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Biology, Clinical Manifestations, and Treatment of Cancer

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Cancer

Derived from Greek word for crab, karkinoma

Malignant tumor Tumor

Also referred to as a neoplasm—new growth Let’s review the two different types:

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Benign vs. Malignant Tumors

Benign MalignantGrow slowly Grow rapidly

Well-defined capsule Not encapsulated

Not invasive Invasive

Well differentiated Poorly differentiated

Low mitotic index High mitotic index

Do not metastasize Can spread distantly (metastasis)

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Classification and Nomenclature

Benign tumors Named according to the tissues from which

they arise and include the suffix “-oma”• Lipoma• Glioma• Leiomyoma• Chondroma

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Classification and Nomenclature (cont’d)

Malignant tumors Named according to the tissues from

which they arise• Malignant epithelial tumors are referred to

as carcinomas Adenocarcinoma

• Malignant connective tissue tumors are referred to as sarcomas

Rhabdomyosarcomas

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Classification and Nomenclature (cont’d)

Cancers of lymphatic tissue are lymphomas

Cancers of blood-forming cells are leukemias

Carcinoma in situ (CIS) Preinvasive epithelial malignant tumors of

glandular or epithelial origin that have not broken through the basement membrane or invaded the surrounding stroma

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Histology and Genetics

Tumors are classified based on immunohistochemical analysis of genetic alterations for improved treatment Determine specific genetic mutation Identify multiple subdivision

• Breast cancer—six different types

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Tumor Markers

Tumor cell markers (biologic markers) are substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF, or urine Hormones Enzymes Genes Antigens Antibodies

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Tumor Markers (cont’d)

Tumor markers are used to: Screen and identify individuals at high risk for

cancer Diagnose specific types of tumors Observe clinical course of cancer Problem: false positives and negatives

What tumor markers can you state? What are the values?

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Cancer Stem CellsNew Research

Stem cells self-renew Cell divisions create new stem cells

Stem cells are pluripotent Ability to differentiate into multiple different cell

types Current cancer chemotherapy does not kill

cancer stem cells

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Inflammation and Cancer

Chronic inflammation is an important factor in the development of cancer Cytokine release from inflammatory cells Free radicals Mutation promotion Decreased response to DNA damage Examples: ulcerative colitis, chronic viral

hepatitis

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Immune System and Cancer

Normal immune system protects against cancer

Immunosuppression fosters cancer Non-Hodgkin lymphoma (10X) Kaposi sarcoma (1000X)

In some cases cancer promotes secretion of cytokines that foster cancer

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Viruses and Cancer

Implicated Hepatitis B and C viruses Epstein-Barr virus (EBV) Kaposi sarcoma herpesvirus (KSHV) Human papillomavirus (HPV) Human T cell leukemia–lymphoma virus

(HTLV)

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Bacterial Cause of Cancer

Helicobacter pylori Chronic infections are associated with:

• Peptic ulcer disease • Stomach carcinoma• Mucosa-associated lymphoid tissue lymphomas

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Three-Step Theory of Invasion

Tumor cell attachment Fibronectin and laminin

Degradation or dissolution of the matrix Enzymes

Locomotion into the matrix Invadopodia (pseudopodia)

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Sequential Process of Metastasis

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Clinical Manifestations

Many Different clinical manifestations occur:

Syndrome of cachexia Most severe form of malnutrition Present in 80% of cancer patients at death Includes anorexia, early satiety, weight loss,

anemia, asthenia, taste alterations, and altered protein, lipid, and carbohydrate metabolism

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Cachexia

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Clinical Manifestations

Anemia A decrease of hemoglobin in the blood Mechanisms:

• Chronic bleeding resulting in iron deficiency• Severe malnutrition• Medical therapies• Malignancy in blood-forming organs

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Clinical Manifestations (cont’d)

Leukopenia and thrombocytopenia Direct tumor invasion to the bone marrow causes

leukopenia and thrombocytopenia Chemotherapy drugs are toxic to the bone marrow

Infection Risk increases when the absolute neutrophil and

lymphocyte counts fall

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Clinical Manifestations (cont’d)

Paraneoplastic syndromes Symptom complexes that cannot be explained by

the local or distant spread of the tumor or by the effects of hormones released by the tissue from which the tumor arose

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Environmental Risk Factors

Tobacco Multipotent carcinogenic mixture Linked to cancers of the lung, lower urinary tract,

upper aerodigestive tract, liver, kidney, pancreas, cervix uterus

Linked to myeloid leukemia Secondhand smoke (ETS) contains many toxic

chemicals Cigar and pipe smoking equally harmful

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Environmental Risk Factors

Diet May account for 30% of the overall risk factors for

cancer Xenobiotics

• Hydrocarbons and amines produced during cooking of meat protein

• Toxic, mutagenic, and carcinogenic chemicals in food• Examples:

– Compounds produced in the cooking of fat, meat, or proteins

– Alkaloids or mold by-products• May influence epigenetics

Research ongoing regarding vitamin influe

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Cancer in Children

Incidence Rare but is leading cause of death from disease in

children In 2004, mortality rate was 2.4 per 100,000 cases Survival rates have dramatically improved over

past 30 years

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Cancer in Children

Most originate from the mesodermal germ layer Layer gives rise to connective tissue, bone,

cartilage, muscle, blood, blood vessels, gonads, kidneys, and the lymphatic system

Most sarcomas vs. carcinomas in adults Diagnosed during vs. peak growth periods Fast growing and without early signs

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Etiology with Children

Most do not demonstrate predisposing environmental factors

Genetic factors: Chromosome abnormalities

• Aneuploidy, amplifications, deletions, translocations, and fragility

• Certain congenital syndromes and cancers occur together

Wilms tumor and urogenital abnormalities Down syndrome and leukemia

Oncogenes and tumor-suppressor genes• Fanconi anemia, Bloom syndrome

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Prognosis

More than 70% of children cured Survival rates higher in children under 15

years Younger are more likely to be enrolled in

clinical trials Survivors have increased risk of cancer later

in life Residual and long-term effects of treatment Psychologic sequelae

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Components of the hematologic system

Chief functions: Delivery of substances needed for cellular

metabolism Removal of wastes Defense against microorganisms and injury Maintenance of acid-base balance

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Components of the hematologic system

As a review remember what the following functions are:

Bone Marrow Lymphoid Organs Platelets RBC WBC

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Erythropoiesis

Erythrocytes are derived from erythroblasts (normoblasts)

Maturation is stimulated by erythropoietin Erythropoietin causes an increase in red cell

production and release from bone marrow

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Regulation

Numbers of circulating red cells in healthy individuals remain constant

The peritubular cells of the kidney produce erythropoietin

Hypoxia stimulates the production and release of erythropoietin

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Erythropoiesis

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Evaluation of the Hematologic System

Tests of bone marrow function:Bone marrow aspiration

Bone marrow biopsyMeasurement of bone marrow iron stores

Differential cell countBlood tests

Large variety of tests

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Pediatrics and the Hematologic System

Blood cell counts increase above adult levels at birth

Trauma of birth and cutting the umbilical cord

The hypoxic intrauterine environment stimulates erythropoietin production

Results in polycythemia

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Aging and the Hematologic System

Erythrocyte life span is normal but erythrocytes are replaced more slowly

Possible causes:

Iron depletionDecreased total serum iron, iron-binding capacity, and intestinal iron absorption

Lymphocyte function decreases with ageThe humoral immune system is less responsive

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Multiple Myeloma (MM)

Malignant proliferation of plasma cells Infiltrate bone marrow and aggregate into

tumor masses in skeletal system M-proteins Bence Jones protein Hypercalcemia, renal failure, bone lesions

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Multiple Myeloma