Transcript Neoplasia - DDS 2008

General Pathology (DENF 2701)
Topic: Neoplasia
Fall, 2004; Wednesdays, 10:00-12:00 am; Room 132
Course Director: Dr. Jerry Bouquot
Room 3.094B; 713-500-4406; 713-520-1250 (home)
Neoplasia
“New Growth”; From Latin Word for Crab
 Cancer: Neoplasms are not controlled by the body
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– Continue to replicate indefinitely
– Tumors may flourish, even while the host is wasting away
– Cancers induce increased blood supply
Cancer: 2nd leading cause of US deaths
-- After cardiovascular disease
Oncology = study of tumors (“oncos” = tumor, “logos” = study of)
-- Oncologist = physician who treats cancer exclusively
– Hemoncologist = specializes in leukemias, lymphomas, etc.
-- Hematologist = blood doctor, treats leukemias, lymphomas, etc.
– Surgical oncologist; Radiation oncologist
Typically monoclonal
Malignant (cancers): invade, destroy, metastasize (distant spread)
Benign: nonmalignant neoplasm; add suffix “-oma”
Features of Neoplasms
Benign v. Malignant
Benignant
Malignant
Rate of growth
Slow
Rapid
Type of growth
Expansile only
Expansile and/or invasive
Similarity to original
tissue/cells
Very similar
Not similar
Uniformity of cells
Uniform
Cells vary in shape
(pleomorphic) and size
Mitotic rate
Low (few mitoses) Medium to high (many
mitoses), may be abnormal
or in abnormal location
Nuclear/cytoplasmic ratio
Normal
High
Nuclei
Normal, uniform
Enlarged, pleomorphic,
dark (hyperchromatic)
Neoplasia
Benign v. Malignant
Leiomyoma
Benign Smooth Muscle Neoplasm
Photos: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003; Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Neoplasms
Benign v. Malignant
Thyroid Adenoma
Breast Adenocarcinoma
Breast Adenocarcinoma
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Tumor Names
Tissue of Origin
Benign
Malignant
Fibrous
Fibroma
Fibrosarcoma
Bone
Osteoma
Osteosarcoma
Cartilage
Chondroma
Chondrosarcoma
Adipose
Lipoma
Liposarcoma
Nerve
Neurofibroma
Neurofibrosarcoma
Smooth muscle
Leiomyoma
Leiomyosarcoma
Skeletal muscle
Rhabdomyoma
Rhabdomyosarcoma
Gland
Adenoma
Adenocarcinoma
Squamous
epithelium
Papilloma
Squamous cell carcinoma
Melanocyte
Nevocellular nevus
Malignant melanoma
Lymphoid
Lymphoid hyperplasia
Lymphoma
Neoplasia
Differentiation of Cells/Tissue
 Well differentiated: cells look mature and similar to original cells
-- Grade I = cells are well differentiated
-- Grades II and III: moderately differentiated
--Grade IV = poorly differentiated
 Not very good at prognosis
 Poorly differentiated: cells look immature and irregular
-- Grade IV; high grade
-- Often means worse prognosis
 More mature or differentiated cells retain function
– e.g. squamous cell carcinoma makes keratin
(keratin pearls, epithelial pearls)
-- e.g. mucoepidermoid carcinoma makes mucus (mucin)
Neoplasia
Differentiation of Cells/Tissue
 Anaplasia (“to form backwards”): very undifferentiated
-- Primitive cells
 Stem cells of some tumors undergo divergent differentiation
– e.g. pleomorphic adenoma (mixed tumor) of salivary glands
– e.g. fibroadenoma of breast
 Certain tumors induce stromal change (not differentiation)
-- Fibrosis (desmoplasia)
-- New vessels (angiogenesis)
Squamous Cell Carcinoma
Microscopic Grading
Grade I
Grade II
Grade III
Grade IV
Loss of Differentiation & Maturity
Well differentiated
adenocarcinoma of colon
Benign neoplasm of colon
Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Loss of Differentiation
Anaplastic carcinoma of colon
Poorly differentiated
adenocarcinoma of
colon
Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Signs of Dysplasia
Not Necessarily Associated with Cancer
 Pleomorphic (abnormal shape)
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-- Cells and/or nuclei
Enlargement...cells or nuclei
Reduced cytoplasmic/nuclear ratio
-- Large nucleus compared to cell size
-- 1:1 vs. 1:4 - 1:6 for normal
Hyperchromatic nuclei
-- Chromatin is course, clumped
Increased mitotic rate
-- Numerous mitotic figures
Bizarre mitoses: abnormal shape
-- e.g. tripolar/quadripolar mitoses
-- e.g. abnormal location
Signs of Dysplasia
Not Necessarily Associated with Cancer
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Lack of cohesion (detached cells)
Prominent, perhaps multiple nucleoli
Loss of polarity (no orientation)
Bizarre cells
 Problem: some dysplasias are not related to cancer
e.g. Developmental anomalies
Bone dysplasias
 Problem: not all dysplasias progress to malignancy (precancer)
Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995; Kumar, Cotran, Robbins. Robbins Basic pathology, 7 th ed., Saunders, Philadelphia, 2003.
The Dysplastic Cell
Photo: J. Bouquot. Pract Perio Aesth Dent, 1995.
Extra Credit Question
Melanoma is a malignancy of which of the following cells?
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B.
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Fibroblast
Osteoblast
Melanocyte
Nevus cell
Smooth muscle cell
Teratoma
A Type of Neoplasm as Well as Developmental Anomaly
 Usually congenital
 More than one germ-cell type
 From multipotential cells
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-- Therefore usually found in ovary or testis
Usually helter-skelter mix of tissue types
-- May be so mature that small “babies” develop
May be benign or malignant
Not a hamartoma (mass of disorganized tissue indigenous to the
site)
Not a choristoma (congenital anomaly, a heterotopic rest of cells)
Cervical teratoma is usually fatal
-- Because it presses on vessels, airways, esophagus
Ovarian Teratoma
Cervical Teratoma
Pituitary Teratoma
With Teeth
Photo: Dr. J. Bouquot, West Virginia University, Morgantown, West Virginia
Pituitary Teratoma
Neoplasia
Invasion
Cuniculatum (Verrucous?)
Carcinoma
 One of two things that most clearly separate benign from cancer
– Exceptions: Basal cell carcinoma (skin)
Verrucous carcinoma (mouth)
Prostate carcinoma
-- Exceptions: Hemangioma
Lymphangioma
Lipoma
 Not all benign neoplasms are encapsulated
Hemangioma
-- Usually a well-defined cleavage plane
 After the ability to metastasize, the ability to invade is the most
reliable feature of malignancy
Photos: P. Morgan, Guys Hospital, London, England; J. Bouquot, West Virginia University, Morgantown, West Virginia.
Carcinoma in situ
Top-to-Bottom Dysplasia
Severe Dysplasia
Photos: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Local Invasion
Colonic adenocarcinoma (left) invades into muscle (right)
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Neoplasia
Metastasis
 Secondary implants of cancer cells separate from 10 tumor
 The most unique thing about malignancy (v. benignancy)
 Carcinomas spread via lymphatics to local lymph nodes
– Oral cancer: cervical enlarged, firm, fixed (perhaps matted)
lymph nodes
– Breast cancer (usually is in upper outer quadrant): axillary
lymph node involvement (perhaps with lymphedema)
– Lung cancer: bronchial lymph node involvement
 Usually ipsilateral (on same side of body) node
-- May be contralateral (opposite side of body)
 Sarcomas spread via blood stream
-- Therefore: pulmonary mets usually
 Usually metastasis is from long-standing, large cancers
-- There are exceptions!!
Cellular Events Needed for Metastasis
Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Local Lymphatic Invasion
Para-Aortic Lymph Nodes
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Main Routes of Tumor Spread
Carcinoma of the Lung
Hilar Lymph Nodes
(cancer = white deposits
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Most Common Sites of Distant Metastasis
Liver Metastases
Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995; Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Epidemiologic Terms
 Incidence rate: number of newly diagnosed cancers/year
 Mortality rate: number of patients dying from cancer/year
 Prevalence rate: number of cancers diagnosed in a certain
population at a given point in time (point prevalence)
 Relative frequency rate: proportion of all cancers represented by an
individual cancer
 Epidemiologic studies (case-control studies, differences in
incidence between groups, etc.) are the best “proof” of etiology
(cause), but they are very expensive and time-consuming
Incidence of Cancer
More than 100 Different Types of Cancer
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Cancer
Age as an Etiologic Factor
 Frequency of cancer generally increases with age
 Cancers are constantly arising in our bodies, but our immune system
kills them off
 With increasing age:
-- Less effective immune system
-- Less controlled cell division (more mutations)
-- More exposure to carcinogens
 Young age = sarcomas; old age = carcinomas
 The major cancer deaths in children under 15 years of age:
-- Leukemia
-- CNS tumors
-- Lymphomas
-- Soft tissue sarcomas
-- Bone sarcomas
Cancer Risk Increases with Age
Long-term exposure & less effective immune system
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Trends in Cancer Incidence
1930 - 2000
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Oral Cancer
Age- & Gender-Specific Incidence Rates
Photo: Neville, et al. Oral and maxillofacial pathology, 2002.
Cancer
Hereditary Factors
 Hereditary predisposition toward cancer development is common
 Inherited cancer syndromes
-- 5-10% of cancers
-- Often have specific molecular markers
 Familial retinoblastoma: autosomal dominant (AD)
-- 40% are familial
-- 10,000x more risk
 Familial adenomatous polyposis (FAP) of colon (AD)
-- Gardner’s syndrome also has jaw osteomas
 Colon cancer (other than FAP): familial
Cancer
Hereditary Factors
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Multiple endocrine neoplasia (MEN) syndrome (AD)
Neurofibromatosis types 1 and 2 (AD)
Breast cancer: familial; BRCA gene
Ovarian cancer: familial
Xeroderma pigmentosum: autosomal recessive (AR)
Ataxia telangiectasia: AR
Bloom syndrome: AR
Fanconi anemia: AR
Inherited Syndromes Associated with Cancer
Associated Genetic Defect
Syndrome
Tumor
Genetic Defect
Multiple endocrine
neoplasia syndrome
(MEN)
Tumors of endocrine
organs
Mutation, chromosomes
10 & 11
Polyposis coli
Adenomas and
adenocarcinomas of
colon
Absent tumor
suppressor gene
Li-Fraumeni
Breast carcinoma and
sarcomas
Mutated tumor
suppressor gene
Xeroderma pigmentosum Skin carcinoma
Abnormal DNA repair
Familial retinoblastoma
Retinoblastoma
Absent tumor
suppressor gene
Neurofibromatosis, type I
Neuroma,
neurofibroma,
neurofibrosarcoma
Abnormal tumor
suppressor gene
Genetically Associated Cancers
The cancer may not be in the mouth
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MEN (Multiple Endocrine Neoplasia) IIB or III.
Painless yellow-white nodules of the tongue.
Photo: ESTOP.
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Acanthosis nigricans
Ataxia-Telangiectasia
Cowden syndrome
Dyskeratosis congenita
Gardner’s syndrome
Gorlin syndrome (nevoid basal
cell carcinoma syndrome)
Mucosal neuroma syndrome
(MEN IIB, MEN III)
Neurofibromatosis
Peutz-Jeghers syndrome
Trisomy 21 (Downs syndrome)
Tuberous sclerosis
Xeroderma pigmentosum
Progression of
Cancer
Pathogenesis
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Cancer Phenotypes
Genetic Requirements
 Self-sufficiency (promotes cell growth without signals)
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-- Mutated protooncogenes >> oncogenes >>
oncoproteins (not regulated)
Cancer cells produce the same growth factors which influence them
Cancer cells create excess receptors to these growth factors
-- e.g. excess epidermal growth factor receptors are in 80% of
squamous cell carcinomas of lungs
Example: Overexpression of MYC protooncogene
-- MYC is in nucleus of all cells
-- When overexpressed: increased cyclin-dependent kinases (CDKs)
to move cell cycle into an active phase (especially G1 to S)
Example: Mutation of RAS gene
--Most common oncogene abnormality in tumors (30%)
-- Cell is told to continue to proliferate
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Cancer Phenotypes
Genetic Requirements
 Insensitivity to growth-inhibitory signals
– TP53 (p53) tumor suppressor gene: exerts antiproliferation effects,
regulates DNA-damage repair, regulates apoptosis; affected by
stress
-- TP53 is one of the most common mutations in cancers
 Evasion of apoptosis
 Limitless replicative potential
– Telomere length maintenance is seen in virtually all cancers
Cancer Phenotypes
Genetic Requirements
Increased Expression of Growth
Factor Receptors
Oncogenes in Neoplastic
Transformation
Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Cancer Phenotypes
Genetic Requirements
Mutant Transcription Factor
Production
Mutation in Transducer Protein Gene
Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Cancer Phenotypes
Genetic Requirements
Over-Production of Factors that Prevent Cell Death
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Cancer Phenotypes
Genetic Requirements
 Development of sustained angiogenesis
– Cannot metastasize without angiogenesis
– When the angiogenic switch is turned on:
cancer proliferations and then metastasis
 Ability to invade and metastasize
-- Tumor cells must detach from themselves, attach to stroma >>
degrade/destroy the stroma (via metalloproteinases) >> migrate
 Some tumors show organ tropism (metastases favor certain organs)
-- Related to adhesion molecules and receptors
Karyotype Changes in Cancer
 Balanced translocations
-- Philadelphia chromosome (chronic myelogenous leukemia)
-- Usually 22 & 9
-- Burkitt lymphoma (usually 8 & 14)
-- Follicular B-cell lymphoma (usually 14 & 18)
 Deletions (more common in solid tumors)
-- Retinoblastoma (13q)
-- Colorectal carcinoma (17p, 5q, 18q)
 3. Gene amplification
-- neuroblastoma
-- Breast cancer (N-MYC and HER-2 genes)
Carcinogenesis
 Major problem: nonlethal genetic damage or mutations
 Probably “cause” 65% of all cancers
-- Heredity is “cause” of 26-40%
 Carcinogens:
-- Chemical
-- Radiant energy
-- Microbial agents
 Carcinogenesis is a multistep phenomenon (tumor progression)
– Involves genes regulating DNA repair, angiogenesis, invasion,
metastasis
Carcinogenesis
 Three classes of regulatory genes are the main targets:
1) Protooncogenes (promote growth)
-- Mutant alleles = oncogenes (dominant genes)
2) Antioncogenes (growth-inhibiting cancer suppressor genes)
-- Tumor suppressor genes
-- Both alleles must be damaged (recessive oncogenes)
3) Genes controlling apoptosis (programmed cell death)
 DNA repair genes affect cell proliferation and survival
-- If disabled: widespread mutations
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Carcinogenesis
Ionizing Radiation
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003.
Human Papillomaviruses in Oral Lesions
24 genotypes have been isolated from oral lesions & mucosa
Lesion
Genotype(s) *
Herpes simplex virus
Normal mucosa
6, 7, 11, 16, 18, 31, 33, etc.
was a red herring?
Verruca vulgaris (common wart)
2 a – e, 4, 6, 40
Papilloma (squamous papilloma)
6 a – f, 11 a, b
Condyloma acuminatum
2, 6, 11 a, b, 16, 18, 53, 54
Focal epithelial hyperplasia (Heck’s disease)
13, 32
Smokeless tobacco keratosis
2, 6
Leukoplakia, no dysplasia
2, 6,11,16,18
Leukoplakia with epithelial (koilocytic) dysplasia
2, 6, 11, 16, 18, 31, 33, 35
Carcinoma in situ
2, 6, 11, 16, 18, 31, 33, 35
Keratoacanthoma
26, 37
Verrucous carcinoma
2 a – e, 6, 11, 16, 18
Squamous cell carcinoma
16, 18, 31, 33, 35
* genotypes in bold yellow are isolated in at least 1/3 of all cases with HPV
Carcinogenesis
Viruses Implicated in Human Neoplasia
Virus
Neoplasm
Burkitt’s lymphoma
Epstein-Barr virus (EBV)
Nasopharyngeal carcinoma
Some B-cell lymphomas
Some Hodgkin’s disease
Hepatitis B virus (HBV)
Hepatocellular carcinoma
Human papillomavirus (HPV)
Cervical carcinoma
Some skin carcinomas
Human papillomavirus (HPV)
Some oral and laryngeal carcinomas
HTLV-1
T-cell leukemia/lymphoma
Neoplasia
Environmental Etiologic Factors
Carcinogens (chemicals associated with cancer production):
– Arsenic (lungs, skin, hemanigiosarcoma)
-- e.g. smelting metals, fungicides
– Asbestos (lungs, mesothelioma, GI tract)
-- e.g. fire retardant, sound insulator
– Benzene (leukemia, Hodgkin’s lymphoma)
-- e.g. light oils, dry cleaning, solvents
– Berylium (lungs)
-- e.g.. rocket fuel, nuclear reactors
– Cadmium (prostate)
-- e.g. yellow dyes including food dyes, batteries
Carcinogenesis
Associated Chemicals
 Chromium (lungs)
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e.g. preservative, metal alloys, pigments
Ethylene oxide (leukemia)
e.g. ripening of fruits & nuts; rocket fuels, fumigation, sterilizing
Nickel (nose, lungs)
e.g. metal plating and alloying, ceramics, batteries,
stainless steel welding
Radon (lungs)
e.g. from decay of uranium, in quarries, mines,
seeps into home basements
Vinyl chloride (liver, angiosarcoma)
e.g. refrigerant, monomer for vinyl polymers, plastic adhesive
Causes of Oral Carcinoma
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The happy, toothless smoker
Tobacco smoking
Tobacco chewing
Betel/pan/areca chewing
Alcohol abuse
Precancer
Plummer-Vinson disease
(severe Fe deficiency)
Human papillomavirus 16/18
Chronic infection?
Syphilitic glossitis
History of irradiation
History of sun damage (lip)
History of H&N carcinoma
Increasing age
Cancer
Host Defenses
 Tumor elicits CD8+ cytotoxic T-cell response
– e.g carcinoembryonic antigen (CEA)
– e.g Oncogenic viruses (EBV, HPV)
– e.g Prostate-specific antigen (PSA)
 Antitumor effector mechanisms
– Cytotoxic T lymphocytes (especially against virus-induced
cancers)
– Natural Killer (NK) cells (don’t need prior sensitization;
may be first line of defense)
– Macrophages (once activated, exhibit selective cytotoxicity
against tumor cells)
– Humoral mechanisms from complement activation and induction
of antibody-dependent cellular cytotoxicity by NK cells
 Immunosurveillance
– Without it: increased cancer risk (5% in congenitally
immunosuppressed patients (usually lymphoma)
Neoplasia
Clinical Features
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Typically a mass, with or without surface ulceration
Compression on surrounding tissues
Ulceration with bleeding
May produce hormones (even if tumor is from tissue which normally
produces no hormones)
 Cachexia (wasting syndrome): progressive weight loss and
“wasting”
– Usually terminates with fatal infection
– Usually correlated with extent of tumor and metastasis
– Anorexia is common
– May be from TNF and IL-1 from activated macrophages
– No good explanation for how this happens
Tumor Markers
Some tumors create unique molecules -- may be used in diagnosis
Marker
Tumor
Alpha fetoprotein (AFP)
Hepatocellular carcinoma
Germ cell tumors
Human chorionic gonadotrophin (HCG)
Trophoblastic tumors
Acid phosphatase
Prostatic carcinoma
Carcinoembryonic antigen (CEA)
Gastrointestinal carcinoma
Hormones
Endocrine tumors
Precancers and Preneoplastic Conditions
 Cancer development is NOT inevitable!
 Persistent regeneration
-- Squamous cell carcinoma at edge of fistula or draining wound
e.g. osteomyelitis
-- Hepatocarcinoma in cirrhosis of the liver
e.g. alcoholism
 Hyperplastic proliferations
-- Endometrial carcinoma in atypical endometrial hyperplasia
 Dysplastic proliferations
-- Bronchogenic carcinoma in dysplastic bronchial mucosa
e.g. cigarette smoking
-- Colorectal carcinoma
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Precancers and Preneoplastic Conditions
 Chronic atrophic gastritis
-- Gastric carcinoma in pernicious anemia
i.e. vitamin B12 deficiency
 Chronic ulcerative colitis
-- Colorectal carcinoma
 Villous adenoma of colon
-- Colorectal carcinoma
 Leukoplakia of mouth, vulva, penis
-- Squamous cell carcinoma
Photo: E. Lalonde, West Virginia University, Morgantown, West Virginia.
Clinical Appearance Matters
Verruciform Leukoplakia, Granular leukoplakia, Verrucous Leukoplakia
Carcinoma in situ
Hyperkeratosis
Photo: J. Pindborg, Univ. Copenhagen,
Copenhagen, Denmark.
Photo (left): J. Pindborg, Royal College of Dentistry, Copenhagen, Denmark.
Erythroleukoplakia
Speckled Leukoplakia
Corrugated thick and thin leukoplakia of the oral floor and
ventral tongue, with pink areas surrounded by white.
Oral Precancers
Increased Risk (Not 100%!)
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Leukoplakia in syphilitic glossitis
From: Schwimmer, 1876, Budapest
Leukoplakia
Erythroplakia
Smokeless tobacco keratosis
Lichen planus (erosive)
Reverse smoker’s palate
Oral submucous fibrosis
Smooth, red tongue in PlummerVinson disease
Actinic cheilosis
Paraneoplastic Syndromes
 No good explanation for how this happens
 Hypercalcemia
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-- Ttumor cells make parathyroid hormone-related protein (PTHrP)
Cushing syndrome
-- Tumor cells make ACTH or ACTH-like peptides
Nonbacterial thrombotic endocarditis
-- Hypercoagulability state induced by tumor cells
Venous thrombosis
-- Hypercoagulability
Polycythemia
-- Tumor cells make erythropoietin
Staging of Cancers
Clinical Classification
 Stage shows severity of clinical features of the tumor
 Usually staged without sophisticated imaging technologies
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-- This may change soon
Stage I = small, localized tumor
Stage IV = huge or metastatic tumor
Not bad at forming prognosis
-- Stage I is good
-- Stage IV is very bad
TNM staging system:
– T = tumor size, in cm.
– N = presence of tumor in local/regional lymph nodes
– M = presence of tumor at a distant site
(beyond local lymph nodes; e.g. “below the clavicles”)
Tables used to establish the stage, combining the TNM evaluations
The TNM Staging System
Tumor size:
T0 = no tumor
T1 = <2 cm. in size
T2 = 2-4 cm. in size
T3 = >4 cm. in size
Lymph node involvement:
N0 = no positive nodes
N1 = few ipsilateral nodes
N2 = many ipsilateral nodes
or contralateral nodes
Distant metastasis:
M0 = no metastasis
M1 = metastasis below the
clavicle
Mx = suspected metastasis
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Prognosis Varies with Cancer Site
5-Year Survival Rates
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
Cancer
Once Uniformly Lethal
 1900: <5% survival
 1945: 20% survival
 1986: 50% survival
 2003: 63% survival
 ACS 2015 goal: 50% reduction in
mortality rates
 ACS 2015 goal: 25% reduction in
incidence rates
How: prevention,
early detection,
Adenocarcinoma 
at autopsy,
circa 1856
quality management, research