Neoplasia well differentiated – poorly differentiated (undifferentiated)

 New growth
 Related to inflammation
 Oncology – oncos means tumor
 Cancer – common term for malignant tumor - crab
 Abnormal mass of tissue. The growth of which exceeds and is uncoordinated
with that of normal tissue and persist in the same excessive manner after
cessation of stimuli which evoked the change
 Purposeless
 Preys on the host
 Virtually autonomous?
 May require blood supply, nutrition and endocrine support

Nomenclature
Benign or Malignant
2 basic components
1. proliferatingneoplasmic cells that constitute the parenchyma
2. supportivestroma( connective tissue, blood vessels)
Desmoplasia – parenchymal cells stimulate formation of abundant collagen stroma
Undifferentiated – anaplastic
Benign tumors lack of differentiation – anaplasia
suffix - “oma” hallmark of malignant transformation
fibroblastic cells - fibroma proliferation without maturation
cartilage - chondroma
bone – osteoma Anaplasia shows
adenoma- benign epithelial neoplasm that forms glandular pattern 1. pleomorphism
papilloma - finger like projections 2. hyperchromasia
cystadenoma– large cystic mass 3. increase in mitosis
Papillary cystadenomas– papillary pattern protrude into cystic spaces 4. increase in nuclear size
Polyp- macroscopically visible projection above a mucosal surface 5. tumor giant cells
restricted to benign 6. loss of polarity
polypoidcancers if malignant 7. dysplasia
Malignant Pleomorphism– variation in shape and size
Sarcomas – arise in mesenchymal tissues cells are larger than their normal neighbor
sarc – means flesh – have little connective tissue and so are
fleshy Hyperchromasia
fibrosarcoma, liposarcoma, leiomyosarcoma Cells tend to be darkly stained
Epithelial in origin in any of the 3 germ layers – carcinoma Increase in DNA
endodermal, ectodermal, mesodermal
Glandular growth – adenocarcinoma
Squamous epithelium – squamous cells carcinoma – specify the organ of origin ( renal Increase in mitosis
cell carcinoma, bronchogenic carcinoma)
 Mitotic figures are seen
Cell differentiation – cancer cells may have undifferentiated cells
or more abundant

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  Chromatin is clumped Rate of growth
 Does not always indicate malignancy Benign tumors – grow slow
 Rapid turnover of cells Malignant – grow rapidly , erratic pace
Some benign tumors may grow rapidly than malignant eg..
Increase in nuclear size lieomyomas – hormone dependent (estrogens)
Normal cells may have 1:4 – 1:6 nulear cytoplasmic ratio after menopause undergo atrophy

In general, the growth rate of tumors correlates with their level of differentiation, and thus
most malignant tumor grow more rapidly than do benign lesions
some slow Cancers grow for years but suddenly become aggressive – due to formation of
Nuclear shape is extremely variable subclones of transformed cells.
Cancer cells have 1:1 But some may just disappear!!! Rare!!!
Some become dormant!!!
Tumor giant cells
 May possess single huge polymorphic nucleus Invasiveness
 Others may have 2-3 nuclei  Benign tumors – cohesive expansile masses, remain localized to the site of origin
they don’t infiltrate, nor invade ,nor metastasize
Loss of polarity contained by a rim of compressed connective tissue ( capsule ) but some
 Orientation of cells are disturbed are not like hemangiomas
 Growth is anarchic, disorganized  Malignant tumors – is accompanied by progressive infiltration, invasion and
destruction of surrounding tissue
DYSPLASIA Poorly demarcated from surrounding normal tissue
 Encountered principally in the epithelia, and it is characterized by a constellation Invasive – can penetrate the wall of colon and uterus ,fungate through the
of changes that include a loss of uniformity of individual cells as well as a loss of surface the skin , no anatomic boundaries
their architectural orientation. Surgical resection is difficult
Well it’s the shortcut of everything!!!! Invasiveness is the second feature after metastasis
 Dysplasia may show hyperchromasia, loss of polarity, variability in size ,
Metastasis
increased in mitosis
Metastasis marks the malignant from benign
 Carcinoma in situ – when dysplastic changes are marked and involve the entire
3 Pathways of spread
thickness of the epithelium and considered a pre-invasive neoplasmmay not
1. seeding of body cavities and surfaces
necessarily progress- Ca
pleural, pericardial, subarachnoid, peritoneal and joint spaces
 Carcinomas may be well differentiated – means it closely resemble the normal 2. lymphatic spread – follows the natural routes of lymphatic drainage
cells 3. hematogenous spread – veins are more affected. If arterial may form an emboli
 Poorly differentiated – far from normal cells or resemble immature cells
 Some carcinomas produce antigens – fetal proteins Epidemiology
 Some produce endocrine hormonesbronchogenic tumors –ACTH, parathyroid  Environmental
like hormone, insulin, glucagon  Racial ( heredity )
 Despite exceptions, the more rapidly growing and the more anaplastic the tumor  Cultural influences and practices
the less likely it is that there will be specialized functional activity.  Incidence and mortality rate
 The cells in benign tumors are almost always well differentiated and resemble U.S 1 out 5 deaths due to Cancer
their normal cells of origin; the cells of cancer are more or less differentiated, but Last 50 years cancer death rate significantly increased in men and in women fall slightly
some loss of differentiation is always present Ca deaths related to women decreased by early detection – Paps smear
Lung cancer in men slightly decreased and in women slightly increased

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 alcohol abuse – increases risk of carcinoma in oropharynx, lip, larynx, esophagus
and cirrhosis – (hepatoma)
Smoking ( cigarettes ) – ca in mouth, pharynx, larynx, esophagus , pancreas, and bladder
responsible for 77% lung ca in men and
47% in women
Alcohol and tobacco – multiply the danger of incurring Ca in upper aerodigestive tract
Cervical cancer – linked to early sexual intercourse and number sexual partners
viral infections!!
Age
Most cancers - >55 years
<15yo are not spared
Children – mc ca are neuroblastoma, wilms tumor, retinoblastoma, acute leukemias,
rhabdomyosarcoma

Heredity
Lung ca – 4x risk with non smoking relative
3 categories of hereditary forms
1. inherited cancer syndromes (autosomal dominant)
2. familial cancers
3. autosomal recessive syndromes of defective DNA repair

Familial cancers
Evident familial clustering of cancer but role of inherited predisposition may not be
clear in an individual case
breast cancer
ovarian cancer
colon cancers other than adenomatous polyps

Preneoplastic disorder
Regenerative
Dysplasia cancer
Hyperplasia
Geographic and Environmental factors
replication
 Stomach cancer – 7-8X in japan than in US
 Lung ca – 2x in the US than in japan Endometrial hyperplasia – endometrial carcinoma
inbelgium is slightly higher than US Smoking- metaplasia and dysplasia – lung cancer
 Melanomas – 6X in new zealand than in 80% hepatic carcinoma – cirrhotic livers
iceland Chronic atrophic gastritis of pernicious anemia, solar keratosis of the skin, chronic
sun exposure ulcerative colitis, leukoplakia of the oral cavity- precancerous may end up to cancer
Environmental
1. workplace – UV rays, asbestos, vinyl chloride , 2 naphthylamene Most benign neoplasm don’t become cancerous
2. food – low fiber diet but some like villous adenoma, leiomyoma and pleomorphic adenoma may become
3. personal practice cancerous ( in rare conditions)
overweight - 25% higher death rate than slimmer individual
Molecular basis of cancer

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 1. genetic damage – mutation May not affect DNA directly
radiation, chemicals, viruses or inherited germ line may only render cells susceptible to additional mutations
2. defect in regulatory gene
growth promoting protooncogenes Carcinogenic chemicals
cancer suppressor genes -Rb gene, p53gene, BRCA 1 @2 (anti oncogenes,  Direct acting alkylating agents - chemotherapeutic agents – anti-cancer dg
genes that regulate cell death or apoptosis- bcl -2 , bax) ( cyclophosphamide, chlorambucil, melphalan, busulfan)
3. regulate repair of damaged DNA  Polycyclic aromatic hydrocarbons
disability in DNA repair predispose most potent
to mutation  Aromatic amines and azo dyes
4. carcinogenesis is a multi step process at both the phenotypic and the genetic levels  Naturally occurring carcinogens
excessive growth  Nitroamines and amides
local invasiveness  Miscellaneous agents – asbestos, vinyl chloride, chromium , nickel , insecticides ,
distant metastasis polychlorinated biphenyls
Oncogenes Radiation carcinogenesis
Cancer causing genes
 Ultraviolet rays of sunlight, UVA,UVB, UVC
Derived from protooncogenes
UVB is more related to cancer
Protooncogenes – promote normal growth and differentiation
 Ionizing electromagnetic radiation/ particulate radiation
Retroviruses – transduction
medical ,occupational and atomic bombs
Produce oncoproteins
x-rays , gamma rays
Biology of tumor growth
4 phases of malignant tumor growth
1. malignant change in the target cell referred as transformation
Microbial carcinogenesis
2. growth of transformed cells
3. local invasion  DNA oncogenic viruses
4. distant metastasis papilloma viruses, epsteinbarr virus, hepatitis B virus, kaposi sarcoma
herpesvirus
Mechanism of invasion and metastasis stable association of human genome
2 phases HPV 16, 18 – SCCa
1. invasion of extracellular matrix EBV – lymphomas, nasopharyngeal Ca
2. vascular dissemination and homing of tumor cells HBV , HCV – hepatocellular ca
 RNA oncogenic virus
Carcinogenic agents and their cellular interactions Human Tcell leukemia virus type 1 – T cell leukemia and lymphoma
Categories of carcinogenic agents endemic in japan and carribean
1. chemical carcinogens  Helicobacter pylori
2. radiant energy gastric lymphoma and gastric carcinoma
3. oncogenic microbes ( chiefly viruses)  Fungi – aflatoxin – liver ca

Chemical carcinogens Host defense against tumors- Tumor immunity

Initiator- likely to give rise to tumors  Immune mediated recognition of tumor cells
initiated cells are altered  Immune surveillance ?– recognition of a non self tumor
may affect DNA directly imperfect! Some may escape
Promoter – can induced tumor in initiated cells
non tumorigenic by itself

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Tumor antigens – antigens that elicit an immune response – experimental tumors or
human cancers
2 categories
1. tumor specific antigens – melanoma cell produce tyrosinase – antigenic
reaction with cytotoxic T cells
2. tumor associated antigens – antigens produced by tumor and normal cells

 Antigens resulting from mutations – mutated tumor suppressor gene – p53, K

ras, CDK4
 Overexpressed antigens – c-erbB2 (neu) – found in 30% of breast ca and
ovarian ca
 Viral antigens – E7 proteins of HPV 16
 Others ( TAA ) –
oncofetal proteins – AFP, CEA, CALLA (CD10)

Anti tumor effector mechanism

 Cytotoxic T lymphocyte
 Natural killer cells
 Macrophages
 Humoral mechanisms – complement activation

Clinical features of tumor

1. effects of tumor to host
2. grading and clinical staging of cancer
3. laboratory diagnosis of cancer

Effects of tumor to host

1. location and impingement on adjacent structures
2. functional activity such as hormone synthesis
3. bleeding and secondary infections when they ulcerate through adjacent natural
surfaces
4. initiation of acute symptoms caused by either rupture or infarction
( responsible for cachexia and paraneoplastic syndrome )

Paraneoplastic syndrome
Symptoms complexes in cancer patients thatcant be readily explained, either by local
or distant spread of the tumor or by the elaboration of hormones indigenous to the
tissue from which the tumor arose
<endocrinopathies - hypercalcemia(PTHrP)
neuromyopathicparaneoplastic syndrome>
<acanthosisnigricans>, <hypertrophic osteoarthropathies>
<vascular and hematologic manifestations (trousseau syndrome), non bacterial
thrombotic endocarditis,> , others nephrotic syndromes

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  Stage – extent of spread of a cancer within the patient , deals with size of
the primary lesion, presence and absence of blood borne metastases (TNM),
stage 0-IV

Laboratory diagnosis of Cancer

 Excision biopsy
 Needle aspiration
 Cytologic smears
 Immunocytochemistry
 Molecular diagnosis- FISH, PCR
 Flow cytometry
 Tumor markers- cell surface antigens, cytoplasmic proteins, enzymes and
hormones

Grading and staging of tumors

 Grade - level of differentiation, number of mitosis , correlates of neoplasm
aggression
classifiedca from Grade I-IV

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