N EOPLASIA 1 D R. HIBA AL ZOU ’ BI

- Neoplasia literally means "new growth“ - In medicine it is referred to as a tumor, - The study of tumors is called oncology.

A CCORDING TO CLINICAL BEHAVIOUR, TWO MAIN TYPES OF NEOPLASMS : Benign neoplasm = Limited new growth without local invasion or spread Malignant neoplasm (Cancer) = Invasive growth locally, which also can spreads to distant sites.

- All tumors, benign and malignant, have two basic components: 1. The neoplastic cells (the parenchyma) : determines its biologic behavior, and the component from which the tumor derives its name 2. The non-neoplastic (host derived) stroma: made up of connective tissue, blood vessels, and inflammatory cells, important to the growth of the neoplasm

N OMENCLATURE In general, benign tumors are designated by attaching the suffix -oma to the cell type from which the tumor arises. I. Benign mesenchymal Tumors: a. A benign bone tumor is called: osteoma b. A benign smooth muscle tumor : leiomyoma c. A benign fibrous tissue tumor: Fibroma d. A benign cartilagenous tumor: Chondroma

II. Benign epithelial tumors 1. Adenomas : producing glands or derived from glands (but not necessarily exhibiting glandular pattern) such as colonic adenoma. 2. Polyp : Is a mass projects above a mucosal surface, as in gut. Most polyps are benign but a few are malignant. 3. Cystadenomas : cystic mass (as in ovary) 4. Papillomas grow on any surface, and produce microscopic or macroscopic finger-like fronds.

C OLONIC POLYP

S QUAMOUS PAPILLOMA

M IXED TUMOR Single germ cell tumors: - Derived from one germ cell layer that differentiates into more than one cell type: e.g. - Mixed tumor of Salivary Gland, - Fibroadenoma of breast OR :

M IXED TUMORS Teratoma : - Made of a variety of cell types that derive from more than one germ cell layer formed by totipotent germ cells that are able to form ectoderm, endoderm& mesoderm - contains mature or immature tissues - present in ovaries and testes. - Contain bone, epithelium, muscle, fat, nerve,.....

M ISNOMERS Choristoma called (heterotopia) - Is a congenital anomaly not a neoplasm. - Means presence of normal organized tissue in an abnormal location such as presence of normal pancreatic tissue in stomach. Hamartoma - Mass of disorganized tissue native to the particular site. - Hamartomatous nodule in the lung containing islands of cartilage, bronchi, and blood vessels

EXCEPTIONS OF NOMENCLATURE a. Lymphoma :Malignant tumor of lymphocytes b. Melanoma,: Malignant tumor of melanocytes c. Mesothelioma: Malignant tumor of mesothelial cells d. Seminoma: Malignant tumor of testicular germ cells.

III. Malignant mesenchymal neoplasms - In solid tissue: sarcomas - Malignant bone tumor: osteosarcoma - Malignant fibrous tissue: Fibrosarcoma - Malignant cartilagenous tissue: Chondrosarcoma - Mesenchymal cells of blood: Leukemia or lymphoma IV. Malignant tumors of epithelium are carcinomas - Those arise from glands: adenocarcinomas - Those produce squamous cells: squamous cell carcinomas

N OTE Table (5-1) on page 164: Nomenclature of tumors

CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS Differentiation & anaplasia Rate of growth Local invasion Metastases

B ENIGN VERSUS MALIGNANT TUMORS

D IFFERENTIATION AND ANAPLASIA - Diffrentiation means how much neoplastic cells resemble their normal forebears morphologicaly and functionaly 1. Benign neoplasms : - Composed of well-differentiated cells that resemble their normal counterparts. - Example: Lipoma and chondroma. 2. Malignant neoplasms: - Characterized by a wide range of differentiation, from well differentiated to poorly differentiated.

The better the differentiation of the cell, the more completely it retains the functional capabilities found in its normal counterparts. 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.

Anaplasia means lack of differentiation, is considered a hallmark of malignancy. Anaplastic cells display: Marked pleomorphism (i.e., marked variation in size and shape of cells) Nuclei are extremely hyperchromatic (darkly stained) and large. The nuclear-to-cytoplasmic ratio is high: ( normally1:4 or 1:6) Giant cells. Anaplastic nuclei are variable and bizarre in size and shape, Chromatine coarse and clumped. Nucleoli may be of astounding size Mitoses are often numerous and distinctly atypical (tripolar or quadripolar mitotic figures) Fail to develop recognizable pattern of orientation to one another (Lose normal polarity)

D YSPLASIA Dysplasia is a proliferation of cells with loss of uniformity of individual cells and in their architectural orientation When involve the entire thickness of the epithelium: Carcinoma in Situ (limited by basement membrane, preinvasive stage of cancer) Not synonymous with cancer May regress completely (mild to moderate dysplasia) especially if inciting causes are removed

R ATE OF G ROWTH - Most benign tumors grow slowly and most cancers grow faster - Poorly differentiated tumors grow more rapidly than well-differentiated tumors. - Cancers are immortal: have limitless proliferative capacity, so must contains cells with “stem-like” properties - Cancer stem cells could arise from normal tissue stem cells or from more differentiated cells that acquire the property of self-renewal.

L OCAL I NVASION : 1- Benign neoplasms: remain localized, do not have the capacity to invade the normal tissue. - However, not all benign neoplasms are encapsulated. 2- Cancers grow by progressive invasion, and penetration of the surrounding tissue - It is necessary to remove a wide margin of surrounding normal tissue after excision of a malignant tumor - The pathologists carefully examine the margins of resected tumors to ensure that they have (clean margins) Next to the development of metastases, local invasiveness is the most reliable feature that distinguishes malignant from benign tumors.

M ETASTASIS : - Are secondary implants of a tumor, discontinuous from the primary tumor and located in remote tissues - However, not all cancers have ability to metastasize (such as basal cell carcinomas of the skin). - Approximately 30% of newly diagnosed patients with solid tumors present with clinically evident metastases, 20% have occult (hidden) metastases - The more anaplastic and larger neoplasm, the more likely metastatic spread. - Dissemination strongly may prevent, the possibility of curing the disease

M ETASTASIS OCCURS BY : 1-Spread by seeding (Transcoelomic Spread) : - Occurs when neoplasms invade a natural body cavity. Examples: - Ovarian cancer, which spread to the peritoneal surfaces.

2. L YMPHATIC SPREAD : - Is more typical of carcinomas. - Enlargement of lymph nodes near primary neoplasm should arouse concern for metastatic spread. However, it does not always imply metastasis. - Depends on lymphatic drainage of the organ. - Sentinel lymph node: First regional lymph node receives lymph flow from a primary tumor. There are numerous interconnections, however, between the lymphatic and vascular systems, and so all forms of cancer may disseminate through either or both systems

3. H EMATOGENOUS SPREAD : - Is the favored pathway for sarcomas - Arteries are penetrated less than veins. - Liver and lungs are the most common secondary sites for hematogenous metastasis. - Prostate and thyroid cancer metastasize to the vertebra - Certain cancers grow within veins: Renal cell carcinoma, hepatocellular carcinoma - Tissue specific homing of the tumor (Not always explained by venous drainage): Bronchogenic carcinoma metastasis to brain and adrenal gland. - The skeletal muscles are rarely the site of metastatic deposits

SUMMARY : D IFFERENCES BETWEEN BENIGN & MALIGNANT NEOPLASMS  Various or Anaplastic  High mitotic index  Rapid growth  No capsule  Invasion  Metastases  Well-differentiated  Low mitotic index  Slow Growth  With capsule  No invasion  No metastases