Clinical aspects of Cancer Diagnosis

B. PATHOPHYSIOLOGY

 Cancer, as a single word, incorporates a vast diversity of diseases since there

are as many tumor types as there are cell types in the human body.
 Cancer is not a single disease, but a group of heterogenous diseases that share
common biologic properties (e.g., clonal cell growth and invasive ability).
 Each specific cancer occurs through mutations in specific genes.

Proliferative Growth Patterns

 Cell proliferation is the process by which cells divide and reproduce.

 Neoplasm. Abnormal cell differentiation and growth results in an abnormal
mass of tissue.
 Neoplasms are classified as benign or malignant.
 Cancer is the common term for all malignant tumors.

Benign Growth Patterns

 Hypertrophy, Hyperplasia, Metaplasia, and Dysplasia are the most significant

benign growth patterns.
 Hypertrophy – an increase in cell size resulting in an increase in organ size.
 Hyperplasia – a reversible increase in the number of cells in an organ or a
tissue in response to a specific growth stimulus.
 Metaplasia – the conversion of one cell type to another cell type not usually
found in the involved tissue.
 Dysplasia – characterized by abnormal changes in the size, shape, or
organization of cells.

Comparison of Benign and Malignant Tumors

CHARACTERISTIC BENIGN MALIGNANT
Differentiation/Anaplasia Well-differentiated; Some lack of
structure may be typical of differentiation with
tissue of origin. anaplasia; structure is
often atypical.
Rate of Growth Usually progressive and Erratic and may be slow to
slow; may come to a rapid; mitotic figures may
standstill or regress; be numerous and
mitotic figures are rare and abnormal.
normal.
Clinical aspects of Cancer Diagnosis

Local Invasion Usually cohesive and Locally invasive,

expansile; well demarcated infiltrating the surrounding
masses that do not invade normal tissues; sometimes
for. may be seemingly
cohesive and expansile.
Metastasis Absent Frequently present; the
larger and more
undifferentiated the
primary, the more likely
are metastases.

Tumor Terminology

 Two types of tissues of Neoplasms: 1. Parenchymal Tissues 2. Supportive

stroma of Connective Tissue and Blood Vessels.
 Benign tumors (-oma, Greek root for tumor)
 Malignant tumors of epithelial origin (carcin, root for crablike) + (-oma)
 Malignant tumors from mesenchymal cells (sarc, root for fleshy) + (-oma)

Classification of Human Tumors

TUMOR CELL/TISSUE BENIGN MALIGNANT TUMORS
TYPE OF ORIGIN TUMORS
Mesenchymal Fibroblast Fibroma Fibrosarcoma
Tumors Fat Cell Lipoma Liposarcoma
Blood Vessels Hemangioma Angiosarcoma
Smooth Muscle Leiomyoma Leiomyosarcoma
Cell
Striated Muscle Rhabdomyosarcom Rhabdomyosarcoma
Cell a
Cartilage Chondroma Chondrosarcoma
Bone cell Osteoma Osteosarcoma
Epithelial Squamous Epithelioma Squamous Cell Carcinoma
Tumors Epithelium (Papilloma)
Transitional Transitional Cell Transitional Cell
Epithelium Papilloma Carcinoma
Glandular/ductal Adenoma Adenocarcinoma
epithelium
Neouroendocrine Carcinoid Oat Cell Carcinoma
cells
Internal Liver cell Liver cell adenoma Liver cell carcinoma
organ- Kidney cell Renal cell adenoma Renal cell carcinoma
specific
Tumors of White blood stem - Leukemia
Clinical aspects of Cancer Diagnosis

blood cell cells

and Lymphoid cells - Lymphoma
lymphocytes
Plasma cells - Multiple myeloma
Tumors of Neuroblast Ganglioneuroma Neuroblastoma
neural cell
precursors
Tumors of Glial cells - Glioma
glial cells and Meningial cells Meningioma -
neural Schwann cells Schwannoma Malignant Schwannoma
supporting
cells
Germ cell Embryonic cells Teratoma Embryonal schwannoma;
tumors Teratocarcinoma;
Seminoma/dysgerminoma

Characteristics of Cancer cells

Altered Cell Differentiation

 Differentiation. Cells become more specialized and acquire specific structural

and functional characteristics as they mature.
 Altered differentiation – changes in appearance and metabolism of the cell,
presence of tumor-specific antigens, and loss of normal function.

Appearance Changes

 Pleomorphism. Cancer cells vary in size and shape.

 Aneuploidy. Abnormal number of chromosomes or abnormal arrangement of
chromosomes.
 In cancer, differentiation refers to the extent to which cancer cells resemble
similar normal cells.
 Anaplastic or Undifferentiated Cells. Cells that grow rapidly and do not
have the original tissue’s morphologic characteristics and specialized cell
functions.

Altered Metabolism

 Cell membrane changes may result in the production of surface enzymes that
aid invasion and metastasis.
Clinical aspects of Cancer Diagnosis

 Loss of glycoproteins results in a loss of cell-to-cell adhesion and increases

cell mobility.
 Production of abnormal growth factor receptors may independently signal cell
to grow.
 Cancer cells may inappropriately secrete hormones in an organ or tissue that
does not release those hormones.

Tumor-Specific Antigens

 Some tumors produce an excess of specific antigens or produce new tumor-

associated antigens marking the cancer cell as “non-self”.

Altered Cellular Function

 The need for cell renewal or replacement is the usual stimulus for cell
proliferation.
 Cell production stops when the stimulus is gone.
 In cancer, proliferation continues once the stimulus initiates the process, and
cancer cells progress is continued, uncontrolled growth.
 Cancer cells also demonstrate a loss of contact inhibition.
 Cancer cells are less genetically stable than normal cells.
 Chromosomal instability results in new, increasingly malignant mutants as
cancer cells proliferate.
 Metastasis. The spread of cancer cells from a primary site to distant
secondary sites.

Tumor Growth

 The rate of tissue growth in normal and cancerous tissue depends on three
factors: 1. the duration of Cell Cycle 2. The numbers of cells that are actively
dividing 3. The cell loss.

Cell Cycle

 Cell cycle – a coordinated sequence of events resulting in duplication of DNA

and division into two daughter cells.
Clinical aspects of Cancer Diagnosis

The four phases of the Cell Cycle are:

1. G1 or Gap 1. RNA and protein synthesis occurs in preparation for DNA

replication.
2. S Phase or Synthesis. DNA replication occurs in preparation for division.
3. G2 or Gap 2. DNA synthesis ceases while RNA and protein synthesis
continues. In addition, precursors of the mitotic spindle apparatus are
produced.
4. M Phase or Mitosis. Cell division occurs. (Prophase, Prometaphase,
Metaphase, Anaphase, & Telophase).
5. G0 or Resting Phase. Cells in G0 phase are activated to reenter the cell cycle
in response to various stimuli that signal for cell renewal.

 Cyclins. Proteins that control entry and progression of cells through the cell
cycle.
 The cyclins (D, E, A, B) combine with and activate enzymes called cyclin-
dependent kinases (CDKs).

Two Critical Checkpoints occur in the Cell Cycle

1. Restriction Point. Occurs at the G1 – S transition when the cell checks for
DNA damage and decides whether to proceed with replication.
Clinical aspects of Cancer Diagnosis

2. Second Checkpoint. G2 – M transition, where the cell verifies accurate DNA

replication and determines if mitosis can safely occur.

 Defects in cell-cycle checkpoint components, such as the p53 protein, are a

major cause of genetic instability in cancer cells.

CELL-CYCLE TIME

 Amount of time required for a cell to move from one mitosis to another
mitosis, or the sum of M, G1, S, and G2.
 Cancer cells proliferate at the same rate as the normal cells of the tissue of
origin.
 The difference is that the proliferation of cancer cells is continuous.

DOUBLING TIME

 The length of time it takes for a tumor to double its volume.

 Tumor cells undergo a series of doublings as the tumor increases in size.
 The average doubling time for most primary solid tumors is approximately 2
months.
 A tumor is usually clinically undetectable until it has doubled 30 times and
contains more than 1 billion cells.
 Tumor contains more than 1 trillion cells or weighs 1 kg, which is enough to
cause death.
Clinical aspects of Cancer Diagnosis

GROWTH FRACTION

 The ratio of the total number of cells to the number of dividing cells.
 As tumor volume increases, growth fraction decreases as a result of hypoxia,
decreased nutrient availability, and toxins.
 In the later stages of tumor growth, only a small portion of cells are actively
dividing.

Molecular Pathogenesis of Cancer

Seven fundamental changes in cell physiology have been proposed that collectively
determine malignant cell growth.

1. Self-sufficiency in growth signals

2. Insensitivity to growth-inhibitory signals
3. Evasion of apoptosis
4. Defects in DNA repair
5. Limitless replication potential
6. Sustained angiogenesis
7. Ability to invade and metastasize
Clinical aspects of Cancer Diagnosis

Carcinogenesis

 The process by which normal cells are transformed into cancer cells.
 The theories proposed that the process of transforming a normal cell into a
cancer cell consist of three stages:
1. Initiation. Cells are exposed to an initiating agent or carcinogen that makes
them susceptible to malignant transformation.
2. Promotion. Promoting agents or cocarcinogens cause unregulated accelerated
growth in previously initiated cells.
3. Progression. The tumor cells acquire malignant characteristics that include
changes in growth rate, invasive potential, metastatic frequency, morphologic
traits, and responsiveness to therapy.

Carcinogenic Factors

 Heredity
 Hormonal Factors
Clinical aspects of Cancer Diagnosis

 Environmental Agents (Chemicals & Radiation)

 Oncogenic Viruses
 Bacteria and Parasites
 Immune System Deficiencies (Tumor Cell Camouflage, Antigenic
Modulation, Overwhelming Antigen Exposure, & Blocking Agents)

Routes of Tumor Spread

 Local invasion is the first in the metastatic process and may occur as a
function of direct tumor extension.
 Tumor growth, mechanical pressure, tumor-secreted enzymes, decreased
cellular adhesion, and increased motility – mechanisms important in local
invasion.
 Serosal seeding – occurs when tumors, which have invaded a body cavity
from surrounding tissue, attach to a surface of an organ within the cavity.
 Lymphatic system – the most common route for metastases.
 Tumor cells > lymphatic vessels > regional lymph nodes
 Skip metastasis. The cell may bypass the first node and spread to more distant
sites.
 A mass in the regional lymph nodes – first indication of spread.
 Circulatory system – the tumor cells usually follow the venous flow that
drains the site of the neoplasm.
 Venous blood from GIT, pancreas, and spleen is routed through the portal vein
of the liver before entering a circulation.

METASTASIS

 The spread of cancer cells from a primary tumor to organs and distant sites in
the body.

These steps must be completed for a metastatic lesion to develop:

 Growth and progression of the primary tumor

 Angiogenesis at the primary site
 Local invasion
 Detachment and embolization
Clinical aspects of Cancer Diagnosis

 Arrest in distant organ capillary beds

 Extravasation
 Proliferation

Source: Oncology Nursing, 5th

Ed. Langorne, Martha E.,
Fulton, Janet S., & Otto, Shirley
E.