Neoplasia basics
- 1. NEOPLASIA A brief presentation on general aspects of neoplasia
- 2. Defination, nomenclature and classification of tumours Rate of growth and features of tumours 02 INTRODUCTION CHARACTERISTICS OF TUMOUR 01 To predict tumour behavior and guide therapy GRADING AND STAGING OF CANCER 04 SPREAD OF TUMOUR Local invasion/direct spread and metastasis/distant spread 03 MAIN TOPICS
- 4. Definition: A mass of tissue formed as a result of abnormal, excessive, uncoordinated, autonomous and purposeless proliferation of cells even after cessation of stimulus for growth which caused it NEOPLASIA
- 5. The branch of science dealing with neoplasms or tumours is called oncology(oncos=tumour, logos=study). Neoplasms may be ‘benign’ when they are slow-growing and localized without causing much difficulty to the host, or ‘malignant’ when they proliferate rapidly, spread throughout the body and may eventually cause death of the host. The common term used for all malignant tumours is cancer. NOMENCLATURE
- 6. All tumours, benign as well as malignant, have 2 basic components: ‘Parenchyma’ comprised by proliferating tumour cells; parenchyma determines the nature and evolution of the tumour. ‘Supportive stroma’ composed of fibrous connective tissue and blood vessels; it provides the framework on which the parenchymal tumour cells grow. The tumours derive their nomenclature on the basis of the parenchymal component comprising them- The suffix ‘-oma’ is added to denote benign tumours. Malignant tumours of epithelial origin are called carcinomas, while malignant mesenchymal tumours are named sarcomas (sarcos = fleshy) However, some cancers are composed of highly undifferentiated cells and are referred to as undifferentiated malignant tumours. NOMENCLATURE cont…
- 7. Although, this broad generalization regarding nomenclature of tumours usually holds true in majority of instances, some examples contrary to this concept are: melanoma for carcinoma of the melanocytes, hepatoma for carcinoma of the hepatocytes, lymphoma for malignant tumour of the lymphoid tissue, and seminoma for malignant tumour of the testis Leukaemia is the term used for cancer of blood forming cells.
- 8. These tumours are made up of a mixture of various tissue types arising from totipotent cells derived from the three germ cell layers—ectoderm, mesoderm and endoderm. Most common sites for teratomas are ovaries and testis (gonadal teratomas). But they occur at extra-gonadal sites as well, mainly in the midline of the body such as in the head and neck region, mediastinum, retroperitoneum, sacrococcygeal region etc SPECIAL CATEGORIES OF TUMOURS 2. Teratomas 1. Mixed tumours When two types of tumours are combined in the same tumour, it is called a mixed tumour i) Adenosquamous carcinoma is the combination of adenocarcinoma and squamous cell carcinoma in the endometrium. ii) Adenoacanthoma is the mixture of adenocarcinoma and benign squamous elements in the endometrium. iii) Carcinosarcoma is the rare combination of malignant tumour of the epithelium (carcinoma) and of mesenchymal tissue (sarcoma) such as in thyroid. iv) Collision tumour is the term used for morphologically two different cancers in the same organ which do not mix with each other. v) Mixed tumour of the salivary gland (or pleomorphic adenoma) is the term used for benign tumour having combination of both epithelial and mesenchymal tissue elements.
- 9. Hamartoma is benign tumour which is made of mature but disorganised cells of tissues indigenous to the particular organ e.g. hamartoma of the lung consists of mature cartilage, mature smooth muscle and epithelium. Thus, all mature differentiated tissue elements which comprise the bronchus are present in it but are jumbled up as a mass. 5. Choristoma Choristoma is the name given to the ectopic islands of normal tissue. Thus, choristoma is heterotopia but is not a true tumour, though it sounds like one. Blastomas or embryomas are a group of malignant tumours which arise from embryonal or partially differentiated cells which would normally form blastema of the organs and tissue during embryogenesis. These tumours occur more frequently in infants and children Some examples of tumours in this age group: neuroblastoma, nephroblastoma (Wilms’ tumour), hepatoblastoma, retinoblastoma, medulloblastoma, pulmonary blastoma. 3. Blastomas (Embryomas) 4. Hamartoma
- 10. CLASSIFICATION . Currently, classification of tumours is based on the histogenesis (i.e. cell of origin) and on the anticipated behaviour
- 11. CHARECTERISTICS OF TUMOUR (INCLUDING SPREAD OF TUMOURS)
- 12. Majority of neoplasms can be categorised clinically and morphologically into benign and malignant on the basis of certain characteristics. However, there are exceptions—a small proportion of tumours have some features suggesting innocent growth while other features point towards a more ominous behaviour. Therefore, it must be borne in mind that based characteristics of neoplasms, there is a wide variation in the degree of deviation from the normal in all the tumours.
- 13. CHARECTERISTICS OF TUMOUR RATE OF GROWTH Causes of, cancer cells exhibiting antisocial behaviour CANCER PHENOTYPE AND STEM CELLS Features of benign and malignant tumours CLINICAL AND GROSS FEATURES MICROSCOPIC FEATURES SPREAD OF TUMOURS 1.Rate of cell production, growth fraction and rate of cell loss 2.Degree of differentiation of the tumour. Patterns and arrangement s of tumour cells Local invasion and metastasis
- 14. RATE OF GROWTH Doubling time of tumour cells Growth fraction no. of cells remaining in the proliferative pool Rate of loss of tumour cells(cell shedding) In general, malignant tumour cells have increased mitotic rate (doubling time) and slower death rate i.e. the cancer cells do not follow normal controls in cell cycle and are immortal. If the rate of cell division is high, it is likely that tumour cells in the centre of the tumour do not receive adequate nourishment and undergo ischaemic necrosis. At a stage when malignant tumours grow relentlessly, they do so because a larger proportion of tumour cells remain in replicative pool but due to lack of availability of adequate nourishment, these tumour cells are either lost by shedding or leave the cell cycle to enter into G0 (resting phase) or G1 phase.
- 15. DEGREE OF DIFFERENTIATION The rate of growth of malignant tumour is directly proportionate to the degree of differentiation. Poorly differentiated tumours show aggressive growth pattern as compared to better differentiated tumours. The regulation of tumour growth is under the control of growth factors secreted by the tumour cells. Out of various growth factors, important ones modulating tumour biology are listed below. Epidermal growth factor (EGF) Fibroblast growth factor (FGF) Transforming growth factors-β (TGF-β) Platelet-derived growth factor(PDGF) Colony stimulating factor (CSF) Interleukins (IL) Vascular endothelial growth factor (VEGF) Hepatocyte growth factor (HGF)
- 16. CANCER PHENOTYPE AND STEM CELLS Normally growing cells in an organ are related to the neighbouring cells—they grow under normal growth controls, perform their assigned function and there is a balance between the rate of cell proliferation and the rate of cell death including cell suicide (i.e. apoptosis). Thus normal cells are socially desirable. However, cancer cells exhibit antisocial behaviour as under: Cancer cells disobey the growth controlling signals in the body and thus proliferate rapidly. Cancer cells escape death signals and achieve immortality. Imbalance between cell proliferation and cell death in cancer causes excessive growth. Cancer cells lose properties of differentiation and thus perform little or no function. Due to loss of growth controls, cancer cells are genetically unstable and develop newer mutations. Cancer cells overrun their neighbouring tissue and invade locally. Cancer cells have the ability to travel from the site of origin to other sites in the body where they colonise and establish distant metastasis.
- 17. Cancer cells originate by clonal prolferation of a single progeny of a cell (monoclonality). Cancer cells arise from stem cells normally present in the tissues in small number and are not readily identifiable These cancer stem cells are called tumour-initiating cells. Their definite existence in acute leukaemias has been known for sometime and have now been found to be present in some other malignant tumours.
- 18. CLINICAL AND GROSS FEATURES Slow growing may remain asymptomatic (e.g. subcutaneous lipoma), or may produce serious symptoms (e.g. meningioma in the nervous system). grow rapidly may ulcerate on the surface , invade locally into deeper tissues may spread to distant sites (metastasis) also produce Systemic features such as weightloss, anorexia and anemia
- 19. They have a different colour, texture and consistency. Gross terms such as papillary, fungating, infiltrating, haemorrhagic, ulcerative and cystic are used to describe the macroscopic appearance of the tumours. Benign tumours are generally spherical or ovoid in shape. They are encapsulated or well-circumscribed, freely movable, more often firm and uniform, unless secondary changes like haemorrhage or infarction supervene Malignant tumours, on the other hand, are usually irregular in shape, poorly-circumscribed and extend into the adjacent tissues. Secondary changes like haemorrhage, infarction and ulceration are seen more often. Sarcomas typically have fish- flesh like consistency while carcinomas are generally firm Benign tumours Malignant tumours
- 20. 01 03 02 04 MICROSCOPIC FEATURES . microscopic pattern cytomorphology of neoplastic cells (differentiation and anaplasia) tumour angiogenesis and stroma inflammatory reaction. For recognising and classifying the tumours, the microscopic characteristics of tumour cells are of greatest importance. These features which are appreciated in histologic sections are as under:
- 21. MICROSCOPIC PATTERN The tumour cells may be arranged in a variety of patterns in different tumours as under: The epithelial tumours generally consist of acini, sheets, columns or cords of epithelial tumour cells that may be arranged in solid or papillary pattern. The mesenchymal tumours have mesenchymal tumour cells arranged as interlacing bundles, fasicles or whorls, lying separated from each other usually by the intercellular matrix substance Certain tumours have mixed patterns e.g. fibroadenoma of the breast, carcinosarcoma of the uterus and various other combinations of tumour types. Haematopoietic tumours such as leukaemias and lymphomas often have none or little stromal support.
- 22. Cytomorphology of Neoplastic Cells (Differentiation and Anaplasia) The neoplastic cell is characterised by morphologic and functional alterations Differentiation is defined as the extent of morphological and functional resemblance of parenchymal tumour cells to corresponding normal cells. If the deviation of neoplastic cell in structure and function is minimal as compared to normal cell, the tumour is described as ‘well-differentiated’ such as most benign and low-grade malignant tumours. ‘Poorly differentiated’, ‘undifferentiated’ or ‘dedifferentiated’ are synonymous terms for poor structural and functional resemblance to corresponding normal cell. Anaplasia is lack of differentiation and is a characteristic feature of most malignant tumours. Depending upon the degree of differentiation, the extent of anaplasia is also variable i.e. poorly differentiated malignant tumours have high degree of anaplasia. As a result of anaplasia, noticeable morphological and functional alterations in the neoplastic cells are observed.
- 23. Tumour Angiogenesis and Stroma TUMOUR ANGIOGENESIS. In order to provide nourishment to growing tumour, new blood vessels are formed from pre-existing ones (angiogenesis), TUMOUR STROMA. The collagenous tissue in the stroma may be scanty or excessive. In the former case, the tumour is soft and fleshy (e.g. in sarcomas, lymphomas), while in the latter case the tumour is hard and gritty (e.g. infiltrating duct carcinoma breast). Growth of fibrous tissue in tumour is stimulated by basic fibroblast growth factor (bFGF) elaborated by tumour cells. If the epithelial tumour is almost entirely composed of parenchymal cells, it is called medullary e.g. medullary carcinoma of the breast, medullary carcinoma of the thyroid. If there is excessive connective tissue stroma in the epithelial tumour, it is referred to as desmoplasia and the tumour is hard or scirrhous e.g. infiltrating duct carcinoma breast. Inflammatory Reaction At times, prominent inflammatory reaction is present in and around the tumours. It could be the result of ulceration in the cancer when there is secondary infection. The inflammatory reaction in such instances may be acute or chronic.This is due to cell-mediated immunologic response by the host The examples of such reaction are: seminoma testis (Fig. 8.10), malignant melanoma of the skin, lymphoepithelioma of the throat, medullary carcinoma of the breast, choriocarcinoma, Warthin’s tumour of salivary glands etc.
- 24. 01 02 03 04 SPREAD OF TUMOURS BENIGN TUMOURS. Most benign tumours form encapsulated or circumscribed masses that expand and push aside the surrounding normal tissues without actually invading, infiltrating or metastasising. MALIGNANT TUMOUR. They are distinguished from benign tumours by invasion, infiltration and destruction of the surrounding tissue, besides distant metastasis. Tumours invade via the route of least resistance, though eventually most cancers recognise no anatomic boundaries. Cancers extend through tissue spaces, permeate lymphatics, blood vessels, perineural spaces and may penetrate a bone by growing through nutrient foramina. invasion infiltration Distant metastasis destruction of the surrounding tissue LOCAL INVASION DIRECT SPREAD
- 25. METASTASIS (DISTANT SPREAD) Metastasis (meta = transformation, stasis = residence) is defined as spread of tumour by invasion in such a way that discontinuous secondary tumour mass/masses are formed at the site of lodgement. Metastasis and invasiveness are the two most important features to distinguish malignant from benign tumours: benign tumours do not metastasise while all the malignant tumours with a few exceptions like gliomas of the central nervous system and basal cell carcinoma of the skin, can metastasise. Routes of Metastasis 1.Lymphatic spread 2.Haematogenous spread 3.Spread along body cavities and natural passages Cancers may spread to distant sites by following pathways: Transcoelomic spread Spread along epithelium-lined Surfaces spread via cerebrospinal fluid implantation Lymphatic permeation. The walls of lymphatics are readily invaded by cancer cells and may form a continuous growth in the lymphatic channels called lymphatic permeation. Lymphatic emboli. Alternatively, the malignant cells may detach to form tumour emboli so as to be carried along the lymph to the next draining lymph node. SYSTEMIC VEINS PORTAL VEINS PULMONARY VIENS ARTERIAL SPREAD RETROGRADE SPREAD
- 26. MECHANISM AND BIOLOGY OF INVASION AND METASTASIS
- 28. ‘Grading’ and ‘staging’ are the two systems to predict tumour behaviour and guide therapy after a malignant tumour is detected. Grading is defined as the gross and microscopic degree of differentiation of the tumour, while staging means extent of spread of the tumour within the patient. Thus, grading is histologic while staging is clinical. GRADING grading is largely based on 2 important histologic features: the degree of anaplasia, and the rate of growth. Grade I: Well-differentiated (less than 25% anaplastic cells). Grade II: Moderately-differentiated (25-50% anaplastic cells). Grade III: Moderately-differentiated (50-75% anaplastic cells). Grade IV: Poorly-differentiated or anaplastic (more than 75% anaplastic cells). However, grading of tumours has several shortcomings. It is subjective and the degree of differentiation may vary from one area of tumour to the other. Therefore, it is common practice with pathologists to grade cancers in descriptive terms (e.g. well-differentiated, undifferentiated, keratinising, non-keratinising etc) rather than giving the tumours grade numbers. More objective criteria for histologic grading include use of flow cytometry for mitotic cell counts, cell proliferation Neoplasia markers by immunohistochemistry, and by applying image morphometry for cancer cell and nuclear parameters
- 29. The extent of spread of cancers can be assessed by 3 ways— -by clinical examination, -by investigations, and -by pathologic examination of the tissue removed. Two important staging systems currently followed are: -TNM staging -AJC staging. STAGING TNM STAGING T for primary tumour, N for regional nodal involvement, and M for distant metastases. For each of the 3 components namely T, N and M, numbers are added to indicate the extent of involvement, as under: T0 to T4: In situ lesion to largest and most extensive primary tumour. N0 to N3: No nodal involvement to widespread lymph node involvement. M0 to M2: No metastasis to disseminated haematogenous metastases. AJC staging. American Joint Committee staging divides all cancers into stage 0 to IV, and takes into account all the 3 components of the preceding system (primary tumour, nodal involvement and distant metastases) in each stage. Currently, clinical staging of tumours does not rest on routine radiography (X-ray, ultrasound) and exploratory surgery but more modern techniques are available by which it is possible to ‘stage’ a malignant tumour by non-invasive techniques like CT, MRI, PET etc
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