NEOPLASIA

Synonyms:

new growth
Tumor
Neoplasm

 Cancer
crab

all malignant tumors

adheres to any part that it

seizes upon in an obstinate manner.

 Neoplasm
the

an abnormal mass of tissue

growth of which is autonomous and

exceeds that of normal tissues
cell proliferation persists after cessation of the
stimuli that evoked the change

NOMENCLATURE
Two basic components of tumors
1. proliferating neoplastic cells constituting
the parenchyma

2. supportive stroma connective tissue

(framework) and BV

scant stromal support: soft. Fleshy tumor

abundant collagenous stroma (desmoplasia);
stony hard, scirrhous tumor

BENIGN TUMORS
oma suffix + cell of origin

 Benign

mesenchymal tumors
eg. Fibroma, lipoma, angioma, osteoma,
leiomyoma

 Benign

epithelial tumors: complex

nomenclature
adenoma

arise from glands or glandular

pattern
cystadenoma adenomas producing large
cystic masses,
Eg.

ovarian cystadenomas

papilloma

with papillary structures (fingerlife projections)

polyp tumor projecting from the mucosa into
the lumen.

Malignant Tumors

2 categories
1. Carcinomas from epithelial cells derived from
any 3 germ layers
Eg.
renal cell adenocarcinoma
bronchogenic squamous cell Ca
Undifferentiated / poorly differentiated Ca
2. Sarcomas from mesenchymal tissues

Greek sar fleshy, little connective tissue stroma

eg.
fibrosarcoma
liposarcoma
leiomyosarcoma
rhabdomyosarcoma

bronchogenic squamous cell

Ca

bronchogenic squamous cell

Ca

Liposarcoma

Liposarcoma

Mixed Tumors
Mixed

Tumors derived from one germ

cell layer that differentiates into more
than one parenchymal cell type

eg.

pleomorphic adenoma (mixed tumor of

salivary gland)
epithelial

cells, myxoid stroma, island of

cartilage/bone
arise from epithelial and myoepithelial cells

Teratomas of various parenchymal

cell types from more than one germ
cell layer

arise from totipotential cells

common in ovary and testis

***Melanoma/Seminoma/Hepatoma

Teratoma

Teratoma

Two non-neoplastic tumors stimulating

tumors:
choristoma

ectopic rest of nontransformed

tissues

eg.
Pancreatic

cells under small bowel mucosa

Adrenal cells under the kidney capsule

Hamartoma

disorganized tissue
indigenous to the particular site

Eg.
Hamartomatous

nodule in the lung may contain

cartilage, bronchi, BV

CHARACTERISTICS OF BENIGN
AND MALIGNANT NEOPLASMS

The distinction is based on morphology and

behaviour using four criteria
1.
2.
3.
4.

differentiation and anaplasia

rate of growth
local invasion
Metastases

with exceptions there also exists marked

discrepancy between morphologic appearance
and its biologic behaviour

DIFFERENTIATION AND
ANAPLASIA

Differentiation extent to which parenchymal cells

resemble comparable normal cells, both morphologically
and functionally

benign tumors in general are well-differentiated

malignant tumors in general from well-diff. to undifferentiated
better differentiation parallels functional capabilities comparable
to normal counterparts

WD SCCa- elaborates keratin

WD HCCa- bile

unanticipated tumor functions may emerge

Bronchogenic oat cell Ca. synthesize ectopic
Hormones: ACTH, PTH, insulin, glucagons

Anaplasia
Anaplasia-

to form backward

lack of differentiation
hallmark of malignant transformation
characterized by cytologic features:

Nuclear and cellular pleomorphism wide variation in the size

and and shape of cells and nuclei
Hyperchromatism- darkly stained nuclei frequently containing
Nucleolie
Nuclear- Cytoplasmic (NC) Ratio approaches 1:1 instead of
the
normal 1:4 1:6

Anaplasia
malignant

tumors are invasive, infiltrating,

and destroying normal surr. tissues
surgical treatment requires removal of a
considerable margin of surr. uninvolved
tissues
next to the devt. of metastases,
invasiveness is the most reliable feature
that differentiates malignant from benign
tumors

Anaplasia
CIS:

displays cytologic features of malignancy

without invasion of the BM

METASTASES
distant

spread of tumors
single most impt. feature distinguishing
benign from malignant tumors
almost all malignant tumors have the
capacity to metastasize
major

exceptions: CNS malignant neoplasm of

the alial cells basal cells
Ca. of skin

METASTASES

Three Routes:
1.

Spread into body cavities seeding of surfaces in

peritoneal, pleural, pericardial, subarachnoid
spaces

2.

Eg. Ovarian Ca spreads transperitoneally to the surfaces

of the liver.
Pseudomyxoma peritonei mucus-secreting appendiceal
Ca fill the peritoneal cavity with gelatinous neoplastic
mass

Invasion of lymphatics followed by transport to

regional nodes, then other parts of the body. *skip
metastases

METASTASES
3. Hematogenous spread typical of sarcomas and
also renal Ca

veins (thinner) more frequently invaded than arteries

lung and liver are common sites of hematogenous
metastases because these receive both systemic and
venous outflow.

Abundant atypical mitoses reflect proliferative activity

Tumor giant cells - with single huge polymorphic nucleus
or multiple nuclei
Loss of polarity markedly disturbed orientation of
anaplastic cells
Ischemic necrosis of large central areas

Dysplasia
Dysplasia

disordered growth

encountered in epithelia loss of uniformity of

individual cells
tumor cells display a total disarray of tissue
architecture - loss of normal polarity
Carcinoma in-situ: marked dysplastic changes
involving the entire thickness of the epithelium with
the basement membrane not breached
-a pre-invasive neoplastic lesion
dysplasia does not necessarily progress to cancer

mild to moderate changes that do not involve the entire

thickness of epithelium may be reversible

RATE OF GROWTH

most Ca grow more rapidly, sometimes at an erratic

pace and eventually spread
most benign tumors grow slowly over the years
factors: hormone dependence, adequacy of blood
supply, unknown influences may affect growth

eg. Leiomyoma estrogen-dependent

rapidly growing Ca often contain central areas of

ischemic necrosis
growth fraction of tumor cells has a profound effect
on their susceptibility to cancer chemotherapy.
*most antiCa agents act on cells that are in cycle

LOCAL INVASION
most

benign tumors grow as cohesive

expansile masses that develop a rim of
condensed CT, or fibrous capsule
plane of cleavage between capsule and
suur. Tissue facilitates surgical enucleation.

HOST FACTORS AFFECTING

TUMOR GROWTH
Angiogenesis
vascularization

of tumors by host-derived
blood vessels has a profound influence on
tumor growth
ischemic necrosis occurs when the pace of
vascularization is exceeded by rapid tumor
growth

HOST FACTORS AFFECTING

TUMOR GROWTH
Hormones
tumors

of hormonally responsive tissues

(breast, endometrium, prostate) frequently
retain cellular hormone receptors
hormonal manipulation
orchiectomy

to arrest growth of prostatic Ca

estrogen receptor antagonist drugs to treat
breast Ca

CARCINOGENESIS

Oncogenes cancer-causing genes

Protooncogenes cellular genes that promote normal
growth and differentiation
Tumor suppressor genes apply brakes to cellular
proliferation

Eg. Rb gene: cancer develop when the cell becomes

homozygous for the mutant allele or, put in another way, loses
heterozygosity for the normal Rb gene because Rb gene is asso
with cancer when both normal copies are lost.
p53 gene: located in chr 17p13.1, p53 protein as a guardian of
the genome

over 50% of human tumors contain mutations in this gene

functional activities: cell-cycle arrest DNA repair and apotosis
initiation.

CARCINOGENESIS
Oncoproteins

encoded in oncogenes

Properties:
a. devoid of impt. regulatory elements
b. production in transformed cells
does
not depend on growth
factors or
the external signals.

KARYOTYPIC CHANGES IN
TUMOR CELLS
many

human neoplasms are associated

with nonrandom chromosomal
abnormalities

KARYOTYPIC CHANGES IN
TUMOR CELLS
Balanced translocations
Philadelpia (Ph) chromosome reciprocal balance
translocation between chr 22 and (usually) 9 or t(9;22)
noted in >90% of cases of CML
Burkitts lymphoma - > 90% with t(8;14)
Deletions
Retinoblastoma associated with deletion of chr 13,
q14
Wilms tumor associated with deletion of chr 11, p13
Cytogenic changes asoociated with gene
amplification
neroblastoma

PREDISPOSITION TO CANCER
Geographical

and Environmental Factors

in Japan, death rate from Ca of the
stomach is 7x 8x higher than in US
death rate from the lung Ca >2x in US than
in Japan, even higher in Belgium
skin Ca death, largely melanoma, 6x more
frequent in New Zealand than Iceland

environmental factors in carcinogenesis

asbestos mesothelioma
vinyl chloride angosarcoma of the liver
berryllium lung Ca
smoking Ca of the mouth, pharynx, larynx,
lung, esophagus, pancreas, bladder
alcohol and tobacco upper aerodigestive tract
Ca
sexual practices cervical Ca
beta-naphtylamine bladder Ca

PREDISPOSITION TO CANCER
Age
most

Ca occur in later life (>55)

under 15 yrs: 60% of cancer deaths due to
acute leukemia and neoplasms of CNS
eg.

Neuroblastoma, Wilms tumor,

retinoblastoma, acute leukemia, rhabdomyosarc

PREDISPOSITION TO CANCER
Heredity

close relatives of cancer patients have higher than

normal incidence of same neoplasm
childhood retinoblastoma: 40 % are familial,
inherited as an autosomal dominant (AD) trait
susceptibility to multiple colonic polyposis is
inherited as an AD trait, and almost all patients
develop Ca in later life

chromosomal-DNA instability syndromes are

inherited as autosomal recessives, char. by some
defect in DNA repair, and greatly increased risk to
develop Ca

eg. Xeroderma pigmentosum

ACQUIRED PRENEOPLASTIC
SYNDROMES
regenerative

hyperplastic and dysplastic

proliferations are fertile soil for the origin of
a malignant transformation
well defined asso. between certain forms of
endometrial hyperplasia and endometrial
Ca, between cervical dysplasia and cervical
Ca

ACQUIRED PRENEOPLASTIC
SYNDROMES
Non-neoplastic
cirrhosis

precancerous conditions:

of liver hepatocellular Ca
atrophic gastritis of pernicious anemia
stomach Ca
chronic ulcerative colitis Ca of the colon
Leukoplakia of genital and oral mucosa
SCCA

ACQUIRED PRENEOPLASTIC
SYNDROMES
Certain

chronic inflammatory disorders:

Ulcerative

colitis
Chrons disease
H. pylori gastritis
Viral hepatitis
Chronic Pancreatitis

ACQUIRED PRENEOPLASTIC
SYNDROMES
Proposed
increase

mechanics:

cytokine production growth of

transformed cells
increase the pool of tissue stem cells,
susceptible to mutagens
ROS produced
genomic instability

ACQUIRED PRENEOPLASTIC
SYNDROMES
Precancerous

benign neoplasia:

Villous

adenoma of colon 50% risk to

become AdenoCa
Longstanding leimyoma leimyosarcoma
(rarely)
Pleomorphic Adenoma rare malignant
transformation
most

benign neoplasms do not become

cancerous, most malignant tumors arise de novo.

GRADING AND STAGING OF

CANCER
grade

and stage provide a semiquantitative

estimate of the clinical gravity of tumor
both valuable for prognostication and for
planning therapy, although staging has
proved to be of greater clinical value

GRADING AND STAGING OF

CANCER
Grading:

based on the degree of

differentiation and the number of mitoses
grades

I-IV, with increasing anaplasia

in general, high grade tumors are more
aggressive
imperfect:

(1). Different areas may show different degrees of

differentiation
(2). Grade of tumor may change as tumor grows

 Staging:

based on anatomic extent of tumor

TNM: tumor, node, metastases

LABORATORY DIAGNOSIS OF
CANCER
Histologic

and Cytologic Methods

histologic

examination is the most

important, aided by:
availability

of relevant clinical data

adequate tissue preservation and sampling
frozen section examination to detect cell surface
receptors

LABORATORY DIAGNOSIS OF
CANCER
Fine

Needle Aspiration

aspiration

of cells and fluids from masses in

readily palpable sites
aspirate is smeared, stained and examined

LABORATORY DIAGNOSIS OF
CANCER
Cytologic

(Papaniculao) Smears

examination of cells that are easily shed / exfoliated

most common used in the Dx of dysplasia, CIS and
invasive Ca of uterine cervix, and also stomach,
bronchus and urinary bladder
interpretation based chiefly on changes in the
appearance individual cells
false negatives do occur because of sampling error
when possible, cytologic Dx must be confirmed
before therapeutic intervention

LABORATORY DIAGNOSIS OF
CANCER
Immunocytochemistry
detection

of cell products or surface

markers by monoclonal antibodies
binding of Ab revelead by fluorescent labels
or generation of colored pdts
uses:

categorization of undifferentiated
malignant tumor, of leukemias vs. lymphomas;
determine site of origin

LABORATORY DIAGNOSIS OF
CANCER
DNA probe

analysis

used

in the Dx of lymphoid neoplasms since

such tumors are associated with clonal
rearrangements of T- and B- cell Ag
receptors genes

DNA flow

cytometry

measurement

of DNA content of tumor cells

LABORATORY DIAGNOSIS OF
CANCER
Tumor

Markers

tumor-derived

or associated molecules that

can be detected in blood or body fluids
adjuncts to the diagnosis
may be of value in determining response to
therapy

Tumor Markers
Cacinoembryonic

antigen (CEA)
used in estimating tumor burden in
colorectal Ca in detecting recurrences after
surgery
inconsistently elevated in alcoholic cirrhosis,
hepatitis, ulcerative colitis

Tumor Markers
Alpha-fetoprotein

(AFP)
normally produced by fetal yolk sac and
liver
elevations
marked: in liver Ca and testicular germ cells
less marked: cirrhosis, hepatitis
measurements useful in indicating presence
of liver or testicular Ca, assessing
recurrence and response to therapy

Tumor Markers
Prostatic

acid phosphate
markedly elevated in invasive prostatic
Ca.

 end