Oncology and Neoplasia Overview

Neoplasm

• Neoplasia means new growth; a new growth is called a neoplasm.
• Tumor originally referred to swelling caused by inflammation, but now is equated with neoplasm.
• Oncology is the study of tumors or neoplasms, based on the Greek word for tumor (oncos).
• A neoplasm is an abnormal mass of tissue, growing excessively and uncoordinated with normal tissue, persisting even after the initial stimulus ceases.
• James Ewing defined a neoplasm as a relatively autonomous growth of tissue.

Normal and Cancer Cell Development

• Normal cell development involves normal cell growth and division, resulting in healthy tissue.
• Abnormal cell growth, due to genetic changes, leads to cancerous cells that divide uncontrollably, forming a malignant tumor.

Oncogenes

• Oncogenes are genetic mutations that can cause cancer, arising from mutated genes that manage cell growth.
• When genes change into oncogenes, cells grow and divide uncontrollably.
• Genes promoting autonomous cancer cell growth are oncogenes; their normal counterparts are proto-oncogenes.
• Oncogenes are created by mutations in proto-oncogenes, promoting cell growth without normal signals.

Proto-oncogenes

• Genes that regulate normal cell growth and division.
• Proto-oncogenes can mutate into oncogenes, causing cancer.

Molecular Basis of Cancer

• Non-lethal genetic damage (mutations) underlies carcinogenesis.
• Mutations can be acquired through environmental factors (chemicals, radiation, viruses/bacteria) or inherited in the germline.
• The term "environmental" includes acquired defects from exogenous agents or endogenous products of cell metabolism.
• Tumors form via the clonal expansion of a single precursor cell with genetic damage.
• Normal regulatory genes—growth-promoting proto-oncogenes, growth-inhibiting tumor suppressor genes, cell death regulators (apoptosis), DNA repair genes, and metastatic genes—are primary targets for genetic damage.
• Carcinogenesis is a multistep process affecting both phenotypic and genetic levels through the accumulation of multiple mutations.

Neoplasm Types

• Neoplastic types include benign and malignant neoplasms.
• Benign tumours are localized, non-invasive, and usually treatable surgically.
• Malignant tumours are invasive, spread to distant sites, and are often fatal if not treated.
• Malignant tumours are more commonly referred to as cancers.

Benign Neoplasms

• Characterized by well-differentiated cells, slow growth rates, cohesive expansive growth patterns, and confinement to their site of origin, lacking the capability for metastasis.
• Examples of common benign neoplasms include fibroids, polyps, and sebaceous cysts.

Malignant Neoplasms

• Consist of undifferentiated cells (anaplastic), having erratic growth patterns, capable of local invasion and metastasis.
• Types include sarcomas (mesenchymal origins), and carcinomas (epithelial origins).

Mechanisms of Tumor Invasion and Metastasis

• Carcinoma in situ refers to a group of abnormal cells found only where they initially formed.
• Malignant cells bind to basement membrane components.
• Cancer cells disrupt and invade basement membranes via collagenase type IV and other proteases.
• Tumor cells invade the extracellular matrix.
• Cancer cells detach and enter the circulatory system (embolization).
• Cancer cells survive in the circulation.
• Cancer cells exit the circulatory system at secondary sites (extravasation).
• Cancer cells evade the host immune system and grow progressively.
• Metastatic colonization occurs at secondary sites.

Pathways of Spread

• Seeding of body cavities and surfaces (transcoelomic spread) involves a malignant neoplasm penetrating a natural "open field" (e.g., peritoneal cavity, pleural, pericardial, subarachnoid, joint spaces).
• Lymphatic spread is the primary pathway for carcinoma dissemination, with lymphatic node involvement proportional to tumor cell numbers reaching nodes.
• Hematogenous spread is common to sarcomas and certain carcinomas, where tumor cells form emboli, aggregating in the circulatory system and adhering to leukocytes, mostly platelets.

Premalignant Disorders

• Hereditary premalignant disorders include familial cancers. Examples include breast, ovarian, colon, and brain cancers.
• Defective DNA repair is an autosomal recessive syndrome. Acquired preneoplastic disorders also exist.

Carcinogenesis

• Genetic damage and neoplastic transformation of cells can result from exposure to a variety of harmful factors, classified into chemical, radiation, and viral/bacterial causes.

Effects of Tumors on the Host

• Local and hormonal effects: Tumors in endocrine glands cause insufficiency through destruction, and in the gut, cause obstruction through expansion.
• Cancer cachexia is a significant symptom, characterized by progressive loss of body fat and lean mass, weakness, anorexia, and anemia, with some correlation to tumor burden.

Immunology

• Immunology is the study of molecules, cells, organs, and systems responsible for recognizing and eliminating foreign material in the body.
• Immunity is the body's protective mechanism against pathogenic microorganisms, classified into non-specific (innate) and specific (adaptive) immunity.

Innate Immunity

• The innate immune system is a body's rapid, non-specific first line of defense against pathogens.
• It employs physical barriers (skin, hair, mucous membranes and acidic content of the GIT, Vagina).
• Certain WBCs (basophils, mast cells, monocytes, neutrophils, macrophages) respond quickly to infections.

Adaptive Immunity

• The adaptive immune system provides a specific defense to pathogens that have breached innate immunity.
• It develops over time, via pathogen encounters or vaccinations.
• It is more specific than innate immunity and has memory, relying on T and B lymphocytes to respond.

Host Defense Against Tumors (Immune Surveillance)

• Tumors are not always entirely self. Paul Ehrlich proposed that the immune system can recognize and eliminate certain tumors.
• Lewis Thomas and Macfarlane Burnet coined the term immune surveillance—a normal immune system function that monitors the body for emerging malignant cells and destroys them.

Anti-Tumor Effector Mechanisms

• Cell-mediated immunity is the dominant anti-tumor mechanism, using T cells like cytotoxic T lymphocytes (CD8+ CTLs) to combat virus-associated neoplasms (e.g., EBV, HPV).
• Natural killer (NK) cells directly destroy tumor cells without prior sensitization, a crucial first line of defense.
• Macrophages exhibit cytotoxicity against tumor cells and collaborate with T and NK cells through cytokine interferon-γ activation.
• Antibodies have limited protective effects against spontaneous tumors but can be therapeutic when targeting tumor cells. Monoclonal antibodies against CD20 (a B-cell surface antigen) are widely used for lymphoma treatment.

Immune Surveillance and Escape

• Most cancers arise in individuals without overt immunodeficiencies, implying that tumor cells have mechanisms to escape or evade immunocompetent immune systems.
• Tumor evasion mechanisms can include the failure to produce tumor antigens, antigen loss variants of tumor cells, mutations in MHC genes, production of immunosuppressive proteins such as TGF-β, etc.

This quiz explores the fundamental concepts of neoplasia, including neoplasms, tumor classifications, and the role of oncogenes in cancer development. Test your understanding of how normal and cancer cell development differs and the implications of genetic mutations. Perfect for students of oncology and related fields.