Neoplasia part-1 with tumour immunity and diagnosis of tumour.

1. Neoplasia Part-1
DR. MARUF RAZA
Associate Professor of Pathology
Based on
Robbins and Cotran, 9th.

2. Neoplasia/ Neoplasm:
• Neoplasia/ neoplasm means new growth.
• Tumor was originally applied to the swelling
caused by inflammation, but the term is now
applied to neoplasm.
• Oncology is the study of tumors or neoplasms.
• Cancer: A common term for all malignant
neoplasm.

3. Neoplasia definition:
• Neoplasm : According to British Oncologist
Willis-
“A neoplasm is an abnormal mass of
tissue, the growth of which exceeds and is
uncoordinated with that of normal tissues
and persist in the same excessive manner
after cessation of stimuli which evoke the
change.”

4. Neoplasia definition:
• In modern molecular pathology:
A neoplasm can be defined as a disorder of
cell growth that is triggered by a series of
acquired mutations affecting a single cell
and its clonal progeny.

5. Neoplasia: Components
All neoplasm have two basic component:
1) Neoplastic cells: Cells that forms the
tumour parenchyma.
2) Reactive Stroma : The connective tissue,
blood vessels and cells of the adaptive and
innate immune system.

6. Neoplasia: Components
• The classification and biologic behavior of
tumors are based on the parenchymal
component (Tumor cells).
• Tumour growth and spread depends on the
stroma of the tumor.
• Some tumors with scant connective tissue are
soft and fleshy. Some with abundant
collagenous stroma called desmoplasia
(scirrhous breast carcinoma).

7. Classification on Biological behavior
• On the basis of biological behaviour and
morphologic characteristics tumor is
divided into:
i. Benign tumor
ii. Malignant tumor

8. Benign Tumor
A tumor is benign when:
i. Tumours gross and microscopic
appearances are innocent
ii. remain localized will not spread to other
sites
iii. local surgical removal is possible.

9. Benign Tumor
• The patient having benign tumour generally
survives.
• Benign tumors are designated by attaching the
suffix -oma to the name of the cell type from
which the tumor originates. Cell type+ OMA
example: fibroma, chondroma, lipoma.

10. Benign Tumor
• Adenoma : Benign epithelial neoplasms
derived from columner epithelium or glands.
• Papilloma: Benign epithelial tumor producing
microscopically or macroscopically visible
finger-like projection from the epithelial
surfaces.
• Polyp: A non neoplastic or neoplastic
macroscopically visible projection above a
mucosal surface is termed a polyp.

11. Papilloma

12. Polyp

13. Papilloma vs Polyp
Papilloma Polyp
Benign epithelial
tumour
Neoplastic or Non
neoplastic
Microscopically or
macroscopically
visible projection
Macroscopically
visible projection
Exp. Squamous
Papilloma
Exp. Juvenile polyp in
rectum, Adenomatous

14. Malignant Tumors
• Malignant tumors are collectively referred to as
cancer.
• Malignant tumors invade and destroy adjacent
structures and spread to distant sites
(metastasize) to cause death.

15. Malignant Tumors
When the tumor has:
1. gross and microscopic appearances
are aggressive
2. which invade and destroy adjacent
structures.
3. spread to distant sites (metastasis).

16. Malignant Tumors: nomenclature
• Malignant tumors arising in mesenchymal
tissues are usually called sarcoma. e.g.
fibrosarcoma, chondrosarcoma,
leiomyosarcoma, rhabdomyosarcoma.
• Malignant tumors arising from blood-forming
cells are designated leukemia or lymphoma.

17. Malignant Tumors: nomenclature
• Malignant tumors arising from epithelial cell
origin are called carcinoma. E.g: Squamous
cell carcinoma, adenocarcinoma.
• Squamous cell carcinoma is a cancer arising
from squamous epithelium.
• Adenocarcinoma is a cancer arising from
glandular/ columner epithelium or forms
glandular pattern.

18. Squamous cell carcinoma

19. Adenocarcinoma

20. Mixed tumor
• Tumor arising from a single clone of cell
capable of forming epithelial, myoepithelial
cells, myxoid stroma containing cartilage
and bone is called mixed tumour.
• Cells of mixed tumors arises from a single
germ layer. e.g: Pleomorphic adenoma of
salivary gland.

21. Teratoma,Hamartoma,Choristoma
• Teratoma is a tumor arising from more than
one germ layer, usually all three. Teratoma
is seen in the ovary and testis (ovarian
dermoid cyst).
• Choristoma is the heterotopic (abnormal
place) rest of normal cells.
• Hamartomas are disorganized masses of
cells composed of cells native to that site.

22. Benign tumor VS Malignant tumor
1) Neoplastic cell criteria
2) Rate of growth
3) Size of the tumor
4) Haemorrhage and necrosis
5) Capsulated or not
6) Local invasion present or not
7) Metatasis
8) Clinical effects

23. Difference between benign and malignant tumor
Characteristics Benign Malignant
1) Neoplastic cells. 1) Neoplastic cells. 1) Neoplastic cells.
a) Differentiation Well differentiated Well differentiated
to undifferentiated
b)Pleomorphism Absent Often present
c)Orientation of
neoplastic cells
No loss of
orientation.
Loss of orientation.
d)Nuclear
cytoplasmic ratio
Normal 1:4 to 1:6
Normal Increased (May be
1:1 )

24. 2) Rate of growth Grow and expand
slowly
Most cancers grow
rapidly
3) Size Usually small Usually large
4)Haemorrhage
and necrosis
Little tendency Common
5)Capsule Mostly
encapsulated
Not capsulated
6)Local Invasion No local invasion Locally invasive
7)Metatasis Never occur Metastasis occurs
8) Clinical effects Usually not fatal Almost invariably
fatal

25. • Some tumor which has “oma” but are not
benign:
Lymphoma, Melanoma, Seminoma.
• Some benign tumor without capsule:
Haemangioma, leiomyoma.
• Locally invasive/ Locally malignant tumor:
Tumor have local invasion but no tendency to
metastasize.
i. Basal cell carcinoma of skin.
ii. Giant cell tumor of bone.

26. Differentiation, Anaplasia, Dysplasia,
Carcinoma in Situ

27. Differentiation
• Differentiation: Differentiation refers to the
extent to which neoplastic tumor cells
resembles the corresponding normal
parenchymal cells, both morphologically
and functionally.
• Benign tumour lipoma’s neoplastic tumour
cells is closely resemble to normal
adipocytes.

28. Differentiation
• Benign tumours are well differentiated.
• Grading of malignant tumor is done based
on differentiation, like:
1. Well differentiated tumor is Grade I.
2. Moderately differentiated is Grade II.
3. Poorly differentiated is Grade III.

29. Anaplasia
• Anaplasia: Lack or loss of differentiation is
called anaplasia.
• Lack of differentiation or anaplasia is
considered as hallmark of malignancy.
• Anaplastic features are found in malignant
tumor.

30. Characteristics of a malignant cells/
Features of Anaplasia
Anaplasia is associated with cellular feature like:
1. Pleomorphism
2. Increased nuclear cytoplasmic ratio
3. Hyperchromasia
4. Increased mitosis and abnormal
mitosis
5. Loss of polarity

31. Pleomorphism
• Pleomorphism is the variation in size and
shape of the cells.
• Cancer cells show pleomorphism. Cells
ranges from small cell to a large atypical
tumor giant cell.
• Some tumor cells possess a huge nucleus
with two or more large, hyperchromatic
nuclei.

32. Abnormal nuclear morphology
• A normal nucleus is large in relation to
cytoplasm. Normal nuclear-to-cytoplasm
ratio is 1:4 to 1:6. In malignancy NC ratio
may become 1:1.
• Nucleus is darkly stained (hyperchromatic)
with coarsely clumped chromatin.
• Abnormally large nucleoli are also
commonly seen.

33. Mitosis:
• In tumours many cells are in mitosis because
of high proliferative activity of the tumor cells.
• There may be atypical, bizarre mitotic figures,
sometimes tripolar, quadripolar mitoses.
Loss of polarity:
• The orientation of anaplastic cells is markedly
disturbed. Tumor cells grow in disorganized
fashion.

34. Fig: Pleomorphism

35. Fig: Atypical Mitosis

36. Dysplasia
• Dysplasia means “disordered growth.”
• Dysplasia is the loss of uniformity of the
individual cells and loss of their
architectural orientation.
• Dysplasia may be a precursor to malignant
transformation. but it does not always
progress to cancer.

37. Dysplasia
• Dysplastic cells may exhibit pleomorphism
and large hyperchromatic nuclei with a high
nuclear-to-cytoplasmic ratio.
• Mitotic figures are more abundant than in
the normal tissue and may be seen at all
levels including surface epithelial cells.

38. Fig: Dysplasia

39. Uterine Cervix dysplasia
(CIN/ Cervical intraepithelial neoplsia)
• CIN –I: When the dysplastic cells involves
lower one third of the epithelium (Mild
dysplasia).
• CIN –II: When the dysplastic cells involves
lower two thirds of the epithelium (Moderate
dysplasia).
• CIN –III: When the dysplastic cells involves
almost full thickness of the epithelium (severe
dysplasia).

40. Cervical dysplasia classification

41. Carcinoma in Situ (CIS)
• When dysplastic changes are marked and
these atypical dysplastic cells involve the
full thickness of the epithelium it is called
carcinoma in situ.
• Carcinoma in situ is limited to the basement
membrane and do not cross the basement
membrane.

42. Carcinoma in Situ (CIS)
• Carcinoma in Situ (CIS) is a malignant
condition but the malignant cells does not
cross the basement membrane.
• Once the tumor cells cross the basement
membrane, it is called invasive carcinoma.
• Management of CIS is same like invasive
carcinoma.

43. Fig: Carcinoma in Situ

44. Invasion and Metastasis
of tumor

45. Invasion
• All benign tumors grow as cohesive masses
that remain localized.
• Benign tumors lack the capacity to infiltrate,
invade or metastasize to distant sites.
• Malignant tumors always invasive and
metastasis occurs.

46. Metastasis
• Metastasis is the spread of a tumor to sites
that are discontinuous with the primary
tumor site. Metastasis marks a tumor
malignant.
• The invasiveness of cancers permits them
to penetrate blood vessels, lymphatics and
body cavities, causing distant spread
(Metastasis).

47. Pathways of metastasis
Pathways of metastasis are:
1.Lymphatic spread (Usually Carcinoma)
2.Haematogenous spread (Usually Sarcoma)
3. Direct seeding of body cavities or
surfaces (Krukenberg tumor)

48. Fig: Metastasis

49. Fig: Metastasis

50. Lymphatic Spread (LC)
• Transport through lymphatics is the most
common pathway for the initial dissemination
of carcinomas.
• The lymphatic spread involves deposition of
cancer cells in the draining lymphnodes.
• Involvement of lymph nodes is important for
assessing course of the disease and
selecting suitable therapeutic strategies.

51. Hematogenous Spread (HS)
• Hematogenous spread is typical route for
metastsis of sarcoma.
• The liver, the lungs, bone marrow are most
frequently involved in hematogenous
metastasis.

52. Seeding of Body Cavities and Surfaces
Peritoneal cavity mostly involved in seeding
pathway but pleural, pericardial, subarachnoid
spaces may also involved. Example:
i. Krukenberg tumor of ovary: when GIT cancer
metastasis in the ovarian surface.
ii. Pseudomyxoma peritonei: When Mucous
secreting carcinoma of appendix fill the
peritoneal cavity with gelatinous neoplastic
mass.

53. Sentinel lymphnode
• A sentinel lymph node is the first draining
lymphnode that receives lymph flow from
the primary tumor.
• Sentinel node mapping is done by injection
of radiolabeled tracers or colored dyes in to
the tumor lymphatics.
• Skip metastasis: Metastasis bypassing the
adjacent or first draining lymph node.

54. Clinical Aspects of Neoplasia
And
Diagnosis of Cancer

55. Clinical Aspects of Neoplasia
• The importance of neoplasms lies in their
effects on patients.
• Effects on the patients are:
i. Cancer Cachexia.
ii. Local and Hormonal Effects.
iii. Paraneoplastic Syndromes.

56. Cancer Cachexia
• Progressive loss of body fat and lean body
mass in cancer bearing patient called
cancer cachexia.
• Profound weakness, anorexia and anemia.
• Elevated basal metabolic rate. And evidence
of systemic inflammation.

57. Local and Hormonal Effects
• A small pituitary adenoma, although benign
can compress and destroy the surrounding
normal gland and thus lead to serious
hypopituitarism.
• A benign beta-cell adenoma of the
pancreatic islets may produce sufficient
insulin to cause fatal hypoglycemia.

58. Paraneoplastic syndrome
• Some cancer-bearing individuals develop
signs and symptoms:
that cannot be explained by the
anatomic distribution of the tumor or by the
production of hormones from the tumor is
known as paraneoplastic syndrome.

59. Example of paraneoplastic syndrome:
Clinical syndrome Underlying cancer
Cushing syndrome Small cell carcinoma of lung.
Pancreatic carcinoma
Hypercalcaemia Squamous cell carcinoma of
lung
Breast carcinoma
Renal carcinoma
Polycythaemia Renal carcinoma
Hypoglycemia Ovarian carcinoma
Fibrosarcoma

60. Grading and Staging of
Tumors

61. Grading of cancer
• Grading of a cancer is based on the degree
of differentiation of the tumor cells.
• Grading correlates with the neoplasms
aggressiveness.
• Grading of cancer are classified as grade I
to grade IV with increasing anaplasia (well
to poorly differentiated).

62. Staging of cancer
• The staging of cancer is based on:
1. The size of the primary lesion.
2. Its extent of spread to regional lymph
node.
3. The presence or absence of blood-born
metastasis.
• Two staging system are in use, Union for
International Cancer Control (UICC) and the
American Joint Committee (AJCC) on cancer
staging.

63. Staging of cancer
• The staging of tumor is very important for
treatment strategies and for the evaluation
of prognosis of the tumor.
• Two staging system are in use:
i. Union for International Cancer Control (UICC).
ii. The American Joint Committee on cancer
staging (AJCC).

64. Staging of cancer
The UICC employs TNM system:
• T for size of the primary tumor.
• N for regional lymph node involvement.
• M for metastasis.
• In general, staging has proved to be of
greater clinical value than grading.

65. Laboratory diagnosis
of cancer

66. Laboratory diagnosis of cancer
1.Histologic and Cytologic method:
1) Biopsy followed by Histopathology
(2) Fine Needle aspiration cytology
(FNAC)
3) Cytologic smear (Cervical smear).
2.Molecular diagnosis.
3.Tumor marker.

67. Histologic method
• Histologic method is the biopsy followed by
histopathology.
• Biopsy is either excitional or incisional and
is done by surgeon.
• Histopathology is the test for the diagnosis
of the tumor.

68. Cytologic method
1. Fine needle aspiration cytology (FNAC):
It is a less invasive, less expensive, reliable
and quick method of diagnosis. It may be :
1) Immage guided (2) Non-
immageguided.
2. Pap smear.
3. Brush cytology.
4. Imprint cytology
5. Cytology of body fluids.

69. Molecular diagnosis
Molecular methods are not the primary modality
of cancer diagnosis:
1) Gene diagnosis and diagnosis of
translocation in certain haematopoietic
malignancy (CML).
2) Certain genetic alteration are associated
with poor prognosis.
3) Diagnosis of hereditary predisposition.

70. Tumor marker
• Tumor marker are tumor-associated
enzymes, hormones and proteins found in
blood for detection of the presence of a
tumor.
• Tumor marker cannot confirm the diagnosis
of cancer.
• For the diagnosis of a tumor histopathology
test should be done.

71. Tumor marker
• Its main utility is to support the diagnosis.
• Some tumor marker are also of value in
determining prognosis of treatment of
tumor.
• Prognostic indicator like after
prostatectomy in prostatic carcinoma the
level of PSA becomes normal, indicating no
residual tumor.

72. Some selected tumor markers
Tumor Marker Associated cancer
α- Fetoprotein Liver cell cancer
Carcinoembryonic
antigen (CEA)
Carcinoma of colon,
Pancreas, Stomach
Prostatic specific
antigen (PSA)
Prostate cancer
CA- 125 Ovarian cancer

73. Tumor Immunity
• The tumor cells can be recognized as foreign
and eliminated by the immune system.
• A normal function of the immune system is to
constantly scan the body for emerging
malignant cells and destroy them, which is
called immune surveillance.

74. Mechanisms of tumors resistance to
immune system
i. High variability of tumor cells and low expression
of tumor antigens.
ii. Sialylation.
iii. Tumor cells do not provide costimulus signals
→T lymphocyte anergy.
iv. Production of factors inactivating T lymphocytes
v. Expression of FasL → T lymphocyte apoptosis.
vi. Inhibition of the function or durability dendritic
cells (NO, IL-10, TGF-ß).

75. Evidence for tumor immunity
• The presence of lymphocytic infiltrates
around tumors.
• Reactive changes in lymph nodes draining
sites of cancer.
• Direct demonstration of tumor-specific T
cells and antibodies in patients, which
protects against cancer.

76. Evidence for tumor immunity
• Response of advanced cancers to
therapeutic agents that act by stimulating
latent host T-cell responses
• Increased cancer risk in patients with
immunosuppression and immunodeficiency.

77. Thank You ALL