5. The Key Points of Medical Science Disease To prevent To diagnose To treat

12. Dysplasia Dysplastic change in cervical epithelium

13. Anaplastic tumor showing cellular pleomorphism

14. Rhabdomyosarcoma: Anaplastic cells

28. Benign vs Malignant Tumor Characteristics Benign Malignant Morphology and Differentiation Well-differentiated appearance Structure similar to tissue origin Little or no anaplasia Usually some lack of differentiation Structure often atypical Variable degree of anaplasia Rate and pattern of growth Slow, progressive expansion Rare mitotic figures Normal-appearing mitotic figures Slow to rapid growth; erratic growth rate Mitotic figures often numerous Mitotic figures sometimes abnormal Local invasion No Invasion Cohesive and expansile growth Capsule often present Local Invasion Infiltrative growth Usually no capsule Metastasis No metastasis Frequent metastasis (definitive criteria for malignancy) Damage to human body Relatively smaller Relatively bigger Prognosis Good Bad

32. Invasion and Metastasis Mammary carcinoma in a lymphatic in the lung

36. TNM : Staging of tumor

37. 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

40. Colon Polyp

41. Pathogenesis of Neoplasia Normal Cell Neoplastic Cell DNA Damage Chemical or physical agents

43. Pathogenesis of Neoplasia: Late Adenoma Normal Crypt Early Adenoma Adenocarcinoma

44. Pathogenesis of Neoplasia (Colon Cancer) Normal Epithelium “ Proliferative ” Epithelium “ Early ” Adenoma “ Intermediate ” Adenoma “ Late ” Adenoma Invasive Carcinoma Metastases APC gene (5q loss or mutation) Abnormalities Methylation k-Ras gene (12p mutation) DCC/SMAD (18q loss) p53 gene (17p loss) Additional mutations

45. Development of squmous cell carcinoma in the mouse skin, UV radiation (Animal Experiments) A B C D 2 weeks 1 months 3 months

50. Paraffin-embedded tissue vs Frozen section Paraffin-embedded tissue section Frozen section Specimens Fixed tissues Fresh tissues Making time 24-48 hours 10-20 minutes Saving time Permanent Months Morphology under microscopy Clarity Opacity Application Pathological Diagnosis Intraoperative consultation

52. Tissue Treatment Procedure

55. Gross Appearance of Tumors

56. Appearance of Tumors ---Gross and histological pattern Benign tumor --- adenoma of thyroid gland

57. Appearance of Tumors ---Gross and histological pattern Benign tumor ---Fibroma Benign tumor ---Lipoma

58. Microscopic Appearance of Tumors ---Histological pattern Carcinoma ---squamous carcinoma Carcinoma --- Papillary carcinoma

60. Microscopic Appearance of Tumors ---Tumor Cell Cytology Normal squamous cells Squamous cell carcinoma

61. Microscopic Appearance of Tumors ---Tumor Cell Cytology Abnormal mitotic figures often seen in malignant tumor

62. Microscopic Appearance of Tumors ---Tumor Cell Cytology Reed-Sternberg cell

65. Immunohistochemistry (IHC) in Tumor Diagnosis Cytokeratin Vimitin Adenocarcinoma Sarcoma

66. Immunohistochemistry (IHC) in Tumor Diagnosis Immunophenotypes of major groups of malignant tumors Tumor type CK VIM S-100 CD45 Carcinoma + - - - Sarcoma - + - - Lymphoma - - - + Melanoma - - + -

67. Immunohistochemistry (IHC) in Tumor Diagnosis Estrogen Receptor (ER) Her-2 (Cerb B2) Breast Cancer

69. Specific Cytogenetic Abnormalities Determined in Tumors Tumor type Chromosomal changes Genes involved or fusion genes Follicular lymphoma t(14;18)(q32;q21) JH/Bcl-2 Mantle cell lymphoma t(11;14)(q13;q32) JH/Bcl-1 Synovial sarcoma t(X;18)(p11;q11) SYT-SSX1 Ewing ’ s sarcoma t(11,22)(q24;12) EWS-FL11 Follicular carcinoma t(2;3)(q13;p25) PAX 8 -PPAR γ

70. Cytogenetic investigations - Fluorescent in situ hybridization (FISH) - Identify chromosome rearrangement detecting specific DNA sequences with fluorescently labeled probe

71. Cytogenetic Changes of Lymphoma Determined by FISH FL diagnosed by FISH: IGH/BCL2 t(14;18)(q32;q21) MCL diagnosed by FISH: IGH/CCND1 t(11;14)(q13;q32)

79. Fine needle aspiration cytology (FNA)

84. Gross appearance

85. Microscopic appearance

88. CK

89. p63

90. p53

93. Learning without thinking leads to confusion, thinking without learning ends in danger. 学而不思则罔 , 思而不学则殆 -Kong Zi Learning is like rowing upstream: not to advance is to drop back 学如逆水行舟 , 不进则退