Neoplasia References: Pathologic Basis of Disease by Robbins and Cotran, 8th Ed. (2010)

Neoplasia

References: Pathologic Basis of Disease by Robbins and Cotran, 8th Ed. (2010)

Neoplasia (TUMOR)Definitions- “New growth” = Neoplasm- TumorOncology- Greek “oncos” = tumor- Study of tumors or neoplasms- Cancer = Malignant tumors

Neoplasia (TUMOR)Tumor- An abnormal mass of tissue- Growth exceeds that of normal tissues- Growth persists after cessation of the stimuli that initiated change- Classified: Benign vs. Malignant

What is the relationship of neoplasia to metaplasia and

dysplasia?

Metaplasia -replacement of one type of cell with another type.

• found in association with tissue damage, repair, and regeneration.

• the replacing cell type is more suited to a change in environment

Dysplasia –means disordered growth.often occurs in metaplastic epithelium,

but not all metaplastic epithelium is also dysplastic

- characterized by changes that include a loss in the uniformity of the individual cells as well as a loss in their architectural orientation.

When dysplastic changes are marked and involve the entire thickness of the epithelium but the lesion remains confined by the basement membrane, it is considered a preinvasive neoplasm and is referred to as carcinoma in situ

Once the tumor cells breach the basement membrane, the tumor is said to be invasive.

However, dysplasia does not necessarily progress to cancer. Mild to moderate changes that do not involve the entire thickness of epithelium may be reversible, and with removal of the inciting causes the epithelium may revert to normal.

Even carcinoma in situ may take years to become invasive.

The growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue.

Malignant tumors are poorly demarcated from the surrounding normal tissue.

Metaplasia and dysplasia are still forms of cellular adaptation in response to stress/injury.

Neoplasia is not.However, metaplasia and dysplasia

may lead to neoplasia.

Table on Nomenclature of Tumorsa. Originb. Cell typec. Benign and Malignant types

NEOPLASIANomenclature

2 Basic Components of TumorThe “transformed” neoplastic cellsParenchyma

The nontransformed elements such as connective tissues & blood vesselsSupporting stroma

Characteristics of Benign vs. Malignant Neoplasms

• Differentiation and Anaplasia

• Rate of Growth

• Local Invasion

• Metastasis

Differentiation & AnaplasiaParenchymal cells of neoplasmsDifferentiation- the extent to which parenchymal cells resemble comparable normal cells- morphologically & functionally

DifferentiationWell-differentiated- resemble mature normal cells of the tissue origin

Poorly differentiated (anaplastic)- Undifferentiated- primitive, unspecialized cells

DifferentiationAll benign tumors- well-differentiated

Malignant neoplasms- range from well-differentiated to undifferentiated

Anaplasia

Definition- lack of differentiation- hallmark of malignant transformation

- “ to form backward”

Lack of differentiation, or anaplasia, is often associated with many other morphologic changes.

Pleomorphism. Both the cells and the nuclei characteristically display pleomorphism—variation in size and shape. Cells within the same tumor are not uniform- some are large, some are small.

Abnormal nuclear morphology. • nuclei contain abundant chromatin and

are dark staining (hyperchromatic)• nuclei are disproportionately large for

the cell, and the nuclear-to-cytoplasm ratio may approach 1 : 1 instead of the normal 1 : 4 or 1 : 6.

• nuclear shape -variable and irregular

Mitoses• undifferentiated tumors possess large

numbers of mitoses, reflecting the higher proliferative activity of the parenchymal cells.

The presence of mitoses, however, does not necessarily indicate that a tumor is malignant or that the tissue is neoplastic.

Loss of polarity• anaplastic cells is markedly disturbed

(i.e., they lose normal polarity). Sheets or large masses of tumor cells grow in an anarchic, disorganized fashion.

Other changes • formation of tumor giant cells, some

possessing only a single huge polymorphic nucleus and others having two or more large, hyperchromatic nuclei

• vascular stroma is scant, and in many anaplastic tumors, large central areas undergo ischemic necrosis.

Rate of GrowthMost malignant tumors grow more rapidly than benign tumorsCancers from hormone sensitive tissues affected by hormone levelsE.g. uterusHormone dependence & adequacy of blood supply

Local InvasionBenign tumors- cohesive expansile masses with capsule- do not penetrate capsule & normal tissues- Discrete, readily palpable and easily movable mass- Surgically enucleated

Local InvasionMalignant tumors- Invasive, infiltrating and destroying normal tissues - Lack encapsulation- Enucleation is difficult - Surgery requires removal of some healthy, uninvolved tissues

Local InvasionCarcinoma in situ- Preinvasive stage- Cytologic features of malignancy without invasion of the basement membrane- e.g. carcinoma of uterine cervix

MetastasisDefinition- This process involves invasion of the lymphatics, blood veseels and body cavities by the tumor- Tumor implants discontinuous with the primary tumor- Single most important feature that differentiates from benign tumors

MetastasisAll cancers can metastasizeFew and major exceptions:- Gliomas- Basal cell carcinomas of the skinThe more aggressive, the more rapidly growing, the larger the primary neoplasm, the greater likelihood of metastasis

Pathways of Spread

1. Spread into body cavities2. Invasion of lymphatics3. Hematogenous spread

Seeding of body cavities and surfaces

Occurs by seeding of surfaces in peritoneal, pleural, pericardial, subarachnoid and joint spacesExample: Carcinoma of the ovary

Lymphatic SpreadMost common pathway for the initial dissemination of carcinomaPattern of lymph node involvement follows the natural routed of drainageLymph nodes are frequently enlarged

Hematogenous spreadTypical of all sarcomasFavored route for some carcinoma e.g. Kidney (renal cell carcinoma)Veins are more frequently invaded than arteriesLung and liver are common sitesOther sites: Brain and bones

Comparisons between benign and malignant tumors

Differentiation/anaplasia

Benign-well differentiated-structure typical of tissue of origin

Malignant-lack of differentiation with anaplasia- structure often atypical

Comparisons between benign and malignant tumors

Rate of growth

Benign-usually progressive and slow-mitotic figures are rare and normal

Malignant-erratic and maybe slow to rapid-mitotic figures maybe numerous and abnormal

Comparisons between benign and malignant tumors

Local Invasion

Benign-cohesive and espansile well demarcated masses-do not invade or infiltrate normal tissues

Malignant-locally invasive, infiltrating surrounding normal tissues

Comparisons between benign and malignant tumors

MetastasisBenign

-absent

Malignant-frequently present-More likely for larger and more undifferentiated masses

Grading and Staging of CancerGrading- classified as grades I to IV with increasing anaplasia

- higher grades tumors are more aggressive than lower grade tumors

Grade refers to the degree of differentiation of a neoplasm.

Grade I (or well differentiated) neoplasms closely resemble the normal tissues from which they are derived.

Grade IV(or poorly differentiated) only slightly resemble the tissues they are derived from.

Patients with Grade IV tumors have a poorer prognosis than those with Grade I tumors.

Grading and Staging of Cancer

Staging- (T) based on the size of the primary tumor- (N) extent of spread to regional lymph nodes- (M) presence and absence of blood-borne metastases- TNM system (tumor,node,metastases)- Higher stages -larger, locally invasive, metastatic tumors

Staging (TNM system)- T1 to T4 (increasing size)- N0 ( no nodal involvement) N1 to N3 (involvement of increasing number and range of nodes)- M0 (no distant metastases) M1 to M2 (presence of metastases)

Stage of a tumor refers to the extent of spread.

system used is the TNM (tumor, node, metastasis)

There are different TNMs developed for various cancers

STAGING (TNM)TNM for breast cancer (different for other

cancers):

Tis - Carcinoma-in-situT1 - Gross size of tumor is less than 2.0 cm diameterT2 - Gross size of tumor is between 2-5 cm diameterT3 - Gross size of tumor is above 5 cm diameterT4 - Tumor of any size involving chest wall or skin

N0 - No axillary node involvedN1 - Metastases to axillary nodes that are freely mobileN2 - Metastases to fixed (immobile) axillary nodesN3 - Metastases to internal mammary nodes

M0 – No metastases outside of local nodesM1 - Metastases present

Use of these grading and staging can predict prognosis for an individual patient and also allows comparison of treatment results from one centre to another.

Predisposition to cancer

• Geographic and Racial factors• Environmental and cultural influences• Age and childhood cancer• Heredity• Acquired preneoplastic disorders

Race and Geographic localeLeading cause of death in males- cancers of the lung, colon & prostateLeading cause of death in females- cancers of the lung, breast & colonEnvironmental factors influence occurrence of specific forms of cancer in different parts of the world

Environmental influences examples of environmental factors* increased risk with occupational exposure to asbestos, vinyl chloride and naphthylamine* association of CA of the oropharynx, larynx and lung with cigarette smoking* alcohol abuse – risk of CA in esophagus and liver carcinoma

AgeMost common = > 55 years of ageCommon in children < 15 yearse.g. leukemias and lymphomas

neuroblastomas, Wilm’s tumor, retinoblastomas and sarcomas

of bone and skeletal muscle

HeredityClose relatives of cancer patients have a higher than normal incidence of the same neoplasmApproximately 40% of retinoblastomas are familialSome defect in DNA repair e.g. xeroderma pigmentosum

Acquired Preneoplastic Disorders

Clinical conditions associated with increased risk of cancersCirrhosis of liver – hepatocellular CAAtrophic gastritis – stomach CAChronic ulcerative colitis – colon CALeukoplakia of the oral and genital

mucosa – squamous cell CA

Acquired Preneoplastic Disorders

Association between- Endometrial hyperplasia and endometrial carcinoma- Cervical dysplasia and cervical carcinoma- Bronchial mucosal metaplasia and dysplasia and bronchogenic CA

Clinical ManifestationsVaried and inconstantAsymptomatic lesions or nonspecific symptoms2 categories for advancing neoplasms:Abnormalities from the tumor massPhysiologic derangements produced

indirectly

Cancer’s 7 Warning Signals1. Change in bowel or bladder habits2. A sore that does not heal3. Unusual bleeding or discharge4. Thickening or lump in breast or elsewhere

5. Indigestion or difficulty in swallowing6. Obvious change in wart or mole7. Nagging cough or hoarseness

Signs of expansile growthNear or on the surface of the body- visible or palpable massGIT,GUT, Respiratory-obstruction, vomiting, jaundice, cough, urinary retentionCNS- pain, paralysis or sensory loss

Signs of infiltrative growthPainNumbnessParalysisSigns of nerve invasion are also signs of incurability

Signs of tumor necrosisTumor necrosis, ulceration, bleedingFatigue and weakness (signs of anemia)Edema, pain, tenderness and fever Fever, leukocytosis, elevation of ESR, anorexia and malaise

CachexiaLoss of body fat , wasting, and profound weakness Cancer cachexiaMultifactorial1. Loss of appetite2. Infections due to immunosuppression3. Bleeding from ulcerative lesions4. Production of cachectin

PAP SMEAR• A cytologic screening (cells are

collected and examined) which aims for cervical cancer prevention and control

• Short for Papanicolaou test to detect potentially pre-cancerous and cancerous processes of the cervix

• recommended for females 21 yrs old and above to be done every 3 years

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