NEOPLASIA

Overview
Characteristics of neoplasms compared to
normal tissues
Types of neoplasms
Benign vs malignant
Cellular differentiation
Classification schemes
Genetic basis for neoplasia
Biology of tumor growth
Terms to know about when
discussing neoplasia
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
More terms.
Parenchyma these are the tumor cells
themselves, usually referring to epithelial
cells in organs.
Stroma connective tissue cells that
support the parenchymal cells not
actually tumor cells, but are stimulated to
grow by the tumor via growth factors, eg
angiogenesis
Cellular differentiation
Tumors are often graded as to how
closely they resemble the normal parent
tissue that they are derived from.
Well-differentiated means the cells are very
similar in appearance and architectural
arrangement to normal tissue of that organ
Normal cervical Pap smear
Malignant cervical Pap smear
Colonic adenoma
illustrating a well-
differentiated neoplasm
similar to normal colon
mucosa
HOW DO NEOPLASTIC CELLS
DIFFER FROM NORMAL CELLS?
Alterations in growth control
proliferation
cell death
factors regulating growth and response
Alterations in cellular interactions
cell-cell
cell-stroma

Differentiation
Poorly-differentiated refers to tumors
that show only minimal resemblance to the
normal parent tissue they are derived from.
Anaplastic means the tumor shows no
obvious similarity to its parent tissue,
usually associated with aggressive behavior
So what??????
Differentiation often provides clues as to the
clinical aggressiveness of the tumor
Tumors often lose differentiation features over
time as they become more malignant and as
they acquire more cumulative genetic mutations
Differentiation often predicts responsiveness to
certain therapies, eg estrogen receptors and
Tamoxifen in breast cancers

Gross (macroscopic)
features of two breast
neoplasms
Benign circumscribed,
often encapsulated,
pushes normal tissue
aside
Malignant infiltrative
growth, no capsule,
destructive of normal
tissues
Classification of neoplasms
Epithelial tumors
Benign forms adenoma , papilloma
Malignant forms carcinoma, eg
adenocarcinoma, squamous cell carcinoma
Mesenchymal tumors
Benign forms fibroma, leiomyoma,
Malignant forms sarcoma, eg fibrosarcoma,
leiomyosarcoma

Classification continued
Tumors of lymphocytes are always
malignant called lymphoma
Tumors of melanocytes
Benign nevus
Malignant - melanoma
BENIGN NEOPLASM
Cells grow as a compact mass and
remain at their site of origin
MALIGNANT NEOPLASM
Growth of cells is uncontrolled
Cells can spread into surrounding tissue
and spread to distant sites
Cancer = a malignant growth
Microscopic features of tumors
Loss of normal architectural arrangement
Microscopic features of tumors
Pleomorphism variation in size and shape
of cells within the neoplasm
Microscopic features of tumors
Mitotic activity - Increased in more
malignant tumors and often abnormal in
shape
Precursors of neoplasia
Hyperplasia
Metaplasia
Chronic inflammation
dysplasia
Metaplasia, dysplasia, neoplasia
Metaplasia an adaptive
change in differentiation,
reversible, no mutations
necessary.
Eg- change of esophageal
mucosa from squamous to
gastric type in the setting
of acid reflux
(heartburn). Better able
to withstand the corrosive
effects of the acid.
Metaplasia is fertile
ground for development of
dysplasia (disordered
growth)
Metaplasia, dysplasia, neoplasia
Dysplasia refers to recognizable morphologic changes in
cells that indicate the presence of genetic mutations
beginning the development of a neoplasm
Often graded, eg PAP smears for uterine cervical cancer
are low and high grade
Causes of Cancer
Most cancer arises as the result of somatic
mutations in the genome resulting from:
Chance (ie, we dont know)
Environmental factors chemical, radiation,
viruses
Ageing
Inherited cancer syndromes- defect in
germline DNA

Environmental carcinogens
Chemicals capable of DNA damage
Initiators vs Promoters
Common denominator is electrophilic
intermediates forming adducts with DNA
Some are direct acting, others are activated
in the body, usually in the liver by
cytochrome P-450 enzymes
Radiation
Ionizing radiation x-rays, gamma rays,
radioactive materials such as Radon gas
all cause a variety of defects to DNA
UV light (non-ionizing) primarily sun-
exposure and T-T dimerization skin
cancers
Common features of viral
carcinogenesis
Oncogenic viruses typically integrate their
genomes into host cells and enter a period
of latency
May be of DNA or RNA type
DNA viruses include EBV, HPV and
Hepatitis B virus
RNA viruses include retroviruses like
HTLV-1 and indirectly HIV
Viral carcinogenesis
Human papilloma virus (HPV) prototype
Cause warts
Some types have stronger cancer causing
associations, esp 16 and 18 with uterine
cervix cancer - Pap smears of cervix can
detect precursor lesions of infection Rx
Viral genes interact with human genes
concerned with cell division
How does HPV cause cancer?
Gene products of certain sub-type (eg 16
and 18) interfere with normal cellular
proteins
Early viral proteins E6 and E7 bind p53
and RB proteins respectively
Other oncogenic viruses
Epstein-Barr virus (EBV) associated with
some lymphomas and nasopharyngeal
carcinoma
Hepatitis B virus associated with malignant
liver tumors