the cessation of stimuli that caused it.

It is thus characterized by being progressive, purposeless, regardless of the surrounding tissue, not related to the body needs, being parasitic and autonomous. Oncology: Oncos: ( Greek ) = tumor. It is the science that deals with the study of both benign and malignant tumors.

INT RO DU CTI ON TO NE OP LA SIA

Neopla sia means ' a new growth '. It is an abnorm al mass of tissue, the growth of which exceed s and is uncoor dinated with that of the normal tissue and persists even after

CLASSIFICATION OF TUMORS
Tumors are classified according to; 1. Histogenesis (tissue of origin ) 2. Biologic behavior ( clinical course )

Tissue of origin 1. Composed of one Parenchymal cell type a. Epithelial 1. Surface epithelial 2. Glandular epithelium 3. Neuroectodermal 4. Placental (Trophoblast) 5. Testicular germ cells b. Mesenchymal tumors

Benign

malignant

Papilloma ( Squamous, transitional, basal) Adenoma Nevus H. mole

Carcinoma Adenocarcinoma Melanoma Choriocarcinoma Seminoma

1. Endothelium-related tissue a. Vessels b. Synovium Lymphangioma Hemangioma Sarcoma Sarcoma Sarcoma

c. Mesothelium d. Meninges 2. Connective tissue 3. Muscles a. smooth muscles b. Striated muscles More than one cell type ( Mixed tumors) 1. Salivary 2. Breast

Meningioma Fibroma, chondroma

Sarcoma Invasive meningioma Sarcoma

Leiomyoma Rhabdomyoma

Sarcoma Sarcoma

PLeomorphic adenoma Fibroadenoma

Malignant mixed tumor Malignant cystosarcoma Phyllodes

3. Renal

Wilm's tumor (nephroBlastoma)

, More than two germ cell layers ( teratogenous) ( 1. Teratoma Mature cystic teratoma

Immature solid teratoma

(ovary)

(Ovary)

TUMOR-LIKE CONDITIONS
'1. Hamartoma: It is a mixture of tissue that is normally found at a particular site. It is a developmental abnormality that is present and often visible at birth. Its enlargement continues until physiologic growth ceases. The condition is essentially benign. 2. Choristoma ( ectopic rest-ectopia ): Ectopic rest of normal tissue that is seen outside its normal anatomic location as seeing pancreatic tissue in the wall of the stomach which presents clinically as a gastric nodule. The condition is essentially benign. In summary; surface epithelial tumors are called papillomas while their malignant counterparts are called carcinomas. Benign tumors of glandular origin are called adenomas while their malignant counterparts are called adenocarcinomas. In benign mesenchymal tumors, we add the suffix" oma " at the end of the word as a tumor of fibrous origin is called fibroma while its malignant counterpart is called fibrosarcoma and add instead sarcoma). (remove the 'oma' suffix

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CHARACTERISTICS OF TUMORS
1. Macroscopic (gross ) appearances: Benign tumors: a. Generally are spherical or ovoid. b. Encapsulated and well circumscribed. c. Firm and uniform. d. Secondary changes can occur as hemorrhage, ulceration and infarction. Malignant tumors: a. Irregular in shape. b. Poorly circumscribed. c. Fixed to underlying and/or overlying tissues. d. Secondary changes do occur, but more pronounced. e. Sarcomas have typically flesh-like appearance while carcinomas are usually firm. 2. Differentiation : Histological term that refers to the extent to which paranchymal tumor cells resemble the normal cells of origin, both structurally and functionally. Benign tumors: e. Mimic the structure of their parent tissue of origin. f. Resemble the cells of their tissue of origin.

g. Shows evidence of normal function comparable to the tissue of origin. h. Have relatively infrequent mitotic figures.

Lack of differentiation anaplasia is marked by morphologic and functional changes. Anaplasia means " to form backwards " which refers to reversion from high level of differentiation to a low level. Malignant tumors that are undifferentiated are called ' anaplastic '. 3. Histologic criteria of malignant cells: a. Pleomorphism: Variation in size and shape of the cell.

Role of non-neoplastic elements within the tumor as connective tissue, mucoid

ctive ti

idtory reaction: It is unsurprisingly to se" '^i^^^^^-^ ^-"" ' -^-^ ^ ..-.^ +u~ tumor mass, in the absence of ulceration. These cells are lymphocytes, plasma cells, macrophages and even granulomatous reactior cellular elements may play a role in the immune response against tumors and this made some of these tumors to have a better prognosis. This is the case with

carcinoma cf the breast, testicular seminoma and some cases of malignant melanoma. It is proposed that here cell mediated immunity plays the key role. 7. Tumor stroma: Tumor stroma contains blood vessels and connective tissue, which both give support and nutrition. In order to provide nutrition for the gujwmg ma ui uue, new blood vessels are formed from pre-existing ones. The process is called ' angiogenesis '. This is mediated through the secretion of TAF (tumor angiogenesis factor) from the tumor cells. Usually collagen stroma in the tumor tissue is scanty and that's why lymphomas and sarcomas are fleshy. If the tumor is almost entirely composed of parenchyma! cells, it is called " medullary ". If excessive fibrous tissue is seen within a tumor, it is called " schirrous " and the fibrous tissue formation is called " desmoplasia ". 8. Local invasion: Nearly all benign tumors grow by expansion, with no invasion, infiltration or metastasis. Growth of malignant tumorsis associated with infiltration, invasion and destruction of the local surrounding tissues and for this reason malignant tumors are poorly demarcated from the surrounding tissues while benign ones are well encapsulated and thus well demarcated. Invasion, in addition to metastasis, is the most reliable feature in distinguishing malignant from benign growths. Mechanisms of invasion: a. Cancer cells have the ability to secrete lytic enzymes as collagenases. b. Cancer cells are less adhesive than normal cells (loss of contact inhibition )due to loss of cell adhesion molecules. c. Spread to surrounding tissue with subsequent replication. d. Increased ameboid movements of the cancer cells that fascilitates penetration and spread. e. Role of chemotactic factors and the complement 9. Distant spread ( metastasis ): With few exceptions, all malignant tumors metastasize. These exceptions include gliomas and basal cell carcinoma of the skin. The more

snaplastic the tumor is, the more "5;;ciy growing and the larger the primary tumor the greater possibility to meiastasize. Benign tjrr.ors never metastasize. Pathways of metastasis: a. Lymphatic spread : It is the most no-r-ocn mode of spread of carcinomas, but rarely of sarcomas. Patterns of lymph node involvement follows the natural routes of drainage. Groups of cells form emboli in the lymphatic stream to the nearest lymph node. Another mode of spread to the node is through the formation of continuous solid columns of cancer cells along lymphatic wail. Tumor ceils invade the affaicnt lymphatics to appear tirst in the subcapsular sinus, then invade the medulla and then pass through the efferent lymphatics to other lymph nodes. Cancer cells may result in occlusion cf afferent and efferent channels and this leads to diversion of lymph flow. This has two effects; 1. Tumor cells may pass to other nodes further from the nearest lymph node and primary tumor. This is called " skip metastasis ". 2. As a result of obstruction of efferent lymphatics, the lymph flow in the efferent lymphatics of non-involved adjacent lymph nodes may be reversed and then tumor cells will gain access to the medulla and then to the subcapsular sinus. Always remember that lymph node enlargement in the proximity of a primary tumor does not necessarily mean lymph node metastasis. Drainage of tumor cells debris or tumor antigens to the lymph node provokes an immune response leading to reactive changes in the node. b. Hematogenous spread: Both carcinomas and sarcomas spread by blood stream. Malignant cells enter blood by either; Direct invasion of venules By lymphatic embolism through the thoracic duct into subclavian vein Direct invasion of arteries and arterioles is very rare, because of thicker walls and abundance of muscular and elastic fibers than venules. Retrograde venous spread: As with lymphatics, growth of tumor within a vein may cause reversal of blood flow. This reversal may happen when: 1. When there is complete obstruction. 2. When veins form rich plexues and are defective in valves ( pelvis and around vertebrae) Changes in the intra-abdominal and intrathoracic pressures easily induce changes in blood flow and for this reason secondary deposits are relatively common in vertebral bodies. Constipation is an example when there is increase in the intra-abdominal pressure which helps in the above process.

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c. Transcelomic spread ( spread through body cavities ): There will be seeding of the surfaces of peritoneal, pleural, pericardial and subarachnoid spaces. d. Spread along epithelial-lined surfaces: Intact epithelium and mucus coat are barriers against invasion. Exceptionally, the cells may spread along fallopian tubes from endometrial carcinoma to the ovary and vice versa e. Intra-epithelial spread: This may occur when cancer develops in a gland, as in ductal carcinoma of the breast. Cancer cells spread in the areolar skin ( paget's disease of the breast) f. Spread via CSF: Tumor cells spread from one area in the CNS to others through CSF. g. Implantation: It is of two types 1. Natural: as in opposing lips. 2. Artificial: As through surgeon's knife, needles and sutures.

GRADING AND STAGING OF CANCER

Grading: It is the study of histological degree of anaplasia. In other words, it is the study of the degree of differentiation of a malignant tumor. Grade levels are I-IV are often used. Grade I: Well differentiated. Grade II: Moderately differentiated. Grade III: Poorly differentiated. Grade IV: Undifferentiated ( anaplastic ). Grading of tumor is imperfect since parts of the same tumor display different degree of differentiation and the tumor grade may change as it grows and metastasizes.

Staging: It is the study of the clinical extent of the tumor in the body. This can be assessed by the following; 1. Clinical examination. 2. Lab. investigations. 3. Histologic study of the tumor tissue. 4. X-Ray, CT scan, MRI, Ultra sound Two important staging systems are used nowadays, TNM and AJC staging systems. TNIVI staging system: It was developed by the UICC ( union international control of cancer) T: Refers to tumor size. N: Refers to nodal involvement. M: Refers to metastasis.

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AJC ( American joint committee ): it includes 5 stages ( 0-IV ) taking in considetation the parameters of previous staging system.

ETIOLOGY OF CANCER
1. Heriditary predisposition: There is a high risk of cancer in some uncommon syndromes as; a. Familial adenomatous polyposis coii with autcscnic! dominant inheritance D. Xeroderma pigmentosa with autosomal recessive trait. In this disease entity, which belongs to chromosomal DNA instability syndrome, there is failure in the DNA repair mechanisms, leading to skin cancers. c. Retinoblastoma with autosomal dominant trait ( defect in Rb gene on chromosome 13 ) d. Neurofibromatosis: There is a risk of 1% incidence in developing sarcoma due to a defect of NF-1 gene on chromosome 17 2. Environmental and cultural factors: a. Cigarette smoking. b. Alcohol. c. Penile cancer is rare in Jews and Arabs. d. Dietary constituents as animal fat, low fiber content, canned food, vitamin-A deficiency, overweight et.... e. Industrial substances as arsenicals, asbestos, benzene and polyvinyl chloride monomers ( PVC). 3. Age: Cancer is most common in persons more than 55 years . However, certain malignancies are common in children under the age of 15 years as leukemia, lymphoma, Wilm's tumor, neuroblastoma and retinoblastoma 4. Sex: Cancer of the female breast is the commonest cancer in women while lung cancer is common in men. This is related to the presence of specific sex hormones as estrogen. 5. Acquired pre-neoplastic conditions. These include chronic atrophic gastritis, ulcerative colitis, leukoplakia of the oral cavity, vulva and penis, solar keratosis, Hashimoto's thyroiditis, endometrial hyperplasias and others.

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THEORIES OF OARGf
1. Genetic theory: It is the most popular. This deals with the concept of mutation. Evidence in support of this includes; a. Chemical and radiational factors. b. Heriditary disorders as xeroderma pigmentosa. c. Viral infection.

2. Epigenetic theory: Carcinogenic agents act on activator and suppressor genes. 3. Immune surveillance theory: There is no proven support. Examples include Aids and the development of Kaposi sarcoma , development of cancer in the elderly. 4. Monoclonal hypothesis: It means that a tumor arises from a single clone of transformed cells as in multiple myeloma and hemopoietic malignancies. 5. Multiple step theory of carcinogenesis: The development of cancer is a multistep process. Thus for cancer to be clinically evident, it has to pass through three stages. a. Stage of initiation. b. Stage of promotion. c. Stage of progression. STAGE OF INITIATION: If a normal cell is exposed to a carcinogenic agent (initiator), as viruses, radiational energy and chemicals, the DNA structure of the chromosomes will show important changes " mutation " but the cell looks histologically normal. The process of initiation is usually short (few days to few weeks ) and the change that takes place is irreversible and when the cell divides, it will carry the same defect to the daughter cells. STAGE OF PROMOTION: If a mutated , initiated cell is exposed to co-carcinogene ( promoter) then the stage of promotion starts. Examples of co-carcinogene are age, sex, race, geography, hormones, heredity, environmental factors and chronic irritation. All of the mentioned should act on the susceptible ( initiated ) cells for a long time in order to produce effect. The exposure to co-carcinogenes must be continuous, in regular optimum doses and at regular intervals. The stage of promotion is reversible. The changes seen during the promotion stage include hyperplasia, dysplasia and lastly carcinoma in situ (intraepitheiial neoplasia ). If the promoter is removed at the end of the promotion stage (intraepitheiial neoplasia ) the process continues with no regression. STAGE OF PROGRESSION: This stage starts when the tumor cells start to invade and become

clinically evident. The exact cause for this is well understood though some attribute this to

failure in the immune system.

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