Title: NEOPLASIA
1NEOPLASIA
Core Pathology
Spencer B. Gilbert, M.D.
2OBJECTIVES
- General Aspects of Neoplasia
- Properties of Cancer Cells
- Clinical Aspects of Neoplasia
- Carcinogenic Agents and Pathogeneses
Reading assignment Robbins Pathologic Basis of
Disease, Chapter 8
3GENERAL ASPECTS Definitions
- Neoplasm ( new growth ) - Two related
definitions - A mass of tissue that results from irreversible
and inheritable transformation in a somatic cell
or cells leading to their uncontrolled
proliferation. The resulting neoplastic tissue is
purposeless, preys on the host, and to some
extent is autonomous.
4GENERAL ASPECTS Definitions (continued)
- Neoplasm ( new growth ) - (continued)
- A neoplasm is an abnormal mass of tissue, the
growth of which exceeds and is uncoordinated with
that of the normal tissue and persists in the
same excessive manner after cessation of the
stimuli that caused the change. -- Rupert Willis
5GENERAL ASPECTS Definitions (continued)
- Neoplasia - The disease process that results from
neoplasms. ( benign or malignant ) - Cancer - the disease produced by malignant
neoplasms.
6GENERAL ASPECTS Definitions (continued)
- Tumor - literally means any mass or swelling. At
present this is mostly used to mean malignant or
benign neoplastic growths. In the old ( clinical
) definition, an abscess or a hematoma, or a
non-neoplastic growth are also referred to as
tumors.
7Nomenclature
- All tumors, benign or malignant, have two basic
components - parenchyma - the proliferating neoplastic
cells - supportive stroma - connective tissue and
blood vessels - desmoplasia - abundant collagenous stroma
- scirrhous - dense, fibrous stroma stony hard
8Nomenclature and Classification of Neoplasms
(continued)
- The cell type or tissue of origin is used to name
the tumor. Examples of cell or tissue types - Epithelial Cells
- squamous epithelium ( squamous cell )
- glandular epithelium ( adeno )
- transitional epithelium ( transitional cell )
9Nomenclature and Classification of Neoplasms
(continued)
- Examples of cell or tissue types (continued)
- Mesenchymal Cells
- fibroblast ( fibro )
- muscle
- (1) skeletal ( rhabdomyo )
- (2) smooth ( leiomyo )
- fat cell ( lipo )
10Nomenclature and Classification of Neoplasms
(continued)
- Examples of cell or tissue types (continued)
- Mesenchymal Cells
- cartilage (chondro)
- bone (osteo)
- endothelium (hemangiopericytoma)
- vascular (angio)
- lymphatic (lymphangio)
11Benign tumors
- In general, benign tumors have the suffix -oma to
the cell of origin. - Fibroma - from fibroblastic cells
- Chondroma - from cartilage
- Osteoma - from bone
12Benign tumors
- Tumors may also be classified because of their
microscopic architecture or macroscopic patterns. - Adenoma - glandular pattern
- Papillomas - finger-like projections (fig. 8-1)
- Cystadenomas - cystic masses
- Papillary cystadenoma - papillary patterns that
protrude into cystic spaces - Polyp -projection above a mucosal surface
(fig. 8-2)
13Benign tumorPapilloma of the colon
14Benign tumors
- Tumors may also be classified because of their
microscopic architecture or macroscopic patterns. - Adenoma - glandular pattern
- Papillomas - finger-like projections (fig. 8-1)
- Cystadenomas - cystic masses
- Papillary cystadenoma - papillary patterns that
protrude into cystic spaces - Polyp -projection above a mucosal surface
(fig. 8-2)
15Benign tumorColonic polyp Adenoma. Gross
16Benign tumorColonic polyp Adenoma. Micro
17Benign Tumors
- Gross Appearance
- Benign tumors are usually surrounded by a fibrous
capsule, otherwise they have well-defined smooth
margins. - Benign Micro
- Benign tumors - all are well differentiated.
Their parenchymal cell component resemble closely
the normal cell in morphology and function.
18Malignant tumors
- Malignant tumors that arise from mesenchymal
tissue are usually called sarcomas - fibrosarcoma - fibrous tissue
- liposarcoma - fat tissue
- leiomyosarcoma - smooth muscle
- rhabdomyosarcoma - striated muscle
19Malignant tumors
- Malignant tumors that arise from epithelial cell
origin (three germ layers) are called carcinomas - Adenocarcinomas - glandular origin
- Squamous cell carcinomas - from epithelium
20Malignant Tumors
- Gross Appearance
- Malignant tumors, most of the time, do not have
capsules. Their tumor margins are irregular due
to "fingers" of malignant cells growing into
adjacent normal tissue. Hemorrhage, necrosis,
and ulceration are usually present.
21Malignant Tumors (continued)
- Malignant Micro
- Nuclear Changes
- Enlargement - increased nucleocytoplasmic ratio
(NC ratio) - Hyperchromasia - darkly staining due to increased
DNA content - Coarsely clumped chromatin
- Nucleoli are prominent, may be multiple
- Increased number of mitoses (not always present)
- Abnormal mitotic forms (tripolar, quadripolar)
22Malignant Tumors (continued)
- Malignant Micro
- Pleomorphism - variation in size and shape of the
cells and nuclei. - Formation of tumor giant cells
23Benign or Malignant Tumors
- Mixed tumor (pleomorphic adenoma) - tumor
contains epithelial components scattered within a
myxoid stroma (fig 8-3) - Teratoma - contains parenchymal cells of all 3
germ layers (hair, sebaceous glands, a tooth,
etc.) (fig. 8-4)
24Benign tumorMixed tumor, parotid gland
25Benign or Malignant Tumors
- Mixed tumor (pleomorphic adenoma) - tumor
contains epithelial components scattered within a
myxoid stroma (fig 8-3) - Teratoma - contains parenchymal cells of all 3
germ layers (hair, sebaceous glands, a tooth,
etc.) (fig. 8-4)
26Benign tumorCystic teratoma (dermoid cyst),
ovary. Gross
27Benign tumorCystic teratoma (dermoid cyst),
ovary. Micro
28Other Tumors
- Non-Neoplastic growths that produce tumor-like
lesions - Hamartoma - ( coined from the Greek words
meaning error and tumor ) an overgrowth of mature
tissue or tissues normally present in an organ
resulting in disorderly histomorphology. Just
like any normal tissue neoplasms may develop in
hamartomas, but rarely.
29Other Tumors
- Hamartoma - ( continued )
Examples
skin hemangiomas
lung hamartomas - a
mass of tissues mostly consisting of normal
cartilage and bronchial epithelium. These are
often present at birth and may regress in time.
30Other Tumors
- Choristomas - normal cells or tissues that are
present in abnormal locations. - Examples normal pancreatic tissue present in
the intestinal mucosa, adrenal cells present in
the kidney or elsewhere. - The terms aberrant or heterotopic
tissues or ectopic rest are applied to the
same conditions.
31Old terminology
- In the old terminology, the terms melanoma,
hepatoma, and hypernephroma were used to denote
malignant tumors of melanocytes, liver, and
kidney, respectively. Presently, the use of
these terms are discouraged. A more specific
terminology would be malignant melanoma,
hepatocellular carcinoma, and renal cell
carcinoma, respectively.
32Eponyms
- People's names are also used to name certain
tumors. Although this is discouraged, some have
their merits since the nature of some tumors are
not exactly clear.
33Eponyms (examples)
- Name of Tumor
- Brenner's Tumor
- Burkitt's Lymphoma
- Ewing's Sarcoma
- Grawitz's Tumor
- Kaposi's Sarcoma
- Cell Tissue of Origin
- Ovary
- Lymph Node
- Bone
- Kidney
- Blood Vessels
34Eponyms (examples)
- Name of Tumor
- Krukenberg's Tumor
- Warthin's Tumor
- Wilm's Tumor
- Hodgkin's Disease
- Cell Tissue of Origin
- Carcinoma of ovary (usually metastatic from
stomach) - Tumor of salivary gland
- Adenomyosarcoma of kidney
- Lymph Nodes
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38Characteristics of Benign Malignant Neoplasms
- Differentiation and Anaplasia
- Rate of growth
- Local invasion
- Metastasis
39Differentiation and Anaplasia
- Differentiation -the extent to which parenchymal
cells resemble comparable normal cells, both
morphologically and functionally. - In general, benign tumors are well differentiated
- fig. 8-5 - leiomyoma of the uterus
- fig. 8-6 - adenoma of the thyroid
40Benign tumorLeimyoma (fibroid), uterus.
41Benign tumorAdenoma, thyroid
42Differentiation
- METAPLASIA - a REVERSIBLE change in which one
adult cell type ( epithelial or mesenchymal ) is
replaced by another adult cell type. - DYSPLASIA - deranged development. Proliferation
and atypical cytologic alterations involving cell
size, shape, and organization. - Carcinoma-in-situ
- cervical lesions (fig. 8-11)
43Carcinoma-in-situ TumorCervix
44Carcinoma-in-situ TumorCervix
45Differentiation and Anaplasia
- Malignant tumors are invasive /or metastatic and
range from well differentiated to
undifferentiated. - Well differentiated adenoCA , colon (fig. 8-7)
- Well differentiated squamous cell carcinoma of
the skin (fig. 8-10) - Anaplasia - lack of differentiation.
- Anaplastic tumor - rhabdomyosarcoma (8-8)
- Anaplastic tumor - ( fig. 8-9)
- Pleomorphism - variation in size shape
46Malignant TumorAdenocarcinoma, colon, micro
47Malignant TumorWell-differentiated squamous cell
carcinoma, skin
48Malignant TumorRhabdomyosarcoma, skeletal muscle
49Malignant TumorAnaplastic tumor, site unknown
50Rate of Growth
- In general, malignant tumors grow more rapidly
than benign lesions. - Factors such as hormone dependence, adequacy of
blood supply, genetics, etc., influence growth.
51Local Invasion
- Almost all benign tumors grow as cohesive
expansile masses. - They develop a rim of compressed connective
tissue, a fibrous capsule, a discrete, easily
movable mass. Benign fibroadenoma of the
breast (figs. 8-12, 8-13)
52Benign tumorFibroadenoma, breast. Gross
53Benign tumorFibroadenoma, breast. Micro
54Local Invasion
- Malignant lesions infiltrate, invade and destroy
surrounding tissue. - Invasiveness is a reliable feature of malignancy.
Carcinoma of the
breast (figs. 8-14, 8-15)
55Malignant TumorInfiltrating duct carcinoma,
breast. Gross
56Malignant TumorInfiltrating duct carcinoma,
breast. Micro
57Metastasis
- Metastasis unequivocally implies malignancy.
- With few exceptions, all cancers can metastasize.
- About 30 of newly diagnosed patients with solid
tumors (excludes most skin cancer) present with
metastases.
58Pathways of Spread
- Seeding of body cavities and surfaces
- ex. Ovary - pseudomyxoma peritonei
- Lymphatic spread - most common follows the
natural routes of drainage. (fig.8-16) - Hematogenous spread - venous most common drain
to liver and lung (figs.8-17, 8-18)
59Malignant Tumor. MetastaticLymph node, breast
60Malignant Tumor. MetastaticAdenocarcinoma,
liver. Gross
61Malignant Tumor. MetastaticAdenocarcinoma,
liver. Micro
62SUMMARY
- Comparisons between benign and malignant tumors
(table 8-2) - Comparisons between benign and malignant tumors
of the myometrium (Fig. 8-19)
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64Cancer StatisticsFigures 8-20 21 p. 272
- Incidence
- Most common male - PROSTATE
- Most common female - BREAST
- Deaths
- Most common male - LUNG
- Most common female - LUNG
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69Geographic Environmental Factors
- Stomach cancer - Japan (smoked fish)
- Melanomas - fair skin (sun exposure)
- Occupational exposure - table 8-3, p. 274
- Alcohol abuse - cancer of GI tract
- Smoking - cancer of lung, bladder, etc.
- Cervical cancer - promiscuity STDs
70Age
- Most cancers occur in the later years of life,
especially 55-74. - No age group is spared
71Heredity
table 8-6, p. 275
- Inherited cancer syndromes (autosomal dominant)
- familial retinoblastoma
- Familial cancers
- breast ovarian colon
- Autosomal recessive syndromes of defective DNA
repair - xeroderma pigmentosum
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73Acquired Preneoplastic Disorders
- Metaplasia leads to dysplasia, carcinoma-in-situ
and then cancer. - Lung, cervix, etc.
- Chronic inflammatory diseases
- ulcerative colitis, hepatitis
- Non-neoplastic disorders
- solar keratosis, leukoplakia
- Benign tumors
- most do not become cancer, BUT...
74Molecular Basis of Cancer
- Nonlethal genetic damage
- Regulatory genes
- growth-promoting protooncogenes (oncogenes)
- growth-inhibiting cancer-suppressor genes
(antioncogenes) - apoptosis (programmed cell death)
- DNA repair genes
- Carcinogenisis is a multistep process at the
phenotypic and genetic level.
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76ONCOGENES
- Cancer-causing genes.
- Derived from protooncogenes (v-onc)which promote
normal growth and differentiation. - DNA of spontaneously arising cancers contains
oncogenes. - Protooncogenes may become oncogenic by retroviral
transduction (v-oncs) or by influences that alter
their behavior in situ, thereby converting them
into cellular oncogenes (c-oncs).
77Protein Products of Oncogenes
- Growth factors
- Growth factor receptors
- Proteins involved in Signal Transduction
- Nuclear regulatory proteins
- Cell cycle regulators
78 Protein Products of Oncogenesmode of
activation
- Fig. 8-25 page 281
- Growth factors
- overexpression c-sis
- amplification
- Growth factor receptors
- overexpression c-erb B2
- amplification
- point mutation
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80Protein Products of Oncogenes mode of activation
- Proteins involved in Signal Transduction
- point mutations ras (mutation of the ras gene
is the single most common abnormality of dominant
oncogenes in human tumors) - translocation
- Nuclear regulatory proteins
- translocation c-myc
- amplification
81Protein Products of Oncogenes mode of activation
- Cell cycle regulators Cyclin-dependent kinases
drive the cell cycle by phosphorylating critical
target proteins that are required for progression
of the cells to the next phase of the cell cycle. - translocation
- amplification
- point mutation
82Activation of Oncogenes
- Changes in the structure of the gene
- Changes in regulation of gene expression
- Point mutations
- Chromosomal rearrangements
- Gene amplification
83Activation of Oncogenes
- Point mutations
- Distinct mutations reduce the GTPase activity of
the ras proteins. - The mutant ras protein is permanently activated
leading to continuous stimulation of cells
without any external trigger.
84Activation of Oncogenes
- Chromosomal rearrangements
- Translocations - results in overexpression of
protooncogenes (fig. 8-28, p. 285). The
Philadelphia chromosome is characteristic of
chronic myeloid leukemia. - Inversions
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86Activation of Oncogenes
- Gene amplification - overexpression may result
from reduplication and manifold amplification of
their DNA sequences. This may produce several
hundred copies of the protooncogene in the tumor
cell. - N-myc in neuroblastoma
- c-erb B2 in breast cancer
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88Cancer-Suppressor Genes
- The function of these genes is to regulate cell
growth, not to prevent tumor formation. If the
genes mutate, the cell will grow deregulated. - The mutations required to produce retinoblastoma
involve the Rb gene (recessive cancer gene). - Table 8-9, p. 287 ( to be learned some day)
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90Protein Products of Tumor-Suppressor Genes
- Growth inhibitory signals originate outside the
cell and use receptors, signal transducers, and
cell cycle and nuclear transcription regulators.
(fig 8-31, p. 289) - Molecules that regulate nuclear transcription and
cell cycle - Rb Gene
- p53 Gene
- BRCA-1 BRCA-2 Genes
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93Rb Gene
- Rb is a nuclear phosphoprotein
- When cells are stimulated by growth factors, the
Rb protein is inactivated by phosphorylation, the
brake is released, and the cells transverse the
G1 -- S checkpoint. (fig 8-31, p. 289) - The state of pRb phosphorylation is a critical
determinant of the cell cycle progression.
94Rb Gene (continued)
- Loss of normal cell cycle control is central to
malignant transformation and that at least one of
the four key regulators of cell cycle (p16,
cyclin D, CDK4, Rb) is mutated in the vast
majority of human cancers.
95p53 Gene (fig. 8-32, p. 291)
- Over 50 of human tumors contain mutations in
this gene. - Functions primarily by controlling transcription
of several other genes. - p53 applies the emergency brakes when DNA is
damaged by irradiation, UV light, or mutagenic
chemicals. - p53 assists in DNA repair or directs the cell to
undergo apoptosis.
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97BRCA-1, BRCA-2 Genes
- Breast, ovarian and other cancers.
- Approximately 5-10 of breast cancers are
familial mutations in BRCA-1 BRCA-2 account
for 80 of the familial cases. - Mutations are rarely found in sporadic breast
cancer. - Involved in transcriptional regulation DNA
repair.
98Molecules that Regulate Signal Transduction
- APC (adenomatous polyposis coli) loss is one of
the first steps in the evolution of colorectal
cancers. - Inactivation of APC gene up-regulates cellular
proliferation. - NF-1 gene (neurofibromatosis type I)
99Cell Surface Receptors
- TGF-B (growth-inhibitory factor) up-regulates
transcription of growth-inhibitory genes. - Cadherins - glue its loss favors local invasion
or metastases. - DCC (deleted in colon carcinoma)
- Others
100Genes that Regulate Apoptosis (fig. 8-33, p. 295)
- Genes that inhibit cell death
- bcl-2
- bcl-xL
- Genes that favor programmed cell death
- bax
- bad
- bcl-xS
101bcl-2
- Overexpression of bcl-2 protects lymphocytes from
apoptosis and allows them to survive for long
periods of time thus, there is a steady
accumulation of B lymphocytes in the blood, lymph
nodes , bone marrow and other organs. - Up-regulation of bax suppresses tumor growth by
promoting apoptosis (fig. 8-33)
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103Genes that Regulate DNA Repair
- DNA repair genes are not oncogenic, but they
allow mutations in other genes during the process
of normal cell division. - replication error
- microsatellite instability
- HNPCC - Hereditary nonpolyposis colon cancer
syndrome - Xeroderma pigmentosum
- Ataxia telangietasia
104Telomeres and Cancer
- With each cell division, telomeres shorten. Once
the telomeres are shortened beyond a certain
point, the loss of telomere function leads to
end-to-end chromosome fusion and cell death.
Telomerase causes considerable extension of cell
life.
105Molecular Basis of Multistep Carcinogenesis
- Multiple steps in initiation and promotion.
- Activation of several oncogenes and loss of 2 or
more cancer-suppressor genes. (fig. 8-34, p.297) - Gatekeeper genes directly regulate the growth
of tumors. - Caretaker genes affect genomic stability (fig.
8-35, p.298) - Summary - Fig.8-36, p. 299
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109Karyotypic changes in Tumors
- Balanced translocations
- Deletions
- Gene amplification
- Whole chromosomes may be gained or lost.
110Biology of Tumor Growth
- Kinetics of tumor cell growth
- Tumor angiogenesis
- Tumor progression and heterogeneity
111Kinetics of tumor cell growth
- Clinically detectable tumor mass and doubling
time (fig. 8-37, p. 300) - The rate of tumor growth depends on the growth
fraction and the degree of imbalance between cell
production and cell loss (fig. 8-38, p.301)
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114Tumor Angiogenesis
- Tumors cant grow over 2mm without their own
blood supply. - Hypoxia induces apoptosis by activation of p53
- Perfusion supplies nutrients and oxygen. Newly
formed endothelial cells stimulate the growth of
adjacent tumor cells by secreting polypeptides
such as insulin-like growth factors, PDGF,
GM-CSF, IL-1.
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116Tumor Angiogenesis
- Tumor-associated angiogenic factors
- VEGF - vascular endothelial growth factor
- bFGF - basic fibroblast growth factor
117Tumor Progression Heterogeneity
- Most malignant tumors are monoclonal in origin
but their cells are extremely heterogeneous.
Subpopulations of cells develop that differ with
respect to - invasiveness
- rate of growth
- metastatic ability
- karyotype
- hormonal responsiveness
- susceptibility to antineoplastic drugs
118Mechanisms of Invasion and Metastasis
- Invasion of the Extracellular Matrix
- Vascular dissemination and homing of tumor cells
- Fig. 8-39, p. 303
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120Invasion of the Extracellular Matrix
- Detachment (loosening up) of the tumor cells
from each other - Attachment to matrix components
- Degradation of the extracellular matrix
- Migration of the tumor cells
- Fig. 8-40, p. 304
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125Vascular Dissemination and Homing of Tumor Cells
- Once in the circulation, tumor cells are
particularly vulnerable to destruction by natural
and adaptive immune defenses. - Formation of platelet-tumor aggregates seems to
enhance tumor cell survival and implantability. - Some target organs may liberate chemoattratants
that tend to recruit tumor cells to the site.
126Molecular Genetics of Metastases
- Certain oncogenes or tumor-suppressor genes may
elicit metastases. - In breast cancer, nm23 levels were highest in
tumors that had 3 or 4 positive nodes. - In prostate cancer, the KAI-I gene suppresses
metastases. - In melanoma, the KiSS-1 gene suppresses
metastases.
127Carcinogenic Agents Their Cellular Interactions
- Chemical carcinogens
- Radiant energy
- Oncogenic microbes, mainly viruses
- Several of the above agents may act in concert or
synergize the effects of others.
128Chemical Carcinogenesis
- Sir Percival Pott showed an increased incidence
of scrotal skin cancer in chimney sweeps due to
chronic exposure to soot. - Dupont - 1919
- Incomplete combustion of fossil fuels.
- Plants, microorganisms, medical drugs.
129Steps Involved in Chemical Carcinogenesis
- Initiation results from exposure of cells to an
appropriate dose of a carcinogenic agent (
initiator ). - Initiation causes permanent DNA damage
(mutations) - Promoters can induce tumors in initiated cells,
but are nontumorigenic by themselves - Fig. 8-41, p. 306
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132Initiation of Carcinogenesis
- Direct and indirect acting (Table 8-10)
- Most of the known carcinogens are metabolized by
cytochrome P-450-dependent mono-oxygenases. - Age, sex,and nutritional status also determine
the internal dose of toxicants. - Ames test - The ability of a chemical to induce
mutations in Salmonella typhi.
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134Initiation of Carcinogenesis
- Almost all chemicals that are mutagenic in vitro
are carcinogenic in vivo. - DNA is the primary target for chemical
carcinogens. - In initiated cells, the damaged DNA template must
be replicated so that the change in DNA becomes
fixed within 72-96 hrs.
135Promotion of Carcinogenesis
- After initiation, promoters lead to proliferation
and clonal expansion of the initiated cell. - The process of tumor promotion includes multiple
steps proliferation of preneoplastic cells,
malignant conversion, and eventually tumor
progression.
136Carcinogenic ChemicalsInitiators
- Direct-acting Alkylating agents
- chemotherapeutic agents
- immunosuppressive agents
- Polycyclic aromatic hydrocarbons
- produced by burning tobacco
- Aromatic amines azo dyes
- B-naphthylamine
- butter yellow
- scarlet red
137Carcinogenic ChemicalsInitiators
- Naturally occurring carcinogens
- aflatoxin B1
- hepatitis B virus
- Nitrosamines amides
- nitrate preservatives
- Others
- asbestos
- vinyl chloride
- chromium, nickel, and other metals
138Carcinogenic ChemicalsPromoters
- Cigarette usage
- Viral infections
- Hormones such as estrogens
- Bile salts
- Diethylstilbestrol
- Intake of high levels of dietary fat
139Radiation Carcinogenesis
- Ultraviolet rays - the carcinogenicity of UVB
light is attributed to its formation of
pyrimidine dimers in DNA. - DNA damage is repaired by nucleotide excision
repair (NER) 5 steps, 20 genes. - Xeroderma pigmentosum, autosomal recessive
disease, caused by a mutation in one of several
genes involved in NER. - Mutations in oncogenes and tumor -suppressor genes
140Radiation Carcinogenesis
- Ionizing radiation - electromagnetic (x-rays,
gamma-rays) and particulate radiations (alpha and
beta particles, protons, neutrons) are all
carcinogenic. - Radiologists
- Miners of radioactive elements
- Survivors of the atomic bombs
- Therapeutic irradiation
141Viral CarcinogenesisDNA Oncogenic Viruses
- Transforming DNA viruses form stable associations
with the host cell genome. - The integrated virus is unable to complete its
replicative cycle. - Those viral genes that are transcribed early in
the viral life cycle are important for
transformation.
142Viral CarcinogenesisDNA Oncogenic Viruses
- Human Papillomavirus- cervical cancer
- Epstein-Barr virus - Burkitts lymphoma, B-cell
lymphomas, and others. - Hepatitis B virus - liver cancer
143Viral CarcinogenesisRNA Oncogenic Viruses
- Hepatitis C virus - liver cancer
- Human T-cell Leukemia virus Type I - T-cell
leukemia/lymphoma (fig. 8-44, p.
314)
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145Microbial Carcinogenesis
- Helicobacter Pylori - bacterium associated with
ulcers also gastric lymphomas. - Treatment of the infection with antibiotics
results in regression of the lymphoma in most
cases.
146TUMOR IMMUNITY
- Immune surveillance - recognition and destruction
of nonself tumor cells. - Tumor-specific antigens (TSAs) are present only
on tumor cells and not on any normal cells. - Tumor-associated antigens (TAAs) are present on
tumor cells and also on some normal cells.
147TUMOR IMMUNITY
- Tumor-Specific shared antigens
- Tissue-Specific antigens
- Antigens resulting from mutations
- Overexpressed antigens
- Viral antigens
- Others
148Antitumor Effector Mechanisms
- Cytotoxic T lymphocytes
- Natural killer cells
- Macrophages
- Humoral mechanisms
- (fig. 8-46, p. 318)
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150Escaping Immunosurveillance
- Selective outgrowth of antigen-negative variants
- Loss or reduced expression of HLA antigens
- Lack of co-stimulation
- Immunosuppression
- Apoptosis of cytotoxic T cells
151Clinical Features of Tumors
- Effects of Tumor on the Host
- Grading Staging of Tumors
- Laboratory Diagnosis of Cancer
152Effects of Tumor on the Host
- Local Hormonal Effects
- Cachexia - wasting syndrome
- Paraneoplastic syndromes (Table 8-11)
- endocrinopathies
- nerve muscle syndromes
- dermatologic disorders osseous, articular, and
soft tissue changes - vascular hematologic changes
- others
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156Grading of Tumors
- Grading of a cancer is based on the degree of
differentiation of the tumor cells and the number
of mitoses within the tumor as presumed
correlates with the tumors aggressiveness. - Tumors are classified as grades I thru IV with
increasing anaplasia.
157Histologic Grading of Malignant Tumors General
Principles
- Grade I (Well differentiated)
- Tumor tissue closely resembles tissue of origin
- (e.g., gland formation in adenocarcinoma,
keratinization and epithelial pearls in squamous
cell carcinoma) - Few mitoses
- Little variation in size and shape of tumor cells
158Malignant TumorAdenocarcinoma, colon, micro
159Malignant TumorWell-differentiated squamous cell
carcinoma, skin
160Histologic Grading of Malignant Tumors General
Principles
- Grade II (Moderately differentiated)
- Tumor tissue resembles tissue of origin less well
- Increased mitoses
- Increased variation in size and shape of tumor
cells
161Histologic Grading of Malignant Tumors General
Principles
- Grades III, IV (Poorly differentiated)
- Tumor tissue does not closely resemble tissue of
origin - Many mitoses
- Large variation in size and shape of tumor cells
162Malignant TumorRhabdomyosarcoma, skeletal muscle
163Malignant TumorAnaplastic tumor, site unknown
164Staging of Tumors
- The staging of cancers is based on the size of
the primary lesion, its extent of spread to
regional lymph nodes, and the presence or absence
of distant (blood-borne) metastases.
165TX
- Primary tumor cannot be assessed, or tumor proven
by presence of malignant cells in sputum or
bronchial washings but not visualized by imaging
or bronchoscopy - TO
- No evidence of primary tumor
166Tis
- Carcinoma in situ
- T1
- Tumor 3 cm or less in greatest dimension,
surrounded by lung or visceral pleura, without
bronchoscopic evidence of invasion more proximal
than the lobar bronchus (i.e., not in the main
bronchus)
167T2
- Tumor with any of the following features of size
or extent more than 3 cm in greatest dimension
involves main bronchus, 2 cm or more distal to
the carina invades the visceral pleura or
associated with atelectasis or obstructive
pneumonitis which extends to the hilar region but
does not involve the entire lung
168T3
- Tumor of any size that directly invades any of
the following chest wall (including superior
sulcus tumors), diaphragm, mediastinal pleura,
parietal pericardium or tumor in the main
bronchus less than 2 cm distal to the carina,
but without involvement of the carina or
associated atelectasis or obstructive pneumonitis
of the entire lung
169T4
- Tumor of any size that invades any of the
following mediastinum, heart, great vessels,
trachea, esophagus, vertebral body, carina or
tumor with a malignant pleural effusion
170Note
- The uncommon superficial tumor of any size with
its invasive component limited to the bronchial
wall, which may extend proximal to the main
bronchus is also classified T1.
171Note
- Most pleural effusions associated with lung
cancer are due to tumor. However, there are a
few patients in whom multiple cytopathologic
examinations of pleural fluid are negative for
tumor. In these cases, fluid is non-bloody and
is not an exudate. When these elements and
clinical judgment dictate that the effusion is
not related to the tumor, the effusion should be
excluded as a staging element and the patient
should be staged T1, T2, or T3.
172REGIONAL LYMPH NODES (N)
- The regional lymph nodes are the intrathoracic,
scalene, and supraclavicular nodes.
173NX
- Regional lymph nodes cannot be assessed
- NO
- No regional lymph node metastasis
174N1
- Metastasis in ipsilateral peribronchial and/or
ipsilateral hilar lymph nodes, including direct
extension - N2
- Metastasis in ipsilateral mediastinal and/or
subcranial lymph node (s)
175N3
- Metastasis in contralateral mediastinal,
contralateral hilar, ipsilateral, or
contralateral scalene or supraclavicular lymph
node(s)
176DISTANT METASTASIS (M)
- MX
Presence of distant metastasis cannot be assessed - MO
No distant metastasis - M1
Distant metastasis
177AJCC/UICC STAGE GROUPING
- OCCULT CARCINOMA TX NO MO
- Stage 0 Tis NO MO
- Stage 1 T1 NO MO T2 NO MO
- Stage II T1 N1 MO T2 N1 MO
178AJCC/UICC STAGE GROUPING
- Stage IIIA T1 N2 MO T2 N2 MO T3 NO
MO T3 N1 MO T3 N2 M0 - Stage IIIB Any T N3 MO T4
Any N MO - Stage IV Any T Any N
M1
179Laboratory Diagnosis of Cancer
180Cytologic Diagnosis
- Exfoliated cells (sputum, urine, CSF, body cavity
fluids) - Brushings or scrapings of epithelium
- Fine needle aspiration (FNA)
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183Histologic Diagnosis
- The definitive method for establishing diagnosis
of a neoplasm.
184Techniques
- Frozen section method
- Paraffin section method
- Immunoperoxidase techniques - ( labeled
antibodies are used to identify marker antigens
in tumors and tissue by producing a colored
product ) - Electron microscopy
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186Information provided by Pathological Diagnosis
- Type of neoplasm
- Biological behavior
- Histologic grade
- Degree of invasion or spread
- Pathologic stage
187Serologic Diagnosis
- Detects cancer cell products in the serum.
Products are - Secreted by cancer cells
- Antigens released by death of some cancer cells
188Serologic Assays for Cancer Diagnosis or Follow-up
- Substance in Serum
- Carcinoembryonic antigen (CEA)
- Cancer Type
- Gastrointestinal tract cancer (especially colon),
breast, and lung cancer, elevated levels in some
non-cancerous states
189Serologic Assays for Cancer Diagnosis or Follow-up
- Substance in Serum
- a-Fetoprotein (AFP)
- Cancer Type
- Hepatoma, yolk sac tumors
190Serologic Assays for Cancer Diagnosis or Follow-up
- Substance in Serum
- Human chorionic gonadotropin (HCG)
- Cancer Type
- Greatly elevated in choriocarcinoma rarely
elevated in other neoplasms
191Serologic Assays for Cancer Diagnosis or Follow-up
- Substance in Serum
- Prostatic acid phosphatase prostate-specific
epithelial antigen
- Cancer Type
- Two separate molecules levels of both are
elevated in metastatic prostatic cancer
192Serologic Assays for Cancer Diagnosis or Follow-up
- Substance in Serum
- Monoclonal immunoglobulin
- Cancer Type
- Myeloma, some B cell lymphomas
193Serologic Assays for Cancer Diagnosis or Follow-up
- Substance in Serum
- Specific hormones
- Cancer Type
- Endocrine neoplasms and "ectopic"
hormone-producing tumors
194Serologic Assays for Cancer Diagnosis or Follow-up
- Substance in Serum
- CA 125
- Cancer Type
- Ovarian carcinoma other neoplasms
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196Radiological Diagnosis
- X-ray
- CT scans (Computed Tomography)
- MRI scans (Magnetic Resonance Imaging)