즐거운 강의되기 바랍니다 June 28, 2002

General Characteristics of Neoplasms Jae Y. Ro, M.D. Asan Medical Center Seoul, Korea June 28, 2002

single organism, cell, or gene Clone : A group of genetically identical descended (progeny) produced by asexual reproduction of single organism, cell, or gene Cancer : Clonal overgrowth Cell proliferation Cell loss

Cancer Incidence Age, sex, race, socioeconomic groups men: 684/100,000 Luxembourg 84/100,000 El Salvador women: 450/100,000 Denmark 126/100,000 El Salvador USA, men 361/100,000 women 283/100,000 Korea, Japan, China: lower than USA

Ten Leading Cancer Sites for the Estimated New Cancer Cases and Deaths by Gender, US, 2002 *

Cancer Statistics in Korea (1/1999 - 12/1999) 1) Stomach (20.7%) 6) Uterine cervix (5.0%) 2) Lung (12.1%) 7) Thyroid (3.5%) 3) Liver (12.0%) 8) Hematopoietic (2.9%) 4) Colon ( 9.9%) 9) Bladder (2.4%) 5) Breast ( 6.4%) 10) Pancreas (2.2%)

For Men 1) Stomach (24.2%) 6) Esophagus (3.2%) 2) Liver (16.3%) 7) Hematopoietic (2.9%) 3) Lung (16.1%) 8) Prostate (2.5%) 4) Colon ( 9.7%) 9) Pancreas (2.4%) 5) Bladder ( 3.3%) 10) Kidney (1.8%)

For Women 1) Stomach (16.2%) 6) Lung (6.7%) 2) Breast (14.7%) 7) Liver (6.3%) 3) Uterine Cervix (11.6%) 8) Ovary (4.2%) 4) Colon (10.2%) 9) Hematopoietic (2.9%) 5) Thyroid ( 6.8%) 10) Pancreas (2.0%)

Definition Neoplasm = new growth Tumor : swelling caused by inflammation : equated with neoplasm Oncology (Greek oncos = tumor) Cancer : common term for all malignant tumors (Latin for crab = cancer) Neoplasm = abnormal mass of tissue 1) exceed growth and uncoordinated with that of normal tissue 2) persists after cessation of stimuli 3) autonomous, purposeless, preys on host

Nomenclature (I) Two basic components : Proliferating neoplastic cells (parenchyma) and supportive stroma (medullary/scirrhous) Benign tumors - oma to cell of origin (mesenchymal tumors) - oma to cell of origin, microscopic architecture, macroscopic patterns (epithelial tumors) Malignant tumors - sarcoma (Greek, sar = fleshy) (mesenchymal tumors) - carcinoma (epithelial tumors) Mixed tumor - divergent differentiation of a single line of parenchymal cells - epithelial & myoepithelial cell (pleomorphic adenoma) Teratoma - more than one germ layer

Nomenclature of Tumors Tissue of Origin Benign Malignant Composed of One Parenchymal Cell Type Mesenchymal tumors Connective tissue and derivatives Fibroma Fibrosarcoma Lipoma Liposarcoma Chondroma Chondrosarcoma Endothelial and related tissue Blood vessels Hemangioma Angiosarcoma Lymph vessels Lymphangioma Lymphangiosarcoma Synovium Synovial sarcoma Mesothelium Mesothelioma Brain coverings Meningioma Invasive meningioma Blood cells and related cells Hematopoietic cells Leukemia Lymphoid tissue Malignant lymphoma Muscle Smooth Leiomyoma Leiomyosarcoma Striated Rhabdomyoma Rhabdomyosarcoma Epithelial tumors Stratified squamous Squamous cell papilloma Squamous cell or epidermoid carcinoma Basal cells of skin or adnexa Basal cell carcinoma Epithelial lining Glands or ducts Adenoma Adenocarcinoma Papilloma Papillary carcinoma Cystadenoma Cystadenocarcinoma

Nomenclature of Tumors Tissue of Origin Benign Malignant Composed of One Parenchymal Cell Type Respiratory passages Bronchogenic ca Bronchial adenoma (carcinoid) Neuroectoderm Nevus Malignant melanoma Renal epithelium Renal tubular adenoma Renal cell carcinoma Liver cells Liver cell adenoma Hepatocellular ca Urinary tract epithelium (transitional) Transitional cell papilloma Transitional cell ca Placental epithelium (trophoblast) Hydatidiform mole Choriocarcinoma Testicular epithelium (germ cells) Seminoma Embryonal carcinoma More Than One Neoplastic Cell Type-Mixed Tumors, Usually Derived From One Germ Layer Salivary glands Pleomorphic adenoma Malig mixed tumor of (mixed tumor of salivary origin) salivary gland Breast Fibroadenoma Malignant cystosarcoma phyllodes Renal anlage Wilms tumor More Than One Neoplastic Cell Type Derived From More Than One Germ Layer-Teratogenous Totipotential cells in gonads Mature teratoma, dermoid cyst Immature teratoma, or in embryonic rests teratocarcinoma

Nomenclature (II) Choristoma - ectopic rest of normal tissue Hamartoma - produce a mass of disorganized but mature specialized cells or tissue indigenous to particular site Differentiation - parenchymal cells resemble comparable normal cells, both morphologically and functionally Anaplasia - lack of differentiation, dedifferentiation - hallmark of malignant transformation - morphologic and functional change * Metaplasia * Dysplasia - loss of polarity, size & shape irregularity * Tumor of borderline malignancy, low grade malignancy, uncertain malignant potential

Characteristics of Benign & Malignant neoplasms 1. Differentiation and Anaplasia 2. Rate of growth 3. Growth patterns 4. Metastasis a) seeding of body cavities and surfaces b) lymphatic spread c) hematogenous spread

Benign vs Malignant Well diff: structure typical of tissue of origin slow growth, mitoses rare and normal expansile and encapsulated no metastasis Lack of diff with anaplasia: structure atypical rapid growth, mitoses numerous and abnormal infiltrative and no capsule metastases

An Approach to the Morphologic Diagnosis of Cancer

Morphologic DX of Cancer Lesions Infectious Mesenchymal Non-neoplastic Epithelial Neoplastic Non-Infectious Benign Malignant (carcinoma) (sarcoma)

Neoplastic vs Non-neoplastic

Neoplastic vs Non-neoplastic

Epithelial vs Mesenchymal oval, round or polygonal cell nests desmoplastic stroma vessels in stroma spindle diffuse no desmoplastic stroma vessels between tumor cells

Epithelial vs Mesenchymal

Epithelial vs Mesenchymal oval, round or polygonal cell nests desmoplastic stroma vessels in stroma spindle diffuse no desmoplastic stroma vessels between tumor cells

Epithelial vs Mesenchymal

Epithelial vs Mesenchymal oval, round or polygonal cell nests desmoplastic stroma vessels in stroma spindle diffuse no desmoplastic stroma vessels between tumor cells

Epithelial vs Mesenchymal

Epithelial vs Mesenchymal oval, round or polygonal cell nests desmoplastic stroma vessels in stroma spindle diffuse no desmoplastic stroma vessels between tumor cells

Epithelial vs Mesenchymal

Epithelial vs Mesenchymal oval, round or polygonal cell nests desmoplastic stroma vessels in stroma spindle diffuse no desmoplastic stroma vessels between tumor cells

Epithelial vs Mesenchymal

e.g., sarcomatoid ca, sarcoma with epithelioid cells, lymphoma, melanoma, NE tumors, small round cell tumors

Immunostain, EM and molecular analysis

Benign vs Malignant Well diff: structure typical of tissue of origin slow growth, mitoses rare and normal expansile and encapsulated no metastasis Lack of diff with anaplasia: structure atypical rapid growth, mitoses numerous and abnormal infiltrative and no capsule metastasis

Malignant Tumors high cellularity necrosis nuclear features enlarged nuclear size (N/C ratio) pleomorphism prominent nucleoli hyperchromatism increased mitoses (atypical mitoses)

Malignant Tumor

Malignant Tumor

Malignant Tumor

Classification of Tumors cellular origin microscopic architectures macroscopic (gross) architectures differentiation (H & E stain) electron microscopic findings immunohistochemistry molecular pathology

Prognostic Factors Category I (well supported): stage, grade Category II (extensively studied but not well established): DNA ploidy, nuclear proliferation, angiogenesis, apoptosis, tumor suppressor gene Category III (currently studying): other oncogenes, cytogenetic analysis, growth factors, detection of circulating tumor cells in blood

TNM Classification T (tumor), N (node) & M (metastasis) Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1-T4 Increasing size and/or local extent (depth of invasion) of tumor

TNM Classification Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1-N3 Increasing involvement of regional lymph node * Direct extension of tumor into a lymph node classified as a lymph node metastasis ** Metastasis in other than regional lymph nodes classified as a distant metastasis *** Tumor nodule up to 3mm in greatest extent is classified in T category. If tumor nodule is greater than 3mm without evidence of residual lymph node tissue, classified as a lymph node metastasis Distant metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis

Stage Grouping (Lung Ca) Stage 0 Tis N0 M0 Stage IA T1 N0 M0 Stage IB T2 N0 M0 Stage IIA T1 N1 M0 Stage IIB T2 (T3) N1 (N0) M0 Stage IIIA T1-T3 N1, N2 M0 Stage IIIB Any T N3 M0 T4 Any N M0 Stage IV Any T Any N M1

Tumor Grade malignant tumors (Arabic no. 1,2,-- ) histologic grade (overall proportional) original Broders’ grading (4 tier) modified Broders' grading (3 tier) high and low grade (2 tier) nuclear grade (worst areas) Black NG for breast ca. Fuhrman’s NG for renal cell ca.

Information for Pathologists demographic data (age, sex, DOB---) name of specimens type of procedures date specimen obtained Submitting physicians symptoms, signs and duration abnormal lab findings image findings preop- and postop clinical diagnosis

Information for Clinicians diagnosis (benign, malignant, uncertain malignant potential): in malignant tumor--grade tumor size/depth of invasion margins; structure involvement vascular invasion nodal status treatment response other abnormalities

Summaries Definition, nomenclatures Neoplastic vs non-neoplastic, epithelial vs mesenchymal, benign vs malignant Type of tumors: architectural patterns, differentiation of cells H&E staining, EM, immunohistochemistry and molecular pathology Prognostic factors: stage and grade

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