1. Pathology of Solid Tumors
Megan Troxell, MD/PhD
OHSU Pathology

2. Objectives Diagnostic Techniques
Common terminology, definitions in cancer
Multi-step carcinogenesis
Invasion & Metastasis
Tumor grading
Tumor staging
Newer prognostic/predictive testing

4. Diagnostic Methods in Tumor Pathology
Histology-morphology
‘Old fashioned’ microscope, H &E slides, formalin fixed paraffin embedded (FFPE)
Immunohistochemistry
Esp. tumor differentiation, mitotic rate
H=hematoxylin, nucleic acids, purple
E=eosin, protein, pink
Undiff. tumor
HMB45+ Melanoma

5. Diagnostic Methods in Tumor Pathology
Pediatric Kidney Cancer
Immunohistochemistry
May help subclassify
Rarely, may imply specific genetic rearrangement
Loss of PMS2 expression, colon cancer
Mismatch repair protein deficient (Lynch)
TFE3 +nuclear
Argani. AJSP 26:
Cancer
Aberrant TFE3 protein expression as a result of t(X;1)(p11.2;q21)
Normal

6. Diagnostic Methods in Tumor Pathology
(courtesy of Helen Lawce)
Diagnostic Methods in Tumor Pathology
t(11;22) Ewing’s
EWS-FLI1
Breakapart FISH probe
FISH & Cytogenetics
Characteristic translocations

7. Diagnostic Methods in Tumor Pathology
Molecular/PCR
Esp. hematopathology
T- B-cell clonality
Characteristic mutations
(Coming: gene arrays, etc)
FISH: Her2 amplification
(breast cancer)
Courtesy Dana Bangs
PCR/HPLC (WAVE) for
C-kit mutations in GIST
Corless Am J Pathol :

8. Nomenclature Hypertrophy: increase in size of cells
Hyperplasia: increase in the # of cells in organ/tissue
Neoplasia: “new growth”
Growth exceeds/uncoordinated with normal tissue
Growth persists after stimulus removed
CLONAL
Benign or malignant
Neoplasm=proliferating cells & associated stroma

9. Neoplasia: Benign Cohesive, expansile masses (tumors) Remain localized
No capacity to invade, metastasize
Slow growing
Often encapsulated
Well differentiated (still resemble normal)
Often named with suffix “-oma”
Chondroma (benign neoplasm of cartilage)
Hemangioma (benign neoplasm of blood vessels)
Leiomyoma (benign neoplasm of smooth muscle)
Adenoma (benign epithelial neoplasm)
Cystadenoma, Papilloma etc

10. Neoplasia: Malignant Invade and destroy surrounding tissue
Capacity for metastasis
Spread through blood vessels/lymphatics to distant sites
Higher rate of growth
Pleomorphism (variation in size/shape)
Abnormal nuclear morphology & hyperchromasia
De-differentiation/Anaplasia
Nomenclature:
Malignant epithelial neoplasm: carcinoma
Malignant mesenchyma: sarcoma
Malignant hematolymphoid: leukemia, lymphoma
Malignant melanocytic: melanoma
Malignant germ cell: seminoma, and others

11. Neoplasia: Benign vs. Malignant
Robbins 7-22
Uterus

12. Normal, Benign, Malignant
Normal colon and invasive adenocarcinoma (right, Malignant)
Normal colon (lower) & tubular adenoma
(benign, upper left)

13. Adenoma, colon (TVA)

14. Normal, Benign, Malignant
Normal breast
Benign hyperplasia
Invasive carcinoma

15. Histologic Features of Malignant Cells

16. Transformation “Malignant change in the target cell”
What features define a transformed cell?
Hanahan and Weinberg.
“The Hallmarks of Cancer”
Cell. 100:
And Genomic Instability

17. Transformation: Darwinian?
“Malignant change in the target cell”
Mechanisms & chronology of acquired capabilities vary
By organ/tumor type
By subtype, etc
Hanahan and Weinberg.
“The Hallmarks of Cancer”
Cell. 100:

18. “The Genomic Landscapes of Breast and Colorectal Cancer”
Wood et al. Science. 2007
318:

19. “Tumors as Complex Tissues” or, “It takes a village”
Hanahan and Weinberg.
“The Hallmarks of Cancer”
Cell. 100:

20. Concept: Carcinoma in situ (CIS)
Malignant cells that have not yet breached the basement membrane (still confined)
DCIS & invasive
DCIS: breast

21. Calponin p63 Carcinoma In Situ (right) and
Invasive carcinoma (left), breast
Calponin
p63

22. Carcinoma in situ (CIS)
Squamous
Cell CIS
Squamous CIS
Invasive SCC

23. Invasion & metastasis Vein Artery Colon CA in lymphatic channel ECM
1’tumor BM
Vein
Artery
Lymph
Colon CA in lymphatic channel
Platelets
ECM
Vein
Artery
Robbins 7-42

24. Tumor growth and spread
Normal cell
(Lung)
Single tumor cell
30 doublings
1 gm=109 cells
Smallest clinically detectable mass
10 doublings
1 kg=1012 cells
Maximum mass compatible w/ life
Liver mets
Robbins 7-12

25. Tumor angiogenesis
Leaky vessels
Robbins 7-41

26. Transformation
Some benign neoplasms have propensity to acquire additional genetic changes and progress to malignancy (precursors)
Example: colonic adenoma carcinoma
Others rarely undergo transformation
Example: Uterine leiomyomas, salivary gland pleomorphic adenomas

27. Histologic and Molecular Progression: Colon
LG dysplasia
HG dysplasia
Carcinoma
P53
18q21
SMAD2,4
Telomerases, etc
Kras
APC
b-cat
APC
Robbins. 7th ed. Figure 17-60

28. It’s never that simple…

29. http://www. mdconsult. com/das/book/body/128522719-2/0/1492/f4-u1
gr5.jpg from Cecil Medicine 23 ed (Saunders, Elsevier)

30. Histologic and molecular progression: Breast
True precursor?
Non-obligate precursor?
Florid
proliferation
Infiltrating
Carcinoma
Normal
ADH
DCIS
Tissue
Invasion
Robbins Fig 23-15