Neoplasia refers to abnormal and uncontrolled cell growth. Benign tumors are non-invasive and do not spread, while malignant tumors can invade nearby tissues and metastasize to distant sites. Malignant cells show properties like anaplasia, increased growth rate, reliance on anaerobic glycolysis for energy, upregulated telomerase activity, angiogenesis, and ability to invade and metastasize via hematogenous or lymphatic routes. Differentiation and growth patterns, as well as local invasion and metastasis, distinguish benign from malignant tumors.

1. NEOPLASIA
BY:
DR ZAHRA MASOOD

2. TOPICS THAT WE WILL DISCUSS…
 DEFINITION OF NEOPLASIA
 NOMENCLATURE
 PROPERTIES OF BENIGN AND MALIGNANT TUMOURS
 EPIDEMIOLOGY OF CANCERS

3. WHAT IS NEOPLASIA
 Neo + Plasia  New + Growth.
 Tumour  Swelling  any swelling
 Willis definition:
“A neoplasm is an abnormal mass of tissue, the growth
of which exceeds and is uncoordinated with that of the
normal tissue and persists in the same manner after
cessation of the stimuli which evoked the change”
 “Cell division without control”

4. Words of wisdom…
This particular nurse said:
“Cancer cells are those which have
forgotten how to die.”
I was so struck by this statement.

6. NOMENCLATURE

7. BENIGN TUMOURS
 Definition: unregulated proliferation of cells that does
not invade or spread to other sites.
 Suffix “-oma” generally indicates a benign tumor.
• Exceptions to the rule are:
 seminomas (testicular cancer)
 lymphoma (malignancy of lymph nodes)
 glioma (malignancy of glial cells in the brain)
 mesothelioma (malignancy of pleural serosa)
 neuroblastoma (malignancy of neuroblasts).

8. Benign
tumours
Epithelial origin
Connective
tissue origin
Unusual
tumours

9. Epithelial origin
Ectoderm
•(squamous epithelium,
transitional epithelium)
Endoderm
(glandular epithelium)

10. Connective tissue tumour
For example:
lipoma
mesoderm

11. Unusual tumours
Neoplastic cells with two
different morphological patterns
but from the same germ cell
layer
(pleomorphic adenoma of the
parotid gland)
Derived from more than one germ cell layers:
ectoderm, endoderm and mesoderm, at or
close to the midline.
(ovary, testes, pineal gland, anterior
mediastinum)
Mixed tumours Teratomas

12. Malignant tumours
Carcinomas
(derived from epithelium)
Sarcomas
(derived from connective
tissue)

13. carcinomas
Squamous
epithelium
Glandular
epithelium
Transitional
epithelium
Oropharynx,
larynx,
upper/middle
esophagus,
lung, cervix,
skin
Lung, distal
esophagus to
rectum, pancreas,
liver, breast,
endometrium,
ovaries,
kidneys, prostate
Urinary bladder,
ureter, renal
pelvis

14. sarcomas
Osteogenic sarcoma,
liposarcoma,
rhabdomyosarcoma,
leiomyosarcoma
Mesodermal origin

15. Tumour like conditions
Hamartoma
(non-neoplastic growth of disorganized
tissue indigenous to a particular site)
For example: bronchial hamartoma, Puetz-
Jeghers polyp
Choristoma
(mass of normal non-neoplastic tissue in a
foreign location)
For example: pancreatic tissue in the
stomach wall, brain tissue in the nasal cavity

16. Tubular adenoma (adenomatous
polyp) of the colon. Note
the fibrovascular stalk (arrow)
lined by normal colonic mucosa
and a branching head surfaced by
dysplastic (blue-staining) epithelial
glands. The epithelium is glandular;
therefore it derives from the
endoderm.

17. Lipoma showing a
well-circumscribed yellow tumor.
Adipose tissue is connective tissue;
therefore it derives from the mesoderm.

18. Cystic teratoma of the
ovary, showing the cystic nature of
the tumor. Hair is present, and a
tooth is visible (arrow). Teratomas
can arise from ectoderm (this photograph),
endoderm, and mesoderm.

19. Squamous cell carcinoma. The many well
differentiated foci of eosinophilic staining
neoplastic cells produce keratin in layers
(keratin pearls).

20. Adenocarcinoma.
Irregular glands infiltrate
the stroma. The nuclei lining
the gland lumens are cuboidal and
contain hyperchromatic
nuclear chromatin. Glandular
cells appear to pile up on each
other. Many of the gland lumens
contain secretory material (arrow)

21. Osteogenic sarcoma of the distal
femur. The light-colored mass of
tumor in the metaphysis abuts the
epiphyseal plate (arrow) and has
spread laterally out through the
cortex and into the surrounding
tissue

22. PROPERTIES OF BENIGN AND
MALIGNANT TUMOURS

23. Components of benign and malignant
tumours
1. Parenchyma
• Definition—neoplastic component that determines biological behavior
2. Stroma
a. Definition—non-neoplastic supportive tissue
b. Most infiltrating carcinomas induce production of a dense, fibrous stroma
(called desmoplasia).

24. Differentiation in benign and
malignant tumours
1. Benign tumors
• Definition—usually well differentiated (resemble parent tissue).
2. Malignant tumors
a. Well-differentiated or low grade cancer:
(1) Cancer cells resemble parent tissue.
(2) Examples—parenchyma shows keratin or glandular lumens with secretions.
b. Poorly differentiated, high grade, or anaplastic:
• No differentiating features (e.g., no glands, no keratin staining material).
c. Intermediate grade:
• Features are between a low- and high-grade cancer (e.g., occasional gland-like
structures are seen, or areas that look like keratin are present, whereas the rest of the tumor
has no differentiation).

25. Anaplasia
It is a characteristic of malignant tumours. Anaplasia means complete lack of
differentiation of cells in a malignant neoplasm; in such a case the tumour has
the following features:
 Poorly differentiated
 Pleomorphism
 Hyperchromatism
 Increased nuclear to cytoplasmic ratio
 Abnormal mitoses
 Cellular dyspolarity
 Prominent nucleoli

26. Cell organelles in malignant versus
normal cells
1. Organelles in the cytoplasm when compared to a normal cell:
a. Fewer mitochondria
b. Less prominent rough endoplasmic reticulum (RER)
c. Loss of cell-to-cell adhesion molecules (cadherin)
• Cadherin are a group of calcium-dependent transmembrane proteins that play an
important role in cell-to-cell adhesion.
2. Nuclear features when compared to a normal cell:
a. Nucleus is larger, has irregular borders, and has more chromatin
(hyperchromatic)
b. Nucleolus is larger and has irregular borders
c. Mitoses have normal and atypical mitotic spindles.

27. Schematic showing normal organelles in a normal cell on the left (A) and a malignant cell (B) on the right.
Note that when compared to a normal cell, a malignant cell has fewer mitochondria, less prominence of the
rough endoplasmic reticulum with an increase in free ribosomes, loss of cell adhesion molecules between cells
(cadherins and occludens), and a larger nucleus with irregular borders, excess chromatin, and a larger, irregular
nucleolus. Tumor antigens are sometimes expressed on the surface of malignant cells (CEA). CEA, Carcinoembryonic
antigen.

28. Biochemical changes in malignant cells
1. Rely on anaerobic glycolysis for energy
• Greater accumulation of lactic acid than a normal cell would make in a hypoxic situation.
2. Increased uptake of glucose analog
a. Special test has been developed in which cancer cells take up a glucose analog with
positron emission tomography (PET).
b. PET scan is widely used in the diagnosis, staging, and monitoring of therapy of various
kinds of cancer.
3. Do not process glucose as well as normal cells, and store glucose in
the form of glycogen within the cytosol
4. Some cancers derive energy from β-oxidation of fatty acids rather
than anaerobic glycolysis (e.g., prostate cancer)

29. Growth rate in benign and malignant
tumors
1. Benign tumors usually have a slow growth rate.
2. Malignant tumors have a variable growth rate.
a. Growth rate correlates with degree of differentiation of the malignant
tumor.
b. Example—anaplastic (high-grade) cancers have an increased growth rate,
whereas low-grade cancers have a slow growth rate.
3. Clinically detectable: 30 population doublings to produce 109 cells
(1 g tissue)
4. Tumors with ↑ed growth rate treated with cell cycle–specific chemotherapy.
a. Role of methotrexate and vincristine.

30. Monoclonality in benign and
malignant tumors
1. Non-neoplastic proliferations derive from multiple cells (polyclonal).
2. Benign and most malignant tumors derive from a single precursor cell.

31. Telomerase activity in benign and
malignant tumors
1. Telomere complexes
a. Definition—repetitive sequences of non-transcribed DNA located at the ends of
chromosomes.
b. Prevent end-to-end fusion of chromosomes during normal mitosis and, along with
other factors, are important in determining the longevity of a cell.
c. Shorten with each round of replication and eventually, when only a few nucleotide bases
remain, the genome becomes unstable, which produces a signal for apoptosis.
2. Benign tumors have normal telomerase activity.
3. Malignant cells have upregulation of telomerase activity, which
prevents the naturally programmed shortening of telomere complexes
with cell replication; hence the cell no longer undergoes apoptosis.

33. Local invasion and metastasis
1. Benign tumors
a. Do not invade
• Exception is a dermatofibroma, which invades tissue but does not
metastasize.
b. Usually enclosed by a fibrous tissue capsule
• Exception is a uterine leiomyoma, which does not have a fibrous tissue
capsule

34. Local invasion and metastasis
2. Malignant tumors
a. Invade tissue
• Second most important criterion for malignancy
b. Some tissues resist invasion.
• Examples—mature cartilage, elastic tissue of arteries
c. All malignant tumors require O2 and nutrients to survive and do so by
stimulating angiogenesis within the tumor and its metastatic sites.

35. Angiogenesis
New capillary sprouts form from parent capillaries.

36. Hematogenous
spread of cancer
from a primary to
a distant site

37. Types of metastasis
1. Benign tumors do not metastasize.
2. Malignant tumors metastasize.
a. Most important criterion for malignancy
b. Basal cell carcinoma (BCC) is a notable exception to the rule, because
these cells invade tissue (a criteria of malignancy) but do not metastasize.

38. Pathways of dissemination
1. Lymphatic spread of cancer
a) Lymphatic spread to regional lymph nodes is the first step for
dissemination in carcinomas.
• Lymph nodes are the first line of defense.
2. Hematogenous spread of cancer
b) Sarcomas initially invade capillaries and/or venules and directly spread to
distant sites without involving the lymph nodes.
• Invade regional lymph nodes before entering the systemic
circulation.

39. Pathways of dissemination
3. Seeding of malignant cells
a) Definition: malignant cells exfoliate from a serosal surface and implant and
invade tissue in a body cavity (pleural, pericardial, peritoneal).
4) Bone metastasis:
a) Vertebral column
(1) Most common metastatic site in bone.
• Breast cancer is the most common cancer metastatic to bone; second most
common is prostate cancer.
b) osteoblastic metastases
(1) Prostate cancer is the most common cancer producing osteoblastic
metastases; second most common is breast cancer.
c) osteoclastic metastases
(1) Cancers that commonly produce lytic metastases include lung cancer, renal
cell
carcinomas, and breast cancer.

40. Metastasis is more common than a
primary cancer…
Metastasis is more common than a primary cancer in the following sites:
a. Lymph nodes (e.g., metastatic breast and lung cancer most common)
b. Lungs (e.g., metastatic breast cancer most common)
c. Liver (e.g., metastatic lung cancer most common)
d. Bone (e.g., metastatic breast cancer most common)
e. Brain (e.g., metastatic lung cancer most common)

41. Cancer Epidemiology

42. General epidemiology
1. Second most common cause of death in the United States
2. Causes of cancer
a. External factors
• Tobacco (#1), alcohol, chemicals, radiation, microbial pathogens
b. Internal factors
• Hormones, immune conditions, inherited mutations
c. Geographic and ethnic factors
3. Age is an important risk factor for cancer.
a. Cancer incidence increases with age.
• Majority of cancers are in persons 55 years or older.
b. Colorectal, lung, and prostate cancer progressively increase in incidence with age, whereas
others reach a peak and begin to decline (e.g., malignant melanoma).
4. Racial differences affect cancer incidence.

43. Cancer incidence by age and sex
1. Cancers in children
a. Malignant neoplasms are the leading cause of disease-related (non injury)
mortality among children 1 to 14 years of age.
b. Top three cancers in children in decreasing order are:
(1) Leukemia (acute lymphoblastic leukemia is the most common leukemia)
(2) Central nervous system (CNS; cerebellar tumors most common)
(3) Neuroblastoma
c. Other common cancers in children that are not common in adults include
embryonal rhabdomyosarcoma, Wilms tumor, retinoblastoma, osteogenic
sarcoma, and Ewing sarcoma.
d. Epithelial tumors of organs, such as lung, colon, and breast are common in
adults but uncommon in children.

44. Cancer incidence by age and sex
2. Top three cancer sites in men in decreasing order are:
a. Prostate
b. Lung
c. Colon/rectum
3. Top three cancer sites in women in decreasing order are:
a. Breast
b. Lung
c. Colon/rectum
4. Top three sites for gynecologic cancers in decreasing order are:
a. Uterine corpus (endometrium)
b. Ovary
c. Cervix

45. Sites for cancer related deaths
1. Top three sites for cancer-related deaths in men in decreasing order are:
a. Lung
b. Prostate
c. Colon/rectum
2. Top three sites for cancer-related deaths in women in decreasing order are:
a. Lung
b. Breast
c. Colon/rectum
3. Top three gynecologic sites for cancer-related deaths in women in decreasing order
are:
a. Ovary
b. Uterine corpus (endometrium)
c. Cervix

46. Cancer and geography
1. Worldwide
• Malignant melanoma increasing at most rapid rate of all cancers
2. China
a. Nasopharyngeal (NP) carcinoma: Associated with Epstein-Barr virus (EBV)
b. SCC of the esophagus: Associated with alcohol abuse, smoking, and unknown
factors
3. Japan
• Stomach adenocarcinoma associated with smoked foods
4. Southeast Asia
• Hepatocellular carcinoma (HCC) associated with hepatitis B virus post necrotic
cirrhosis plus aflatoxins.
5. Sub-Saharan Africa
a. Burkitt lymphoma: Associated with EBV
b. Kaposi sarcoma (KS): Associated with human herpesvirus 8 (HHV-8)

47. Prevention modalities in cancer
1. Modify lifestyle
a. Stop smoking cigarettes
• Most important lifestyle modification.
b. Increase dietary fiber and decrease dietary saturated animal fat
• Decreases the risk for developing colorectal cancer
c. Reduce alcohol intake
d. Reduce weight
(1) More adipose tissue increases aromatase conversion of androgens to estrogen.
(2) Higher estrogen level increases the risk for developing endometrial and breast
cancer.
e. Sunscreen protection
• Decreases risk for developing BCC, SCC, and malignant melanoma

48. Prevention modalities in cancer
2. Immunization
a. HBV vaccination
• Immunization against HBV decreases the risk for developing HCC due to HBV
induced post-necrotic cirrhosis.
b. Human papillomavirus (HPV) immunization
• Decreases the risk for developing SCC of the cervix and penis

49. Prevention modalities in cancer
3. Screening procedures to detect cancer
a. Cervical Papanicolaou (Pap) smears
(1) Decrease the risk for cervical cancer due to HPV 16, 18 subtypes
(2) Pap smears detect cervical squamous dysplasia, which is the precursor lesion
for cervical SCC.
b. Colonoscopy
• Detects and removes polyps that are precancerous
c. Mammography
• Detects non-palpable breast masses
d. Prostate-specific antigen (PSA)
(1) More sensitive than specific for diagnosing prostate cancer
(2) Specificity is decreased, because of increased false positive results due to
benign prostatic hyperplasia.

50. Prevention modalities in cancer
4. Treatment of conditions that predispose to cancer decreases the risk
for cancer.
a. Treatment of Helicobacter pylori infections (peptic ulcer disease, gastritis)
(1) Decreases risk for developing malignant lymphoma (lymphoid hyperplasia →
malignant lymphoma)
(2) It does not decrease the risk for developing adenocarcinoma of stomach.
b. Treatment of gastroesophageal reflux disease (GERD)
• Decreases risk for developing distal adenocarcinoma arising from Barrett
esophagus (glandular metaplasia → adenocarcinoma).

51. THANKYOU! 