NEOPLASIA

Hodgkin lymphoma

METASTASIS spread of a malignant tumor from one site to another

via blood or lymph
BENIGN typically refers to those tumors incapable of metastasis and
having a good clinical outcome (prognosis)
MALIGNANT those tumors capable of invasive growth and or
metastasis, often fatal if not treated effectively.
BASIC COMPONENTS OF TUMORS
PARENCHYMA clonal neoplastic cells themselves usually referring to
epithelial cells in organs
STROMA made up of connective tissue cells, blood vessels,
macrophage & lymphocytes that support parenchyma cells- not
actually tumor. Provides structural framework
stroma = soft & fluffy neoplasm
stroma = collagen = Desmoplasia (stony
hard/schirrhous)
Note: Adequate stromal blood supply is needed for tumor cells to live

Beryllium and
its Compounds

Lung

Cadmium and
its Compounds

Prostate

Chromium
Compounds
Nickel

Lung

Radon and its

Decay Products

Lung

Vinyl Chloride

Angiosarcoma
Liver

Nose
Lung

EPIDEMIOLOGY (Cancer Incidence)

(despite risk)
Used in printing, lithography, paint,
rubber, dry cleaning, adhesives &
coatings, detergents
Formerly widely used as solvent
fumigant
Missile fuel & space vehicles
Hardener for lightweight metal alloys
particularly in aerospace applications
& nuclear reactors
Uses includes yellow pigments &
phosphors found in solders
Used in batteries & as alloys in metal
platings & coatings
Component of metal alloys, paints,
pigments & preservatives
Nickel plating
Component of ferrous alloys, ceramics
& batteries
By product of stainless steel arc
welding
From decay of minerals containing
uranium
Potentially serious hazard in quarries
& mines
Refrigerant
Monomer for vinyl polymer
Adhesive for plastics
Formerly inert aerosol propellant

AGE
MEN

WOMEN

Prostate CA (29%)

Breast CA (29%)

Lungs CA (15%)

Lungs (14%)

Colon & Rectum (9%)

Colon & Rectum

(10%)
Uterine Corpus
(6%)
Thyroid (5%)

CANCER DEATHS
IN US
Lungs both sex
(26%)
Female- breast
(15%)
Male- Prostate
(11%)
Colon & Rectum
(9%)
Pancreas

NHL (4%)
Melanoma (4%)
Kidney (3%)
Ovary (3%)
Pancreas (3%)
Others (20%)

Ovary
Liver
NHL
Leukemia
Esophagus
Urinary bladder

Urinary bladder (7%)

Melanoma of the skin
(5%)
NHL (4%)
Kidney (4%)
Oral Cavity (3%)
Leukemia (3%)
Pancreas (3%)
Others (19%)
GEOGRAPHIC FACTORS

Stomach CA: 7-8 times higher in Japan than US

Lung CA: Higher in US than in Japan
CARCINOGENIC ENVIRONMENTAL FACTORS

UV rays and smog

Medications Methotrexate
Work- asbestos
Home high fat diet, alcohol
White sugar: Carcinogenic
Alcohol Oropharynx (excluding the lip)
Larynx
Esophagus
Hepatic cirrhosis / Hepatocellular CA
Cigarette smoking
Mouth
Pharynx
Lungs (90%)
Larynx
Esophagus
Pancreas
Bladder

OCCUPATIONAL CANCERS
Agents/
Groups of
Agents
Arsenic and its
Compounds
Asbestos

Benzene

Human Cancer
Site for w/c
Reasonable
Evidence is
Available
Lung
Skin
Hemangiosarcoma
Lung
Mesothelioma
Gastrointestinal
tract
Esophagus
Stomach
Large intestine
Leukemia

Typical Use or Occurrence

By product of metal smelting

Component of alloys, electrical &
semiconductor devices, medications &
herbicides, fungicides & animal dips
Formerly used for many applications
because of fire, heat and friction
resistance
Still found in existing construction &
fire resistant textiles, friction
materials, underlayment & roofing
papers & floor tiles
Principal component of light oil

Ages 55 75 : Most cancer deaths occur

Female: 40 79 y/o most common to be affected by cancer
Male: 60 79 y/o
Children: <15 y/o
o
Acute leukemia
o
Neoplasm of CNS
o
Lymphomas
o
Soft tissue
o
Bone sarcoma

GENETIC DISPOSITION
A.

Hereditary Factors

AUTOSOMAL DOMINANT INHERITED CANCER SYNDROMES

Gene
Inherited Predisposition
RB
Retinoblastoma
p53
Li-Fraumeni syndrome (various tumors)
p16/INK4A
Melanoma
APC
Familial adenomatous polyposis/ colon cancer
NF1, NF2
Neurofibromatosis 1 and 2
BRCA1, BRCA2
Breast and ovarian tumors
MEN1, RET
Multiple endocrine neoplasia 1 and 2
MSH2, MLH1,
Hereditary nonpolyposis colon cancer
MSH6
PTCH
Nevoid basal cell carcinoma syndrome
PTEN
Cowden syndrome (epithelial cancer)
LKB1
Peutz-Jeghar syndrome (epithelial cancer)
VHL
Renal cell carcinomas
INHERITED AUTOSOMAL RECESSIVE SYNDROMES OF DEFECTIVE
DNA REPAIR
Xeroderma pigmentosum
Ataxia-telangiectasia
Bloom syndrome
Fanconi anemia
FAMILIAL CANCERS
Familial clustering of cases, but role of inherited predisposition not
clear for each individual
Breast cancer
Ovarian cancer
Pancreatic cancer
B. Non- hereditary Factors
Asbestos, silicosis
Cystitis
Gingivitis
Inflammatory bowel disorder
Reflux esophagus

Mesothelioma, Lung carcinoma

Bladder CA
Oral squamous CA
Colorectal CA
Esopharyngeal CA

INFECTIOUS AGENTS

Opisthorchis
Hepatitis hepatocellular CA
Gastritis
Chronic cholecystitis gall bladder CA

Mononucleosis - B cell non Hodgkin lymphoma

Pelvic inflammatory disease sexually transmitted
o
Gonorrhea
o
Chlamydia
o
HPV
Osteomyelitis- CA in draining sinuses

Fibroma Fibroblastic cells

Chondroma Cartilaginous tumor
Osteoma Osteoblast
Leiomyoma Smooth Muscle
Rhabdomyoma Skeletal Muscle

CHARACTERISTICS OF CANCER

Genetic
o
Caused by DNA mutations
o
DNA methylation & alterations in histone modifications

Heritable
o
Subject to to Darwinian selection (survival of the fittest)

Plays a role in progression & recurrence of CA

Hallmarks of Cancer
o
Self-sufficiency in growth signals
o
Insensitivity to anti-growth signals
o
Evading apoptosis
o
Limitless replicative potential
o
Sustained angiogenesis
o
Tissue invasion & metastasis
o
Abnormal metabolic pathways (switch to aerobic glycolysis
even in presence of abundant oxygen)
o
Evading the immune system

Benign Epithelial Tumors

Adenoma Glandular pattern, derived from glands

Papilloma Finger-like or warty projections in skin, larynx,

urinary bladder, mouth

Cystadenoma Hallow cystic masses (ovary)

Papillary cystadenoma Tumor produce papillary patterns that

protrude into cystic spaces

Polyp Mass that projects above mucosal surface (gut) forming

projections
Villus adenoma, adenoma of GI tract protruding in intestinal
mucosa
If left untreated, may proceed to colorectal CA
Polyp benign
Polypoid cancer malignant polyps

Exceptions:
o
Hepatoma malignant tumor in liver
o
Melanoma malignant melanocytes
o
Seminoma malignant tumor in seminiferous tubules
o
Lymphoma malignant lymphoid cells
o
Glioma malignant glial cells (supporting cells of nervous
system)

NOMENCLATURE

MALIGNANT TUMORS

The Nomenclature of the tumor is based on the parenchymal

component:

Benign Tumor

Malignant Tumor

Gross Appearance
External Surface
Capsule
Hemorrhage
Microscopic Appearance
Architecture
Cell Population
Nucleus
Cytoplasm

Benign Tumor

Malignant Tumor

Smooth
Yes
No

Irregular
No
Yes

Resemble tissue of origin

Uniform
Regularly Shaped
Well-developed
cytoplasm
Well-developed
organelles
Nucleus accounts for
small part of the total cell
volume
Regular, even distribution
of chromatin,
Nucleoli are not
prominent
Normal number
Few

Ends with sarcoma mesenchymal origin

o
Greek: Fleshy
o
Rhabdomyosarcoma Skeletal muscle
o
Leiomyosarcoma Smooth muscle
o
Fibrosarcoma Fibroblast
o
Chondrosarcoma Chondrocytes(Cartilage)
o
Liposarcoma Fat cells
Ends with carcinoma epithelial origin
o
Adenocarcinoma glandular growth
o
Squamous Cell Carcinoma any epithelial of the body
(squamous)

Undifferentiated
Heterogenous
Leukemia/Lymphomas
Pleomorphism

Malignant neoplasms arising from mesenchymal cells of the blood

Very little cytoplasm and
contain reduced number of
Sarcoma
organelles

Malignant neoplasms arising in solid mesenchymal tissues or

derivatives
N/C Ratio
High N/C Ratio

Designated by cell type which they are composed (cell of origin)

Hematogenous route - metastasis (Blood)

Lymph node metastases are unusual

Nuclei
Hyperchromatic, Nucleoli

Most arise in deep soft tissue

are prominent and multiple

All sarcoma are locally invasive

Adult sarcoma have specific chromosomal translocation that

Chromosome
Aneuploidy
initiate tumor formation
Mitosis
Many irregular
Carcinoma
Nomenclature for general categories of neoplasm

Malignant neoplasms of epithelial cell origin

Adenoma benign neoplasm derived from glandular cells

Derived from three germ layers (endoderm, mesoderm, ectoderm)

Carcinoma malignant neoplasm derived from epithelial cells

Locally invasive
(Ectoderm, Endoderm)

Metastasize via LYMPHATIC system, proceeds hematogenous

Sarcoma malignant neoplasm derived from mesenchymal cells

route
(Mesoderm bone, cartilage, connetive tissue, muscles)
o
Adenocarcinoma

Lymphoma malignant neoplasm derived from lymphocytes

o
Squamous cell carcinoma

Melanoma malignant melanocytes

o
Poorly differentiated vs. Undifferentiated carcinoma

Germ cell tumor malignant germ cells (ovaries, testes)

Hamartomas

Benign, focal malformation that resembles neoplasm in the tissue

of its origin

Grows the same rate as surrounding tissues, composed of tissue

elements normally found at site but growing to a disorganized
mass

Excess normal tissue in normal situation

Choristoma

Congenital anomaly consisting of heterotropic rest of cells

Tumors contains normal tissues but in abnormal locations

BENIGN TUMORS
Benign Mesenchymal Tumors

-oma

Tissue of Origin
Benign
COMPOSED OF ONE PARENCHYMAL CELL TYPE
Tumors of Mesenchymal Origin
Connective tissue &
Fibroma
derivatives
Lipoma
Chondroma
Osteoma
Endothelial and Related Tissues
Blood vessels
Hemagioma
Lymph vessels
Lymphangioma
Synovium
Mesothelium
Brain coverings
Meningioma
Blood Cells and Related Cells
Hematopoietic cells
Lymphoid tissue
Muscle
Smooth
Leiomyoma

Malignant

Fibrosarcoma
Liposarcoma
Chondrosarcoma
Osteogenic sarcoma
Angiosarcoma
Lymphangiosarcoma
Mesothelioma
Invasive meningioma
Leukemias
Lymphomas
Leiomyosarcoma

Striated
Rhabdomyoma
Tumors of Epithelial Origin
Stratified squamous
Squamous cell papilloma
Basal cells of skin or
adnexa
Epithelial lining of glands
or ducts

Adenoma
Papilloma
Cystadenoma
Bronchial adenoma
Renal tubular adenoma
Liver cell adenoma
Urothelial adenoma

Rhabdomyosarcoma

Squamous cell or
epidermoid carcinoma
Basal cell carcinoma

Adenocarcinoma
Papillary carcinoma
cystadenocarcinoma
Bronchogenic carcinoma
Renal cell carcinoma
Hepatocellular carcinoma
Urothelial carcinoma

Dysplasia

Disordered growth of epithelium

Loss of cellular uniformity and architectural orientation

Reversible if the inciting agent was removed

Precursor of malignancy, but does not always progress

Respiratory passages
Renal epithelium
Liver cells
Urinary tract epithelium
(transitional)
Placental epithelium
Hydatidiform mole
Choriocarcinoma
Testicular epithelium
Seminoma
(germ cells)
Embryona carcinoma
Tumors of
Nevus
Malignant melanoma
Melanocytes
MORE THAN ONE NEOPLASTIC CELL TYPE - MIXED TUMORS, USUALLY
DERIVED FROM ONE GERM CELL LAYER
Salivary glands
Pleomorphic adenoma
Malignant mixed tumor of
(mixed tumor of salivary
salivary gland
gland
Renal anlage
Wilms tumor
MORE THAN ONE NEOPLASTIC CELL TYPE DERIVED FROM MORE THAN ONE
GERM CELL LAYER TERATOGENOUS
Totipotential cells in
Mature teratoma
Immature teratoma
gonads or in embryonic
Dermoid Cyst
Teratocarcinoma
rests

**Note that not all malignant neoplasms have benign counterpart

(hematopoietic & lymphoid cells, gliomas)
Teratoma

Originate from the totipotential cells such as those are normally

present in the ovary and testes

Contains cells with the capacity to differentiate into any cell type
found in adult body
o
Benign (mature) teratoma

All component parts are well differentiated

o
Malignant teratoma

Less differentiated

E.g. Ovarian cystic teratoma (Dermoid cyst)

Differentiate principally along ectodermal lines to

create a cystic tumor lined by skin, replete with
hair, sebaceous gland, and tooth surface
Mixed Tumors

Tumor derived from more than one type of tissue (undergone

divergent differentiation)

Note that most neoplasms are monoclonal in origin

o
Mixed tumor of salivary gland or Pleomorphic adenoma
(epithelial cells + myxoid stroma + bone or cartilage)
o
Fibroadenoma (proliferating ducts + loose fibrous tissues)
FEATURES TO DISTINGUISH BENIGN FROM MALIGNANT

Differentiation & Anplasia (Histologic features of malignancy)

Rate of growth
Local invasion
Invasion and Metastasis

Differentiation and Anaplasia

Differentiation subjective determination made by the pathologist

Differentiation refers to extent of resemblance with normal tissue

of origin

Seen only in parenchymal cells that constitute transformed

elements of neoplasm
a.
b.
c.
d.

Well differentiated very similar in appearance (benign)

o
Lipoma fat cells laden with cytoplasmic lipid vacuoles
o
Chondroma mature cartilage cells
Poorly differentiated minimal resemblance to the normal parent
tissue
Moderately well differentiated
Anaplastic
o
Tumor show no similarity to its parent tissue, associated
with aggressive behavior (lack differentiation)
o
Hallmark of malignancy
o
backward formation

Histologic Features of Malignancy

Pleomorphism

Abnormal mitotic figures and number of mitotic figures (atypical

mitosis)

Hyperchromasia

Hypocellularity with loss of

anaplastic cells)
Abnormal nuclei size & shape
Coarse or clumped chromatin

normal

polarity

(Displation

of

Carcinoma in-situ

precursor for most carcinoma

full thickness of dysplasia of the epithelium

without evidence of invasion of tumor cells thru the epithelial

basement membrane
*Differentiation provide clues to the aggressiveness of tumor
*Tumors lose differentiation over time as they become more malignant
and acquire more cumulative genetic mutations
*Predicts responsiveness to therapy
Rate of Growth

Benign slower

Malignant grow more quickly at the rate corresponding to their

degree of anaplasia
Invasion and Metastasis

Invasion infiltration of tumor cells into surrounding organ

Metastasis spread of tumor to distant organs

Note: Some malignancies do not metastasize but invade (e.g.

Gliomas and Basal cell carcinoma)
Pathway of Dissemination
1.
Seeding within body cavity
o
Ovarian cancer
o
Medulloblastoma
o
Ependymoma
2.
Lymphatic spread (carcinoma)
o
Skip Metastases - lateral lymph node metastasis without
central lymph node involvement
o
Sentinel lymph node first regional lymph node that
receives lymph flow from primary tumor (helpful in
determination of extent of spread)
o
Necrotic products may trigger immune response
Lymphadenitis (hyperplasia of follicles)
Sinus histiocytosis (proliferation of macrophages in
subcapsular sinuses)
3.
Hematogenous spread (sarcoma)
o
Liver and lungs most frequently involved secondary sites

Characteris
tics
Differentiatio
n/ anaplasia
Rate of
growth

Local
invasion

Metastasis

Benign

Malignant

Well differentiated
Structures usually typical
of tissue of origin
Progressive & slow
May come to
standstill/regress
Mitotic figures: rare &
normal
Usually cohesive
expansile welldemarcated masses that
dont invade/infiltrate
surrounding normal
tissue
Absent

Some lack differentiation

with anaplasia
Structures often atypical
Erratic, slow to rapid
Mitotic figures: numerous
& abnormal
Locally invasive,
infiltrating surrounding
tissue
Sometimes may be
seemingly cohesive &
expansile
Frequently present
The larger & more
undifferentiated the
primary the more likely
to metastases

GRADING AND STAGING OF TUMOR

Differentiation of a tumor determined by the pathologist

Histologic examination of the tumor

Staging

Follow the TNM system

Grade I (well differentiated)

Grade II (moderately well differentiated, poorly differentiated)

Grade III (anaplasia)

American Joint Committee on Cancer Staging

TNM System

T- Primary tumor site

o
T0 in situ lesion
o
T1-T4 increase site of tumor

N Regional lymph node

o
N0 no nodal involvement
o
N1-N3 increase number and range of nodes

M Metastasis
o
M0 no distant metastasis
o
M1-M2 presence of metastasis
CARCINOGENESIS
o
Normal cells are converted to tumor
Steps:
Self-sufficiency in growth signals
o
Proto-oncogene gene used by the cell for growth and
development
o
Oncogene mutated proto-oncogene promotes autologous
independent of external growth signals
Ignore growth inhibitory signals
o
Tumor suppressor genes

genes that form a network that prevent uncontrolled cell

growth

Regulates cell division

E.g. RB (retinoblastoma), p53 (breast and ovarian CA)

Evasion of Apoptosis

Apoptosis bodys mechanism to rid itself with genetic

damage so that it cannot propagate the damage and prevent
accumulation of cells with mutations
Limitless replicative potential

Acquire the ability to divide unlimited number of times

Angiogenesis

Nutrients, oxygen supply, and removal of waste

Invasion and metastasis

Hallmark of malignancy

Major cause of cancer related morbidity and mortality

EFFECTS OF TUMOR

Location
o
2 cm tumor in brain stem vs leg

Space occupying lesion: herniation brain, obstruction

heart valve)

Foramen magnum space in brain stem

o
Growth of a mass can impinge a vasculature arterial and
venous
o
Bone fracture
o
Colon constipation, intestinal obstruction
o
Biliary tract jaundice
o
Blood vessels hemorrhage
o
Cachexia loss of body fat and muscle; anorexia; weakness
o
Sarcopenia decrease of muscle mass
PRENEOPLASTIC LESIONS

Precancers
o
Squamous metaplasia & dysplasia of bronchial mucosa
lung cancer
o
Endometrial hyperplasia & dysplasia endometrial cancer
o
Leukoplakia of oral caviy, vulva or penis squamous cell
carcinoma
o
Villous adenomas of colon colorectal cancer
PRENEOPLASTIC SYNDROME

Hormone production
o
PTH like hormone

Squamous cell carcinoma of the lungs

Breast carcinoma

Renal cell carcinoma

Result to hypercalcemia
o
ACTH like protein

Small cell lung carcinoma

Pancreatic carcinoma

Result to Cushing Syndrome

o
Syndrome of Inappropriate Antidiuretic Hormone Secretion
(SIADH)

Produced by small cell carcinoma of lung

Cerebral neoplasm

Results to water retention

o
Erythropoeitin

Renal cell carcinoma

Hepatocellular carcinoma

Cerebellar hemangioblastoma

Results to polycythemia
o
Nerve and Muscle Syndrome

Lambert Eaton Syndrome

Myasthenia Gravis-like syndrome
Small cell carcinoma of the lungs
Due to antibody against presynaptic calcium channels
at the neuromuscular junction

Clinical Syndromes
ENDOCRINOPATHIES
Cushing syndrome
Syndrome of
inappropriate
antidiuretic hormone
secretion
Hypercalcemia

Major Forms of Underlying

Cancer

Causal Mechanism

Squamous cell carcinoma

of lung
Pancreatic carcinoma
Squamous cell carcinoma
of lung
Intracranial neoplasms

ACTH
ACTH-like substance

Squamous cell carcinoma

of lung
Breast carcinoma
Renal carcinoma
Adult T-cell leukemia/
lymphoma
Hypoglycemia
Ovarian carcinoma
Fibrosarcoma
Carcinoid syndrome
Hepatocellular carcinoma
Bronchial adenoma
(carcinoid)
Pancreatic carcinoma
Polycythemia
Gastric carcinoma
Renal carcinoma
Cerebellar hemangioma
Hepatocellular carcinoma
NERVE AND MUSCLE SYNDROMES
Myasthenia
Bronchogenic carcinoma
Disorders of the CNS
Breast carcinoma
& PNS
DERMATOLOGIC DISORDERS
Acanthosis nigricans
Gastric carcinoma
Lung carcinoma
Uterine carcinoma
Dermatomyositis

Bronchogenic carcinoma
Breast carcinoma
OSSEOUS, ARTICULAR AND SOFT-TISSUE CHANGES
Hypertrophic
Bronchogenic carcinoma
osteoarthropathy &
clubbing of the
fingers
VASCULAR AND HEMATOLOGIC CHANGES
Venous thrombosis
Pancreatic carcinoma
(Trosseau
Bronchogenic carcinoma
phenomenon)
Other cancers
Nonbacterial
Advanced cancers
thrombotic
endocarditis
Red cell aplasia
Thymic neoplasms
OTHERS
Nephrotic syndrome
Various cancers

Antidiuretic hormone
Atrial natriuretic
hormone
Parathyroid hormonerelated protein
(PTHRP)
TGF-
TNF
IL-1
Insulin
Insulin like substance
Serotonin
Bardykinin
Erythropoietin

Immunological

Immunological
Secretion of
epidermal growth
factor
Immunological

Unknown

Tumor products
(mucin that activates
clotting)
Hypercoagulability
Unknown
Tumor antigens
Immune complexes

Microbial Carcinogenesis

HTLV-1

HPV

EBV

HBV, HCV

H. pylori
Human T cell Leukemia Virus -1

T cell leukemia / lymphoma

Endermic in Japan, Carribean

Tropism for CD4 T cell

Require transmission of infected T cell via sexual intercourse,

blood products, breast feeding

Leukemia develops 3-6% of infected individual after 40-60 years

latent period
Human Papilloma Virus

Types 1, 2, 4, 7 cause benign squamous papillomas (warts)

Types 16, and 18 squamous cell carcinoma of the cervix and

anogenital region

Types 6, and 11 cause genital warts, low malignant potential

Epstein Barr Virus

Member of the Herpes family

infects B lymphocytes and epithelial cells of oropharynx

Cause:
o
Burkitt lymphoma

B cell lymphoma (immunosuppressed)

Hodgkin lymphoma

Nasopharyngeal Carcinoma
o
Kissing Disease

Hepatitis B and Hepatitis C Virus

70-80% of hepatocellular carcinoma

Endemic in Far East and Africa

Helicobacter pylori

First peptic ulcer

Adenocarcinoma of the stomach and gastric lymphoma

LABORATORY DIAGNOSIS

Histologic and Cytologic method

Immunohistochemistry
o
Categorization
of
undifferentiated
malignant
(carcinoma, lymphoma, melanoma, and sarcoma)
o
Determine the site of origin of metastatic tumor)

Molecular diagnosis
o
For diagnosis and prognosis of malignant tumor
o
Diagnosis of hereditary predisposition to cancer
o
Detection of minimal residual disease

Tumor Markers
o
Detection of cancer (screening)
o
Determine effectiveness of therapy
o
Determine recurrence

TUMOR MARKERS
HORMONES
Human chorionic gonadotropin
Calcitonin
Catecholamine and metabolites
Ectopic hormones
ONCOFETAL ANTIGENS
-fetoprotein
Carcinoembryonic antigen
ISOENZYMES
Prostatic acid phosphatase
Neuron-specific enolase
SPECIFIC PROTEINS
Immunoglobulins
Prostate-specific antigen and
Prostate-specific membrane
antigen
MUCINS AND GLYCOPROTEINS
CA-125
CA-19-9
CA 15-3
NEW MOLECULAR MARKERS
p53, APC, RAS mutants in stool &
serum
p53, and RAS mutants in stool &
serum
p53, and RAS mutants in sputum &
serum
p53 mutants in urine

tumor

Throphoblastic tumors
Nonseminomatous testicullar
tumors
Medullary carcinoma of thyroid
Pheochromocytoma & related
tumors
See paraneoplastic syndromes
table
Liver cell cancer
Nonseminomatous germ cell
tumors of testis
Carcinomas of the colon,
pancreas, lung, stomach and
heart
Prostate cancer
Small cell cancer of lung
Neuroblastoma
Multiple myeloma
Other gammopathies
Prostate cancer

Ovarian cancer
Colon cancer
Pancreatic cancer
Breast cancer
Colon cancer
Pancreatic cancer
Lung cancer
Bladder cancer