Definitions and nomenclature

1. Tumor2. Neoplasia 3. Oncology4. cancer

a) Study of tumorsb) Swellingc) Malignant d) New growth

Benign epithelial tumors

1. Adenoma 2. Papilloma 3. Polyp4. Cystadenoma

a) Begin tumor with Finger-like projectionsb) Adenoma with cyst formationc) Raised mucosa d) Begin tumor of Glandular grigin

coloncolon

Cell of origin Benign tumor

1. Bone2. Skeletal musle3. Fibroblast4. Cartilage5. Melanocyte6. Smooth musle7. Blood vessel8. Gland 9. Adipocyte10. Squamous cellwith finger like

projection

a) Papilloma b) Adenomac) Lipomad) Fibromae) Chondromaf) Leiomyomag) Rhabdmyoma h) hemangiomai) osteoma j) melanocytic nevus

1. Lipoma2. Fibrosarcoma3. Chondroma4. Mesothelioma 5. Leiomyosarcoma6. lymphoma7. Rhabdmyoma8. Melanoma 9. melanocytic nevus10. Hepatoma

a) Bengin b) Malignant

1. Contain elements of all three germ layers

2. A mass composed of cells native to the organ

3. Contain brain, respiratory and intestinal mucosa, cartilage, bone, skin, teeth, or hair

4. A mass composed of normal cells in a wrong location

• Hamartoma• Choristoma• Teratoma

–

Leiomyoma

Malignant tumors.

Glandular tissuesSquamous cells

Mesenchymal (connective tissue) tissues.

Nomenclature

Sarcoma Carcinoma

Malignant tumors arising in mesenchymal tissues

Fibroblasts Skeletal muscle

Smooth muscleAdipose tissue Bone blood vessels Cartilage

Sarcoma

liposarcomachondrosarcoma rhabdomyosarcoma

leiomyosarcoma fibrosarcoma angiosarcomas

osteosarcoma

Neoplasia nomenclature - …“(oma’s” any growth )

examples : benign - malignant

Malignant tumor

Benign tumor

Squamous (SC) epithelium

Glandular epithelium

Fat

Bone

Muscle

Neoplasia nomenclature - …“(oma’s” any growth )

examples : benign - malignant

Malignant tumor

Benign tumor

SC carcinoma PapillomaSquamous (SC) epithelium

Adenocarcinoma Adenoma Glandular epithelium

Liposarcoma Lipoma Fat

Osteosarcoma Osteoma Bone

Rhabdomyosarcoma

Rhabdomyoma Muscle

Glioma:

CNS glial tissue (astrocytoma, glioblastoma)

Neoplasia nomenclature- historic eponyms – “first described by…”

Hodgkin’s disease

Burkitt lymphoma

Ewing sarcoma

Dysplasia

• premalignant condition

• Increased N/C ratio• Irregular nuclear

membrane• Hyperchromasia

Nuclear abnormality

Dysplasia

• Differences between dysplasia and cancer. lack of invasiveness. Reversibility

Carcinoma in situ - cervix

BM

Ly

Mitoses

Benign and Malignant tumor

Malignant tumors

Pleomorphism, Increased nuclear cytoplasmic ratioHyperchromatism Giant nucleoli

Cells

Rate of growth

Mitotic figures

Mode of growth

Invasion

Metastasis

Spread of tumors to places non contiguous with primary lesion

Grading and staging of cancer

• Staging of tumor

• Grading of tumor

Neoplasia biology: features of malignancy – clinical biology

•Risk factors •Prognostic factors•Influence treatment modalities

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

Definition

I Well differentiated

II Moderately differentiated

III Poorly differentiated

IV Nearly anaplastic

Epidemiology & aetiology

CANCER INCIDENCE

• The number of new cases of specific cancer registered over a specific period in a defined population.

MORTALITY

• The number of death from a given form of cancer during a specified period of time.

AGE

• Most carcinoma occur in the later year of life (55-74 years).

• Children are affected by certain neoplasms, e.g.:

Leukemias and neoplasm of CNSRetinoblastomaNeuroblastomaNephroblastomaRhabdomyosarcoma

Aetiology of cancer CARCINOGENS

Major carcinogens

• Direct-Acting Agents • Require no metabolic conversion to become

carcinogenic e.g., alkylating agents (Anticancer drugs )

• Indirect-Acting Agents • Chemicals that require metabolic conversion

to an ultimate carcinogen before they become active.

Chemicals carcinogens

• Found everywhere in our environment.• Occupational, e.g:

* Beryllium * arsenic component* benzene* nickel

يجعلها مما النحاس سبائك إلنتاج البيريليوم يستخدمالحرارية موصليتها بسبب واسع بشكل تستخدم

العالية .والكهربائيةزرنيخ

عام المواد 1920قبل من الشحوم إلزالة صناعي كمذيب يستخدم البنزين كان) كوقود ) المستخدم البنزين السائل للوقود تضاف مادة

رصاص إيثيل بالتيترا الحلقي البنزين استبدال ,تم

السبائك لـ المكونة العناصر من عنصرالنيكلللفوالذ أساسي مكون أنه إلى باإلضافة المعدنية

للصدأ المقاوم

Chemicals carcinogens

Geographic

• Environmental factors include:* Asbestos

وتسقيف البناء مجال في األسبست يستخدموأنابيب والخارجية الداخلية والعوازل المنازل

والتهوية واألدخنة المياه ،صرف

mesothelioma

Smoking

RADIATION CARCINOGENESIS

• Radiation, whatever its source, UV rays of sunlight, x-rays, nuclear fission, radionuclides is an established carcinogen.

• Miners of radioactive elements have suffered a ten-fold increased incidence of lung cancers.

Radiation

• Follow-up of survivors of the atomic bombs dropped in Hiroshima and Nagasaki developed:

Leukemia Thyroid, breast, colon and pulmonary carcinomas.

• Ionizing radiation causes chromosome breakage, translocations, and less frequently point mutations.

Radiation (contd)

• The oncogenic effect of UV. UV radiation derived from the sun can cause

skin cancers (melanomas, squamous cell carcinomas and basal cell carcinomas).

• UV radiation damage DNA by forming pyrimidine dimers. This type of DNA damage is repaired by a complex set of proteins that affect nucleotide excision repair.

Viral and Microbial Oncogenesis

RNA Viruses

DNA Viruses

Oncogenic viruses

• Hepatitis C Virus• Human papilloma virus • Epstein-Barr Virus• Human T-cell leukemia virus-1 (HTLV-1) • Hepatitis B Virus• Human herpes virur 8

Nasopharyngeal carcinoma.Benign warts Burkitt lymphomas, Hepatocellular carcinoma Uterine cervical cancerT-cell leukemiaKaposi sarcoma

Bacteria

• Gastric adenocarcinomas and gastric lymphomas.

Helicobacter pylori

Molecular basis of cancer“Pathogenesis of cancer”

“Carcinogenesis”

NEOPLASIA

Primary or environment (75%)

Alterations to the human genomeFirst hit Second hit

Normal genome

Cancer genomeTIME

Carcinogenesis is a multistep event with somatic mutations

• Four classes of normal regulatory genes are the principal targets of genetic damage

1. Growth-promoting proto-oncogenes, 2. Growth-inhibiting tumor suppressor genes, 3. Genes that regulate apoptosis4. Genes involved in DNA repair.

a) Oncogenes b) Tumor suppressor genes, c) Genes that regulate apoptosisd) Genes involved in DNA repair.

1. Maintain the integrity of the genome

2. Inhibit growth3. bcl-2 4. Stimulate growth

a) oncogenes, b) tumor suppressor genes, c) Genes that regulate apoptosisd) Genes involved in DNA repair.e) Neuroblastomas f) the most common

transformed gene in human cancer

1. RAS gene2. p53,3. MYC gene4. bcl-25. Retinoblastoma gene 6. ABL gene7. Xeroderma pigmentosum

A 45-year-old man from southern China is diagnosed with a nasopharyngeal tumor. Histologically, this neoplasm is composed of anaplastic cells immunoreactive for cytokeratin admixed with abundant lymphocytes. Which of the following factors is most likely implicated in the pathogenesis of this neoplasm?A. Cigarette smokingB. Epstein-Barr virus infectionC. Ionizing radiationD. Overexpression of the bcl-2 gene