HYPERPLASIA'S AND
NEOPLASMS
REVIEW OF STRUCTURE AND FUNCTION
• Cell division continues into specialized cells including:
• Labile Cells
• Stable Cells
• Epithelial Cells
• Connective Tissue Cells
• Muscle Cells
• Nervous tissue Cells
HYPERPLASIA AND HYPERTROPHY
• Hyperplasia and hypertrophy are exaggerated responses to
a growth stimulus
• This can be a normal response to the body’s demands.
• The words hyperplasia literally means “overgrowth”
HYPERPLASIA VS HYPERTROPHY
Hyperplasia
• Increase in the number of cells
Hypertrophy
• Individual cells become enlarged
METAPLASIA AND NEOPLASIA
• Metaplasia is the replacement of one tissue type with another.
• This can be a normal response, or a pathologic change.
• Neoplasia is similar to hyperplasia in that they are both
increased cell proliferation
• The difference is neoplasia is cell proliferation in the absence
of a stimulus.
• Neoplasia means new growth
HYPERPLASIA AND NEOPLASIA
• The masses produced by these processes cannot be
distinguished from one another without a histological
examination.
• Treatment for each is vastly different. Remember, neoplasias
are autonomous growth, while hyperplasias will stop growing
once the stimulus is removed.
PROLIFERATION OF NEOPLASTIC CELLS
• Autonomous: independent growth factors and stimuli promote the growth
of normal cells
• Excessive: unceasing in response to normal regulators.
• Disorganized: not given to following “the rules” governing the formation
of normal tissue or organs.
CLASSIFICATION OF NEOPLASMS
• Typically put into one of three categories
• Benign
• Malignant
• Uncertain malignant potential
BENIGN NEOPLASMS
• Benign neoplasms generally are localized, and remain
in the tissue in which they originated
• These are a single mass discrete from the surrounding
tissue.
BENIGN NEOPLASMS
• They usually have a fibrous rim or capsule around
them, which makes them easier to excise.
• The cells closely resemble the cells of origin
• Often called undifferentiated
MALIGNANT NEOPLASMS
• Malignant neoplasms are more likely to spread to
entirely different sites, or invade nearby structures.
• Anaplasia: undifferentiated and exhibit new features not
inherent to the tissue they originated from.
• Metastasis often occurs through the lymph nodes.
ETIOLOGY
• Cells must undergo an alteration called initiation to acquire
autonomous growth potential
• Initiation is stimulated by carcinogens which may be physical,
chemical or biologic agents
• Pleomorphism: variances in size, shape, and staining qualities
TUMOR CELLS: UNDER THE MICROSCOPE
Benign Cells
• Regularly shaped nuclei
• Same size
• Normal amount/distribution of chromatin
• Nucleus is small part of cell volume
Malignant cells
• Pleomorphic nuclei: vary on size and
shape
• Hyperchromatic and chromatin is
distributed unevenly
• Well developed cytoplasm
• Large nucleus with little cytoplasm
• Well developed organelles
• Few and undeveloped organelles
• Cell still performs complex functions
• Cells cannot perform normal functions
• More cells are undergoing mitosis
BENIGN VS MALIGNANT
Benign Cells
Malignant cells
• Slow expansive growth
• Fast, invasive growth
• Not able to metastasize
• Able to metastasize
• Smooth surface
• Irregular surface
• No necrosis or hemorrhage
• Can have cause necrosis or hemorrhage
• Cells resemble tissue of origin
• Well differentiated
• Few mitosis, normal nuclei
• Does not resemble tissue of origin
• Undifferentiated cells
• Pleomorphic nuclei
• Many cells undergoing irregular mitosis
METASTASIS
• Metastasis means to change its position, denotes the process of
neoplasms spreading from primary location to other sites in the
body
• 3 main pathways:
• Lymphatic system
• Via blood (hematogenous spread)
• By seeding of the surface of body cavities
HISTOLOGIC CLASSIFICATION (PG 73)
• Tumors are named for cell type they most resemble, usually a tissue of origin
• Mesenchymal cells: connective tissues, muscles, bones
• Add suffix of –oma to the root of the word for benign tumors
• Fibroma: fibroblasts
• Chondroma: chondrocytes (cartilage tissue)
• Lipoma: fat cells
• Osteoma: bone cells
• Adenomas: benign epithelial cells, refers to glands or ducts if no prefix is present
• Liver cell adenoma, parathyroid adenoma,
• GI tract: villous or tubular adenomas are called polyps
• Papillomas: benign protrubent tumors of the skin, bladder, mouth, or larynx
HISTOLOGIC CLASSIFICATION
• malignant tumors of mesenchymal cells get the suffix -Sarcoma:
• Fibrosarcoma, Chondrosarcoma, liposarcoma, etc
• Carcinomas: malignant tumors of epithelial cells
• Squamous cell: squamous cell carcinoma.
• Adenocarcinoma: malignant cells of glands or ducts
• Renal cell carcinoma
• Liver carcinoma
• Adrenocortical carcinoma
EXCEPTIONS TO THE RULE:
Some malignancies end with “-oma”
• Lymphoma: malignant tumors of the lymphoid tissue
• Glioma: malignant brain tumor, glial cells
Some tumors have the same name whether benign or malignant
• Islet cell tumors (pancreas): must clearly be stated benign or malignancy
Blastomas
• Malignant tumors composed of embryonic cells (retinoblastoma)
Some tumors cannot be classified the typical way so they are named after the dude who discovered
them:
• Ewings Sarcoma, Karposi’s Sarcoma, Hodgkin’s Sarcoma
TUMOR STAGING
• Staging is done by assessing the extent of tumor spread
• Done with diagnostic imaging, biopsies, and surgery
• Considers primary tumor size, presence of metastasis and lymph
involvement
• The scale ranges from I-IV (or A-D)
• Stage I is when the tumor is isolated, not metastasis and has
the best prognosis
• Stage IV is when the tumor has spread to multiple sites and
the prognosis is grim
TUMOR GRADING
• Based on histological exam of cells
• Grade I: well differentiated
• Grade II: moderately well differentiated
• Grade III: undifferentiated
• Both staging and grading are used for treatment planning and
prognosis
TNM SYSTEM
• T—tumor, the size and invasion into surrounding tissue
• N—extent of lymph node metastasis
• M—whether distant metastasis has occurred
• Stage I is localized, Stage IV is metastasis
BIOCHEMISTRY OF CANCER CELLS
• Less mitochondria
• Tough endoplasmic reticulum is less prominent (less protein synthesis)
• Use glucose less efficiently, therefore storing it as glycogen
• Metabolize glucose anaerobically
• Require less oxygen
• Produce/Accumulate lactic acid
• Can survive longer in unfavorable conditions and retain the ability to
metabolize and reproduce
CAUSES OF CANCER
• Carcinogen: a substance known to causer or increase the likelihood of
cancer
• Radiation (UV light, X-rays)
• Air pollution
• Inhaled toxins (smoking)
• Viruses and fungi (HPV, EBV, HBV)
• Nitrates (in the food we eat)
• Drugs/medications (steroid hormones, chemo drugs)
• Industrial (steel mill, coal mine, aesbestos, nickel mining, arsenic in pesticides)
ONCOGENES
• C-onc, cellular genes that are mutated versions of our DNA
• Basically genes with proteins and cell information that are mutated
• Can be transformed into cancer genes (mutated) 4 ways:
• Point mutation: single base substitution in DNA
• Gene amplification: increased number of copies, (neuroblastoma)
• Chromosomal rearrangement: translocation of chromosomal fragments (Burkitt’s)
• Insertion of a viral genome: slow acting virus that changes DNA (HBV in liver CA)
ONCOGENES
• Initiators turn oncogenes “on”, which leads to the proliferation of the
cell through growth enhancing products
• Oncogenes are supposed to be kept in check by tumor suppressor
genes; however, there can be mutations in the tumor suppressor genes
that prevent them from functioning properly
TUMOR SUPPRESSING GENES
• Normal cells are designed to regulate and protect against oncogenes
• Malignant cell fused with a normal cell will create a benign tumor
because the tumor suppressing genes will regulate the malignant cell
HEREDITARY CANCER
• Certain cancers occur more in some families and not in others
• Some cancers have been linked to hereditary cancer genes
• Effected by inborn errors in genetic make-up and metabolism
• Increased incidence of breast or colon cancer in some families
IMMUNE RESPONSE
• Benign cells resemble the tissue they originated from
• Malignant cells alter so much they resemble foreign bodies
• Tumor antigens: antibodies created to attack the tumor
• Small tumors that develop during a lifetime are cured this way
• CEA: (carcinoembryonic antigen) colon CA
• Immuno-response therapies and treatments
CELLULAR CHARACTERISTICS OF
NEOPLASM
• self-sufficiency in growth signals,
• insensitivity to antigrowth signals,
• evasion of apoptosis
• limitless replicative potential
• sustained angiogenesis,
• Potential for tissue invasion and metastasis.
• genetic instability
METABOLIC CHANGES IN NEOPLASM
• Simplified metabolic activities
• Increased use of anaerobic pathways
• Increased glucose utilization
• Increased cell division and use of components for mitosis
NEOVASCULARIZATION/ANGIOGENESIS
• Cells require adequate oxygen and blood supply for function and
growth
• Tumors over 1mm will create new vascularities
• Angiogenesis/neovascularization is a key feature of neoplasm
• Malignancies must create new blood supply for growth and metastasis
CLINICAL MANIFESTATIONS OF A
NEOPLASM
• Manifestations depend on:
• Type of cancer
• Location of the tumor
• Histological grade
• Clinical stage
• Immune status of the host/immuno-response
• The tumor cells sensitivity to therapy
SYMPTOMS OF MALIGNANT TUMORS
• Loss of well-being
• Neurologic symptoms
• Bleeding: rectal, urinary,
vaginal
• Obstructive airways
• Dyspnea
• Skin lesions
• Splenomegaly
• Liver enlargement
• Intestinal obstruction
• Ascites
• Abdominal mass
DIAGNOSIS
• Diagnosis can be made by a variety of tests
• Biopsy
• Blood smear
• Cytology
• Radiologic Examination
• Endoscopic Examination
TREATMENT
• Surgical Removal
• Radiation Therapy
• Chemotherapy
• Radioimmunotherapy
FREQUENCY AND SIGNIFICANCE
• The prognosis of cancer depends on several items:
• The type of cancer
• The extent of spread at the time of discovery
• The efficacy of existing therapy
• The incidence of malignant tumors is twice the mortality
rate.
MORTALITY
• Number of deaths attributed to the disease
• Mortality rates for certain types influence prognosis and
treatment options
METASTASES
• Malignant neoplasms disseminate by one of three pathways:
(1) seeding within body cavities—carcinoma of the colon in the peritoneal cavity,
(2) lymphatic spread which is the preferred way of spread by carcinomas in general, or
(3) hematogenous spread which is favored by sarcomas.
METASTASES
• The ability of a tumor to metastasize requires:
(a) invasion by tumor cells through adjacent structures
(b) entrance of tumor cells into blood or lymphatic vessels
(c) survival of tumor cells within the circulation and avoidance of the
immune system, and
(d) implantation in a foreign tissue with establishment of a new tumor
locus.
METASTASES
• Most carcinomas arise in epithelial cell layers with an underlying basement
membrane.
• Invasive tumors frequently secrete enzymes, including collagenases, heparanase, and
stromelysin, that are capable of degrade the epithelium
• Once a tumor has eroded through the wall of a blood or lymphatic vessel, individual
tumor cells may detach and circulate through the body as an embolus.
• Encasing these cells in clots of fibrin or in aggregates of platelets may protect them
from destruction by the immune system.
• The presence of tumor cells in the circulation does not necessary lead to metastases.
• circulating cells have to “home” preferentially to a specific target organ.
APPLICATION TO NM