NEOPLASIA

Synonyms: new growth

Tumor
Neoplasm
 Cancer all malignant tumors

crab adheres to any part that it seizes

upon in an obstinate manner.
 Neoplasm an abnormal mass of tissue
the 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 (finger-
life 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
CHARACTERISTICS OF BENIGN
AND MALIGNANT NEOPLASMS
The distinction is based on morphology and
behaviour using four criteria
1. differentiation and anaplasia
2. rate of growth
3. local invasion
4. 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 glial cells basal cells
Ca. of skin
METASTASES

Three Routes:
1. Spread into body cavities seeding of surfaces in
peritoneal, pleural, pericardial, subarachnoid
spaces
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
2. 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
 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
surrounding 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
neuroblastoma
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 angiosarcoma 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 precancerous conditions:
cirrhosis 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 mechanics:
increase 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 products
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