Week 8: Cancer & Hematology
Readings:
Required: Damjanov: Chapter 4, Chapter 9
Recommended:
Robbins and Cotran Chapters 7, 13, 14
Guyton and Hall Chapters 33, 34, 37
1. Describe neoplasia and cancer
Neoplasia – “new growth”. Unregulated growth of cells whose proliferations cannot be
adequately controlled by normal regulatory mechanisms. The proliferation of normal cells can be
autonomous (independent of growth factors and stimuli that promote growth of normal cells,
excessive (unceasing in response to normal regulators of cellular proliferation), and disorganized
(do not follow rules governing formation of normal tissues).
Cancer – Tumors invade tissues like crawling crabs.
Tumors – proliferation of neoplastic cells that lead to masses. Synonymous with neoplasm.
○ Classify tumors on the basis of their clinical behavior and histopathology
Benign tumors – Limited growth potential and good outcome. Sharply
demarcated from normal tissue and are often encapsulated. Capsule made of connective tissue.
Expansive growth and compress the adjacent normal tissue, which undergoes atrophy and
fibrosis, forming a pseudocapsule. Composed of cells that resemble the tissue from which they
have arisen. Show high degree of differentiation. Made of a uniform cell population with
approximately the same features. Have a normal number of chromosomes. Slow, expansive
growth. No metastases. Smooth external surface. Encapsulated. No necrosis, no hemorrhage.
Few mitoses, well differentiated cells, normal shape and size nuclei.
Malignant tumors – Grow uncontrollably and eventually kill the host. Tumors
lack a capsule and are not clearly separated from normal tissue. Invade surrounding tissue.
Tumors are undifferentiated. Exhibit new features that are not related to the tissue of origin.
Have a heterogeneous cell population. Chromosomes are abnormal. Fast and invasive. Exhibit
metastases. Irregular external surface. No capsule. Necrosis and hemorrhage. Irregular mitoses.
○ Describe typical features of benign and malignant cells
Benign cells – Nuclei resemble those of their normal progenitor cells. Nuclei are
uniform (of the same size and shape). Cells have a well-developed cytoplasm and well-
developed cytoplasmic organelles. The nucleus accounts for a small part of the total cell
volume. Nuclei have a regular, even distribution of chromatin. Nucleoli are not overly
prominent. Benign cells maintain normal function of the normal cells in the tissue of origin.
Malignant cells – Cells show anaplasia (exhibit new features not like those of
their origin). Malignant cells show nuclear pleomorphism (variation in size and shape of nuclei).
Heterogeneous cell population. Cell nuclei are pleomorphic. Malignant cells have very little
cytoplasm and contain a reduced number of cytoplasmic organelles. Undifferentiated cells.
Nucleus is larger, and they have a high nuclear/cytoplasmic ratio. Larger, irregularly shaped
nuclei surrounded by narrow cytoplasm. Nuclei are hyperchromatic (more dark staining
chromatin) and the chromatin is distributed unevenly. Malignant cells have no specialized
functions. Their metabolism is geared toward supporting rapid growth and replication. Have a
modified basic metabolism and function that gives them a growth advantage over normal cells.
Malignant cells are often aneuploid (they do not have a normal diploid, 46, XX or 46, XY,
number of chromosomes. Chromosomes are abnormal due to deletions or translocations due to
, disorderly mitoses. Cells may also regress and assume fetal features.
○ Describe the epidemiology of cancer: global impact, environmental factors, age, acquired
predisposing conditions and genetic predisposing
Prevalence has increased over the years. Likely due to improved diagnostic
measures and life prolonging treatments. Also due to increased exposure to environmental
carcinogens over time. Prostate cancer more common in elderly. Stomach cancer has decreased
in the U.S. due to dietary habits. Lung cancer is increasing. Smoking=major cause of lung
cancer. Sun exposure=major cause of skin cancer. Dietary fats=possible cause of colon cancer.
Asbestos=lung cancer and mesothelioma. Aniline dyes=bladder cancer. Most causes are
unknown.
Some have hereditary tendencies. Neurofibromatosis type 1 (NF1). Autosomal
dominant. Linked to loss of function of the NF1 tumor suppressor gene. Linked to intracranial
meningiomas and adrenal pheochromocytomas. Familial adenomatous polyposis coli linked to
colon cancer. Wilm’s tumor-renal malignant tumor in infancy and childhood. Xeroderma
pigmentation=unable to tolerate UV light. Chromosomal fragility syndromes (Bloom’s and
Fanconi’s syndromes)=linked to cancer. BRCA-1 and BRCA-2 genes linked to breast cancer.
Most common cancers in men:prostate, lung/bronchus, colon/rectum
Deaths in men: lung/bronchus, prostate, colon/rectum
Most common in women: breast, lung/bronchus, colon/rectum
Deaths in women: lung/bronchus, breast, colon/rectum
○ Identify common childhood cancers
Wilm’s tumor-renal malignant tumor in infancy and childhood. Neuroblastoma,
Wilms tumors, retinoblastoma, acute leukemias, and rhabdomyosarcomas.
○ Define metastasis and explain its pathogenesis
Metastasis – process during which tumor cells move from one site to another in
the body. Also called tumor dissemination.
Occurs in three ways: 1) through the lymphatics
2) via blood, known as hematogenous spread
3) seeding the surfaces of body cavities.
Involves the metastatic cascade with 7 steps:
1) primary tumor,
2) metastatic clone evolves
3) proliferation of the clone and invasion of vessel
4) transport by circulation
5) embolization
6) invasion
7) new tumor formation at site of metastasis. Not all cells can metastasize. Some
are capable, and their descendants form distinct subpopulation (clone) that will expand until it
can disseminate. These cells are transported from the primary site to other locations, where the
cells attach and begin forming secondary, or new, tumors. To survive, these cells need their own
blood supply (angiogenesis).
○ Describe the avenues for metastatic spread
, 1.Through the lymphatics. 2.Via blood (hematogenous spread), and 3.by seeding
surfaces of body cavities.
○ Describe angiogenesis
Angiogenesis is the formation of new blood vessels. Tumors can initiate angiogenesis to facilitate nutrient and
oxygen delivery.
● Explain the TNM system
TNM is the major staging system. The staging of solid cancers is based on the size of the primary lesion, its
extent of spread to regional lymph nodes, and the presence or absence of blood-borne metastases. T for
primary tumor (t 0-4) , N for regional lymph node involvement (n 0-3), and M for metastases (0-2). Numbers
increase based on involvement. Important for defining the prognosis, chances of cure, tx
● Describe the evidence for viral carcinogenesis with
○ Human papillomavirus
Linked to human lesions, such as common warts, genital warts, laryngeal
papillomas, dysplasia of cervical epithelium, and cervical carcinoma. HPV type 16 has been
found in 60% of cases of cervical carcinoma.
○ Epstein-Barr virus and
A herpesvirus that has a predilection for B lymphocytes. EBV is related to
Burkitt’s lymphoma (a B cell neoplasia that occurs most often in Africa and typically affects
children). Nasopharyngeal cancer is related to EBV is prevalent in China. EBV causes
chromosomal breaks that result in activation of endogenous cancer genes (oncogenes).
○ Hepatitis B virus
Viral hepatitis B is linked to liver cancer. Not clearly understood how. HBV is
integrated into the DNA of neoplastic cells.
● Describe oncogenes and tumor suppressor genes and explain their clinical significance
○ Oncogenes are Genes that have undergone mutation that direct the synthesis of protein to
accelerate the rate of tissue proliferation
○ Tumor suppressor (aka anti-oncogenes) are normal cells which have regulatory mechanisms to
protect against oncogenes
■ Retinoblastoma gene (Rb-1)
● Retinoblastoma tumor has a portion of the chromosome deleted which carries Rb-1
→ thus tumor may form in retina (bilateral) or in another place later in life
○ This shows that rb-1 is not limited to just protecting the eye
○ In sporadic retinoblastoma, child is born with Rb-1, but exogenous factors affect Rb-1 and eye
tumors develop (usually one-sided)
■ Tumor protein p53 (TP53) acts as both tumor suppressor and oncogene. It can transform normal
cells into neoplastic cells by transfection
● A loss/or mutation of TP53 may lead to tumor formation (most commonly colon or breast)
○
● Describe the morphology of peripheral blood
○ Formed Elements of the blood
● Red cells
● Granulocytes
● Monocytes
● Platelets
● Lymphocytes
● Have a common origin from hematopoietic stem cells (HSCs)
● Pluripotent cells that sit at the apex of a hierarchy of bone marrow progenitors
, ● Describe anemia and list the major forms
Anemia: reduction of the total circulating red cell mass below normal limits
○ Iron deficiency anemia: most common form of anemia
■ Associated with deletion of Fe stores by chronic blood loss
■ Without Fe, hemoglobin synthesis is impeded and new RBCs are small and contain
less Hb than normal
■ Classifications
● Increased Fe loss (chronic bleeding)
● Inadequate Fe intake or absorption (diet or GI disease)
● Increased Fe requirement (childhood growth, metorrhagia and pregnancy)
■ Causes: hypochromic microcytic anemia
● Total body Fe stores are reduced (RBCs have less hemoglobin than usual)
● Bone marrow shows normal hematopoiesis but contains a reduced number of
hemosiderin-laden macrophages
■ Clinical
● Women>Men
● Responds well to Fe intake
● If symptoms are related to other etiology, that disease should be treated
appropriately
○ Megalobastic anemia: deficiency of vitamin B12 and/or folic acid
Readings:
Required: Damjanov: Chapter 4, Chapter 9
Recommended:
Robbins and Cotran Chapters 7, 13, 14
Guyton and Hall Chapters 33, 34, 37
1. Describe neoplasia and cancer
Neoplasia – “new growth”. Unregulated growth of cells whose proliferations cannot be
adequately controlled by normal regulatory mechanisms. The proliferation of normal cells can be
autonomous (independent of growth factors and stimuli that promote growth of normal cells,
excessive (unceasing in response to normal regulators of cellular proliferation), and disorganized
(do not follow rules governing formation of normal tissues).
Cancer – Tumors invade tissues like crawling crabs.
Tumors – proliferation of neoplastic cells that lead to masses. Synonymous with neoplasm.
○ Classify tumors on the basis of their clinical behavior and histopathology
Benign tumors – Limited growth potential and good outcome. Sharply
demarcated from normal tissue and are often encapsulated. Capsule made of connective tissue.
Expansive growth and compress the adjacent normal tissue, which undergoes atrophy and
fibrosis, forming a pseudocapsule. Composed of cells that resemble the tissue from which they
have arisen. Show high degree of differentiation. Made of a uniform cell population with
approximately the same features. Have a normal number of chromosomes. Slow, expansive
growth. No metastases. Smooth external surface. Encapsulated. No necrosis, no hemorrhage.
Few mitoses, well differentiated cells, normal shape and size nuclei.
Malignant tumors – Grow uncontrollably and eventually kill the host. Tumors
lack a capsule and are not clearly separated from normal tissue. Invade surrounding tissue.
Tumors are undifferentiated. Exhibit new features that are not related to the tissue of origin.
Have a heterogeneous cell population. Chromosomes are abnormal. Fast and invasive. Exhibit
metastases. Irregular external surface. No capsule. Necrosis and hemorrhage. Irregular mitoses.
○ Describe typical features of benign and malignant cells
Benign cells – Nuclei resemble those of their normal progenitor cells. Nuclei are
uniform (of the same size and shape). Cells have a well-developed cytoplasm and well-
developed cytoplasmic organelles. The nucleus accounts for a small part of the total cell
volume. Nuclei have a regular, even distribution of chromatin. Nucleoli are not overly
prominent. Benign cells maintain normal function of the normal cells in the tissue of origin.
Malignant cells – Cells show anaplasia (exhibit new features not like those of
their origin). Malignant cells show nuclear pleomorphism (variation in size and shape of nuclei).
Heterogeneous cell population. Cell nuclei are pleomorphic. Malignant cells have very little
cytoplasm and contain a reduced number of cytoplasmic organelles. Undifferentiated cells.
Nucleus is larger, and they have a high nuclear/cytoplasmic ratio. Larger, irregularly shaped
nuclei surrounded by narrow cytoplasm. Nuclei are hyperchromatic (more dark staining
chromatin) and the chromatin is distributed unevenly. Malignant cells have no specialized
functions. Their metabolism is geared toward supporting rapid growth and replication. Have a
modified basic metabolism and function that gives them a growth advantage over normal cells.
Malignant cells are often aneuploid (they do not have a normal diploid, 46, XX or 46, XY,
number of chromosomes. Chromosomes are abnormal due to deletions or translocations due to
, disorderly mitoses. Cells may also regress and assume fetal features.
○ Describe the epidemiology of cancer: global impact, environmental factors, age, acquired
predisposing conditions and genetic predisposing
Prevalence has increased over the years. Likely due to improved diagnostic
measures and life prolonging treatments. Also due to increased exposure to environmental
carcinogens over time. Prostate cancer more common in elderly. Stomach cancer has decreased
in the U.S. due to dietary habits. Lung cancer is increasing. Smoking=major cause of lung
cancer. Sun exposure=major cause of skin cancer. Dietary fats=possible cause of colon cancer.
Asbestos=lung cancer and mesothelioma. Aniline dyes=bladder cancer. Most causes are
unknown.
Some have hereditary tendencies. Neurofibromatosis type 1 (NF1). Autosomal
dominant. Linked to loss of function of the NF1 tumor suppressor gene. Linked to intracranial
meningiomas and adrenal pheochromocytomas. Familial adenomatous polyposis coli linked to
colon cancer. Wilm’s tumor-renal malignant tumor in infancy and childhood. Xeroderma
pigmentation=unable to tolerate UV light. Chromosomal fragility syndromes (Bloom’s and
Fanconi’s syndromes)=linked to cancer. BRCA-1 and BRCA-2 genes linked to breast cancer.
Most common cancers in men:prostate, lung/bronchus, colon/rectum
Deaths in men: lung/bronchus, prostate, colon/rectum
Most common in women: breast, lung/bronchus, colon/rectum
Deaths in women: lung/bronchus, breast, colon/rectum
○ Identify common childhood cancers
Wilm’s tumor-renal malignant tumor in infancy and childhood. Neuroblastoma,
Wilms tumors, retinoblastoma, acute leukemias, and rhabdomyosarcomas.
○ Define metastasis and explain its pathogenesis
Metastasis – process during which tumor cells move from one site to another in
the body. Also called tumor dissemination.
Occurs in three ways: 1) through the lymphatics
2) via blood, known as hematogenous spread
3) seeding the surfaces of body cavities.
Involves the metastatic cascade with 7 steps:
1) primary tumor,
2) metastatic clone evolves
3) proliferation of the clone and invasion of vessel
4) transport by circulation
5) embolization
6) invasion
7) new tumor formation at site of metastasis. Not all cells can metastasize. Some
are capable, and their descendants form distinct subpopulation (clone) that will expand until it
can disseminate. These cells are transported from the primary site to other locations, where the
cells attach and begin forming secondary, or new, tumors. To survive, these cells need their own
blood supply (angiogenesis).
○ Describe the avenues for metastatic spread
, 1.Through the lymphatics. 2.Via blood (hematogenous spread), and 3.by seeding
surfaces of body cavities.
○ Describe angiogenesis
Angiogenesis is the formation of new blood vessels. Tumors can initiate angiogenesis to facilitate nutrient and
oxygen delivery.
● Explain the TNM system
TNM is the major staging system. The staging of solid cancers is based on the size of the primary lesion, its
extent of spread to regional lymph nodes, and the presence or absence of blood-borne metastases. T for
primary tumor (t 0-4) , N for regional lymph node involvement (n 0-3), and M for metastases (0-2). Numbers
increase based on involvement. Important for defining the prognosis, chances of cure, tx
● Describe the evidence for viral carcinogenesis with
○ Human papillomavirus
Linked to human lesions, such as common warts, genital warts, laryngeal
papillomas, dysplasia of cervical epithelium, and cervical carcinoma. HPV type 16 has been
found in 60% of cases of cervical carcinoma.
○ Epstein-Barr virus and
A herpesvirus that has a predilection for B lymphocytes. EBV is related to
Burkitt’s lymphoma (a B cell neoplasia that occurs most often in Africa and typically affects
children). Nasopharyngeal cancer is related to EBV is prevalent in China. EBV causes
chromosomal breaks that result in activation of endogenous cancer genes (oncogenes).
○ Hepatitis B virus
Viral hepatitis B is linked to liver cancer. Not clearly understood how. HBV is
integrated into the DNA of neoplastic cells.
● Describe oncogenes and tumor suppressor genes and explain their clinical significance
○ Oncogenes are Genes that have undergone mutation that direct the synthesis of protein to
accelerate the rate of tissue proliferation
○ Tumor suppressor (aka anti-oncogenes) are normal cells which have regulatory mechanisms to
protect against oncogenes
■ Retinoblastoma gene (Rb-1)
● Retinoblastoma tumor has a portion of the chromosome deleted which carries Rb-1
→ thus tumor may form in retina (bilateral) or in another place later in life
○ This shows that rb-1 is not limited to just protecting the eye
○ In sporadic retinoblastoma, child is born with Rb-1, but exogenous factors affect Rb-1 and eye
tumors develop (usually one-sided)
■ Tumor protein p53 (TP53) acts as both tumor suppressor and oncogene. It can transform normal
cells into neoplastic cells by transfection
● A loss/or mutation of TP53 may lead to tumor formation (most commonly colon or breast)
○
● Describe the morphology of peripheral blood
○ Formed Elements of the blood
● Red cells
● Granulocytes
● Monocytes
● Platelets
● Lymphocytes
● Have a common origin from hematopoietic stem cells (HSCs)
● Pluripotent cells that sit at the apex of a hierarchy of bone marrow progenitors
, ● Describe anemia and list the major forms
Anemia: reduction of the total circulating red cell mass below normal limits
○ Iron deficiency anemia: most common form of anemia
■ Associated with deletion of Fe stores by chronic blood loss
■ Without Fe, hemoglobin synthesis is impeded and new RBCs are small and contain
less Hb than normal
■ Classifications
● Increased Fe loss (chronic bleeding)
● Inadequate Fe intake or absorption (diet or GI disease)
● Increased Fe requirement (childhood growth, metorrhagia and pregnancy)
■ Causes: hypochromic microcytic anemia
● Total body Fe stores are reduced (RBCs have less hemoglobin than usual)
● Bone marrow shows normal hematopoiesis but contains a reduced number of
hemosiderin-laden macrophages
■ Clinical
● Women>Men
● Responds well to Fe intake
● If symptoms are related to other etiology, that disease should be treated
appropriately
○ Megalobastic anemia: deficiency of vitamin B12 and/or folic acid
