Neoplasia PDF

Neoplasia  Neoplasia = abnormal new growth Neoplasm = Tumor = abnormal newly growing mass Greek oma = tumour (examples: chondroma, lipoma, osteoma, ….) In clinical practice, a neoplasm is often called a tumour. This is not strictly correct, since the term tumour refers to all swellings, e....

Neoplasia  Neoplasia = abnormal new growth Neoplasm = Tumor = abnormal newly growing mass Greek oma = tumour (examples: chondroma, lipoma, osteoma, ….) In clinical practice, a neoplasm is often called a tumour. This is not strictly correct, since the term tumour refers to all swellings, e.g. inflammation, haematoma etc., but it is so generally accepted to use "tumour" as synonym to neoplasm. Oncology: Is the science of studying neoplasms  Definition of a Neoplasm An abnormal new growth, of cells independent of physiologic growth stimuli (autonomous). Its presence serves no useful purpose Its growth is uncoordinated with that of the surrounding tissue The growth of a neoplasm persists after cessation of the stimuli which provoked its formation  In neoplasia: proliferation, differentiation and organisation are all disturbed i.e. a neoplasm is characterized by partial or complete loss of regulation of mitosis and cell maturation, reduction or deletion of the specialized function of the cells and loss of the morphologic tissue and organ characteristics. Classification of Neoplasms Tumours are usually classified according to their clinical behaviour into Benign tumours Malignant tumours Usually grow slowly more rapidly growing, do not interfere with the destroy and infiltrate the person's well being or shorten normal structures a his life, unless the tumour encroaches on a vital organ unless effectively treated e.g. the brain or produces interfere with health and harmful substances e.g. excess eventually cause death. hormones. All tumours, benign and malignant are formed of two basic components: 1- Parenchymal neoplastic cells, (proliferating neoplastic cells) 2- Supportive stroma of connective tissue, blood vessels and possibly lymphatics Classification of Neoplasms Benign tumours Malignant tumours Epithelial Epithelial Mesenchymal Mesenchymal Germ cell tumors Germ cell tumors  Tumors of epithelial origin Origin Benign Malignant Surface squamous Squamous cell Squamous cell epithelium Papilloma carcinoma Glandular Adenoma Adenocarcinoma epithelium Neuroectoderm Nevus Melanoma  Tumors of mesenchymal origin Origin Benign Malignant Fat Lipoma Liposarcoma Fibrous tissue Fibroma Fibrosarcoma Smooth muscle Leiomyoma Leiomyosarcoma Striated muscle Rhabdomyoma Rhabdomyosarcoma Cartilage Chondroma Chondrosarcoma Bone Osteoma Osteosarcoma Blood vessels Angioma Angiosarcoma Nerve Schwannoma- Neurofibrosarcoma neurofibroma  Germ Cell Tumors (Tumours derived from totipotential cells) Mature Teratoma (benign) Immature teratoma (malignant) Characterization of benign and malignant tumours 1. Capsulation 2. Differentiation and anaplasia 3. Rate of growth 4. Metastasis 5. Recurrence after excision 6. Fate Characterization of benign and malignant tumours 1- Capsulation Benign tumours grow by expansion leading to pressure atrophy of the surrounding tissue with formation of a fibrous capsule. Though not all benign tumours are encapsulated, but there is always a plane of cleavage around the tumours. Benign tumor Capsule Uterine leiomyoma Benign tumor Plane of cleavage  Malignant tumours grow by an infiltrative manner that destroys and penetrates the surrounding tissue; they do not develop a capsule. The infiltration tends to occur in anatomic planes of cleavage Malignant tumor Malignant tumor 2- Differentiation and anaplasia Differentiation refers to the extent to which the tumour cells resemble their normal counterpart, both morphologically and functionally Anaplasia: implies dedifferentiation or loss of structural and functional differentiation of normal cells. Malignant tumours formed of undifferentiated cells are called anaplastic tumours, anaplasia is a marker of cancer. Differentiation and anaplasia Benign neoplasms are composed of well- differentiated cells that resemble very closely their normal counterpart e.g. lipoma. Mitoses are extremely scant in number and are normal in configuration. No anaplasia  2- Differentiation and anaplasia Follicular adenoma thyroid 2- Differentiation and anaplasia Malignant tumours are characterized by a wide range of parenchymal differentiation from surprisingly well-differentiated to those completely undifferentiated. Well differentiated adenocarcinoma colon Poorly differentiated carcinoma The following cytologic features characterize malignant cells: 1. Nuclear and cellular pleomorphism: wide variation in the shape and size of cells and nuclei. 2. Hyperchromatism: darkly-stained nuclei that frequently contain prominent nucleoli. 3. Nucleo-cytoplasmic ratio: approaches 1:1 instead of 1:4 or 1:6 reflecting enlargement of nuclei. 4. Abundant mitoses: reflect proliferative activity. Mitotic figures may be abnormal (atypical e.g. tripolar, quadripolar or multipolar spindles). 5. Tumour giant cells: containing a single large polypoid nucleus or multiple nuclei. 7. Anaplastic tumours also demonstrate a total loss of tissue architecture e.g. in an anaplastic tumour of uterine cervix, the normal orientation of squamous epithelial cells with respect to each other is lost (loss of polarity). 8. Well-differentiated tumours, whether benign or malignant, tend to retain the functional characteristics of their counterparts such as the production of hormones in tumours of endocrine origin or keratin in squamous epithelial tumours. Anaplastic tumours have no specialized functional activity. 3- Rate of growth qMost benign tumours grow slowly over a period of years, whereas most cancers grow rapidly, spread locally and to distant sites (metastases) and eventually kill their host. qHost factors influence growth rate. qHormones influence the growth rate, particularly of cancers arising in hormonally-responsive tissue (e.g. breast, uterus, endometrium, ovary and prostate). qAdequacy of blood supply to tumour cells is an important factor for growth of cancers. It is suggested that tumour cells themselves secrete an angiogenesis factor that promotes new vascularization. Without such blood supply, solid neoplasms can't grow beyond 2 to 3 mm in diameter. qThere are also unknown influences that may affect the rate of growth. 4- Metastasis Definition of Metastases (secondaries) These are tumour implants discontinuous from the primary tumour possibly in remote tissue. ØMetastasis marks a tumour as malignant because benign neoplasms do not metastasize. ØWith few exceptions all cancers can metastasize. The major exception is basal cell carcinoma of the skin. ØIn general, the more aggressive, the more rapidly growing, and the larger the primary neoplasm, the greater the likelihood that it will metastasize. Mechanism of invasion and metastasis 1-Invasion of extracellular matrix 2-Vascular dissemination and homing of tumor cells. qThe site where tumour cell emboli are lodged and produce secondary growths is influenced by several factors a. Vascular and lymphatic drainage from the site of the primary tumour. b. Interaction of tumour cells with organ-specific receptors c. The microenvironment of the organ or site 5. Recurrence after excision: Usually occurs in malignant tumours 6. Fate: A benign tumour is not fatal unless it is present in a vital area; on the other hand a malignant tumour is usually Differences between benign and malignant tumors Feature Benign Malignant 1-Capsulation Usually present Usually absent 2-Mode of growth By expansion By infiltration 3-Differentiation Well differentiated Variable 4-Anaplasia Absent Present 5-Rate of growth Slow Rapid 6-Metastases Does not happen May occur 7-Recurrence Usually do not Common recur 8-Fate Cured by excision Usually fatal ( if not in vital area)  Differences between benign and malignant tumors 9-Histology Benign Malignant § Cells Uniform Pleomorphic § Nuclei Normal Hyperchromatic § Mitoses Few or absent Many (abnormal) § N/C ratio Normal Increased § Blood vessels Well formed Badly formed Comparison between a benign tumor of the myometrium (leiomyoma) and a malignant tumor of similar origin (leiomyosarcoma).  Spread of malignant tumors: 1)Direct spread: Into the surrounding structures. 2. Natural passages: Tumor cells are carried along natural passages such as bronchi, ureters, and fallopian tubes. 2) Lymphatic spread: Tumor cells are transferred along lymphatic vessels to the draining lymph nodes either By : qLymphatic permeation Or qLymphatic embolization. Tumor cells grow attached to Tumor cells are carried as the endothelium of the wall emboli by the blood stream of the lymphatic till they to distant sites reach the draining lymph node PERMEATION EMBOLIZATION  Tumor cells are carried by lymph current till they lodge in draining lymph nodes where they multiply replacing most of the lymphoid tissue and cause lymph node enlargement. Carcinomas spread early by lymphatics 3. Blood Spread Sarcomas spread early by blood. Sarcomas are rich in small thin-walled, badly formed blood vessels that are easily penetrated by malignant cells. Veins are the main site of invasion as they easily invaded by the malignant cells Because they have thinner walls. Certain carcinomas have a tendency for invasion of veins Renal cell carcinoma: often invades the renal vein to grow in a snake- like fashion up to the inferior vena cava, reaching the right side of the heart to the lung. Hepatocellular carcinoma: often penetrates portal and hepatic radicles to grow within them into the main venous channels. Choriocarcinoma: usually shows widespread dissemination via the blood with its metastases reaching the lungs. Malignant melanoma Tumor cells reach the blood stream through 1. Lymphatic and thoracic duct 2. Lymphatics around the walls of veins 3. The malignant cells invade directly into blood vessels e.g. malignant tumors of stomach and tongue as the motility of these organs squeeze tumor cells into capillaries. Sites of blood borne metastases Are governed by the anatomical distribution of veins e.g. cancer of the portal venous drainage area metastasizes to the liver through portal vein. Cancer of the systemic circulation metastasizes to the lung & left side of the heart and then anywhere in the body. Cancer arising in close proximity to the vertebral column often embolizes through the paravertebral plexus (cancer of the thyroid and prostate). Sites of blood borne metastatic deposits Lung Liver Bone: Ribs, sternum, scapula, pelvic bones and the neck of the femur Brain Metastatic deposits in lung Metastatic deposits in liver Central Umblication Metastatic deposits in vertebral column Certain carcinomas have a tendency for early spread by blood with invasion of veins. And therefore spread early by blood Renal cell carcinoma Hepatocellular carcinoma Choriocarcinoma Malignant melanoma 5.Transcelomic spread Secondary tumors reaching the ovary from Primary malignancies In the stomach and pancreas and colon Krukenberg tumors of the ovary 6. Inoculation: qDuring surgical removal of a malignant tumor, malignant cells may get implanted in the surgical wound. 7. Perineural lymphatics qAlong the nerves. Grading and Staging in Cancer Grading: a pathological term denoting degree of differentiation of a malignant tumour The grading of cancer attempts to establish its aggressiveness or level of malignancy based on the cytologic differentiation of tumour cells and number of mitoses within the tumour Cancer is classified into grade I, II, III, and IV in order of increasing anaplasia. Well differentiated Undifferentiated  Staging: a clinical term denoting the degree of spread of a malignant tumour Staging is based on clinical and radiographic examination (CT, MRI), and in some cases surgical exploration with pathologic examination of resected specimens Two methods of staging are in use: a- TNM system T signifies the extent of the primary tumour in tissues. N stands for the lymph node involvement. M stands for distant metastases. b- Stages 0 to IV Incorporating the size of the primary tumour as well as the presence of nodal spread, and of distant metastases. N.B: When compared with grading, staging has proved to be of greater clinical value. The most important determinant of prognosis in cases of malignancy is its STAGE Hematoma Extravascular collection of blood Hamartoma A mass formed of haphazardly arranged tissue native to the organ from which it arises.  Special forms of neoplasia In situ carcinoma Carcinoma which has not invaded the basement membrane. Carcinoma in situ = stage 0 carcinoma preinvasive carcinoma= intraepithelial carcinoma. There are malignant changes in the epithelial cells with cytologic characteristics of malignancy (marked dysplastic changes, anaplasia, hyperchromatic nuclei, atypical mitoses, and loss of polarity), but without invasion of the basement membrane. Example: Carcinoma in situ of cervix, and all other pre- invasive tumors. Locally malignant tumor A malignant tumor which invades and destroys locally but does not send metastases Eg. Basal cell carcinoma Osteoclastoma Carcinoid tumor Adamantinoma of the jaw. Occult carcinoma: It is the term given to carcinoma which manifests itself primarily as metastases because the original tumor is not sufficiently large to produce symptoms Eg.: Carcinoma of prostate Nasopharynx Maxillary antrum Thyroid gland Adenocarcinoma: Carcinoma arising from glandular epithelium qSites: qAny glandular epithelium qEg. Mucosa of stomach, colon, and gall bladder. qBreast qLiver qPancreas qOvary qKidney qThyroid qEndometrium. Gross appearances A. Polypoid or fungating B. Ulcerative C. Diffuse thickening Polypoid adenocarcinoma Fungating or polypoid mass: The tumor appears as a cauliflower mass bulging in the lumen. Gross adenocarcinoma II II- Ulcerating: The tumour ulcerates forming a malignant ulcer with: Everted edges Hard fixed indurated base Necrotic floor  Edge Wall Floor base Gross adenocarcinoma III Diffuse infiltrating: The tumor infiltrates the whole thickness of the wall causing diffuse thickening e.g. annular carcinoma where the tumor infiltrates the wall circumferentially in a segment leading to narrowing of this part Microscopic Examination Histologically, adenocarcinoma may be: Well-differentiated. Moderately differentiated. Poorly differentiated. Well differentiated adenocarcinoma Gland formation Moderately differentiated adenocarcinoma Gland formation Poorly differentiated adenocarcinoma No gland formation + Signs of malignancy Mucoid carcinoma In this case the adenocarcinoma is characterized by excessive mucin secretion. The cells show evidenes of mucin secretion in the form of foamy with central nuclei Later on they become signet-ring like with eccentric crescent-like hyperchromatic nuclei and clear cytoplasm. Rupture of these cells may lead to mucin pools. Endoscopic appearance of mucoid carcinoma of the colon Gross appearance Adenocarcinoma colon Microscopic appearance Mucoid carcinoma: mucoid lakes  Mucoid carcinoma Mucin lakes: Foam cell Foamy cell Signet ring cell Nucleus Mucin vacuole Mesenchymal tumors  Fibroma It is a benign tumor of fibrous tissue origin. Solid firm mass Fibrocytes running in bundles Lipoma & Liposarcoma Lipoma It is a benign tumor of adult fat cells. Superficial Deep ( more likely to be malignant )  Lipoma Gross Caspsulated mass Yellow in color Soft in consistency Greasy to touch Lipoma Microscopic appearance Leiomyoma It is benign tumor of smooth muscle cells. Well circumscribed False capsule (compressed surrounding normal myometrium) CS: Whorly Intersecting bundles of smooth muscle fibers and fibrous tissue Chondroma It is a benign tumour of cartilage. Chondroma Capsulated Compartments Osteoma A benign tumor of osteoblasts Osteoma Hemangioma Benign tumor of vascular endothelium Hemangioma Microscopic Appearance Sarcomas: Malignant tumor of mesenchyme General characters: qOccurs in children and young adults. qRapid growth than carcinoma. qForm a huge bulky mass, homogeneous, white, fish- flesh like with areas of hemorrhage and necrosis (sarc-flesh). qThey are highly vascular tumors with very thin and badly formed blood vessels which lead to hemorrhage and are easily penetrated by malignant cells leading to early blood-borne metastases. Differences between carcinomas and sarcomas Carcinoma Sarcoma Late > 4th Very young age Age decade Slower Faster Rate of growth Less More Vascularity Firm to hard Soft Consistency Lymphatics Blood Spread Epithelial Mesenchymal Origin Malignant Bulky mass Form ulcer