Neoplasia

ASCUS

Atypical squamous cells of uncertain significance.

Normal progression in cervical cancer

Normal ➔ Cell changes (dysplasia) ➔ ASCUS: Mild cell changes ➔ LSIL: Moderate cell changes ➔ HSIL: Serious cell changes ➔ Cancer ➔ Carcinoma in situ (CIN) ➔ Invasive carcinoma.

LSIL

Low grade squamous intraepithelial lesion.

Risk factors for cervical carcinoma

Early age at first intercourse, Multiple sexual partners, Male partner with multiple previous sexual partners, High risk male sexual partners, Smoking, Sexually transmitted diseases, HPV infection.

Percentage of dysplasia, carcinoma in situ, and carcinomas with HPV DNA

>99.7%.

Persistent infection with oncogenic HPV types causes cancer in

Oropharynx and anogenital regions.

High-risk types of HPV associated with cervical carcinoma

HPV 16 (50%), HPV 18 (25%), HPV 6, and HPV 11.

Gardasil®9

Protective against HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58.

Continuous spectrum of neoplasia

Normal ➔ premalignant (field cancerization) ➔ neoplasia (hyperplasia ➔ metaplasia ➔ dysplasia ➔ neoplasia).

Metaplasia

Change from one cell type to another.

Dysplasia

Bad growth.

Components of a neoplasm

Neoplastic cells, stroma and blood vessels, other cells (dendritic cells, lymphocytes).

Two main theories of neoplasia

Somatic mutation theory and Tissue organization field theory.

Multistep process in Somatic Mutation Theory

Initiation ➔ promotion ➔ progression.

Hallmarks of neoplasia

Sustain proliferative signaling, evade growth suppressors, resist cell death, enable replicative immortality, induce angiogenesis, activate invasion and metastasis, reprogramming energy metabolism, evading immune destruction.

Role of tumor suppressor genes

Control cell cycle, apoptosis, and DNA repair.

Oncogenes

Derived from proto-oncogenes.

Suffix for benign neoplasm

-oma.

Suffixes for malignant neoplasm

-carcinoma and -sarcoma.

Local and hormonal effects of neoplasia

Lymph node obstruction.

Mediator of cancer cachexia

Cachexin – TNFα.

Best method for prognosis of neoplasia

Phenotype; biopsy determines the phenotype.

Tests on samples from neoplasm or body fluids

Cytology, Histology, liquid biopsy.

Grade of a neoplasm refers to

Histological assessment of mass linked to outcome.

Stage of a neoplasm refers to

Spread to other tissues.

Staging criteria for neoplasms

Local invasion, Vascular invasion, Lymph node metastases, Distant metastases.

Cytology in staging detects

Metastases in lymph nodes.

Biopsy

Taking samples and looking at them; 'bios' = life, 'opsis' = to look.

Histology on tissue

Histopathology.

Cytology on cells

Fine needle aspiration.

Components evaluated in a liquid biopsy

Circulating tumor cells, cell free DNA – circulating tumor DNA, microRNA.

Grading of a neoplasm based on

Histological features, features of ‘malignancy’, degree of dysplasia, cell division - proliferation (mitotic count), apoptotic rate.

Pathways of metastasis

Haematogenous (angiosarcoma), Lymphatic (mammary adenocarcinoma), Surfaces and cavities (mesothelioma).

Express prognosis statistically

Death rate, Median survival, Survival ‘curve’, Survival rate (1, 2, 5, 10, 15 years).

Local disease therapies for neoplasia

Surgical excision, Cytoreduce + Radiation therapy + treat as metastatic.

Therapies for metastatic disease

Chemotherapy (cytotoxic, directed/targeted), Immune modulation.

Important tumor suppressor gene

P53.

Define disease

Failure of the adaptive mechanisms of the body; an imbalance of homeostasis.

Pathology

The study of suffering; encompasses cause, mechanisms of development, structural alterations, and functional consequences of a disease process.

Incidence of a disease

The number of new cases of a disease each year.

Prevalence of a disease

The total number of occurrences of the disease in a year.

Koch's postulates

Four criteria to establish a causative relationship between a microbe and a disease.

Three steps in pathogenesis of disease

Cause, Mechanisms, Outcome.

Cell responses to demand or insult

Adaptation, reversible injury, irreversible injury and cell death.

Causes of cell injury

Oxygen deprivation, Physical agents, Chemical agents and drugs, Infectious agents, Immunological reactions, Genetic defects, Nutritional imbalances.

Free radicals

Molecules with unpaired electrons that cause cellular damage.

Role of antioxidants

Neutralize reactive oxygen species.

Telomeres and telomerase in cell division

Telomeres shorten with division; telomerase repairs them and is abundant in stem cells and cancer cells.

Four stages of the cell cycle

G1, S, G2, M; resting cells are in G0.

Hyperplasia

Increase in number of cells due to increased demand.

Hypertrophy

Increase in cell or tissue size.

Atrophy

Reduction in size of a tissue or cell.

Two main groups of cell death

Accidental Cell Death (ACD) and Regulated Cell Death.

Define neoplasia

Disturbance of growth with continuous growth and potential to invade and metastasize.

Terms for neoplasia

Cancer and tumor.

Criteria of malignancy

Demarcation, Invasion, Rate of growth, Differentiation, Pleomorphism, Metastasis, Mitotic count.

Naming malignant epithelial neoplasms

Carcinomas.

Naming malignant stromal neoplasms

Sarcomas.

Purpose of staging a neoplasm

To determine how far the neoplasm has spread.

Factors considered in neoplasm staging

Local infiltration, vascular invasion, metastasis to lymph node, and distant metastasis.

Classification of neoplasms

Based on phenotype.

Define carcinogenesis

A multistep process of nonlethal damage at genetic and epigenetic levels.

Angiogenesis in neoplasia

Growth of new blood vessels to supply nutrients to tumors.

Steps in invasion and metastasis

Detachment, Basement membrane invasion, Vascular invasion, Circulation survival, Extravasation and homing.

DNA viruses that predispose to neoplasia

HPV, Epstein Barr virus, hepatitis B and C viruses.

HPV types associated with cervical carcinoma

HPV 16 and HPV 18, with HPV 6 and 11 also recognized.