1. Neoplasia Basics, Grading and Staging Kimiko Suzue MD, Ph.D. Department of Pathology Mt. Sinai Hospital

2. Neoplasia Unregulated cell proliferation Monoclonal –single precursor cell clone genetically altered Benign vs Malignant

3. Assessing Clonality Evaluate a gene which should be heterogenous or heterozygous Plasma Cells Each cell produces either kappa or lambda light chains

4. Plasma Cells All kappa light chain positive

5. Assessing Clonality In practice, most often used for hematologic malignancies T cell receptor gene rearrangement B cell immunglobulin gene rearrangement Normally very heterogenous

6. Assessing Clonality Evaluate a gene which should be heterogenous or heterozygous X-linked markers such as Glucose-6-phosphate dehydrogenase (G6PD) Human androgen receptor (HUMARA), methylation pattern

8. Neoplasia Unregulated cell proliferation Monoclonal –single precursor cell clone genetically altered Benign vs Malignant

9. Malignant Tumors Invasive Can cross basement membrane Downloaded from: StudentConsult (on 8 September 2011 06:01 PM)

10. Downloaded from: StudentConsult (on 8 September 2011 07:25 PM) © 2005 Elsevier Basement Membrane

11. Downloaded from: StudentConsult (on 8 September 2011 07:25 PM) © 2005 Elsevier Basement Membrane

12. Downloaded from: StudentConsult (on 8 September 2011 07:25 PM) © 2005 Elsevier Invasion

13. Malignant Tumors Invasive Can cross basement membrane Invade local structures Invade blood vessels/lymphatics Metastasis to distant sites Downloaded from: StudentConsult (on 8 September 2011 06:01 PM)

14. Metastasis Implantation at distal site Mode of spread Lymphatic Hematogenous Seeding of body cavity/ surface

15. Malignant Tumors Grossly may be unencapsulated or not well- circumscribed Histologic features Increased nuclear to cytoplasmic ratio Nuclear changes Hyperchromatic, Vesicular Prominent nucleoli Pleomorphism Mitotic activity increased/abnormal forms Loss of cell polarity

16. Benign Tumors Do not metastasize Grossly may be encapsulated or well-circumscribed Histologic features Well-differentiated, resemble tissue of origin Uniform cells Low mitotic activity

17. Tumor Nomenclature Robbins Table 7-1 Many benign tumors have –oma Malignant Carcinoma Sarcoma Melanoma Lymphoma Mesothelioma Teratoma (benign/malignant)

18. Lipoma

19. Liposarcoma

20. Fibroadenoma Breast Carcinoma

21. Fibroadenoma

22. Breast, Invasive Carcinoma

23. Adenoma

24. Colonic Adenocarcinoma

26. Malignant Tumors - Histologic Grade Well differentiated Moderately differentiated Poorly differentiated Undifferentiated Grade cannot be assessed sometimes small sample size therapy

27. Malignant Tumors - Histologic Grade Well to moderately differentiated tumors retain functional capabilities Squamous cell carcinoma – Keratin pearls Adenocarcinoma – glands, mucin, bile Can try special stains to verify tumor type Immunohistochemistry (antibody) Histochemical reaction

28. Histologic Grade – Breast Glandular formation Nuclear size Mitotic activity

29. Histologic Grade - Prostate Downloaded from: StudentConsult (on 8 September 2011 07:25 PM) © 2005 Elsevier

30. Well-DifferentiatedAdenocarcinomaWell-Differentiated Squamous Cell Carcinoma

31. Histologic Grade - Poorly Differentiated

32. Cancer Staging Size Extent of invasion Lymph node involvement Distant metastasis

33. Cancer Staging TNM Primary Tumor (T) Size Extent of invasion Lymph node involvement (N) Number Distant metastasis (M)

34. Colonic Adenocarcinoma

35. Lymph Node

37. Metastasis

38. Metastasis

39. Metastasis Well to moderately differentiated adenocarcinoma, but high stage

40. Tumor Grade and Stage Stage correlates better with prognosis than grade Low histologic grade/High stage High histologic grade/Low stage

41. Neoplasia Unregulated cell proliferation, Molecular Basis Damage of regulatory genes Please review from your handout

42. Multistep Carcinogenesis APCAPCK-RASp53

43. Damage of regulatory genes Growth-promoting proto-oncogenes Oncogenes-Constitutively active Growth-inhibiting tumor suppressor genes Two-hit Knudson hypothesis Genes which regulate apoptosis Genes involved in DNA repair

44. Multistep Carcinogenesis APCAPCK-RASp53

45. The End