1. Pathology of Neoplasia

2. Tumor – tissue mass
Neoplasm – “new growth”, clonal expansion of
cells with somatic mutations and
variable autologous growth regulation
Cancer – neoplasm with invasive or metastatic
properties

3. Morphology of Neoplasia

4. Malignant neoplasms invade normal tissues and cause mechanical disruption of normal function
mesothelioma
gastric cancer

5. Superior vena cava syndrome

6. Invasion and metastasis of colon cancer
primary invasive
colon cancer
colon cancer
metastases
to liver

7. tubular adenoma with in situ and early invasive cancer

8. tubular adenoma with in situ and early invasive cancer

9. “Benign tumors” are not invasive
(leiomyoma of uterus)

10. Lymph node metastasis

11. Determinants of Cancer Metastatic Growth Sites
Colorectal Cancer
Breast Cancer
Pathways of lymphatic and
vascular drainage
2. Molecular determinants
for cell survival and growth

12. Summary: Growth of Metastatic Cancer
Spread of cancer cells to distant sites generally follows pathways of lymphatic and vascular drainage.
Growth of cancer cells in metastatic site depends on ability of neoplastic cells to accommodate to new tissue (e.g., altered molecular composition of cell surface).

13. Features of Benign and Malignant Tumors
Poorly circumscribed
Penetrates capsule if present
Invasive into adjacent tissues, lymphatics and vasculature
Metastases
Poorly organized aggregates of cells
Well circumscribed, sometimes encapsulated
Non-invasive
No associated metastases
Organized tissue structures

14. Features of Benign and Malignant Cells
High N/C ratio
Irregular nuclear shape
Clumped chromatin
Prominent nucleoli
Loss of differentiation
Common mitoses, often atypical
Low N/C ratio
Round nucleus, even distribution of chromatin
Maintenance of differentiation
Uncommon mitoses

15. Cellular Features of Benign and Malignant Cells

16. Leiomyoma of Uterus

17. Leiomyosarcoma of Uterus

18. Follicular adenoma (left) with intact capsule
Follicular carcinoma (right) invading through capsule

19. Nomenclature of tumors
Pathological features of benign and malignant tumors
Grading and staging cancer
Ancillary techniques to diagnose and classify neoplasms

20. Nomenclature of Tumors
bile duct adenoma
tissue/ organ of origin

21. Nomenclature of Tumors
bile duct adenoma
pattern of differentiation

22. Nomenclature of Tumors
bile duct adenoma
benign

23. Nomenclature of Tumors
adenocarcinoma
malignant,
epithelial

24. Nomenclature of Tumors
squamous cell carcinoma
malignant,
epithelial

25. Nomenclature of Tumors
leiomyosarcoma
malignant,
mesenchymal

26. -oma as a suffix for malignant tumors
Lymphoma
Melanoma
Hepatoma (hepatocellular carcinoma)
Astrocytoma

27. Common terms for epithelial tumors
Epidermoid – a synonym for squamous cell
Adeno – glandular or ductal
Transitional cell – urothelial cells lining bladder, renal pelvis, ureters

28. Common terms for mesenchymal tumors
Leiomyo – smooth muscle
Rhabdomyo – skeletal muscle
Chondro – cartilage
Osteo – bone (osteoid)
Fibro - fibrous

29. Features of Benign and Malignant Tumors
Poorly circumscribed
Penetrates capsule if present
Invasive into adjacent tissues, lymphatics and vasculature
Metastases
Poorly organized aggregates of cells
Well circumscribed, sometimes encapsulated
Non-invasive
No associated metastases
Organized tissue structures

30. Features of Benign and Malignant Cells
High N/C ratio
Irregular nuclear shape
Clumped chromatin
Prominent nucleoli
Loss of differentiation
Common mitoses, often atypical
Low N/C ratio
Round nucleus, even distribution of chromatin
Maintenance of differentiation
Uncommon mitoses

31. Cellular Features of Benign and Malignant Cells

32. Leiomyoma of Uterus

33. Leiomyosarcoma of Uterus

34. Follicular adenoma (left) with intact capsule
Follicular carcinoma (right) invading through capsule

35. Tubular Adenoma of Colon

36. Invasive Colon Cancer

38. Descriptive terms used in cancer nomenclature
Cystic
Papillary
Polypoid
Mucinous
Scirrhous
Annular

41. Neoplasms with intermediate levels of malignancy
Borderline / Low malignant potential tumors (e.g., ovary)
Carcinoid tumors (e.g., lung and gastrointestinal system)

42. Pulmonary Carcinoid

43. Pulmonary Carcinoid

44. Clinical situation as a determinant of cancer diagnosis
Site – smooth muscle tumor in uterus or in retroperitoneum/ mesentery.
Gender – teratoma in woman (ovary) or in man (testis).
Age – teratoma in testis of child or in testis of adult man

45. Preinvasive neoplasia defies traditional definitions of benign and malignant tumors
Carcinoma in situ (or severe dysplasia) of squamous mucosa
Tubular adenoma of colon

46. In situ neoplasia
Atypical cells
Loss of maturation
Mitotic activity

49. Examples of early (pre-invasive) neoplasia
risk for malignancy
neoplasm
“tumor”
adenoma of colon
yes
variable
dysplasia of cervix no
variable
dysplasia of bronchial epithelium no
unknown
atypical junctional
nevus
yes
moderate

50. Examples of “benign tumors”
risk for malignancy
neoplasm
“tumor”
leiomyoma
yes
minimal
lipoma
yes
minimal
fibroadenoma
of breast
yes
minimal
intradermal nevus
of skin
yes
minimal
variable
adenoma of colon
yes

51. Grading and Staging Cancer

52. Grade: Loss of differentiation and atypical nuclear features
Grade 1 – low grade
Grade 2 – intermediate grade
Grade 3 – high grade

53. Grade 1
Grade 2
Grade 3

54. Stage: size of tumor and extent of spread
Stage 0 – non-invasive
Stage I –
Stage II –
Stage III -
Stage IV – metastatic
Variable extent of invasion
and lymph node metastases

55. TNM staging of cancer T – size and extent of local invasion
N – lymph node metastases
M – metastases to other organs

56. T Staging for Lung Cancer
No evidence of primary tumor T1
Primary tumor < 3 cm, does not affect pleura or main bronchus T2
Tumor > 3 cm or involves pleura or involves main bronchus T3
Tumor involves chest wall or bronchus within 2 cm of trachea T4
Tumor involves mediastinum, trachea, or esophagus, or has pleural effusion

57. T Staging for Breast Cancer
No evidence of primary tumor T1
Primary tumor < 2cm T2
Tumor > 2 cm, < 5 cm T3
Tumor > 5 cm T4
Tumor invades chest wall, or inflammatory carcinoma

58. N Staging for Lung Cancer
No lymph node metastases N1
Involves ipsilaterial hilar or peribronchial nodes N2
Involves ipsilateral mediastinal nodes N3
Contralateral spread

59. N Staging for Breast Cancer
No lymph node metastases N1
Metastases to same-side movable nodes N2
Metastases to same-side fixed nodes N3
Metastases to internal mammary nodes

60. Group Staging for Lung Cancer
Overall Stage
T Stage
N Stage
M Stage
Stage 0
Tis (In situ) N0 M0
Stage IA T1 N0 M0
Stage IB T2 N0 M0
Stage IIA T1 N1 M0
Stage IIB T2 N1 M0 T3 N0 M0
Stage IIIA T1 N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0
Stage IIIB
Any T N3 M0 T4
Any N M0
Stage IV
Any T
Any N M1

61. Stage-specific survival for lung cancer
1.0
Stage I
Stage II
Stage IIIa
Stage IIIb
Stage IV
0.8
0.6
Survival
0.4
0.2 1 2 3 4 5
Years after diagnosis

62. Ancillary techniques to diagnose and classify neoplasms

63. Immunohistochemistry in diagnosis and classification of cancer
Markers can help to recognize normal structures (e.g., basal cell layer)
Some markers are differentially expressed in normal and benign tissues
Markers can identify pattern of differentiation

64. (malignant glands lack staining)
Basal cell marker p63
(malignant glands lack staining)
Cancer marker α-methylacyl-CoA racemase
(malignant glands stain positive)

65. Cytokeratin 20 Cytokeratin 7 Colon Breast Urinary tract Lung Gastric
Pancreas/ biliary
Breast
Lung
Pancreas/ biliary
Ovary/ uterus
Salivary gland

66. Metastatic cancer in brain
CK 20
CK 7

67. Prognostic and Predictive Markers for Cancer
Pathological stage – most types of cancer
Pathological grade
Gleason score (prostate cancer)
Biochemical and molecular markers
Estrogen receptor (breast cancer)
Proliferation markers (many types of cancers)
Large numbers of other markers tested

68. Estrogen Receptor in Breast Cancer
Favorable prognosis
Responds to anti-estrogen therapy

69. Markers for early detection and monitoring cancer
Proteins – PSA is prototype
RNA – usually inadequate stability
DNA – stable and potentially fingerprint of neoplasia
Cancer specific mutations
Cancer specific methylation patterns

70. Prostate-Specific Antigen (PSA)
A protease that is made by prostate epithelial cells
Has the best positive predictive value of any biochemical assay for cancer
0 – 2 ng/ml 1%
2 – 4 ng/ml 15%
4 – 10 ng/ml 25%
> 10 ng/ml 50%

71. PSA screening for Prostate Cancer
Mortality rate has declined in post-PSA era.
Comparison of incidence to mortality in post-PSA era suggests over-diagnosis and over-treatment