general aspect of neoplasia
TRANSCRIPT
General Aspects of Neoplasia
Dr. Deepak K. Gupta
Introduction
• Neoplasia literally means "new growth
• “A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change” – Willis.
• Its often referred to as a tumor, and the study of tumors is called oncology.
• Neoplasms can be of two types i.e. benign and malignant
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Basic Structure• All tumors, benign and malignant,
have two basic components: • Parenchyma: made up of
transformed or neoplastic cells,– Largely determines its biologic
behavior, – Tumor derives its name.
• Stroma: supporting, host-derived, non-neoplastic, made up of connective tissue, blood vessels, and host-derived inflammatory cells– crucial to the growth of the neoplasm
- carries the blood supply – provides support for the growth of
parenchymal cells
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Benign Tumors
• A tumor is said to be benign when its microscopic and gross characteristics are considered to be relatively innocent, remain localized, non-metastatic and can be surgically removaed; the patient generally survives.
• Designated by attaching the suffix –oma
– Fibrous tissue: fibroma;
– Cartilaginous tumor: chondroma
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Benign Tumors
• Adenoma– benign epithelial neoplasms producing gland patterns – derived from glands but not necessarily exhibiting gland
patterns
• Papillomas– Benign epithelial neoplasms, growing on any surface, – Produce microscopic or macroscopic finger-like fronds
• Polyp– a mass that projects above a mucosal surface, as in the
gut, to form a macroscopically visible structure
• Cystadenomas– hollow cystic masses; typically they are seen in the ovary
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Malignant Tumors
• the lesion that can invade and destroy adjacent structures and spread to distant sites (metastasize) to cause death
• Malignant neoplasms arising in
– Mesenchymal tissue or its derivatives: sarcomas
– Epithelial cell origin: carcinomas
– Glandular pattern: adenocarcinomas
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Benign and Malignant Tumours
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SPECIAL CATEGORIES OF TUMOURS
• Mixed tumours– Two types of tumours are combined in the same
tumour– Adenosquamous carcinoma– Pleomorphic adenoma: salivary benign tumour
having combination of both epithelial and mesenchymal tissue
• Teratomas– mixture of various tissue types arising from totipotent
cells derived from the three germ cell layers—ectoderm, mesoderm and endoderm.
– Common sites: ovaries and testis
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SPECIAL CATEGORIES OF TUMOURS
• Blastomas (Embryomas)– arise from embryonal or partially differentiated cells which
would normally form blastema of the organs and tissue during embryogenesis
– more frequently in infants and children (under 5 years of age)
– neuroblastoma, nephroblastoma (Wilms’ tumour), hepatoblastoma, retinoblastoma, medulloblastoma,pulmonary blastoma
• Hamartoma– benign tumor which is made of mature but disorganised
cells of tissues indigenous to the particular organ– Pulmonary Hamartoma
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TUMOR CLASSIFICATION
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CHARACTERISTICS OF TUMOURS
• The characteristics of tumours are described under the following headings
– Rate of growth
– Cancer stem cells
– Clinical and gross features
– Microscopic features
– Local invasion (Direct spread)
– Metastasis (Distant spread)
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Rate of growth
• Generally proliferate more rapidly than the normal cells.
• Benign tumours grow slowly and malignant tumours rapidly
• Many exceptions to this generalization are there.
• Rapidly growing tumors tend to be poorly differentiated
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Rate of growth
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Cancer Stem Cells
• Cancer cell – heterogeneous population of cell which may contain Cancer Stem Cells
• It has been hypothesized that these cells -capacity to initiate and sustain the tumor
• So killing of these cells may be the principle of certain therapies.
• Whether cancer stem cells exist in all tumors is not yet clear
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Cancer Stem Cells
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Clinical Features• Benign
– Generally slow growing,
– Depending upon the location, may remain• Asymptomatic: subcutaneous lipoma
• Symptomatic: meningioma in the nervous system
• Malignant– malignant tumours grow rapidly,
– may ulcerate on the surface,
– invade locally into deeper tissues,
– may spread to distant sites (metastasis),
– systemic features such as weight loss, anorexia and anemia
– cardinal clinical features : invasiveness and metastasis
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Gross appearance
• Benign– spherical or ovoid in shape– encapsulated or well-circumscribed, – freely movable, – more often firm and uniform, unless secondary
changes like haemorrhage or infarction supervene
• Malignant– Irregular in shape,– poorly-circumscribed and extend into the adjacent
tissues– Secondary changes like haemorrhage, infarction and
ulceration are seen more often.
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Gross appearance
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Microscopic Features
• Its of greatest importance for recognising and classifying the tumours.
• These should be considered under
– Microscopic pattern
– Differentiation and anaplasia
– Tumour angiogenesis and stroma
– Inflammatory reaction.
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Microscopic Pattern
• Tumors may be either– Epithelial tumours
• acini, sheets, columns or cords of epithelium
• arranged in solid or papillary pattern
– Mesenchymal tumours• Interlacing bundles, fasicles or whorls,
• Separated from each other usually by the intercellular matrixsubstance
• Ex: cartilaginous matrix in chondroma, osteoid in osteosarcoma,
– Mixed patterns
– Haematopoietic tumours: leukaemias and lymphomas
• Benign tumours and low grade malignant tumoursreduplicate the normal structure
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Differentiation
• Extent of morphological and functional resemblance of parenchymal tumour cells tocorresponding normal cells.
• Well-differentiated: minimal deviation of neoplastic cell in structure and function as compared to normal cell
• ‘Poorly differentiated’; ‘undifferentiated’ or ‘dedifferentiated’: poor structural and functionalresemblance to corresponding normal cell.
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Anaplasia
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Anaplasia
• Following changes are noted in anaplastic cells• Loss of polarity
– basal polarity: Normally, the nuclei of epithelial cells are oriented along the basement membrane
– nuclei tend to lie away from the basement membrane
• Pleomorphism– Variation in size and shape of the tumour cells– often bigger than normal
• Nucleas:Cytoplasmic ratio– Nuclei are enlarged - disproportionate to the cell size – increased from normal 1:5 to 1:1
• Anisonucleosis– variation in size and shape of nuclei
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Anaplasia
• Hyperchromatism
– Nuclear chromatin of malignant cell is increased and coarsely clumped.
– Due to increase in the amount of nucleoprotein resulting in dark-staining nuclei
• Nucleolar changes
– prominent nucleolus or nucleoli in the nucleus reflecting
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Anaplasia
• Mitotic figures: mainly of 2 types– Normal mitotic figures: seen in some non-neoplastic
proliferating cells • like haematopoietic cells, intestinal epithelium, hepatocytes
• Certain benign tumours and some low grade malignant tumours
– Abnormal or atypical mitotic figures: malignant tumoursand are identified as tripolar, quadripolarand multipolar spindles
• Tumour giant cells– Multinucleate giant cells containing a single large and
bizarre nucleus
– Found mainly in anaplasia in malignant tumours
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Anaplasia
• Functional (Cytoplasmic) changes
– functional anaplasia as appreciated from the cytoplasmic constituents of the tumour cells
– The functional abnormality in neoplasms may bequantitative, qualitative, or both
• Chromosomal abnormalities
– abnormal genetic composition
– on division they transmit the genetic abnormality to their progeny.
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LOCAL INVASION (DIRECT SPREAD)
• BENIGN TUMOURS
– Form encapsulated or circumscribed masses
– Expand and push aside the surrounding normal tissues
– Without actually invading, infiltrating or metastasising
• MALIGNANT TUMOURS
– Initially enlarge by expansion and some well-differentiated tumours may be partially encapsulated as well
– But later they can be distinguished by invasion, infiltration and destruction of the surrounding tissue,
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METASTASIS (DISTANT SPREAD)
• defined as the development of secondary implants (metastases) discontinuous with the primary tumor, in remote tissues
• Benign tumours do not metastasise, EXCEPTION: gliomas of CNS and BCC.
• Approximately 30% of newly diagnosed patients with solid tumors (excluding skin cancers other than melanomas) present with clinically evident metastases
• An additional 20% have occult (hidden) metastases at the time of diagnosis
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Routes of Metastasis
• Cancers may spread to distant sites by following pathways:
– Lymphatic spread
– Haematogenous spread
– Spread along body cavities and natural passages
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LYMPHATIC SPREAD
• Carcinomas metastasise by lymphatic route while sarcomas favour haematogenous route.
• Lymphatic permeation: walls of lymphaticsare readily invaded by cancer cells.
• Lymphatic emboli: tumor detach to form emboli so as to be carried along the lymph to the next draining lymph node.
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HAEMATOGENOUS SPREAD
• Common route for sarcomas but certain carcinomas also frequently metastasise by this mode.
• Ex: liver, lungs, brain, bones, kidney and adrenals
• Few organs such as spleen, heart, and skeletal muscle - do not allow tumour metastasis to grow due to anatomical consideration
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HAEMATOGENOUS SPREAD
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CARCINOGENESIS: ETIOLOGY and PATHOGENESIS OF CANCER
• pathogenesis of cancer undergoes in the following 4 mechanism
– Molecular pathogenesis of cancer (genes and cancer)
– Chemical carcinogens and chemical carcinogenesis
– Physical carcinogens and radiation carcinogenesis
– Biologic carcinogens and viral oncogenesis.
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Molecular pathogenesis of cancer• Also known as genetic mechanisms of cancer• It may be either based on • Monoclonality of tumours
– single clone of cells by genetic transformation or mutation– Ex: multiple myeloma
• Genetic theory of cancer: various gene regulate the normal mechanism of growth in human body like– Proto-oncogenes: growth-promoting genes – Anti-oncogenes: growth-inhibiting or growth suppressor genes.– Apoptosis regulatory genes control the programmed cell
death.– DNA repair genes
• In cancer cell these are replaced by • Activation of growth-promoting oncogenes• Inactivation of cancer-suppressor genes• Abnormal apoptosis regulatory genes• Failure of DNA repair genes
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Molecular pathogenesis of cancer
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Chemical carcinogens and chemical
carcinogenesis
• Chemical carcinogens can be classified into• DIRECT-ACTING CARCINOGENS: do not require metabolic
activation– Alkylating agents: various anti-cancer drugs (e.g. cyclophosphamide,
chlorambucil, busulfan, melphalan, nitrosourea etc), β-propiolactoneand epoxides.
– Acylating agents: acetyl imidazole and dimethyl carbamyl chloride
• INDIRECT-ACTING CARCINOGENS (PROCARCINOGENS): prior metabolic activation before becoming potent carcinogens.– Polycyclic aromatic hydrocarbons: Anthracenes, Benzapyrene,
Methylcholanthrene– Aromatic amines and azo-dyes: β-naphthylamine, Benzidine– Naturally-occurring products: Aflatoxin Bl, Actinomycin D,
Mitomycin C, Safrole, Betel nut– Miscellaneous: Nitrosamines and nitrosamides, Vinyl chloride
monomer, Asbestos, Saccharin and cyclomates,www.facebook.com/notesdental
PHYSICAL CARCINOGENESIS
• Radiation– ultraviolet light and ionising radiation like X-rays, α-, β-
and γ-rays, radioactive isotopes, protons and neutron
– Higher dose and with high LET (linear energy transfer) caused carcinogenic effect
• Non-radiation– Continous mechanical injury to the tissues such as
from intrinsic stone
– implants of inert materials such as plastic, glass etc in prostheses
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BIOLOGIC CARCINOGENESIS• Various studies have proved the direct role of MCO’s in causing
cancer.• Parasites: Schistosoma haematobium - squamous cell carcinoma of
the urinary bladder, – Clonorchis sinensis, the liver fluke - cholangiocarcinoma.
• Fungus: Aspergillus flavus (in certain grains) - hepatocellularcarcinoma.
• Bacteria: Helicobacter pylori - chronic gastritis and peptic ulcer; its prolonged infection may lead to gastric lymphoma and gastric carcinoma,
• Viral: most important organism– Oncogenic RNA Viruses : human T-cell leukemia virus-1 (HTLV-1) , only
retrovirus that has been demonstrated to cause cancer in humans– Oncogenic DNA Viruses : -human papillomavirus (HPV), Epstein-Barr
virus (EBV), Kaposi sarcoma herpesvirus (KSHV) also called human herpesvirus 8), and hepatitis B virus (HBV)
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References
• Robbinson's basic pathology 8 ed
• Harsh Mohan - Textbook of Pathology 6th Ed.
• Color atlas of pathology
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