Pathology Neoplasia Lec. 1 PDF

Lectures No. 1 PATHOLOGY Dr. Nazar Jewher Neoplasia - 1 Definition: Literally: ▪ It is an abnormal mass of tissue the growth of which exceeds & is uncoordinated with that of the normal tissue...

Lectures No. 1 PATHOLOGY Dr. Nazar Jewher Neoplasia - 1 Definition: Literally: ▪ It is an abnormal mass of tissue the growth of which exceeds & is uncoordinated with that of the normal tissues & persists in the same excessive manner after cessation of the stimuli that evoked the change. ▪ It is purposeless, preys on the host & is autonomous (loss of responsiveness to normal growth control). ▪ It behaves like a parasite, competes with normal tissue for their metabolic needs. ▪ Cancer is not one disease but many disorders that share a profound growth dysregulation. ▪ Results from genetic alterations that are passed down to the progeny of the tumor cells. These genetic changes allow excessive and unregulated proliferation that becomes autonomous (independent of physiologic growth stimuli), Oncology: ▪ Tumor: Swelling. ▪ Cancer: A common term for all type of malignant tumors. Derived from the Latin cancer (for crab), because cancer adheres to any part that seizes upon in an obstinate manner like a crab. INCIDENCE: ▪ More than 1 million individuals develop cancer every year, and cancer causes more than 560000 annual deaths in the state. ▪ It is the second leading cause of death after cardiovascular diseases. ▪ Neoplasms are important not only because of the mortality rate but also because of the great physical and emotional impact they inflict on the patients and their families. 1 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher ▪ Recently, there has been dramatic improvements in the survival rates in some cancers ( especially leukemias & lymphomas). A greater proportion of cancers are being cured or arrested today than ever before. ▪ The only hope for controlling cancer lies in learning more about its etiology & pathogenesis. Classification: Clinically Tumors Are Classified Into: 1. Benign tumors: 2. Malignant tumors: 3. Borderline malignant tumors: 1. Benign tumors: Characterized by ▪ Innocent features. ▪ Localized. ▪ Cannot spread. ▪ Surgical excision. ▪ No affect survival. 2. Malignant tumors: ▪ Morphological features. ▪ Invade & destroy. ▪ Metastasize). ▪ Can cause death. 3. Borderline malignant tumors: Nomenclature All tumors have two basic components: ▪ Proliferating neoplastic cells that constitute the parenchyma. ▪ Supportive stroma made up of connective tissue & blood vessels 2 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher NOTE: Some tumors have scanty stroma so the neoplasm is soft & fleshy, other tumors especially some cancers stimulate the formation of an abundant collagenous stroma ( referred to as desmoplasia) imparting a stony hard consistency to the tumor ( as scirrhous carcinoma of the breast). ▪ Tumor either arises from epithelial cells, mesenchymal cells, hemopoietic, lymphoid cells, nerve cells, or from totipotential cells. ▪ Any of these tumors could be benign or malignant. ▪ Tumors are named according to the type of cells from which they arise or according to the tissue they resemble. BENIGN TUMORS Are designated by attaching the suffix –Oma to the cell of origin. Either of benign epithelial tumors or benign mesenchymal tumors: Benign Epithelial Tumors: ⚫ Adenoma: Applied to benign tumor derived from glands (e.g. salivary, sweat glands) or tumor forming glandular pattern (renal cell adenoma). 3 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher ⚫ Papilloma: Benign epithelial neoplasm that produces finger like projections from epithelial surfaces (e.g. squamous papilloma). ⚫ Cystadenoma: Benign tumor producing hollow cystic mass, mostly seen in the ovary. Sometimes papillary cystadenoma. ⚫ Polyp: Benign epithelial tumor produces a mass that projects above a mucosal surface. Mostly seen in the GIT. Benign Mesenchymal Tumors ▪ Named by attaching the suffix –Oma to the cell of origin. ▪ Example: fibroma. Lipoma, neuroma, leiomyoma, osteoma, chondroma…. 4 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher MALIGNANT TUMORS Carcinoma: Malignant tumors of epithelial cell origin. They are further classified into: ▪ Squamous cell carcinoma. ▪ Adenocarcinoma. ▪ Transitional cell carcinoma. ▪ Basal cell carcinoma. Sarcoma: Malignant tumors arising from mesenchymal tissues.e.g., ▪ Fibrosarcoma ▪ Liposarcoma ▪ Leiomyosarcoma ▪ Osteosarcoma ,Etc. MIXED TUMORS ▪ This term applied to a small group of tumors that are composed of a mixture of epithelial & mesenchymal components. They result from divergent differentiation of a single line of parenchymal cells. ▪ Benign mixed tumors: e.g., pleomorphic adenoma ( These tumors contain epithelial components scattered within a myxoid stroma that sometimes contains islands of cartilage or bone), fibroadenoma, ▪ Malignant mixed tumors: e.g., malignant mixed tumor of the salivary gland & carcinosarcoma. TERATOMA ▪ This tumor arises from totipotential cells, so they have the capacity to differentiate into any cell types present in the body i.e., it contains tissue representative of more than one germ layer. 5 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher ▪ Since they arise from totipotential cells, so they are principally encountered in the gonads (although rarely found in sequestered rest). e.g. dermoid cyst of the ovary. Teratoma could be benign or malignant. N.B: There are some exception to this nomenclature e.g. lymphoma, melanoma, glioma, seminoma , …….. Table: Nomenclature of tumors 6 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher ⚫ What Is Hamartoma? ▪ aberrant differentiation produce mass or developmental malformation 1. consist of mature tissues but disorganized 2. tissues related to site of origin. ▪ e.g. lung hamartoma: islands of cartilage/blood vessels/bronchial mucosa ⚫ What Is Choristoma? ▪ presence of a normal tissue in an unexpected location e.g. pancreatic tissue in wall of esophagus or stomach or small intestine, may form masse mimicking neoplasm grossly. 7 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher CHARACTERISTIC OF BENIGN & MALIGNANT TUMORS ⚫ The differentiation between benign and malignant tumors is one of the most important distinctions a pathologist can make. In the great majority of instances, a benign tumor may be distinguished from a malignant tumor with considerable confidence on the basis of: ▪ Differentiation & anaplasia: ▪ Rate of growth: ▪ Local invasion: ▪ Metastasis: Differentiation & Anaplasia ⚫ Refers to the extent to which parenchymal neoplastic cells resemble comparable normal cells, both morphologically & functionally. ⚫ Neoplasm could be: ✓ Well-differentiated ✓ Moderately differentiated ✓ Poorly differentiated ✓ Undifferentiated ⚫ Benign tumors are well differentiated. Malignant tumors vary from well- undifferentiated. ⚫ Anaplasia implies a reversal of differentiation to a more primitive level. It usually results from lack of differentiation rather than dedifferentiation. ⚫ Determination of differentiation depends on a no. of morphological changes: ✓ Architectural pattern &Cytological features (degree of atypia): ✓ No. of mitosis &configuration:. ✓ Others as loss of polarity, tumor giant cells, necrosis 8 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher Adenomatous polyp of the colon. Well differentiated tumor. The glands are well-formed and normal-looking Malignant tumor (adenocarcinoma) of the colon. The cancerous glands are irregular in shape and size and do not resemble the normal colonic glands. This tumor is considered differentiated because gland formation can be seen. The malignant glands have invaded the muscular layer of the colon. 9 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher The normal squamous epithelium at the left merges into the squamous cell carcinoma at the right, which is infiltrating downward. The neoplastic squamous cells are still similar to the normal squamous cells, but are less orderly. This is a well-differentiated squamous cell carcinoma Here is a moderately differentiated squamous cell carcinoma in which some, but not all, of the neoplastic cells in nests have pink keratin. In general, neoplasms with less differentiation are more aggressive. 10 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher The microscopic appearance of a leiomyoma indicates that the cells do not vary greatly in size and shape and closely resemble normal smooth muscle cells. Lipoma: Mature fatty tissue The microscopic appearance of the pituitary adenoma is shown here. Note the monotonous appearance of these small round cells, i.e no pleomorphism. This is a well differentiated tumor. 11 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher This neoplasm is so poorly differentiated that it is difficult to tell what the cell of origin is. It is probably a carcinoma because of the polygonal nature of the cells. Note that nucleoli are numerous and large in this neoplasm. Neoplasms with no differentiation are said to be anaplastic. Anaplastic tumor of the skeletal muscle (rhabdomyosarcoma). Note the marked cellular and nuclear pleomorphism, hyperchromatic nuclei, and tumor giant cells. Mitotic figure is seen in the center 12  Lectures No. 1 PATHOLOGY Dr. Nazar Jewher Here are three abnormal mitoses. Mitoses by themselves are not indicators of malignancy. However, abnormal mitoses are highly indicative of malignancy. The marked pleomorphism and hyperchromatism of surrounding cells also favors malignancy. This sarcoma has many mitoses. A very large abnormal mitotic figure is seen at the right. ▪ The better the differentiation of the transformed cell, the more completely it retains the functional capabilities found in its normal counterparts. Thus, benign neoplasms of endocrine glands frequently elaborate the hormones characteristic of their origin. Increased levels of these hormones in the blood are used clinically to detect and follow such tumors. Well- differentiated squamous cell carcinomas of the epidermis elaborate keratin, just as well- differentiated hepatocellular carcinomas elaborate bile. 13 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher ▪ Highly anaplastic undifferentiated cells, whatever their tissue of origin, lose their resemblance to the normal cells from which they have arisen. ▪ Despite exceptions, the more rapidly growing and the more anaplastic a tumor, the less likely it will have specialized functional activity. The cells in benign tumors are almost always well differentiated and resemble their normal cells of origin; the cells in cancer are more or less differentiated, but some derangement of differentiation is always present Rate of growth ▪ In general, most benign tumors grow slowly over a period of years, whereas most cancers grow rapidly and the rate of growth of malignant tumors correlates with their level of differentiation. HOW? ▪ There are some exceptions to this generalization. Local invasion ▪ Nearly all benign tumors grow as cohesive expansile masses that remain localized to their site of origin and do not have the capacity to infiltrate, invade, or metastasize to distant sites, as do malignant tumor. ▪ Because they grow and expand slowly, they usually develop a rim of compressed connective tissue, sometimes called a fibrous capsule, which separates them from the host tissue. ▪ This capsule is derived largely from the extracellular matrix of the native tissue due to atrophy of normal parenchymal cells under the pressure of an expanding tumor. Such encapsulation does not prevent tumor growth, but it keeps the benign neoplasm as a discrete, readily palpable, and easily movable mass that can be surgically enucleated. Some benign tumors are not encapsulated. For example, hemangiomas (neoplasms composed of tangled blood vessels) are often unencapsulated and may appear to permeate the site in which they arise. 14 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher Benign Tumor ▪ Cohesive expansile growth. Encapsulated. Localized, circumscribed &mobile. Amenable to surgical resection (enucleation). ▪ N.B: Not all benign tumors are encapsulated. Uterus with leiomyomas of varying size, but all benign and well- circumscribed firm white masses. Malignant Tumor ▪ The growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue. ▪ In general, malignant tumors are poorly demarcated from the surrounding normal tissue, and a well- defined cleavage plane is lacking. Most malignant tumors are obviously invasive and can be expected to penetrate the wall of the colon or uterus, for example, or fungate through the surface of the skin. They recognize no normal anatomic boundaries. Such invasiveness makes their surgical resection difficult or impossible. ▪ Progressive infiltration, invasion, & destruction of adjacent tissues. Not encapsulated (no plane of cleavage). Excision with safety margin. 15 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher ▪ N.B: Next to the development of metastasis, local invasion is the most reliable feature that distinguishes malignant from benign tumors. Cut section of an invasive ductal carcinoma of the breast. The lesion is retracted, infiltrating the surrounding breast substance, and would be stony hard on palpation. Metastasis ▪ Indicates the development of secondary implants away from the site of primary tumor. Is the single most important feature that distinguishes malignant from benign tumors. ▪ The probability of metastasis increases as the primary tumor becomes more aggressive, the more rapidly growing, and the larger the primary neoplasm, the greater the likelihood that it will metastasize ▪ Benign tumors do not metastasis. All malignant tumors eventually metastasis except: ▪ Approximately 30% of newly diagnosed patients with solid tumors present with distant metastasis. Metastasis strongly reduces the probability of cure. 16 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher Pathways Of Spread: A. Lymphatic Spread: ▪ is the most common pathway for the initial dissemination of carcinomas. The pattern of lymph node involvement follows the natural routes of lymphatic drainage. ▪ Enlargement of regional lymph nodes may be caused by: 1. The spread and growth of cancer cells or 2. Reactive hyperplasia. ▪ Therefore, nodal enlargement in proximity to a cancer, while it must arouse suspicion, does not necessarily mean dissemination of the primary lesion. The Sentinel Node To avoid the considerable surgical morbidity associated with a full axillary lymph node dissection, biopsy of sentinel nodes is often used to assess the presence or absence of metastatic lesions in the lymph nodes. A sentinel lymph node is defined as "the first node in a regional lymphatic basin that receives lymph flow from the primary tumor.“ Sentinel node mapping can be done by injection of radiolabeled tracers and blue dyes, and the use of frozen section upon the sentinel lymph node at the time of surgery can guide the surgeon to the appropriate therapy. Sentinel node biopsy has been used for detecting the spread of melanomas, colon cancers, and other. B. Hematogenous Spread: (Artery Vs Vein, Favored Sites) ▪ Arteries, with their thicker walls, are less readily penetrated than are veins. With venous invasion the blood-borne cells follow the venous flow draining the site of the neoplasm, and the tumor cells often come to rest in the first capillary bed they encounter. ▪ Understandably the liver and lungs are most frequently involved in such hematogenous dissemination, because all portal area drainage flows to the liver and all caval blood flows to the lungs. ▪ Other. N.B: Carcinoma vs sarcoma 17 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher C. Seeding The Body Cavities: ▪ Occur whenever a malignant neoplasm penetrates into a body cavity as peritoneum & pleura. Such seeding is particularly characteristic of carcinomas arising in the ovaries, when, not infrequently, all peritoneal surfaces become coated with a heavy layer of cancerous glaze. Microscopically, metastatic adenocarcinoma is seen in a lymph node here. It is common for carcinomas to metastasize to lymph nodes. The first nodes involved are those draining the site of the primary. 18 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher DYSPLASIA ▪ Disordered growth. ▪ Dysplasia is encountered principally in epithelia. It means an abnormal but yet non-neoplastic proliferation of cells as a result of injury. There is loss of uniformity of the individual cells and loss of architectural orientation. ▪ Grading of dysplasia: ▪ Epithelial dysplasia does not indicate cancer but almost antedates the appearance of cancer ( i.e premalignant). The probability of progression depends on: Carcinoma in situ ▪ This term indicates the presence of severe architectural and cytological atypia in the epithelium (i.e., malignant features) BUT such changes are confined to the epithelium & do not extend beyond the basement membrane into the adjacent or subjacent tissue. ▪ This is the next step toward neoplasia. Here, there is normal cervical squamous epithelium at the left, but dysplastic squamous epithelium at the right. Dysplasia is a disorderly growth of epithelium, but still confined to the epithelium. Dysplasia is still reversible. 19 Lectures No. 1 PATHOLOGY Dr. Nazar Jewher ▪ When the entire epithelium is dysplastic and no normal epithelial cells are left, then the process is beyond dysplasia and is now neoplasia. If the basement membrane is still intact, as shown here, then the process is called "carcinoma in situ" because the carcinoma is still confined to the epithelium. 20