1. Neoplasia
Dr. Gehan Mohamed

2. Learning objectives Understand the definition of neoplasia.
List the Classification of neoplasia.
Describe the General characters of benign tumors.
Understand the Nomenclature of benign tumors.
Nomenclature of Malignant tumors.
Nomenclature of some Malignant tumors with Exceptions.
Describe etiology of malignant tumors

3. Learning objectives
definition,Microscopic changes and types of dysplasia.
Describe Pathogenesis of tumor formation.
Describe General characters of malignant tumors.
Understand method of gading and stagging of Malignant Neoplasms.
Understand definition of Carcinoma in-situ
Describe methods of Spread of malignant tumors.
Describe laboratory diagnosis of malignant tumors.
Identify the causes of death in malignant tumors.
Describe the paraneoplastic syndrome.

4. Neoplasia Neoplasia = new growth Neoplasm = onco tumor = swelling
The study of neoplasms = Oncology
Onco = tumor
ology=study

5. Neoplasia Definition:
It is a self controlling growth formed by unlimited multiplication of abnormal cells

6. Neoplasia Classification Benign Malignant Locally malignant tumors
Epithelial
Mesenchymal
Malignant
Primary
Epithelial (carcinoma)
Mesenchymal (sarcoma)
Secondary (metastatic)
Locally malignant tumors

7. General characters of benign tumors
Pathology
Gross pathology
Size: Usually small in size
Shape: usually ovoid or rounded in shape
Capsule: usually capsulated
Cut section solid or cystic
Hemorrhage and necrosis: usually absent
Microscopic pathology
Differentiation: The cells are well differentiated i.e tumor cells closely similar to the tissue of origin.
Nucleocytoplasmic ratio (N/C) ratio: small or normal
Stroma: is usually well formed with few blood vessels

8. Behavior of benign tumors
Rate of growth: usually slow
Mode of growth: by expansion
Localization: usually localized
Effects on the host: usually do not destroy the surrounding structures and do not kill the patient (except in certain sites as in brain)
Recurrence: usually not recurrent
Metastasis: Do not metastatise
Malignant change: may occur

9. Benign tumors Nomenclature Benign tumors: prefix + suffix
Type of cell + (-oma)

10. Neoplasia Examples: Benign tumor arising in fibrous tissue:
Fibro + oma = Fibroma
Benign tumor arising in fatty tissue:
Lipo + oma = lipoma

11. Benign epithelial tumors Benign mesenchymal tumors
Papilloma
Adenoma
Benign mesenchymal tumors
CT tumors
Fibroma
Lipoma
Chondroma
Osteoma
Benign tumors of muscles
Leiomyoma
Rhabdomyoma
Benign tumors of vessels
Haemangioma
lymphangioma

12. Lipoma

13. Chondroma

14. Adenoma : benign epithelial neoplasms producing gland pattern…
Adenoma : benign epithelial neoplasms producing gland pattern….OR … derived from glands but not necessarily exhibiting gland pattern
Examples :
Respiratory airways: Bronchial adenoma
Renal epithelium: Renal tubular adenoma
Liver cell : Liver cell adenoma
Papilloma : benign epithelial neoplasms growing on any surface that produce microscopic or macroscopic finger-like pattern
Squamous epithelium: squamous papilloma

15. Adenoma

16. Fibroadenoma

17. Papilloma

18. Malignant tumors have two basic components:
Parenchyma: made up of neoplastic cells
Stroma: made up of non-neoplastic, host-derived connective tissue and blood vessels.
The parenchyma:
Determines the biological behavior of the tumor
From which the tumor derives its name
The stroma:
Carries the blood supply
Provides support for the growth of the parenchyma

19. Adenocarcinoma formed of malignant glands and stroma

20. Malignant tumors:
Malignant tumor arising in mesenchymal tissue : SARCOMA
From fibrous tissue: Fibrosarcoma
From bone : Osteosarcoma
From cartilage : chondrosarcoma

21. Osteosarcoma

22. Malignant tumors arising from epithelial origin : CARCINOMA
Squamous cell carcinoma
Renal cell adenocarcinoma
cholangiocarcinoma

23. Carcinomas arising from any epithelium of the body that exhibit squamous differentiation are termed squamous cell carcinoma.

24. Papillary Cystadenocarcinoma of the Ovary
Nomenclature
other descriptive terms may be added such as:
Papillary Cystadenocarcinoma of the Ovary

25. Nomenclature of some Malignant tumors with Exceptions
Melanoma ( skin )
Mesothelioma (mesothelium )
Seminoma ( testis )
Lymphoma ( lymphoid tissue )

26. Neoplasm (Tumors) Etiology of malignant tumors
A- Precancerous lesions
Examples of some lensions that exhibit a tendency to
undergo malignant transformation
1- Endometrial hyperplasia endometrial carcinoma.
2- Fibrocystic disease of the breast cancer breast
3- Liver cirrhosis hepatocellular carcinoma

27. Dysplasia
Definition:Abnormal development or growth of cells (i.e maturation abnormality).
Commonest sites :
Cervix(cervical intraepithelial neoplasia) (CIN)
Vagina(vaginal intraepithelial neoplasia) ( VIN).
bronchi(bronchial intraepithelial neoplasia BIN)

28. Microscopic changes of dysplasia
Dysplasia is characterized by :
-Anisocytosis (cells of unequal size)
-Poikilocytosis (cells of variable shape)
-Hyperchromatism
-Presence of mitotic figures (an unusual number of cells which are currently dividing).

29. Types of dysplasia 1- low grade dysplasia:
-not affect the whole thickness of epithelium.
-it is reversible if the irritant is removed.
High grade dysplasia:
- it is precancerous (not reversible)
-affect the whole thickness of epithelium.
-it is also called carcinoma in situ as the basement membrane not invaded by the abnormal cells

31. Here, there is normal cervical squamous epithelium at the left, but dysplastic squamous epithelium at the right. The dysplastic epithelial cells are darker, smaller, and more crowded,. Dysplasia is still confined to the epithelium. Dysplasia is still reversible.

32. At high magnification, the normal cervical squamous epithelium at the left merges into the dysplastic squamous epithelium at the right in which the cells are more disorderly and have darker nuclei with more irregular outlines.

33. This is "carcinoma in situ" because the carcinoma is still confined to the epithelium, as the entire portion of epithelium is composed of abnormal cells and the basement membrane is still intact.

34. This is invasive squamous cell carcinoma
This is invasive squamous cell carcinoma.the squamous epithelial cells in these large nests with pink keratin in the centers.

35. Neoplasm (Tumors) Etiology of tumors
A- Precancerous lesions
4- Squamous metaplasia lead to squamous cell carcinoma as in :
a- Urinarry bladder in bilharziasis
b- Bronchial mucosa with chronic bronchitis and smoking
5- Benign tumors
a- Papilloma of urinary bladder
b- Adenoma of thyroid or colon

36. Neoplasm (Tumors) Etiology of tumors
B- Helping factors (Cocarcinogens)
1- Age
With aging there is a more chance of exposure to
the carcinogen
2- Sex
Most of tumors are common in male

37. Neoplasm (Tumors) Etiology of tumors
B- Helping factors (Cocarcinogens)
3- Diet
Fat may be related to colonic cancer.
Smoked fish is related to gastric carcinoma.
Excess alcohol is related to liver cancer.
4- Smoking
May lead to lung cancer
5- Heredity
Some tumors are inherited i.e. retinoblastoma
and colonic cancer

38. Neoplasm (Tumors) Etiology of tumors
C- Carcinogens
Types of carcinogens
1- Chemical carcinogens
Methylated hydrocarbons-A 20 dyes bladder cancer
Aflatoxins produced from Aspergillus fungus liver cancer
2- Viruses
Hepatitis B virus liver cancer
Human papilloma virus cancer cervix

39. Neoplasm (Tumors) Etiology of malignant tumors C- Carcinogens
3- Radiations
Ionizing radiation, ultraviolet or prolonged exposure
to sunlight
Cancer of the skin
Leukemia

40. Neoplasm (Tumors) Etiology of malignant tumors
C-mechanism of action of Carcinogens
Chemical carcinogens, viruses and radiation result in
DNA damage and initiation of cancer by :
1- Activation of oncogenes e.g myc gene,K-ras (genes responsible for
abnormal growth and proliferation of cell).
2- Inactivation of cancer suppressor genes e.g RB ,P53 genes.

41. Neoplasm (Tumors) Etiology of tumors
C-mechanism of action of Carcinogens
Hormones act as promoters i.e. they stimulate the
proliferation of the already transformed cells e.g.
Estrogen cancer breast and endometrial cancer
Androgen prostatic cancer

42. Pathogenesis of tumor formation

43. General characters of malignant tumors
Pathology
Gross pathology
Size: Usually reach large size
Shape
Polypoid or fungating mass in tumors of solid organs
Malignant ulcer in tumors of surface epithelium
Infiltrating annular mass in tumors of hollow organs
Capsule: non-capsulated
Cut section sold or cystic
Hemorrhage and necrosis: common
Microscopic pathology
Differentiation: The cells show loss of differentiation
The cells show some or all features of malignancy as loss of polarity of the cells ,hyperchromatic neuclei, increase N/C ratio,abnorml mitosis and prominent neucleolus.
Stroma: is usually desmoplastic with rich vascularity

44. Behavior of malignant tumors
Rate of growth: usually rapid
Mode of growth: by infiltration
Localization: usually not localized
Effects on the host: can kill the patient wherever present
Recurrence: may recur
Metastasis: may occur
Precancerous lesions
Chronic inflammatory lesions
Hyperplastic lesions
Some benign tumors
Other lesions as peptic ulcer and un-descended testis

45. Grading of Malignant Neoplasms
Grade
Definition I
Well differentiated II
Moderately differentiated
III
Poorly differentiated IV
Nearly anaplastic

46. Oat cell carcinima of the lung Undifferenciated carcinoma Grade IV
Poorly differentiated neoplasms
have cells that are difficult to
recognize as to their cell of origin.
Higher grade means:
a lesser degree of differentiation
and the worse the
biologic behavior
Adenocarcinoma of the colon
Well differenciated carcinoma
A well differentiated neoplasm
is composed of cells
that closely resemble
the cell of origin.

47. Clinical Staging T (primary tumor): T1, T2, T3, T4
N (regional lymph nodes): N0, N1, N2, N3
M (metastasis): M0, M1

48. TNM staging system in cancer

50. Staging of Malignant Neoplasms
Stage
Definition
Tis
In situ, non-invasive (confined to epithelium) T1
Small, minimally invasive within primary organ site T2
Larger, more invasive within the primary organ site T3
Larger and/or invasive beyond margins of primary organ site T4
Very large and/or very invasive, spread to adjacent organs N0
No lymph node involvement N1
Regional lymph node involvement N2
Extensive regional lymph node involvement N3
More distant lymph node involvement M0
No distant metastases M1
Distant metastases present

51. Carcinoma in-situ
Definition: an intraepithelial malignancy in which malignant cells involve the entire thickness of the epithelium without penetration of the basement membrane.
Applicable only to epithelial neoplasm

52. Carcinoma in situ

53. Spread of malignant tumors
Mechanism of spread
Invasion of the matrix
Vascular dissemination and homing of tumor cells
Routes of spread
Direct or local spread
Malignant cells infiltrates the surrounding structures in all direction
Distant spread: as
Lymphatic spread
Lymphatic permeation
Lymphatic embolization
Blood spread
Course of tumor emboli
Organ metastasis
Transcoelomic spread
Spread by implantation

54. Localy malignant tumors
Definition
Groups of malignant tumors that spread only locally
Characters
Slow rate of growth
Spread only locally by direct infiltration
The cells show features of malignancy
Examples
Basal cell carcinoma of skin
Osteoclastoma
Adamantinoma in jaw
Bronchial adenoma
Carcinoid tumor
Astrocytoma in brain
Craniopharyngioma from pituitary gland

55. Laboratory Diagnosis of malignant tumors
Morphologic methodes
Biochemical assays
Molecular diagnosis

56. Laboratory Diagnosis Microscopic Tissue Diagnosis
the gold standard of cancer diagnosis.
Several sampling approaches are available:
Excision or biopsy
Frozen section
fine-needle aspiration
Cytologic smears

58. Immunohistochemical diagnosis

59. Laboratory Diagnosis Biochemical assays:
Useful for measuring the levels of tumor associated enzymes, hormones, and tumor markers in serum.
Useful in determining the effectiveness of therapy and detection of recurrences after excision
Only few tumor markers are proved to be clinically useful, example CEA in colonic adenocarcinoma and α- fetoprotein in hepatoma.

60. Molecular diagnosis Polymerase chain reaction (PCR)
example: detection of BCR-ABL transcripts in chronic myeloid leukemia.
Fluorescent in situ hybridization (fish)
it is useful for detecting chromosomes translocation characteristic of many tumors
Both PCR and Fish can show amplification of oncogenes (HER2 and N-MYC)

61. Neoplasm (Tumors) Causes of death in malignant tumors
1- Destruction of vital tissues such as brain, liver, kidney
2- Malnutrition due to interference of food intake,
digestion and absorption.
3- Obstructive effects e.g. urinary tract obstruction.
4- Anemia due to
a- Continuous blood loss from bleeding malignant ulcers.
b- Destruction of red bone marrow by metastatic deposites.
5- Malignant cachexia with wasting, loss of weight and
muscular weakness.
6- Secondary infection by bacteria, viruses and fungi.

62. Paraneoplastic syndromes
They are symptoms that occur in cancer patients due to secretion of some hormone like substances and not due to distant metastasis.
They are diverse and are associated with many different tumors.
They appear in 10% to 15% of pateints.
They may represent the earliest manifestation of an occult neoplasm.
They may represent significant clinical problems and may be lethal.
They may mimic metastatic disease.

63. The most common paraneoplastic syndrome are:
Hypercalcemia
Cushing syndrome
Nonbacterial thrombotic endocarditis
The most often neoplasms associated with these syndromes:
Lung and breast cancers and hematologic malignancies