ONCOLOGY
ONCOLOGY
Objectives
Upon completion of this section, students will be able to:
Describe the characteristics of various neoplasms.
Explain the basic characteristics of a cancer cell.
Discuss how cancer cells are spread.
Define grading and staging of cancer cells and the appropriate classification systems.
Explain various neoplasms, their pathogenesis and pathophysiology.
Key Terms
Neoplasm: An abnormal mass of tissue that forms where cell growth has escaped normal regulatory controls.
Benign: Non-cancerous neoplasms that do not spread and are usually well-moderated in their growth, resembling normal tissue.
Malignant: Cancerous neoplasms that grow rapidly, invade nearby tissues, and can metastasize to distant sites.
Metaplasia: The transformation of one differentiated cell type to another, often in response to chronic inflammation or injury.
Metastasis: The spread of cancer cells from the primary site to other areas of the body.
Heterogeneity: The existence of variations among cancer cells within the same tumor.
Undifferentiated: Cells that lack specialized features and functions typical of their tissue of origin.
Microenvironment: The surrounding environment of a tumor, including neighboring cells, extracellular matrix, and signaling molecules.
Neoplasms
Understanding malignancy and metastatic disease involves the study of how abnormal cell growth occurs, differentiates, and spreads.
Review of Structure and Function
Cell division continues into specialized cells, which include:
Labile Cells: Cells that continuously divide (e.g., skin, gastrointestinal lining).
Stable Cells: Cells that do not normally divide but can be stimulated to divide (e.g., liver cells).
Epithelial Cells: Cells that line surfaces of organs and structures in the body.
Connective Tissue Cells: Provide support and structure.
Muscle Cells: Cells that contract to facilitate movement.
Nervous Tissue Cells: Conduct electrical impulses for signaling throughout the body.
Hyperplasia and Hypertrophy
Hyperplasia and hypertrophy are exaggerated responses to a growth stimulus:
Hyperplasia means "overgrowth" of cells, e.g., skin tags.
Hypertrophy means "oversized" cells, e.g., cardiac hypertrophy (enlargement of heart muscle).
Hyperplasia vs. Hypertrophy
Hyperplasia: Increase in the number of cells (e.g., skin tag).
Hypertrophy: Individual cells become enlarged (e.g., enlarged heart).
Alterations in Cell Growth and Replication
Neoplasia = "new growth" that lacks normal regulatory controls.
Can originate in one organ, with prostate cancer being most common in men and breast cancer in women.
Lung cancer is the leading cause of cancer death in both genders and can spread from another site.
Benign vs. Malignant Cancer
Benign:
Slow-growing, localized, well-defined, resembles host tissue (more differentiated).
Grows by expansion without invading adjacent tissues, generally non-fatal.
Malignant:
Rapidly growing, can spread (metastasis) quickly, fatal, highly undifferentiated.
Metaplasia and Neoplasia
Metaplasia: Replacement of one tissue type with another, can be a normal response or pathologic change.
Neoplasia: Increased cell proliferation in the absence of a stimulus. It signifies a pathologic form of hyperplasia.
Hyperplasia and Neoplasia
Neoplasias cannot be distinguished from hyperplasias without a histological examination (biopsy).
Treatment differs significantly; neoplasias are autonomous in growth, unlike hyperplasias which cease growth once the stimulus is removed.
Proliferation of Neoplastic Cells
Autonomous Growth: Independent growth factors and stimuli promote normal cell growth.
Excessive Proliferation: Unceasing growth, unregulated by normal cellular signals.
Disorganized Growth: Neoplastic tissue formation disregards the rules governing normal tissue formation.
Classification of Neoplasms
Neoplasms typically fall into three categories:
Benign
Malignant
Uncertain malignant potential
Benign Neoplasms
Generally localized and remain within the tissue where they originated.
Present as a single discrete mass, encapsulated for easier excision, with cells resembling the cells of origin.
Malignant Neoplasms
Likely to invade nearby structures or spread to distant sites.
Anaplasia: Cells lose differentiation and display new features uncharacteristic of their tissue of origin.
Anaplastic cells are cancer cells, characterized by aggressive proliferation.
Etiology of Cancer Cells
Cancer development begins with an alteration called initiation, which grants autonomous growth potential.
Initiated by carcinogens, which can be physical (radiation), chemical, or biological agents.
Pleomorphism: Variation in size, shape, and staining properties of the cancer cells.
Causes of Cancer
Carcinogens: Substances that cause or increase cancer risk:
Radiation (UV light, X-rays)
Air pollution
Inhaled toxins (e.g., smoking)
Certain viruses and fungi (e.g., HPV, EBV, HBV)
Nitrates from food
Certain drugs/medications (e.g., steroid hormones, chemotherapy drugs)
Industrial exposure (e.g., steel mills, coal mines, asbestos, arsenic in pesticides)
Carcinogenesis
Steps in carcinogenesis:
Initiation: Introduction of the carcinogenic agent.
Promotion: Induction of uncontrolled growth following the initiation.
Progression: Permanent malignant changes occur after promotion.
Factors include heredity, oncogenes, and carcinogens.
Oncogenes
C-onc: Cellular genes that are mutated versions of our DNA, leading to abnormal protein expression promoting cell growth.
Can transform into cancer genes by:
Point mutation: A single base substitution in DNA.
Gene amplification: Increased number of copies (e.g., in neuroblastoma).
Chromosomal rearrangement: Translocation of chromosomal fragments (e.g., in Burkitt’s lymphoma).
Insertion of a viral genome: A slow-acting virus that alters DNA (e.g., HBV in liver cancer).
Oncogenes and Tumor Suppressing Genes
Initiators turn oncogenes "on", leading to cell proliferation through growth-enhancing products.
Tumor suppressor genes usually keep oncogenes in check, but mutations can lead to loss of their function.
Tumor Suppressing Genes
Normal cells regulate oncogenes; when a malignant cell merges with a normal cell, it may create a benign tumor due to the tumor suppressor genes regulating the malignant cell.
Hereditary Cancer
Some cancers occur more frequently in particular families due to inherited cancer genes and errors in genetic make-up affecting metabolism, resulting in increased incidence (e.g., breast or colon cancer).
Immune Response
Benign cells usually resemble their tissue of origin, while malignant cells have significantly altered appearances, making them resemble foreign bodies.
Tumor antigens: Antibodies produced to attack tumor cells (e.g., CEA in colon cancer).
Some small tumors can be cured through immune responses, leading to treatment development like immunotherapies.
Tumor Cells under the Microscope
Benign Cells:
Regularly shaped nuclei.
Consistent size.
Normal distribution of chromatin.
Cells perform their normal functions due to well-developed cytoplasm and organelles.
Malignant Cells:
Pleomorphic nuclei (varied sizes and shapes).
Hyperchromatic nuclei and uneven chromatin distribution.
Large nuclei relative to cytoplasm, few organelles, diminished functionality.
Increased rates of mitosis.
Clinical Manifestations of Neoplasms
Depend on:
Type of cancer
Tumor location
Histological grade
Clinical stage
Immune status of the host/immuno-response
Tumor cell sensitivity to therapy
Symptoms of Malignant Tumors
Loss of well-being, neurologic symptoms, obstructive airways, skin lesions,
liver enlargement, ascites, rectal/urinary/vaginal bleeding, dyspnea, splenomegaly, intestinal obstruction, abdominal mass.
Clinical Manifestations
Change in bowel or bladder habits, a sore that doesn’t heal,
unusual bleeding or discharge, thickening or lump in the breast or elsewhere,
indigestion or difficulty swallowing, changes in a wart or mole, nagging cough or hoarseness.
Complications of Cancer
Common complications:
Anemia
Cachexia
Fatigue
Infection
Leukopenia
Thrombocytopenia
Pain
Diagnosis of Cancer
Diagnostic methods include:
Biopsy
Blood smear
Cytology
Radiologic Examination
Endoscopic Examination
Biopsy Details
Can be performed through:
Needle aspiration
Endoscopy
Laparoscopy
Excision
Tumor markers: Substances found on the surface of tumor cells, used for screening, diagnosing, monitoring treatment, and assessing remission.
Miscellaneous procedures: Include X-rays, isotope scanning, CT scans, endoscopies, ultrasonography, MRI, PET scans.
Metastasis
Metastasis denotes the process of neoplasms spreading from a primary location to other body sites.
Main pathways for metastasis:
Lymphatic system
Hematogenous spread: Spread via blood.
Seeding: Describes the process of tumors spreading to the surfaces of other organs or body cavities.
Histologic Classification
Tumors are named based on the cell type they most resemble, usually correlating with tissue of origin.
Mesenchymal cells: Connective tissues, muscles, bones.
Suffix "-oma" for benign tumors:
Fibroma (fibroblasts)
Chondroma (cartilage tissue)
Lipoma (fat cells)
Osteoma (bone cells)
Adenomas: Benign epithelial tumors.
Malignant Tumors
Malignant tumors of mesenchymal cells typically use the suffix -sarcoma:
Examples: Fibrosarcoma, Chondrosarcoma.
Carcinomas are malignant tumors of epithelial origin:
Examples: Squamous cell carcinoma, adenocarcinomas (malignant glandular cells).
Exceptions to the Classification Rules
Some malignancies, such as lymphoma and glioma, end with “-oma” despite being malignant.
Some have the same name for benign or malignant forms.
Tumor Staging
Staging assesses the tumor's spread extent.
Done through imaging, biopsies, and surgical assessment.
Assessments include primary tumor size, presence of metastasis, and lymph node involvement.
Scale ranges from I-IV or A-D.
Stage I: Isolated tumor with the best prognosis.
Stage IV: Tumor has spread significantly, leading to a grim prognosis.
Tumor Grading
Grading relies on histological examination of cells:
Grade I: Well-differentiated cells.
Grade II: Moderately well-differentiated.
Grade III: Undifferentiated.
Staging and grading are critical for treatment planning and prognostication.
TNM System
The TNM classification system evaluates three aspects of cancer:
T: Size and invasion of the primary tumor.
N: Lymph node metastasis extent.
M: Distant metastasis presence.
Table 6-4 Example of TNM Grouping for Colon Carcinoma
Tumor Characteristics:
T1: Invades through the basement membrane into submucosa.
T2: Invasions into the smooth muscle layer of the bowel wall.
T3: Invades through smooth muscle into pericolic fat.
T4: Malignant cells present on the peritoneal surface or adjacent organs.
Lymph Node Characteristics:
NO: No lymph node metastasis.
N1: Metastasis to 1-3 regional lymph nodes.
N2: Metastasis to 4 or more regional lymph nodes.
Distant Metastasis:
M0: No distant metastasis.
M1: Presence of distant metastasis.
Frequency and Significance
Cancer prognosis is influenced by:
Type of cancer.
Disease extent at discovery.
Efficacy of available therapies.
Notably, the incidence of malignant tumors is approximately double the mortality rate.
Mortality
Mortality refers to the number of deaths attributed to cancer, with specific rates impacting prognosis and treatment strategies.
Peak Age of Occurrence of Particular Malignancies
0-10 Years: Acute lymphocytic leukemia.
10-20 Years: Hodgkin lymphoma, cervical cancer.
20-30 Years: Testicular cancers, thyroid cancer, leukemia.
30-40 Years: Breast cancer, endometrial carcinoma.
40-50 Years: Ovarian cancers, lung cancer.
Estimated Deaths and New Cases by Cancer Type
Males:
Most common cancers include prostate, lung & bronchus, colon & rectum.
Females:
Breast cancer, lung & bronchus, uterus corpus cancer.
Estimated Figures for 2024
Prostate: 299,010; Lung & bronchus: 118,270; Colon & rectum: 71,270; Breast: 310,720.
Treatment Modalities
Surgical Removal: Most common initial treatment approach.
Radiation Therapy: Various methods including traditional therapy, Gamma Knife, and proton therapy.
Chemotherapy: Various forms including traditional chemical drugs and novel immunotherapies.
Targeted Therapies: Innovations aimed at specific pathways in cancer cells (e.g., radioiodine therapy).
Non-PET Oncology Imaging Techniques
Ga-67 tumor imaging, Peptide imaging, Molecular breast imaging, Lymphoscintigraphy.
PET Oncology Imaging Techniques
FDG utilized for general oncologic imaging, with specific tracers for prostate, breast cancer, and neuroendocrine tumors.
Inflammation and Hypoxia Targeting
A) Targeting Inflammation
NSAIDs - Aspirin, Ibuprofen, Naproxen.
NF-κB inhibitors such as Curcumin, Resveratrol.
JAK inhibitors and anti-inflammatory signaling blockade.
B) Targeting Hypoxia in Tumor Microenvironment (TME)
Inhibition of HIF-1 and GLUT signaling pathways.
Targeting mTOR pathways to improve treatment responses.
C) Nerve Supply Targeting in TME
Surgical and chemotherapeutic approaches to block nerve inputs to tumors may enhance treatment efficacy.
Most advanced treatments involve specific immunotherapies, creating engineered T-cells to target tumor antigens more effectively.