Neoplasia: Is the abnormal growth and proliferation of abnormal cells or abnormal amounts of cells due to a benign or malignant process. There can be benign tumors, or neoplasms, and malignant ones.

1. Neoplasia
Neoplasia: Is the abnormal growth and proliferation of
abnormal cells or abnormal amounts of cells due to a benign
or malignant process. There can be benign tumors, or
neoplasms, and malignant ones.

2. Neoplasm is an abnormal growth of tissue which, if it forms
a mass, is commonly referred to as a tumor. This abnormal
growth (neoplasia) usually (but not always) forms a mass.
ICD-10 classifies neoplasms into four main groups: benign
neoplasms, in situ neoplasms, malignant neoplasms, and
neoplasms of uncertain or unknown behavior. Malignant
neoplasms are also simply known as cancers and are the focus
of Oncology.
Prior to the abnormal growth of tissue, as
neoplasia, cells often undergo an abnormal pattern of growth,
such as metaplasia or dysplasia. However, metaplasia or dysplasia
does not always progress to neoplasia.
The word (neoplasia) is from Ancient Greek νέος- neo "new" and
πλάσμα plasma "formation, creation".

3. (Epigenetic: relating to or
arising from non-genetic
influences on gene
expression. For example:
"epigenetic carcinogens“
Epigenetics is the study of
heritable changes in gene
function that do not involve
changes in the DNA
sequence)
Somatic Mutation: An alteration in DNA that
occurs after conception. Somatic
mutations can occur in any of the cells of the
body except the germ cells (sperm and egg)
and therefore are not passed on to children.
These alterations can (but do not always)
cause cancer or other diseases.

5. 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

6. Biology of tumor growth
Its the development of secondary malignant
growths at a distance from a primary site of
cancer.

7. PMC full
text:
Genome Res. 2016 Sep; 26(9): 1268–1276.
doi: 10.1101/gr.205682.116
Copyright/License ►Request permission to reuse
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Figure 4.

8. The genomic distribution of chemically induced mutations. The circular plot summarizes the
distribution of chemically induced mutations in the six chromosomal (Chr 1–6), mitochondrial (M), and
ribosomal (R) DNAs.

9. 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

10. 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

11. 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

12. Normal cervical “Pap smear”

13. Malignant cervical “Pap smear”

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

15. 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

16. 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

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

18. 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

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

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

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

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

23. Precursors of neoplasia
 Hyperplasia
 Metaplasia
 Chronic inflammation
 Dysplasia

24. 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)

25. 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 (Papanicolaou test )

26. 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

27. 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

29. 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
 (Induction of T-T Dimers by UV radiation. Thymidine Dimers are produced
when adjacent thymidine residues are covalently linked by exposure to
ltraviolet radiation. Covalent linkage may result in the dimerbeing replicated
as a single base, which results in a frameshift mutation).
 Pyrimidine dimers are molecular lesions formed from thymine or cytosine
bases in DNA via photochemical reactions. ... In dsRNA (double-stranded
RNA), uracil dimers may also accumulate as a result of UV radiation.

30. 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

31. 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

32. 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

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