Anaplasia : means loss of structural & functional differentiation of normal cells.

1. Anaplasia: means loss of structural & functional differentiation of normal cells. Characteristics of anaplastic cells: 1.Pleomorphism(variation in the size & shape of cells). 2. Large hyperchromatic nuclei. 3. Increase Nucleus/ Cytoplasm (N/C) ratio1:1 (1:4 or 1:6 in normal). 4. Anisonucleosis (variation in the size of nucleus) & poikilonucleosis (variation in the shape of nucleus). 5.Chromatin is coarse, large prominent nucleolus. Numerous, atypical mitosis. 6. Loss of normal orientation of cells (lose of gland formation).

2. According to degree of differentiation: three grade of differentiation of malignant tumors, • Well differentiated malignancy (like normal tissue). • Moderately differentiated malignancy. • Poor differentiated, undifferentiated, anaplastic malignancy. Important notes: Usually benign & well differentiated cancer have functional capacity e.g. like well differentiated malignancy of endocrine glands secrete hormones resemble the normal endocrine cells.

3. Dysplasia: It is non neoplastic growth disorder; mainly occur in epithelia (not stroma). It is a loss of uniformity of the individual cells & a loss in their architectural orientation. Characteristics of dysplastic cells: 1. Pleomophism. 2. Large, hyperchromatic cells. 3. Mitosis more than normal (mitosis not restricted to the basal layer, it involves the all layers). 4. Loss of normal maturation of cells e.g. loss of maturation of squamous epithelium. When dysplastic changes involve the entire thickness of the epithelium, they are called Carcinoma in Situ or preinvasive stage of cancer.

4. However; foci of carcinoma in situ can present adjacent to area of cancer. • Dysplasia does not necessarily progress to cancer, & dysplasia not involve full thickness may be reversible. II.Rate of growth: Most benign tumors grow slowly, & most of cancers grow faster & eventually spread locally & to distant sites (metastasis) & causing death. In some exception, some benign tumors grow more rapidly than some cancers, e.g. leiomyoma (uterine fibroid), which is benign smooth muscle tumor influence by estrogen & so increase in size during pregnancy . In malignant tumors, rate of growth is inversely directed to level of differentiation (well differentiated cancer is slowly growing while undifferentiated cancer are grow rapidly).

5. Some of malignant tumors undergo spontaneous regression, regress the whole primary cancers & leave only their metastasis e.g. Choriocarcinoma. • Rapidly growing malignant tumors usually have central area of necrosis (ischemic) because inadequate bloods supply to provide the rapid growth of cancer. III. Local invasion: Benign tumors are: 1. Localized at the site of origin, 2. Not invade the surrounding tissue. 3. Not metastasized. 4. Most of benign tumors have surrounding capsule (derived from the original normal tissue as a result of atrophy of parenchymal cells & by the pressure of benign tumors. e.g. leiomyoma of uterus.

6. Important not: Not all benign tumors are capsulated. Malignant tumors are: 1. Rapid progressive growth 2. Infiltration, invasion, & penetration of the surrounding,. 3. Malignant tumors not develop well defined Capsule, 4. Always metastasized Local invasion is the second most reliable feature (after metastasis) that distinguishes Malignant from benign tumors IV. Metastasis: It means development of secondary implants discontinuous with primary tumor, possibly in remote tissues. Metastasis is the most important characteristic of malignancy

7. Not all cancers have equal ability of development metastasis, e.g. Basal cell carcinoma of skin & most of CNS malignancies are highly locally invasive but rarely metastasis. • While osteosarcoma is usually metastasize to lung at the time of initial diagnosis. • In general, the more anaplastic & the larger the primary neoplasm, the more likely is metastatic spread, with some exception extremely small cancers have been known to metastasize. Pathways of Metastasis: 1. Seeding within body cavities: These occur when cancers invade the body cavities (pleura, peritoneum, pericardium, & meninges in CNS tumors), e.g. carcinoma of colon invade the peritoneal cavity, carcinoma of lung invade the pleura, & malignancy of ovary invade the peritoneum

8. 2. Lymphatic spread: This is characteristically seen in carcinomas, while sarcomas are more spread by vascular system. There are numerous interconnections between lymphatic & vascular systems, so all forms of cancer may spread through either or both systems. The pattern of involvement of lymph node depends principally on the site of the primary neoplasm & lymphatic pathways of this site e.g. lung carcinoma metastasize first to the regional bronchial lymph nodes, then to the hilar lymph nodes. In some cases, the cancer cells seem to traverse the lymphatic channels within the immediately proximate nodes to be trapped in subsequent lymph nodes, this is called Skip lesions.

9. It should be remembered, that lymph nodes enlargement with cancers, not always means cancerous nodal involvement, it may be due to necrotic debris of the cancer & tumor antigens, which may induce nodal enlargement in form of lymphadenitis, & sinus histiocytosis. 3. Hematogenous spread: is the most feared consequence of a cancer; it is the favored pathway for sarcomas. Arteries are penetrated less readily than veins; because of the wall thickness is more in arteries. The liver & lungs are the most frequently involved secondary sites in such hematogenous spread (all portal area drainage flows to the liver, & all caval blood flows to the lungs). Cancers arising near the vertebral column often embolize through the paravertebral venous plexus to set into vertebrae (e.g. carcinoma of thyroid & prostate).

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