Neoplasia (Part 1) PDF

Neoplasia (part1) Prepared by: Dr. Rasha Arafa Abd-elmaksoud Pathology Department  Dysplasia It is disordered but non neoplastic cellular proliferation characterized by loss of individual cell uniformity and loss of normal arrangement within the tissue. It often accompanies meta...

Neoplasia (part1) Prepared by: Dr. Rasha Arafa Abd-elmaksoud Pathology Department  Dysplasia It is disordered but non neoplastic cellular proliferation characterized by loss of individual cell uniformity and loss of normal arrangement within the tissue. It often accompanies metaplasia or hyperplasia. Sites: - Skin - mucous membranes - Liver NE: Difficult to be detected by gross examination. ME: The dysplastic cells show varying degree of cellular atypia as: 1. Hyperchromasia: increased nuclear staining in comparison to normal. 2. Pleomorphism: variation in size and shape within a tissue. 3. Show mitotic activity. 4. Loss of normal orientation(polarity) and disordered maturation (as loss of normal arrangement of epidermal layers). Causes: Chronic inflammation, irritation and chronic infection. Grades: 1. If the change are restricted to lower third of surface epithelium, it is grade I 2. If involves the middle third, it is grade II. 3. If involves nearly the whole thickness, it is grade III. Prognosis: - Grade I and II dysplasia is commonly reversible; may persist or regress when the irritating cause stops. - Grade III progress to carcinoma in situ (whole thickness dysplasia but basement membrane is intact and no invasion of underlying connective tissue) and finally invasive carcinoma TUMOR (NEOPLASIA) In ancient Greek, neo = new and plasia = creation. “tumor” in Latin stands for “swelling”. It is defined as an abnormal mass of tissue characterized by: -Its rate of growth exceeds and is uncoordinated with normal tissue, progressive, unlimited and autonomous, uncontrolled by the normal growth control, and Competes with normal cells for metabolic needs. - Any tumor is composed of: 1) Parenchymal component (the neoplastic cells) that may be benign or malignant and the tumor is named according to it. 2) Supporting non-neoplastic stroma Classification of Tumors: A) According to cell of origin: 1) Epithelial 2) Mesenchymal 3) Miscellaneous A) According to their characters and behavior: 1) Benign 2) Malignant 3) Locally malignant Neoplasia Characteristics of benign and malignant neoplasms Differentiation and anaplasia: Differentiation means : the extent to which the parenchymal cells of the tumor resemble their normal counterparts morphologically and functionally Rate of growth: Benign tumors: grows slowly are affected by blood supply, hormonal effects , location Malignant tumors : grows faster Correlate with the level of differentiation. Local invasion: Benign tumors : Remain localized Cannot invade Usually capsulated Malignant tumors : Progressive invasion Destruction Usually not capsulated metastasis Table: Differentiating Features between Benign and Malignant Neoplasms Neoplasia Nomenclature Benign tumors: prefix + suffix Type of cell + (-oma). Examples: Benign tumor arising in fibrous tissue: Fibro + oma = Fibroma Benign tumor arising in fatty tissue: Lipo + oma = lipoma Neoplasia Benign tumor arising in cartilage chondro + oma = chondroma Benign tumor arising in smooth muscle Leiomyo + oma = leiomyoma Benign tumor arising in skeletal muscle Rhabdomyo + oma = rhabdomyoma Neoplasia epithelial benign tumors are classified on the basis of : The cell of origin Microscopic pattern Macroscopic pattern Neoplasia Adenoma : benign epithelial neoplasms producing gland pattern….OR … derived from glands but not necessarily exhibiting gland pattern Papilloma : benign epithelial neoplasms growing on any surface that produce microscopic or macroscopic finger-like pattern Neoplasia Malignant tumors: Malignant tumor arising in mesenchymal tissue : SARCOMA From fibrous tissue: Fibrosarcoma From bone : Osteosarcoma From cartilage : chondrosarcoma Neoplasia Malignant tumors arising from epithelial origin : CARCINOMA Squamous cell carcinoma Renal cell adenocarcinoma cholangiocarcinoma Neoplasia Melanoma ( skin ) Mesothelioma (mesothelium ) Seminoma ( testis ) Lymphoma ( lymphoid tissue ) LOCALLY MALIGNANT TUMORS * Def: These are tumors, which infiltrate locally but don’t send distant metastases. * Characters: Rate of growth is slower than malignant tumors. Mode of growth is by infiltration. No blood or lymphatic spread. Microscopically the cells are malignant. *Prognosis: May turn malignant. Recur after incomplete removal. * Examples: 1. Basal cell carcinoma of skin. 2. Giant cell tumor of bone “osteoclastoma”. 3. Adamantinoma of the mandible. 4. Craniopharyngioma. 5. Gliomas: tumors of neuroglial cells. 6. Carcinoid tumor.  SPREAD OF MALIGNANT TUMORS I. Local (direct) spread (invasion) II. Distant spread (metastasis) I. LOCAL SPREAD “INVASION” Presence of tumor cells away from their site of origin without loss of continuity with the primary tumor. *Mechanism: Invasion of the extracellular matrix “E.C.M” (basement membrane & interstitial connective tissue) following the way of least resistance. Occurs along 4 steps; 1. Detachment of tumor cells from each other: 2. Attachment of the tumor cells (through receptors) 3. Degradation of E.C.M 4. Migration of tumor cells through the degraded E.C.M *Effects: - This leads to adhesion of the tumor cells to the surrounding structures. - It can cause functional insufficiency. - It can cause severe hemorrhage when invading a blood vessel. - It can cause pain when invading a nerve - It can cause obstruction of hollow organs, ulcer, fistula.  II. DISTANT SPREAD (METASTASIS) It is the presence of the tumor cells away from the primary tumor mass without continuity with it. Metastasis is the main difference between the benign & malignant tumor and is the main cause of death. ❖ METHODS OF DISTANT SPREAD 1. Lymphatic spread: favored by carcinomas Breast carcinoma → axillary lymph nodes Lung carcinomas → bronchial lymph nodes 2. Blood (hematogenous) spread: favored by sarcomas, veins are commonly invaded. 3. Transcoelomic (through serous sacs) spread. 4. Implantation. 5. Inoculation.  1. HEMATOGENOUS (BLOOD) SPREAD -It is the most common pathway of distant spread in sarcoma than carcinoma. -Some carcinomas have early tendency for haematogenous spread as: Follicular thyroid carcinoma Hepatocellular carcinoma Renal cell carcinoma Prostatic carcinoma Choriocarcinoma Lung small cell carcinoma Breast carcinoma -Veins, with thinner walls are more susceptible to penetration than arteries. - Arteries resist penetration because of their thick elastic muscular wall however; they may be eroded causing fatal hemorrhage Mechanism 1. intravasation: the tumor cells invade the extracellular matrix and blood vessel wall to reach blood (by same mechanism of local spread). 2. Embolization: The malignant cells pass with blood stream as tumor emboli by adhering to leukocytes and platelets (so the tumor cells are hidden from the immune system). 3. Extravasation: The tumor emboli are impacted in a narrow blood vessel, invade its basement membrane and pass outside blood vessels by the same mechanism of intravasation. 4. Homing: Tumor cells proliferate in the new site to form the metastatic deposits. ►The site of vascular metastasis depends on anatomical factors; 1. Emboli derived from primary tumors drained by systemic veins, pass with venous return to right side of the heart to lung causing lung metastasis, however, there are some exceptions; a. The tumor cells bypass lung through ventricular or atrial septal defect to the systemic circulation directly. b. The tumor cells are small enough to pass through lung capillaries without arrest. c. Metastasis of some pelvic, abdominal or thoracic tumors through the paravertebral system of veins with absent valves directly pass to brain & spinal cord. d. Metastasis of cancer kidney to left testis through left testicular vein (retrograde hematogenous spread). 2. Emboli derived from tumors of the lung either primary or secondary are carried by pulmonary veins to left side of the heart to systemic arterial circulation causing metastasis in different organs. 3. Emboli derived from tumors of organs drained by portal blood (tumors of GIT) are carried to liver causing liver metastases. ► Homing of tumor cells:  The most common sites for metastasis are; Liver, lung, brain, bones and adrenals.  Certain tumors prefer certain sites (organ tropism) e.g., prostatic carcinoma preferentially spread to bone, bronchial carcinoma tends to involve adrenals and brain. Neuroblastoma spreads to liver and bone. Such organ tropism may be related to the following: 1. Anatomical vascular distribution. 2. The tumor cells express adhesion molecules to be attached to the endothelial cells of target organ. 3. Some target organs may liberate chemo-attractants that tend to recruit tumor cells to the site  Rare sites for metastases are; muscle, spleen, pancreas and intestine (high concentration of protease inhibitors). Pathology of metastatic deposits: *Grossly: Metastatic deposits appear as scattered round nodules of variable sizes related to vascular distribution, hard in consistency, grayish white in color and may shows areas of hemorrhage and necrosis. *M/P: Metastatic deposits resemble the primary tumor. 2. Lymphatic spread The lymphatic vessels have no basement membrane, so the tumor cells invade the wall easily and disseminate. Is the major pathway of distant spread of carcinoma. Methods of lymphatic spread: Tumor cells pass by two ways; a. Lymphatic embolism: Aggregates of tumor cells intravasate in lymphatics then detach and pass with lymphatic vessels as tumor emboli to reach the afferent lymphatic of the draining lymph node. The tumor cells arrested at subcapsular sinuses then proliferate and gradually destroy and replace the substance of the lymph node. The tumor cells can infiltrate the capsule to the perinodal tissue. Spread from one lymph node to another occurs by efferent lymphatic. The tumor cells may pass from one lymph node to another one in a distant group directly “skip metastasis”. a. Lymphatic embolism: *Grossly: The affected nodes are enlarged, firm in consistency, grayish in color, separated or fused (when the perinodal tissue is infiltrated). C/S appears grayish white. *M/P: Loss of the nodal architecture and replacement of by metastatic tumor deposit that resemble the primary neoplasm. b. Lymphatic permeation: The malignant cells multiply inside the lumen of the lymphatic as solid columns (cord like structure)not reaching the lymph node causing lymphatic obstruction and lymphatic edema. Occurs in small lymphatic as in cases of:  Breast carcinoma causing peau d’orange appearance of the covering skin.  Perineural lymphatics in prostatic and biliary tract carcinoma causing nerve compression, infiltration leading to pain  Serous sacs. NB: Causes of lymph node enlargement draining region affected by carcinoma: 1. Reactive hyperplasia with sinus histiocytosis resulting from stimulation by tumor antigen. 2. Secondary infection. 3. Lymphatic spread.  3. Spread through body cavitis (TRANSCOELOMIC SPREAD) Occurs through serous cavities from organs covered by serous membranes. Mechanism: The malignant cells infiltrate the serous layer, detach, and drop mechanically to implant itself on the surface of another organ or in the distal dependent part of the cavity. Effects: - Multiple secondaries. -Hemorrhagic effusion(exudate); rich in protein and contain neoplastic cells. Sites: a. Metastasis through peritoneal cavity: GIT tumors send to the ovary (Krukenberg’s tumor). b. Metastasis through Pleural cavity: Malignant cells from cancer bronchus and cancer breast deposited on the surface of the diaphragm, costophrenic recess and paravertebral gutter. c. Metastasis through cranial cavity: Brain tumors send to the base of the skull and the dorsal aspect of the spinal cord.  4. SPREAD BY IMPLANTATION From the upper lip to lower lip ( kissing ulcer). 6. SPREAD BY INOCULATION Direct transplantation of tumor cells by surgical instrument may occur but extremely rare.