2. Neoplasia I Introduction Husni Maqboul, M.D.

3. Terminology Tumor : Pathologic disturbance of growth, characterized by excessive and unnecessary proliferation of cells Galen (131 - 201 AD ) –Swelling according to nature ( pregnancy ) –Swelling exceeding nature ( Callus ) –Swelling contrary to nature

4. Terminology Hamartoma : Excessive but focal overgrowth of cells and tissues native to the organ in which it occurs. Cellular elements are mature, but do not produce normal architecture –Hamartroma of lung –Angiomas –Pigmented nevi

5. Terminology Choristoma (Heterotopia) : Normal cells or tissues, that are present in abnormal locations –Pancreatic cells in the wall of stomach or intestine –Nests of adrenal cells in kidney, lung or ovaries

6. Terminology Neoplasms : Persistent, abnormal and relatively autonomous proliferation of cells occurring as a result of permanent cellular defect that is passed to the progeny. Usually develops due to a factor(s), but once developed, becomes independent of them.

7. Types of neoplasms Neoplasms –Parenchyma made up of neoplastic cells –Supporting host derived stroma Benign: localized and amenable to surgical removal; patient usually survives Malignant: invasive tumor capable of destroying structures and spread to distant sites (metastasis); may result in early death of the patient

8. Examples of benign tumors Epithelial –Adenoma: benign glandular tumor –Papilloma : benign surface epithelial tumors –Polyp : benign tumor projecting over mucosal surface –Cystadenoma : benign epithelial tumor forming hollow cystic mass

9. Examples of benign tumors Mesenchymal –Chondroma: benign cartilaginous tumor –Leiomyoma: benign smooth muscle tumor –lipoma: benign tumor of fat –Fibroma: benign tumor of fibrous tissue Mixed –Benign Mixed Tumor –divergent differentiation of stem cell (pleomorphic adenoma) –Fibroadenoma – neoplastic fibrous component More than one germ cell layer –Benign teratoma – mature components

10. leiomyomas

11. adenoma

12. Examples of malignant tumors Sarcoma (mesenchymal derivation: fibrosarcoma, chondrosarcoma) Carcinoma (epithelial derivation: adenocarcinoma, squamous cell carcinoma) –Squamous –Adeno –Transitional Lymphoma/leukemia

13. adenocarcinoma

14. carcinoma

15. The terms “benign” and “malignant” describe the biologic behavior of a tumor The biologic behavior is characterized by degree of differentiation of the tumor, rate of growth (and rate of cell death), infiltration of surrounding tissue, and dissemination to distant sites

17. Differentiation Well-differentiated tumors contain cells that resemble the normal cells of origin Poorly-differentiated or undifferentiated tumors contain cells that do not resemble their normal counterparts (ancillary studies may be needed to determine the cell of origin)

18. well-differentiated

19. poorly-differentiated

20. Benign tumors are composed of well- differentiated cells. Malignant tumors are characterized by a wide range of cellular differentiation. Anaplasia (cellular pleomorphism, hyperchromatic nuclei, high N:C ratio, giant cells, bizarre nuclei) is a feature of malignant tumors. Differentiation

21. anaplasia

22. Dysplasia denotes a loss of architectural organization and a loss of cell uniformity in epithelium pleomorphism and mitoses are more prominent than in the normal usually graded: mild, moderate, severe, and carcinoma-in-situ mild to moderate dysplasia is potentially reversible

23. normal epithelium

24. dysplasia

25. Dysplasia Dysplasia is a non-neoplastic proliferation. Dysplasia may or may not progress to cancer.

26. Rate of growth In general, benign and well-differentiated malignant tumors have a slower rate of growth than moderately-differentiated and poorly-differentiated malignant tumors. There are exceptions. Blood supply, site, and hormonal stimulation are factors that can affect the growth rate of tumors.

27. Invasion Benign tumors usually grow by slow expansion. Malignant tumors usually infiltrate and may destroy surrounding tissue (cell surface and the extracellular matrix play an important role).

28. Functional characteristics Benign tumors are more likely to function Epithelial tumors can produce mucin Hormonal production can be unregulated Inappropriate production of hormones by different type of cells Abnormal receptor and antigenic expression

29. Metastasis indicates malignancy a discontinuous spread of the tumor Methods of metastasis include: (1)seeding of body cavities, (2) lymphatic spread, and (3) hematogenous spread.

30. metastatic ovarian carcinoma

31. MRI: metastatic adenocarcinoma

32. metastatic adenocarcinoma

33. Grading and staging Grading is based on the microscopic features of the cells which compose a tumor and is specific for the tumor type. Staging is based on clinical, radiological, and surgical criteria, such as, tumor size, involvement of regional lymph nodes, and presence of metastases. Staging usually has more prognostic value.

34. Morbidity and mortality metastases rupture into major vessels compression of vital organs organ failure infection

35. meningioma

36. basal cell carcinoma

37. melanoma

38. Diagnostic procedures FNA (fine needle aspiration) Cytological smears Biopsy Frozen sections Biochemical assays Molecular diagnosis Flow cytometry

39. cytology smear: adenocarcinoma

40. Pap smear with dysplasia

41. frozen section

42. staining a frozen section

43. Ancillary studies Immunohistochemistry Cytogenetics Flow cytometry Electron microscopy

44. cytokeratin stain on a carcinoma

45. AFP stain on a yolk sac tumor

46. EM: neurosecretory granules

47. EM: microvilli, tight junction in an adenocarcinoma

48. Biochemical assays Tumor markers: sometimes diagnostic or prognostic Can be helpful in monitoring effectiveness of therapy or in detecting relapses/recurrences

50. Summary Neoplasia- an abnormal mass of tissue which has lost its responsiveness to growth controls Benign neoplasms tend to be slow-growing, well-differentiated tumors which lack the ability to metastasize Benign neoplasms, in general, remain localized and are amenable to surgery

51. Summary Malignant neoplasms tend to be fast- growing lesions which invade normal structures Malignant neoplasms vary in the degree of differentiation and some show anaplasia Malignant neoplasms are capable of metastasis

52. Summary The prognosis of a patient with any type of neoplasm depends on a number of factors including: the rate of growth of the tumor, the size of the tumor, the tumor site, the cell type and degree of differentiation, the presence of metastasis, responsiveness to therapy, and the general health of the patient.