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(Neoplasia)

.. , .., .. ()

Non-neoplastic proliferation

Versus

Neoplastic proliferaton.

Cellular Proliferation and Growth ( )

Enlargement of Tissue and Organ

Non-neoplastic proliferation Neoplastic proliferation

Non-neoplastic proliferation

Cellular adaptation

(Stimulus)

(Stimulus)

Pathological process Physiological change

Hormonal change

Exercise

Non-neoplastic proliferation Cellular Adaptation

Hypertrophy.

Hyperplasia.

Metaplasia.

Hamartomas and Choristomas

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Hamartomas

(Developmental abnormality) (Neoplasia)

Chondroid hamartoma of Lung

Picture pathhsw5m54.ucsf.edu

Chondroid hamartoma of Lung

Picture pathhsw5m54.ucsf.edu

Choristomas

(Developmental abnormality)

Preneoplastic process

Dysplasia

Adaptation

Neoplasia

Dysplasia

(Cytological feature of malignancy) Premalignancy

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Mild cervical dysplasia with HPV infection

Severe cervical dysplasia with HPV infection

Neoplastic proliferation

Tumor, Cancer and Neoplasm.

Benign neoplasm.

Malignant neoplasm.

Neoplastic Proliferation

Tumor, Cancer and Neoplasm Tumor

(Tissue Swelling)

Neoplasia

Tumor, Cancer and Neoplasm Cancer

Cancer Crab

Benign NeoplasmTumor (Well differentiation)

Benign tumor Salivary gland

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Malignant NeoplasmTumor Cancer Invasion

Lung carcinoma

Benign neoplasm versus

Malignant neoplasm

(Characteristic of Benign and Malignant neoplasms)

Differentiation

Anaplasia

Rate of growth

Local invasion

Metastasis

Differentiation Differentiation

(Function)

Well differentiation -

Poorly differentiation -

Moderately differentiation - 2

Well differentiated neoplasm

Leiomyoma

Adenoma

(Benign neoplasm)

Leiomyomas

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(Malignant neoplasm)

Well differentiation Poorly differentiation Lack of differentiation, Anaplasia

Anaplasia Lack of differentiation Anaplasia

Pleomorphism DNA

Nuclear hyperchromatism

Cytoplasm (Nuclear-to-Cytoplasmic ratio) 1:1 1:4 1:6

Malignant melanoma

Mitoses (Higher proliferative activity) Mitoses Mitoses Mitoses ( Atypical, bizarre mitotic figures) tripolar, quadripolar,

Abnormal mitosis

( Rate of Growth )

Poor differentiation

Leiomyoma

( Inadequate blood supply )

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( Local Invasion )

( Local Invasion )

Benign tumors Fibrous capsules Connective tissue Benign tumors Fibrous capsules Hemangioma

Leiomyomas

Hemangioma

Cancers Cancers Crabs Cancers Fibrous capsules Cancers ( Vascular invasion ) ( Neural invasion )

Breast carcinoma (Invasive ductal carcinoma)

Metastasis Cancers

3 Body cavities

( Ovary ) Peritoneal cavity Pseudomyxoma peritonei.

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( Lymphatic Spread ) Cancers Upper Outer quadrant Inner quadrant Internal mammary arteries

Lymphatic Spread

( Hematologic Spread ) Mesenchymal cells Sarcomas Glandular epithelium Carcinomas Pulmonary arteriovenous shunts Tumor emboli

; ( Benign Tumors ) ( Malignant Tumors or Cancer )

( Cell or Tissue of Origin)

Benign Tumors

oma Mesenchym ( Epithelium )

Mesenchyme

Fibroma ( Fibroblastic

cells or tissue )

Lipoma ( Fatty or Adipose cells or tissue)

Leiomyoma ( Smooth muscle )

Rhabdomyoma ( Striated muscle )

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Mesenchyme

Chondroma

( Chondroblasts or Cartilage )

Osteoma ( Osteoblasts or Bone )

Hemangioma or Angioma (Blood vessels)

Lymphangioma (Lymphatic vessels)

( Epithelium )

Adenoma ( Gland or Tubule )

( Epithelium )

Papilloma (Finger-like or warty projections from epithelial surfaces)

Cystadenoma (Cystic mass) Mucinous cystadenoma Papillary cystadenoma Mucinous cystadenoma

Malignant Tumors or Cancer

Mesenchym sarcoma

( Epithelium ) carcinoma

Mesenchym

Fibrosarcoma ( Fibroblastic cells or tissue )

Liposarcoma ( Fatty or Adipose cells or tissue)

Leiomyosarcoma ( Smooth muscle )

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Mesenchym

Rhabdomyosarcoma ( Striated muscle )

Chondrosarcoma ( Chondroblasts or Cartilage )

Osteosarcoma ( Osteoblasts or Bone )

Angiosarcoma (Blood vessels)

( Epithelium )

Ectoderm Squamous cell carcinoma Squamous epithelium Squamous cell.

Mesoderm Renal cell carcinoma Renal tubule

Endoderm Adenocarcinoma

Adenocarcinoma

1 1 1 2

Mixed tumor Pleomorphic adenoma

2 Myxoid stroma Epithelial sheets glands Myoepithelial cells

Teratoma Totopotential cells or Germ

cells Ectoderm, Mesoderm and Endoderm Ectoderm, Mesoderm and Endoderm Dermoid cyst

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Mature cystic teratomaor

Dermoid cyst

Melanoma Melanocytes Carcinoma of melanocytes Melanocarcinoma

Seminoma Germ cell

Lymphoma Lymphocyte

Melanoma

Melanocytes

(Cancer incidence)

2

(National incidence)

(Mortality rate)

6

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(Geographic and Environmental Factors)

(Age)

(Hereditary)

(Preneoplastic lesions)

(Geographic and Environmental Factors)

6 7

Melanoma 6

(Geographic and Environmental Factors)

(Age)

55 (Leukemia)

Osteosarcoma 2 10-20 60

(Hereditary)

3 Inherited Cancer Syndromes

Familial Cancers

Autosomal Recessive Syndromes of Defective DNA Repair.

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Inherited Cancer Syndromes

Autosomal dominant pattern 40% Retinoblastoma

10,000

Familial adenomatous polyposis (FAP) 100% 50

Familial Cancers

(Multifactors) BRCA 1 BRCA 2

Autosomal Recessive Syndromes of Defective DNA Repair

Autosomal recessive DNA (DNA repair) Xeroderma pigmentosum

(Preneoplastic lesions)

(Cancerous transformation)

(Regeneration)

(Hyperplastic proliferation) (Dysplastic proliferation)

Endometrial hyperplasia Endometrial carcinoma

Cervical dysplasia Cervical carcinoma

Squamous metaplasia and dysplasia Bronchogenic carcinoma

Molecular basis of cancer Oncogenes

Protooncogenes

OncogenesProtooncogenes

:

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3 Chemical carcinogens Radiant energy Oncogenic microbes

Viral carcinogenesis

(Chemical Carcinogens)

(The initiation-promotion sequence)

( Initiation) Promotion

(Promotion) Promoter

Initiation Promotion

Initiator 2 Direct-acting

compound

Indirect-acting compound (Procarcinogen)

(Detoxification)

(Early menarche) (Late menopause) (A later age of first pregnancy)

Polycyclic aromatic hydrocarbons benzopyrene 3-methylcholanthrene dibenzanthracene

Aflatoxin Aflatoxin B1 Aspergillus flavus

Aromatic Amines Azo Dyes

Nitrosamines

Asbestos Bronchogenic carcinoma, Mesothelioma Vinyl chloride Angiosarcoma Arsenic

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( Radiant energy) (Ultraviolet Radiation)

Basal cell carcinoma, Squamous cell carcinoma Melanoma Melanoma

(Ionizing radiation) Leukemia

(Oncogenic microbes)

Viral carcinogenesis Helicobacter pylori Lymphoma DNA DNA virus RNA RNA virus

DNA virus

Human papilloma virus (HPV) 70 HPV type 1, 2, 4 7 Squamous papilloma Wart HPV type 16, 18, 31, 33, 35 51 Squamous cell carcinoma HPV type 6 11 Squamous dysplasia

DNA virus

Epstein-Barr virus (EBV) B Infectious mononucleosis Burkitt lymphoma B ( ) Nasopharynx Squamous cell carcinoma

Hepatitis B virus (HBV) Hepatocellular carcinoma

RNA virus

Human T-Cell Leukemia Viruses I (HTLV I) T T T cell leukemia lymphoma

CLINICAL FEATURES OF TUMORS

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Effects of Tumor on Host

Pituitary adenoma

Intussusception

Beta-cell adenoma Beta ()

Melena Hematemesis

(Hematuria)

Hepatic capsule

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CANCER CACHEXIA

Cytokines

PARANEOPLASTIC SYNDROMES

( ) 10%

Paraneoplastic syndromes (Ectopic hormone production)

Cushing syndrome Adrenocorticotropic hormone (ACTH) ACTH 50% Cushing syndrome Small cell carcinoma

(Hypercalcemia) Calcium humeral substances Parathyroid hormone-related protein Multiple myeloma Paraneoplastic syndrome Paraneoplastic syndromes Squamous cell carcinoma

Neuromyopathic paraneoplastic syndromes A myasthenic syndrome Myasthenia gravis

Acanthosis nigricans - (Gray-black patches of verrucous hyperkeratosis)

Hypertrophic osteoarthropathy Distal ends of long bones, Metatarsals, Metacarpals Proximal phalanges Periosteum Clubbing of Fingers

Migratory thrombophlebitis (Trousseau syndrome) Thrombi

Disseminated intravascular coagulation Acute promyelocytic leukemia

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Grading and Staging of TumorsGrade Stage

Grading

Differentiation Mitoses 4 Grade Grade Differentiation (Function) Well differentiation Mitoses Grade I Mitoses Grade IV Grading Staging

Staging

3 (T)

(N)

(M)

The Union International Centre Cancer (UICC) 3

4 5 (T0-T3 or 4) T0

3-4 (N0-N2 or 3) N0

3 (M0-M2) M0

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Laboratory Diagnosis of Cancer

Histologic and Cytologic Methods

Molecular Diagnosis

Flow Cytometry DNA

Tumor Markers.

Tumor Markers.

Tumor markers cell surface antigens cytoplasmic proteins enzymes hormones.

hormones Human chorionic gonadotropin Trophoblastic tumors

nonseminomatous testicular tumors

Calcitonin Medullary carcinoma of thyroid

Catecholamine and metabolites Pheochromocytoma

cell surface antigens

alpha-fetoprotein Liver cell cancer nonseminomatous germ cell tumors of testis

Carcinoembryonic antigen Carcinomas of the colon, pancreas, lung, stomach, and breast

cytoplasmic proteins

Immunoglobulins Multiple myeloma

Prostate-specific antigen Prostate cancer CA-125 Ovarian cancer

CA-19-9 Colon cancer, pancreatic cancer

CA-15-3 Breast cancer

enzymes

Prostatic acid phosphatase Prostate cancer

Neuron-specific enolase Small cell cancer of lung Neuroblastoma