Neoplasia Overview Characteristics of neoplasms compared to normal tissues Types of neoplasms Benign vs malignant Cellular differentiation Genetic basis for neoplasia What is a “neoplasm”? Lay term of “tumor” conveys usual connotations – ie a new growth or mass Definition revolves around these features: Monoclonal proliferation of cells with specific mutations Excessive and unregulated growth of these cells, often at the expense of surrounding normal tissue 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 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 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 it’s 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 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 Precursors of neoplasia Hyperplasia Metaplasia Chronic inflammation dysplasia Metaplasia, dysplasia, neoplasia

1. Neoplasia

2. Overview
 Characteristics of neoplasms compared to
normal tissues
 Types of neoplasms
 Benign vs malignant
 Cellular differentiation
 Genetic basis for neoplasia

4. What is a “neoplasm”?
 Lay term of “tumor” conveys usual
connotations – ie a new growth or mass
 Definition revolves around these features:
 Monoclonal proliferation of cells with
specific mutations
 Excessive and unregulated growth of these
cells, often at the expense of surrounding
normal tissue

5. Biology of tumor growth

6. 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

7. 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

8. 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

9. Normal cervical “Pap smear”

10. Malignant cervical “Pap smear”

11. Colonic “adenoma”
illustrating a “well-
differentiated” neoplasm
similar to normal colon
mucosa

12. 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 it’s parent tissue,
usually associated with aggressive
behavior

13. 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

14. Gross (macroscopic)
features of two breast
neoplasms
Benign – circumscribed,
often encapsulated,
pushes normal tissue
aside
Malignant – infiltrative
growth, no capsule,
destructive of normal
tissues

15. 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

16. Classification continued
 Tumors of lymphocytes are always
malignant – called lymphoma
 Tumors of melanocytes
 Benign – nevus
 Malignant - melanoma

17. Microscopic features of tumors
 Loss of normal architectural arrangement –

18. Microscopic features of tumors
 Pleomorphism – variation in size and shape
of cells within the neoplasm

19. Microscopic features of tumors
 Mitotic activity - Increased in more
malignant tumors and often abnormal in
shape

20. Precursors of neoplasia
 Hyperplasia
 Metaplasia
 Chronic inflammation
 dysplasia

21. 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)

22. 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

23. Causes of Cancer
 Most cancer arises as the result of somatic
mutations in the genome resulting from:
 Chance (ie, we don’t know)
 Environmental factors – chemical, radiation,
viruses
 Ageing
 Inherited cancer syndromes- defect in
germline DNA

24. 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

26. 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

27. 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

28. 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

29. 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

30. Other oncogenic viruses
 Epstein-Barr virus (EBV) associated with
some lymphomas and nasopharyngeal
carcinoma
 Hepatitis B virus associated with malignant
liver tumors