Makindo Medical Notes

Cancer is a group of diseases characterized by uncontrolled cell growth, invasion into surrounding tissues, and potential spread (metastasis) to distant body parts. It results from genetic mutations and epigenetic alterations that disrupt normal cellular processes, including cell cycle regulation, apoptosis, and DNA repair mechanisms.

Types of Cancer

• Carcinomas:
  • Originates from epithelial cells that line internal organs and body surfaces.
  • Includes adenocarcinomas (glandular cells) and squamous cell carcinomas (squamous epithelium).
• Sarcomas:
  • Arises from connective tissues, such as bone, muscle, fat, and cartilage.
  • Includes osteosarcoma (bone), liposarcoma (fat), and rhabdomyosarcoma (muscle).
• Leukaemias:
  • Cancers of the blood and bone marrow, characterized by the proliferation of abnormal white blood cells.
• Lymphomas:
  • Cancers of the lymphatic system, including Hodgkin lymphoma and non-Hodgkin lymphoma.
• Central Nervous System (CNS) Cancers:
  • Includes cancers of the brain and spinal cord, such as gliomas and meningiomas.

Pathogenesis of Cancer

• Genetic Mutations:
  • Oncogenes: Mutated genes that promote cell proliferation and survival (e.g., RAS, MYC).
  • Tumour Suppressor Genes: Genes that normally inhibit cell division and promote apoptosis (e.g., TP53, RB1). Mutations lead to loss of function.
• Epigenetic Alterations:
  • Changes in DNA methylation, histone modification, and non-coding RNA expression that regulate gene expression without altering the DNA sequence.
• Cell Cycle Dysregulation:
  • Disruption of the normal cell cycle checkpoints, leading to uncontrolled cell division.
• Apoptosis Evasion:
  • Resistance to programmed cell death, allowing survival of abnormal cells.
• Angiogenesis:
  • Formation of new blood vessels to supply nutrients and oxygen to the tumour.
• Metastasis:
  • Spread of cancer cells from the primary tumour to distant organs via the bloodstream or lymphatic system.

Hallmarks of Cancer

• Sustaining Proliferative Signaling:
  • Cancer cells continuously receive signals to divide, often through mutations in growth factor receptors.
• Evading Growth Suppressors:
  • Mutations in tumour suppressor genes prevent normal regulation of cell growth.
• Resisting Cell Death:
  • Cancer cells evade apoptosis through mutations in pro-apoptotic and anti-apoptotic genes.
• Enabling Replicative Immortality:
  • Cancer cells maintain telomere length, allowing unlimited cell division.
• Inducing Angiogenesis:
  • Tumours stimulate the formation of new blood vessels to sustain growth.
• Activating Invasion and Metastasis:
  • Cancer cells acquire the ability to invade surrounding tissues and spread to distant sites.

Diagnosis of Cancer

• Imaging Techniques:
  • X-rays, CT scans, MRI, and PET scans are used to visualize tumours and assess their size, location, and spread.
• Biopsy:
  • Removal of tissue samples for histopathological examination to confirm the presence and type of cancer.
• Laboratory Tests:
  • Blood tests, including tumour markers (e.g., PSA, CA-125), can support diagnosis and monitoring.
• Molecular Diagnostics:
  • Genetic and genomic tests identify specific mutations and guide targeted therapy.

Treatment of Cancer

• Surgery:
  • Removal of the primary tumour and, in some cases, surrounding tissues and lymph nodes.
• Radiation Therapy:
  • Use of high-energy radiation to kill cancer cells and shrink tumours.
• Chemotherapy:
  • Use of cytotoxic drugs to kill or inhibit the growth of cancer cells.
• Targeted Therapy:
  • Drugs that specifically target molecular pathways involved in cancer growth and progression.
• Immunotherapy:
  • Stimulation of the immune system to recognize and attack cancer cells.
• Hormone Therapy:
  • Use of hormones or hormone-blocking drugs to treat cancers that are hormone-sensitive (e.g., breast, prostate cancer).
• Stem Cell Transplant:
  • Replacement of damaged bone marrow with healthy stem cells after high-dose chemotherapy or radiation therapy.

Prevention and Risk Factors

• Modifiable Risk Factors:
  • Tobacco use, excessive alcohol consumption, unhealthy diet, physical inactivity, and exposure to carcinogens (e.g., asbestos, UV radiation).
• Non-Modifiable Risk Factors:
  • Genetic predisposition, family history of cancer, age, and certain infections (e.g., HPV, Hepatitis B and C).
• Prevention Strategies:
  • Lifestyle modifications, vaccination (e.g., HPV, Hepatitis B), regular screenings, and early detection.

Summary

Cancer is a complex disease characterized by uncontrolled cell growth and the potential to invade and metastasize. It results from genetic mutations, epigenetic alterations, and disruptions in cellular processes. Diagnosis involves imaging, biopsy, and molecular diagnostics. Treatment options include surgery, radiation, chemotherapy, targeted therapy, immunotherapy, hormone therapy, and stem cell transplant. Prevention focuses on modifiable risk factors and regular screenings to detect cancer early and improve outcomes.

Overview of Cancer Histology

Cancer histology involves the microscopic examination of tissue samples to study the appearance and structure of cancer cells. Histological analysis is crucial for diagnosing cancer, determining its type, grade, and stage, and guiding treatment decisions. It helps distinguish between benign and malignant tumours and provides insight into the biological behavior of the cancer.

Histological Types of Cancer

• Carcinomas:
  • Arise from epithelial cells lining the body's internal and external surfaces.
  • Subtypes include:
    • Adenocarcinomas: Originate from glandular epithelium (e.g., breast, prostate, colon).
    • Squamous Cell Carcinomas: Arise from squamous epithelium (e.g., skin, oesophagus, lung).
    • Transitional Cell Carcinomas: Found in the urinary system, particularly the bladder.
• Sarcomas:
  • Originate from mesenchymal tissues such as bone, muscle, fat, and cartilage.
  • Subtypes include:
    • Osteosarcoma: Bone tissue.
    • Liposarcoma: Fat tissue.
    • Rhabdomyosarcoma: Skeletal muscle.
    • Chondrosarcoma: Cartilage.
• Leukaemias:
  • Cancers of the blood and bone marrow characterized by the proliferation of abnormal white blood cells.
• Lymphomas:
  • Cancers of the lymphatic system, including:
    • Hodgkin Lymphoma: Characterized by the presence of Reed-Sternberg cells.
    • Non-Hodgkin Lymphoma: A diverse group of lymphatic cancers.
• Central Nervous System (CNS) Cancers:
  • Cancers arising in the brain and spinal cord, such as gliomas and meningiomas.

Histological Features of Cancer

• Cellular Atypia:
  • Cancer cells often show abnormal size, shape, and organization compared to normal cells.
  • Features include increased nuclear size, irregular nuclear contours, and prominent nucleoli.
• Increased Mitotic Activity:
  • Higher number of cells undergoing division (mitosis), indicating rapid cell proliferation.
  • Presence of atypical mitotic figures.
• Loss of Normal Tissue Architecture:
  • Disruption of the normal arrangement of cells and tissues.
  • Formation of disorganized masses or nests of cancer cells.
• Invasion and Metastasis:
  • Cancer cells infiltrate surrounding tissues and structures.
  • Evidence of spread to distant sites via lymphatic or blood vessels.
• Necrosis:
  • Areas of dead or dying tissue within the tumour due to insufficient blood supply.

Grading and Staging of Cancer

• Grading:
  • Assessment of the degree of differentiation and aggressiveness of the cancer cells.
    • Well-Differentiated: Cancer cells resemble normal cells and tend to grow slowly.
    • Moderately Differentiated: Cancer cells show more differences from normal cells and have a faster growth rate.
    • Poorly Differentiated: Cancer cells look very different from normal cells and grow rapidly.
  • Grading systems vary by cancer type (e.g., Gleason score for prostate cancer, Bloom-Richardson grading for breast cancer).
• Staging:
  • Assessment of the extent of cancer spread in the body.
    • T (Tumour): Size and extent of the primary tumour.
    • N (Nodes): Involvement of regional lymph nodes.
    • M (Metastasis): Presence of distant metastasis.
  • Common staging systems include TNM (Tumour, Node, Metastasis) and stage grouping (I-IV).

Techniques in Cancer Histology

• Histopathological Examination:
  • Microscopic analysis of tissue sections stained with hematoxylin and eosin (H&E) to evaluate cell morphology and tissue architecture.
• Immunohistochemistry (IHC):
  • Use of antibodies to detect specific antigens in cancer cells, aiding in diagnosis and classification.
  • Markers can indicate cell type, origin, and molecular characteristics (e.g., HER2 in breast cancer).
• Molecular Pathology:
  • Analysis of genetic and molecular alterations in cancer cells using techniques like PCR, FISH, and next-generation sequencing (NGS).
  • Provides information on mutations, gene expression, and potential targets for therapy.

Clinical Relevance

• Diagnosis and Classification:
  • Histological examination is essential for confirming cancer diagnosis and identifying the type and subtype.
• Treatment Planning:
  • Grading and staging provide critical information for selecting appropriate treatment strategies.
• Prognosis:
  • Histological features, grade, and stage are important prognostic factors that help predict disease outcome and survival.
• Research and Development:
  • Histological studies contribute to understanding cancer biology and developing new diagnostic and therapeutic approaches.

Summary

Cancer histology involves the microscopic examination of tissue samples to diagnose and classify cancers, determine their grade and stage, and guide treatment decisions. Histological features include cellular atypia, increased mitotic activity, loss of normal tissue architecture, invasion, and necrosis. Techniques such as histopathological examination, immunohistochemistry, and molecular pathology are essential for accurate diagnosis and effective management of cancer.