure culture on laboratory media, iii. It must cause the same disease when injected into a susceptible animal, and iv. It must be recovered from the experimental animal.

• Front: Describe the three steps in the pathogenesis of disease. Back: i. Cause: Providing a cause, ii. Mechanisms: Outlining the mechanisms involved, iii. Outcome: Clinical signs or lesions.

• Front: List the three responses of a cell to demand or insult. Back: Adaptation, reversible injury, and irreversible injury and cell death.

• Front: What are some potential causes of cell injury? Back: Oxygen deprivation (hypoxia), Physical agents, Chemical agents and drugs, Infectious agents, Immunological reactions, Genetic defects, Nutritional imbalances.

• Front: Define free radicals and how they cause injury. Back: Molecules that have an unpaired electron and release considerable energy. They can damage lipids and phospholipids of cell membranes, proteins, and nucleic acids and nucleotides.

• Front: How do antioxidants protect against free radical damage? Back: They neutralize reactive oxygen species.

• Front: What is the role of telomeres and telomerase in cell division? Back: Telomeres are nontranscribed sequences at the end of chromosomes that shorten with each division. Telomerase is an enzyme that repairs shortened telomeres and is abundant in stem cells, germ cells, and cancer cells, contributing to their potential for immortality.

• Front: List the four stages of the cell cycle. Back: G1 (presynthetic), S (DNA synthesis), G2 (premitotic), M (mitotic). Resting cells are in the G0 phase.

• Front: Define hyperplasia. Back: An increase in the number of cells and it is a common response to increased demand of cells that are continuously dividing (labile).

• Front: Define hypertrophy. Back: An increase in cell size or tissue size because of an enlargement in the size of the cell or cells.

• Front: Define atrophy. Back: A tissue or a cell reduces its size, usually in response to decreased demand.

• Front: What are the two main groups of cell death? Back: Accidental Cell Death (ACD) and Regulated Cell Death.

• Front: Define neoplasia. Back: A disturbance of growth involving changes in the size of organs, tissues, or cells. Neoplastic cells exhibit continuous growth, cellular atypia, and may have the ability to invade and metastasize. They have often avoided checkpoints in the normal cell cycle.

• Front: What are some scientific and popular terms for neoplasia? Back: Cancer and tumour.

• Front: What are the criteria of malignancy when comparing benign and malignant neoplasms? Back:

  • Demarcation: Benign - well, Malignant - poor

  • Invasion: Benign - expansile, Malignant - Yes

  • Rate of growth: Benign - low, Malignant - high

  • Differentiation and anaplasia: Benign - well, Malignant - poor

  • Pleomorphism: Benign - little, Malignant - marked

  • Metastasis: Benign - no, Malignant - yes

  • Mitotic count: Benign - low, Malignant - high

• Front: How are malignant epithelial neoplasms named? Back: Carcinomas.

• Front: How are malignant stromal or mesenchymal neoplasms named? Back: Sarcomas.

• Front: What are the main ways metastasis occurs? Back:

  1. Surfaces and cavities

  2. Via the lymphatics

  3. Haematogenously

  4. By contact (unusual)

• Front: What is the primary purpose of staging a neoplasm? Back: To determine how far the neoplasm has spread throughout the body.

• Front: What factors are considered when staging a neoplasm? Back: Local infiltration, vascular invasion, metastasis to a local lymph node, and distant metastasis.

• Front: How are neoplasms classified? Back: Based on phenotype.

• Front: Define carcinogenesis. Back: A multistep process involving nonlethal damage at the genetic and epigenetic levels, and there is progression from one step to the next. The basic steps are initiation, promotion, and progression.

• Front: What is angiogenesis in the context of neoplasia? Back: The growth of new blood vessels that many neoplasms develop to obtain nutrients. This occurs because of the production of tumour-associated angiogenic factors, especially Vascular Permeability Factor – Vascular Endothelial Growth Factor (VPF-VEGF).

• Front: Outline the steps involved in invasion and metastasis. Back:

  1. Detachment

  2. Invasion of the basement membrane and tissue

  3. Invasion of vasculature

  4. Survival in circulation

  5. Extravasation and homing

• Front: Name some DNA viruses that predispose to neoplasia. Back: Human papilloma virus, Epstein Barr virus (Burkitt's lymphoma), and hepatitis B and C viruses.

• Front: Which types of HPV are most commonly associated with cervical carcinoma? Back: HPV 16 (about half of the cases) and HPV 18 (one quarter). HPV 6 and 11 are also commonly recognized types.