Pathology of Pathology of NeoplasiaNeoplasia

Neoplasia

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Introduction:Introduction:

Inflammatory, Inflammatory, DegenerativeDegenerative & & NeoplasticNeoplastic

Growth Growth – Increase in size due to – Increase in size due to synthesis of tissue components.synthesis of tissue components.

Proliferatation-Proliferatation- Cell division. Cell division. Differentiation: Differentiation: functional and functional and

structural maturity of cells.structural maturity of cells. TumorTumor – Swelling / new growth / mass – Swelling / new growth / mass

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Controls of Growth:Controls of Growth:

Cytokines: Cyclins, Cyclin dependent Cytokines: Cyclins, Cyclin dependent kinases (CDK).kinases (CDK).

Growth factors – PDGF, FGFGrowth factors – PDGF, FGF Growth Inhibitors.Growth Inhibitors. Cancer suppressor genes – p53Cancer suppressor genes – p53 Oncogenes – c-onc, p-onc, v-onc etc.Oncogenes – c-onc, p-onc, v-onc etc.

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Non-Neoplastic Proliferation:Non-Neoplastic Proliferation:

*Controlled & Reversible*Controlled & Reversible Hypertrophy – Hypertrophy – SizeSize Hyperplasia – Hyperplasia – NumberNumber Metaplasia – Metaplasia – ChangeChange Dysplasia – Dysplasia – DisorderedDisordered

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Neoplastic Proliferation:Neoplastic Proliferation:

Uncontrolled & Irreversible*Uncontrolled & Irreversible*BenignBenign

– Localized, non-invasive.Localized, non-invasive.MalignantMalignant ( (CancerCancer))

– Spreading, Invasive.Spreading, Invasive.

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Neoplasia:Neoplasia: ProgressiveProgressive, , Purposeless, Purposeless,

Pathologic, ProliferationPathologic, Proliferation of cells of cells characterized by characterized by loss of controlloss of control over over cell division.cell division.

DNA damage at growth control genes DNA damage at growth control genes is central to development of is central to development of neoplasm.neoplasm.

Carcinogens – Chemical, physical & Carcinogens – Chemical, physical & genetic genetic DNA damage DNA damage Neoplasm. Neoplasm.

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Willis Definition:Willis Definition:

Neoplasm is an abnormal mass of Neoplasm is an abnormal mass of tissue the growth of which exceeds tissue the growth of which exceeds and is uncoordinated with that of and is uncoordinated with that of normal tissue and persists in the same normal tissue and persists in the same excessive manner after cessation of excessive manner after cessation of the stimuli which evoked the changethe stimuli which evoked the change

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Pathogenesis of Neoplasia:Pathogenesis of Neoplasia:

Normal Normal Hyperplasia Hyperplasia Metaplasia Metaplasia (DNA (DNA

damage)damage) Dysplasia Dysplasia (DNA damage)(DNA damage) (DNA damage)(DNA damage) AnaplasiaAnaplasia (DNA damage)(DNA damage) Infiltration Infiltration (DNA (DNA

damage)damage) Metastasis…. Metastasis…. Progressive DNA Damage – features of Progressive DNA Damage – features of

neoplasia.neoplasia.

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Pathogenesis of Neoplasia:Pathogenesis of Neoplasia:

Non lethal DNA Damage leading to Non lethal DNA Damage leading to uncontrolled cell division.uncontrolled cell division.

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Non-Neoplastic Neoplastic (Polyclonal) (Monoclonal)

Normal Adaptation Benign MalignantNormal Adaptation Benign Malignant Mechanism of Neoplams

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Structure of Neoplasm:Structure of Neoplasm:

Neoplastic cells Neoplastic cells parenchymaparenchyma..Non-neoplastic - Non-neoplastic - stromastroma

(Connective tissue & BV) (Connective tissue & BV)

Fast growth Fast growth less stroma less stroma Less stroma Less stroma more necrosis, more necrosis,

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Biology of Neoplasm:Biology of Neoplasm:

Cell of originCell of origin

Rate of growthRate of growth DifferentiationDifferentiation Local InvasionLocal Invasion MetastasisMetastasis

Lung cancerLung cancer Grade - low, highGrade - low, high Well, Mod, P, Un.Well, Mod, P, Un. StagingStaging StagingStaging

Lung cancer:Squamus cell carcinoma.Poorly differentiated, high grade, stage 4, Liver+

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Benign Benign Malignant:Malignant: Slow growing,Slow growing, capsulated, capsulated, Non-invasive Non-invasive do not do not

metastasize, metastasize, well well

differentiated, differentiated, suffix “oma” eg. suffix “oma” eg.

Fibroma.Fibroma.

Fast growing, Fast growing, non capsulated, non capsulated, Invasive & Invasive &

Infiltrate Infiltrate Metastasize. Metastasize. poorly poorly

differentiated, differentiated, Suffix Suffix

“Carcinoma” or “Carcinoma” or “Sarcoma”“Sarcoma”

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Nomenclature: Nomenclature: Cell of origin + SuffixCell of origin + Suffix

Suffix - omaSuffix - oma Fibroma Fibroma OsteomaOsteoma AdenomaAdenoma Papilloma Papilloma Chondroma Chondroma

Carcinoma / SarcomaCarcinoma / Sarcoma FibrosarcomaFibrosarcoma OsteosarcomaOsteosarcoma AdencarcinomaAdencarcinoma Squamous cell carcinomaSquamous cell carcinoma ChondrosarcomaChondrosarcoma

ExceptionsExceptions: Leukemia, Lymphoma, Glioma, : Leukemia, Lymphoma, Glioma,

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Grading & Staging of TumorGrading & Staging of Tumor

GradingGrading – Cellular Differentiation – Cellular Differentiation (Microscopic)(Microscopic)

StagingStaging – Progression or Spread – Progression or Spread (clinical)(clinical)

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TNMTNM: Staging of tumor:: Staging of tumor:

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Pathways of Spread:Pathways of Spread:

Direct SpreadDirect SpreadBody cavitiesBody cavitiesBlood vesselsBlood vesselsLymphaticLymphatic vesselsvessels

LungsLungs – Systemic Venous blood – Systemic Venous blood LiverLiver – GIT venous return, nutrition. – GIT venous return, nutrition. BrainBrain – End arteries. – End arteries.

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Tumor Diagnosis:Tumor Diagnosis:

HistoryHistory and Clinical examinationand Clinical examination ImagingImaging - X-Ray, US, CT, MRI - X-Ray, US, CT, MRI Tumor markers Tumor markers Laboratory analysis Laboratory analysis CytologyCytology –Pap –Pap smear, FNABsmear, FNAB BiopsyBiopsy - Histopathology, markers. - Histopathology, markers. MolecularMolecular TechTech – Gene detection. – Gene detection.

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Clinical Features.Clinical Features.

Tumor Impingement on nearby Tumor Impingement on nearby structuresstructures– Pancreatic ca on bile duct Pancreatic ca on bile duct Obst. Jaund. Obst. Jaund.

Ulceration/bleedingUlceration/bleeding– Colon, Gastric, and Renal cell carcinomasColon, Gastric, and Renal cell carcinomas

Infection (often due to Infection (often due to obstruction)obstruction)– Pneumonia, Urinary inf.Pneumonia, Urinary inf.

Rupture or InfarctionRupture or Infarction– Ovarian, Bladder, colon,Ovarian, Bladder, colon,

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Cancer CachexiaCancer Cachexia

Progressive weakness, loss of Progressive weakness, loss of appetite, anemia and profound appetite, anemia and profound weight loss (>20%)weight loss (>20%)

Often correlates with tumor mass Often correlates with tumor mass & spread& spread

Etiology includes a generalized Etiology includes a generalized increase in metabolism and increase in metabolism and central effects of tumor on central effects of tumor on hypothalamushypothalamus

Probably related to macrophage Probably related to macrophage production of TNF-aproduction of TNF-a

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Paraneoplastic SyndromesParaneoplastic Syndromes Due to Products released by tumorDue to Products released by tumor Cushing’s SyndromeCushing’s Syndrome

Adrenal, Lung Ca – ACTHAdrenal, Lung Ca – ACTH Inappropriate ADH syndrome (Hyponatremia) Inappropriate ADH syndrome (Hyponatremia)

– lung ca– lung ca Hypothalamic tumors (vasopressin)Hypothalamic tumors (vasopressin) Hypercalcemia – Ca is the common cause. – Hypercalcemia – Ca is the common cause. –

lung.lung. Hypoglycemia - insulin or insulin like Hypoglycemia - insulin or insulin like

activities Fibrosarcoma, Cerebellar activities Fibrosarcoma, Cerebellar hemangioma.hemangioma.

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summarysummary neoplasia- uncontrolled cell division neoplasia- uncontrolled cell division

non responsive to growth controls.non responsive to growth controls. Benign and MalignantBenign and Malignant Naming – Cell of origin + Suffix Naming – Cell of origin + Suffix Oma, Carcinoma, SarcomaOma, Carcinoma, Sarcoma benign benign slow-growing, well- slow-growing, well-

differentiated, localized, do not differentiated, localized, do not metastasize, amenable to surgery.metastasize, amenable to surgery.

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summarysummary

malignant neoplasms tend to be fast-malignant neoplasms tend to be fast-growing lesions which invade normal growing lesions which invade normal structuresstructures

malignant neoplasms vary in the malignant neoplasms vary in the degree of differentiation and degree of differentiation and somesome show anaplasia.show anaplasia.

malignant neoplasms are capable of malignant neoplasms are capable of infiltration, invasion & metastasis.infiltration, invasion & metastasis.

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summarysummary

The prognosis of a patient with any The prognosis of a patient with any type of neoplasm depends on a type of neoplasm depends on a number of factors including: the rate number of factors including: the rate of growth of the tumor, the size of of growth of the tumor, the size of the tumor, the tumor site, the cell the tumor, the tumor site, the cell type and degree of differentiation, type and degree of differentiation, the presence of metastasis, the presence of metastasis, responsiveness to therapy, and the responsiveness to therapy, and the general health of the patient.general health of the patient.

NEOPLASM NEOPLASM

Uncontrolled cell DivisionUncontrolled cell Division

(DNA abnormality)(DNA abnormality)