number Done by Corrected by Doctor Maha Shomaf

Transcription

1 number 16 Done by Waseem Abo-Obeida Corrected by Zeina Assaf Doctor Maha Shomaf

2 MALIGNANT NEOPLASMS The four fundamental features by which benign and malignant tumors can be distinguished are: 1- differentiation and anaplasia 2- rate of growth 3- local invasion 4- Metastasis. Differentiation and Anaplasia The extent to which they resemble their normal tissues (the parenchymal cells that constitute the transformed elements of neoplasms morphologically and functionally. The stroma (fibrous tissue) does not aid in the separation of benign from malignant tumors, and the differentiation only depends on parenchymal cells of the tumor. The stroma only supports the tumor, and the amount of stromal connective tissue determines the consistency and hardness of a neoplasm, certain cancers induce a dense, abundant fibrous stroma this process is known as desmoplasia, making them hard, so-called scirrhous tumors. Benign neoplasms are composed of well differentiated cells that closely resemble their normal counterparts morphologically & functionally. The better the differentiation of the cell, the more completely it retains the functional capabilities found in its normal counterparts In well-differentiated benign tumors, mitoses are extremely scant in number and are of normal configuration. Benign tumors will be localized and have a prominent boundaries separating it from the normal tissue.

3 Lipoma (macroscopic) As the picture shows : the tumor is well localised, the boundaries are soft in consistency and the tumor is yellowish in color just as how other adipose tissues appear in our body.so we conclude that this tumor is benign.

4 Lipoma (microscopic) This lipoma particularly is seen in sub-mucosa. You can clearly notice the seperation between the lipoma and the normal tissue which is a sign of benign tumor (no infiltration). -Lipoma is one of the most benign tumors that can occur in any tissue. Mature adipose tissue (lipoma) Lipoma: Adipocytes with peripheral nuclei, which resemble normal adipose tissue, cells appear empty due to specimen preparations ;During preparation of H & E slides the fat is dissolved and the cell appears empty, with a very thin rim of cytoplasm and the nucleus along the edge.

5 Leiomyoma Multiple tumors with different sizes in the uterus which appear well demarcated and separated from the normal tissue. -Uterine leiomyomas are commonly refferd as uterine fibroids.

6 Leiomyoma smooth muscle bundles Spindle shaped cells with elongated, cigar shaped nuclei as in normal tissue. Even with these similarities with normal tissue microscopically, benign tumors appear as enlarged masses separated from the normal tissue grossly.

7 Malignant tumors: Malignant neoplasms are characterized by a wide range of parenchymal cell differentiation ranging from well differentiated to completely undifferentiated. Between the two extremes lie tumors loosely referred to as moderately differentiated. Benign neoplasms and even well differentiated cancers of endocrine glands frequently elaborate the hormones characteristic of their origin. Well-differentiated squamous cell carcinomas elaborate keratin Well-differentiated hepatocellular carcinomas elaborate bile. Well differentiated squamous cell carcinoma (keratin formation-arrow): well differentiated carcinomas are usually associated with keratin production and presence of intercellular bridges between adjacent cells.

8 Normal colonic mucosa (left) vs adenoma (right) The nuclei of the glandular cells in adenoma are darker with more haematoxylin staining due to increase in chromatin. Nuclei of the mucosa are located in different locations in the cell from basal layer to the top, which is different from normal cells where the nuclei should be located at the base of the cells near the basement membrane.

9 Moderately differentiated adenocarcinoma In adenocarcinoma the glands are disorganized and somehow overlapping. -Well differentiated tumor helps us to define the nature and origin of the tumor, in contrast with anaplastic tumor in which it is hard to define its origin, and whether it is carcinoma or sarcoma. -The more the differentiated tumor the more it will simulate the function or structure of normal tissue. Moderately differentiated Liposarcoma There is variation in the sizes of the nuclei and cells, often the nuclei are extremely hyperchromatic (darkly-stained) and large resulting in an increased nuclear-to-cytoplasmic ratio that may approach 1:1, Instead of the normal 1:4 or 1:6 ratio, these features are not seen in benign tumor which simulates normal adipose tissue.

10 Anaplasia: Malignant neoplasms that are composed of undifferentiated cells are said to be anaplastic. Lack of differentiation, or anaplasia, is considered a hallmark of malignancy. The term anaplasia literally means "to form backward." It implies dedifferentiation, or loss of the structural and functional differentiation of normal cells. At least some cancers arise from stem cells in tissues; in these tumors failure of differentiation, rather than dedifferentiation of specialized cells, accounts for undifferentiated tumors. Despite exceptions, the more rapidly growing and the more anaplastic a tumor, the less likely it is to have specialized functional activity. Anaplastic cells display:

11 1-marked pleomorphism (i.e., marked variation in size and shape). 2-Nuclear hyperchromatic (darkly stained) and large. 3-increased nuclear-to-cytoplasmic (N/C) ratio, it may approach 1: 1 instead of the normal 1: 4 or 1: 6. 4-Giant cells that are considerably larger than their neighbors may be formed and possess either one enormous nucleus or several nuclei, anaplastic nuclei are variable and bizarre in size and shape. 5-The chromatin is coarse and clumped, and nucleoli may be of outstanding size. 6-mitosis are often numerous and distinctly atypical; sometimes appear as tripolar or quadripolar forms. -In general mitotic activity in normal cells is low, some exceptions are: progenitor cells in the bone marrow and the basal cells in epithelial tissue where the mitotic activity is relatively high. -Mitotic activity in benign tumors is usually scarce, in contrast with malignant tumor where there is an increase in mitotic activity. -Mitotic activity was evaluated as the number of mitotic figures per 10 highpower fields (mitotic activity index). e.g: Differentiating benign tumors from malignant tumors of smooth muscles origin ; benign tumors (leiomyoma) MAI=5 per 10 high-power fields,whereas in malignant tumors (leiomyosarcoma) MAI>=10 per high-power fields. If MAI is between 5 to 10 per 10 high-power fields the patient should be monitored carefully. 7-anaplastic cells usually lose normal polarity. 8-cells fail to develop recognizable patterns of orientation to one another.

12 9-Cells may grow in sheets with total loss of communal structures such as gland formations or stratified squamous architecture. Anaplasia Multi nuclear cells, varying sizes,unknown origin. Anaplastic tumor of the skeletal muscle (rhabdomyosarcoma), note the marked cellular and nuclear pleomorphism, hyperchromtic nuclei and tumor giant cells. Anaplastic tumor with abnormal mitosis

13 The prominent cell in the center has abnormal tripolar spindle indicating malignancy. Abnormal mitotic figures highly suggestive of malignancy MAI explained above. Dysplasia

14 Dysplasia, a term used to describe disorderly but non-neoplastic proliferation. Dysplasia is encountered principally in the epithelia. It is a loss in the uniformity of individual cells and in their architectural orientation. Dysplastic cells exhibit considerable pleomorphism and often possess hyperchromatic nuclei that are abnormally large for the size of the cell. Mitotic figures are more abundant than usual. Frequently the mitoses appear in abnormal locations within the epithelium. In dysplastic stratified squamous epithelium, mitoses are not confined to the basal layers, where they normally occur, but may appear at all levels and even in surface cells. The usual progressive maturation of tall cells in the basal layer to flattened squamous on the surface may be lost and replaced by a disordered scrambling of dark basal-appearing cells When dysplastic changes are marked and involve the entire thickness of the epithelium, the lesion is referred to as carcinoma in situ, a pre-invasive stage of cancer The term dysplasia without qualifications does not indicate cancer, and dysplasias do not necessarily progress to cancer, but it is important in control and prevention of cancer. Mild-to-moderate changes that do not involve the entire thickness of epithelium may be reversible, and with removal of the putative inciting causes, the epithelium may revert to normal. Carcinoma in situ: A Low-power view shows the entire thickness of the epithelium is replaced by atypical dysplastic cells. There is no orderly differentiation of squamous cells. The basement membrane is intact, and there is no tumor in the sub epithelial stroma. B, High-power view shows failure of normal differentiation, marked nuclear and cellular pleomorphism, and numerous mitotic figures extending toward the surface.

15 -The normal epithelium should be differentiated with mature cells ascending from the basement membrane and gradually becoming smaller with smaller and less basophilic nuclei as we go up. -Dysplasia is encountered principally in epithelial lesions and it shares many characteristics of cancer, but it is not considered malignant because it is not invasive and does not reach the underling connective tissue, the basement membrane remain is intact. Rate of growth Most benign tumors grow slowly & increase in size slowly over the span of months to years.

16 Most cancers grow much faster,but exceptions do occur E.g. The rate of growth of leiomyomas (benign smooth muscle tumors) of the uterus is influenced by the circulating levels of estrogen, they may increase rapidly in size during pregnancy then cease growing, becoming largely fibrocalcific, after menopause. Other influences, such as adequacy of blood supply or pressure constraints, also may affect the growth rate of benign tumors. Adenomas of the pituitary gland locked into the sella turcica have been observed to shrink suddenly. Presumably, they undergo a wave of necrosis as progressive enlargement compresses their blood supply. The rate of growth of malignant tumors correlates in general with the level of differentiation, rapidly growing tumors tend to be poorly differentiated. Most cancers progressively enlarge over time, some slowly, others rapidly. Rapidly growing malignant tumors often contain central areas of ischemic necrosis because the tumor blood supply, derived from the host, fails to keep pace with the oxygen needs of the expanding mass of cells.