Neoplasia Lecture PDF

Principles of Diseases Neoplasia Lecture-I Neoplasia Neoplasia – Latin, ‘new growth’ Cancer – ‘crab’ Rupert Willis, 1950s Sir Rupert Willis defined the neoplasm as an abnormal mass of tissue the growth of which exceedsand is uncoordinated with that of the normal tissues and persists in the same exce...

Principles of Diseases Neoplasia Lecture-I Neoplasia Neoplasia – Latin, ‘new growth’ Cancer – ‘crab’ Rupert Willis, 1950s Sir Rupert Willis defined the neoplasm as an abnormal mass of tissue the growth of which exceedsand is uncoordinated with that of the normal tissues and persists in the same excessive manner even after cessation of the stimuli which evoked the change. Definition Neoplasia is new, uncontrolled growth; a "tumor" or "mass lesion" is simply a "growth/swelling" or "enlargement" which may not be neoplastic (such as a granuloma). The term "cancer" implies malignancy, but neoplasms can be either benign or malignant. Properties of neoplastic cells 1. transformed. 2.monoclonal 3. autonomy, though not complete. 4.immortality. 5. genetic instability Types of neoplasms Neoplasms – Parenchyma made up of neoplastic cells – Supporting host derived stroma Benign: localized and amenable to surgical removal; patient usually survives Malignant: invasive tumor capable of destroying structures and spread to distant sites (metastasis); may result in early death of the patient nomenclature 2 components: 1/ histogenic component. 2/ behavioral component. Benign Tumors Usually designated by adding “-oma” to cell type adenoma – benign tumor arising from glandular cells leiomyoma – benign tumor arising from smooth muscle cells chondroma – benign tumor arising from chondrocytes Benign Tumors Other benign tumor names papilloma – has finger-like projections polyp – projects upward, forming a lump cystadenoma – has hollow spaces (cysts) inside Examples of benign tumors Epithelial – Adenoma: benign glandular tumor – Papilloma : benign surface epithelial tumors – Polyp : benign tumor projecting over mucosal surface – Cystadenoma : benign epithelial tumor forming hollow cystic mass Examples of benign tumors Mesenchymal – – – – Chondroma: benign cartilaginous tumor Leiomyoma: benign smooth muscle tumor lipoma: benign tumor of fat Fibroma: benign tumor of fibrous tissue Mixed – Benign Mixed Tumor –divergent differentiation of stem cell (pleomorphic adenoma) – Fibroadenoma – neoplastic fibrous component More than one germ cell layer – Benign teratoma – mature components leiomyomas adenoma Nomenclature of Neoplasia Based upon origin: Maligant neoplasms arising from tissue embryologically derived from ectoderm or endoderm are usually carcinomas. Examples include: – Squamous cell carcinoma of cervix – Adenocarcinoma of stomach – Hepatocellular carcinoma – Renal cell carcinoma Nomenclature of Neoplasia Malignancies arising from mesoderm are usually sarcomas. Examples include: – Leiomyosarcoma – Chondrosarcoma – Osteosarcoma – Liposarcoma Examples of malignant tumors Sarcoma (mesenchymal derivation: fibrosarcoma, chondrosarcoma) Carcinoma (epithelial derivation: adenocarcinoma, squamous cell carcinoma) – Squamous – Adeno – Transitional Lymphoma/leukemia adenocarcinoma carcinoma Pitfalls tumors ending by the suffix oma but not benign: melanoma: malignant skin tumor. Myeloma :malignant tumor of plasma cells. Teratoma: totipotential tumors, arise from cells capable of differentiation to any adult cell types. Hamartoma: is a malformation that presents as a mass of disorganized tissue indigenous to the particular site. E.g a hamartomatous nodule in the lung consists of islands of cartilage, bronchi and blood vessels in disorganized fashion. Choristoma:cong. Anomaly. Implies a heterotropic rest of cells.e.g anodule of organized pancreatic tissue present in the submucosa of the stomach. Differences between benign and malignant tumors benign malignant Rate of growth Slow Capsulated. rapid Mode of growth expansion Infilteration and invasion spread localized Distant spread(metastasis). benign malignant Degree of differention Well differentiated Closely resemble the normal counter part. Wide range of differentiation Well, moderate, undifferentiated or anaplastic. Hormone secretion appropriate Inappropriate or ectopic cure Amenable to cure by Usually incurable because surgical excision of metastasis. Cytological features Benign ------------------------------- Malignant Cellular pleomorphism Nuclear pleomorpism and hyperchromatism High N/C ratio. Multiple nucleoli. Abnormal mitotic figures. terms Anaplasia: lack of differentiation. Dysplasia: loss in the uniformity of individual cells as well as loss in their architectural orientation. Dysplastic cells exhibit some cytological features of malignancy. Carcinoma in situ: marked dysplastic changes involving the entire epithelium but not breaching the basement membrane. Invasive cancer: when breaching the BM. Benign vs. Malignant Cancer Invasion Malignant Neoplasms grow by progressive infiltration, invasion, destruction, and penetration of the surrounding tissue Do not develop capsules This is why surgeons do Wide Excisions For a cancer cell to invade it has to: Detachment from other tumor cells. Adhesion to the extracellular matrix. Proteolytic degradation of the extracellular matrix. Motility and migration into the extracellular matrix. This process requires a number of genes to be activated. The extracellular matrix is a thick environment rich in collagen, glycoproteins and proteoglycans. Cells have to detach from the tumour mass and they can do that by reducing the cell-cell adhesion molecules on their surface They then have to adhere to proteins in the extracellular matrix by producing molecules on the surface called Integrins. Tumor cells produce proteolytic enzymes that degrades ECM and BM. In the blood vessels they migrate as single cells or tumor emboli attatched to plts and this help to bypass anti tumor host defence mechanisms. The site of metastasis is predicted by the location of the 1ry tumor & its lymph and vascular drainage. However some organ tropism is not predicted by the normal drainage & is related to expression of adhesion molecules`by the tumor cellswhose ligands are expressed preferentially on the endothelium of target organs. The ability to invade and metastasize: Occurs in two steps: 1/ invasion and peneteration of the ECM (requires loosening attatchements btwn tumor cells and penetrating the basement membrane by proteolytic enzymes. 2/ vascular dissemenation and homing of tumor cells. Tumor homing : Seed and soil theory Expression of adhesion molecules by tumor cells , their legands present on 2ndry sites. Expression of chemokine receptors by tumor cells , their legands on 2ndry sites. Cancer metastasis Metastasis is defined as the development of secondary implants discontinuous with the primary Malignant neoplasm and possibly in remote tissues. Once metastases are detected a cure becomes difficult if not impossible. Cancers spread by : 1. Direct spread into natural cavities.(seeding) Such as peritoneum, pleura, etc 2. Lymphatic spread (via lymphatic vessels) 3. Haematogenous spread (via veins) Neoplasia Cancer metastasis Figure 4 Adhesion to endothelial cells Tumour cells express E-Selectins Molecules that bind to Sialyl-Lewis X on endothelial cells Hematogenous Spread Arteries are rarely invaded Veins are the route of hematogenous spread Liver and Lungs are the usual endpoints of hematogenous spread, Facts about metastasiscan also metastasise. but remember that metastases Portal flow to liver and vena caval flow to lungs Renal Cell Ca has a propensity to invade the renal vein. Tumors near to the vertebral column can peneterate the paravertebral plexus and infilterate the bone like Prostate cancer and thyroid cancer. Some cant be predicted by the natural drainage, e.g: Bronchogenic cancer tends to involve adrenals and brain Neuroblastoma spread to liver and bones. Why do some cancers metastasise to certain organs and other organs such as Skeletal muscle and spleen are rarely involved??? Lymphatic Spread More typical of carcinomas rather than sarcomas (hematogenous)e.g Breast, stomach, Papillary thyroid carcinoma Cancer cells travel in lymphatics and reach regional lymph nodes. They get arrested, die or grow or travel to other nodes Sts skip lesions occur. Regional Lymph nodes draining the cancer area are first involved breast cancer in the upper-outer quadrant is likely to metastasise to the axillary lymph nodes, while a upper-inner breast cancer (medial) tends to metastasise to supraclavicular lymphnodes Seeding through body cavities. E.g CA colon CA stomach involve both ovaries (krukenberg tumors) A liver with metastatic cancer. Grading and staging Grading is based on the microscopic features of the cells which compose a tumor and is specific for the tumor type, refers`to degree of differentiation and thus aggressiveness. Staging is based on clinical, radiological, and surgical criteria, such as, tumor size, involvement of regional lymph nodes, and presence of metastases. Staging usually has Grading of Tumors Is the degree of differentiation Well diff G1 Moderately Poorly G2 G3 Anaplastic G4 Staging of Tumors  Is description of tumor spread  TNM system: Tumor  Node (Lymph)  Metastasis Tumor markers Tumor markers: sometimes diagnostic or prognostic Can be helpful in monitoring effectiveness of therapy or in detecting relapses/recurrences Summary Neoplasia- an abnormal mass of tissue which has lost its responsiveness to growth controls Benign neoplasms tend to be slow-growing, well-differentiated tumors which lack the ability to metastasize Benign neoplasms, in general, remain localized and are amenable to surgery Summary Malignant neoplasms tend to be fastgrowing lesions which invade normal structures Malignant neoplasms vary in the degree of differentiation and some show anaplasia Malignant neoplasms are capable of metastasis Summary (Prognosis) The prognosis of a patient with any type of neoplasm depends on a number of factors including: the rate of growth of the tumor, the size of the tumor, the tumor site, the cell type and degree of differentiation, the presence of metastasis, responsiveness to therapy, and the general health of the patient. ETIOLOGY OF CANCER: CARCINOGENIC AGENTS 48 ETIOLOGY OF CANCER: CHEMICALS AGENTS RADIATION MICROBIAL AGENTS Cancer grading and staging Grading and staging tumours are important because of their clinical relevance and so that different clinicians know how to standardise, plan and organise patients ‘ treatment. Grading is based on the degree of differentiation and the number of mitosis within a tumour. Cancers are classified as grades I to IV with increasing metaplasia. In general, Higher-grade tumours are more aggressive than lower grade tumours. It is important to note that within the same tumour Some cells have different grades and this is because of tumour Primary tumor (T) T0 T1 T2 No evidence of primary tumor Tumor 5 cm Lymph nodes (N) N0 N1 No regional metastasis Regional node metastasis Distant metastasis (M) M0 M1 No distinct metastasis Distant metastasis Histopathalogic grading (G) G1 G2 G3 G4 Well differentiated (low grade) Moderately differentiated (intermediate grade) Poorly differentiated (high grade) Undifferentiated Stage IA IB IIA IIB IIIA IIIB IVA IVB G1 G1 G2 G2 G3 G4 G3 G4 Any G Any G T1 T2 T1 T2 T1 T1 T2 T2 Any T Any T N0 N0 N0 N0 N0 N0 N0 N0 N1 Any N M0 M0 M0 M0 M0 M0 M0 M0 M0 M1 American Joint Committee on Cancer AJCC of soft tissue sarcomas classification Tumour effects on Host Tumours can effect the host in the following ways: Local Effects Cancer Cachexia Paraneoplastic Syndromes –Endocrinopathies –Neuromyopathies –Osteochondral Disorders –Vascular Phenomena –Fever –Nephrotic Syndrome Local Effects Tumor Impingement on nearby structures – Pituitary adenoma on normal gland, Pancreatic carcinoma on bile duct, Esophageal carcinoma on lumen Ulceration/bleeding – Colon, Gastric, and Renal cell carcinomas. Patient presents with anaemia. Infection (often due to obstruction) – Pulmonary infections due to blocked bronchi (lung carcinoma), Urinary infections due to blocked ureters (cervical carcinoma) Rupture or Infarction – Ovarian, Hepatocellular, and Adrenal cortical carcinomas; Melanocarcinoma metastases Thank you