Differentiation and anaplasia:
Apply to the parenchymal cells of neoplasms
Differentiation
Extent to which parenchymal cells resemble comparable normal cells, both morphologically and functionally
Well-differentiated tumors- cells resemble the mature normal cells of tissue of origin; better retains the fx of normal cells
Evolves from maturation or specialization of undifferentiated cells as they proliferate
Poorly-differentiated tumors – primitive-appearing, unspecialized cells
Does retain fx of normal cell; may acquire other fx’s such as elaboration of fetal ptns or ectopic hormone production
Derives from proliferation w/out maturation
Benign tumors usually well-differentiated
Malignant tumors usually range from anaplastic to well-differentiated
Anaplasia
Lack of differentiation
Example of anaplastic tumors = malignant neoplasms composed of undifferentiated cells
More rapidly growing and the more anaplastic a tumor, the less likely it is that there will be specialized functional activity
Morphology of Anaplasia:
Pleomorphism – variation in size and shape of both cell and nuclei
Hyperchromatic nuclei; nuclei contain an overabundance of DNA
Nuclei are too large for the cell
Nuclear to cytoplasmic ratio may reach 1:1 instead of normal 1:4 or 1:6
Chromatin is often coarsely clumped and distributed along the nuclear mbr
Usually see large nucleoli
High proliferative activity
Large numbers of mitoses
Atypical, bizarre mitotic figures sometimes w/ tripolar, quadripolar, or multipolar spindles
Tumor giant cells
Some possess only a single huge polymorphic nucleus, others w/ two or more nuclei
Loss of normal polarity; grow in sheets or large masses tumors in an anarchic, disorganized fashion
Vascular stroma is often scant; large central areas may undergo necrosis
Variations in cell growth and differentiation: normal and abnormal.
Increased growth.
Increased growth occurs in a tissue or organ due to increased functional demand. It can be the result of hyperplasia, hypertrophy or a combination of both. Stimuli for increased growth include hormones, growth factors and work against resistance.
Hyperplasia is an increase in cell number by cell division, often leading to an increase in the size of an organ.
Hypertrophy is an increase in cell size without cell division, usually leading to an increase in the size of an organ.
Both hyperplasia and hypertrophy can be physiological or pathological.
Some examples of physiological hyperplasia
The breast undergoes hyperplasia during puberty, pregnancy, and lactation, stimulated by hormones such as oestrogens, progesterone and prolactin.
Red cell precursors in the bone marrow undergo hyperplasia at high altitude, stimulated by erythropoietin, which has been evoked by hypoxia.
The thyroid undergoes hyperplasia in puberty and pregnancy, stimulated by increased metabolic demand.
Some examples of physiological hypertrophy
Skeletal muscle undergoes hypertrophy stimulated by increased muscle activity on exercise.
Cardiac muscle undergoes hypertrophy stimulated by sustained outflow increase in athletes.
Myometrium undergoes hypertrophy in pregnancy stimulated by oestrogens
Some examples of pathological hyperplasia
The prostate gland undergoes hyperplasia, stimulated by oestrogen.
The adrenal cortex undergoes hyperplasia (Cushing’s syndrome) stimulated by ACTH produced by pituitary, lung or other tumours.
The thyroid gland undergoes hyperplasia in Graves’ disease, stimulated by Thyroid-stimulating autoantibody.
The parathyroid gland undergoes hyperplasia stimulated by hypercalcaemia.
The endometrium undergoes hyperplasia stimulated by oestrogen.
Myointimal cells undergo hyperplasia in atheromatous plaques stimulated by Platelet Derived Growth Factor.
Keratinocytes in skin undergo hyperplasia in psoriasis, stimulated by cytokines released in an immune response.
Some examples of pathological hypertrophy
Cardiac muscle of the left ventricle undergoes hypertrophy because of increased outflow pressure eg systemic hypertension, aortic valve disease
Cardiac muscle of the right ventricle undergoes hypertrophy because of increased outflow pressure eg pulmonary hypertension, pulmonary valve disease.
Arterial smooth muscle undergoes hypertrophy in hypertension.
Decreased size of tissue or organ
This can occur in a tissue or organ due to developmental failure, or to reduction in size of a previously normal organ. This is atrophy.
Atrophy is a decrease in cell size and/or number in a previously normal tissue or organ. Decrease in cell number is mediated by apoptosis; decrease in cell size by a reduction in cell growth. Atrophy can be physiological or pathological.
Some examples of physiological atrophy
In the embryo & fetus, the notochord and branchial clefts undergo atrophy.
In the neonate, the umbilical vessels and ductus arteriosus undergo atrophy.
In early adulthood, the thymus undergoes atrophy.
In old age the uterus, testes, brain and bone all atrophy.
Some examples of pathological atrophy
Loss of function causes muscle atrophy and osteoporosis in immobilisation or weightlessness.
Loss of innervation causes muscle atrophy in nerve transection or poliomyelitis.
Loss of blood supply causes skin atrophy or bedsores in peripheral vascular disease or excess pressure.
Severe malnutrition causes atrophy in many tissues.
Loss of hormonal stimulation causes atrophy of adrenal cortex, thyroid, and gonads in hypopituitarism.
Excess hormones can cause atrophy: excess corticosteroids cause skin atrophy.
Abnormal differentiation
When mature tissues grow and differentiate abnormally, they can undergo metaplasia, dysplasia or both.
Metaplasia
Is defined as the transformation of one fully differentiated cell type into another.
Is an adaptive response to environmental stress, usually chronic irritation or inflammation; metaplastic tissues are better able to withstand the adverse environmental changes than are normal tissues
Is caused by activation and/or repression of groups of genes involved in the maintenance of cellular differentiation
There is no intrinsic gene defect (as there is in neoplasia), therefore metaplasia is reversible.
But, metaplastic tissues are more genetically unstable than their normal counterparts, so they may undergo further transformation to dysplasia and neoplasia
Can affect epithelial or connective tissue cells
Epithelial metaplasia can be:
Squamous: other epithelia transform to squamous epithelium.
Glandular: other epithelia transform to glandular epithelium.
Some examples of Squamous metaplasia are:
Ciliated pseudostratified columnar epithelium of respiratory tract; due to smoking, bronchiectasis, or chronic bronchitis.
Simple columnar epithelium of endocervix; due to changes of pH, injury, inflammation.
Transitional cell epithelium of bladder; due to Schistosomal infection or bladder calculi.
Some examples of Glandular metaplasia are:
Stratified squamous epithelium of oesophagus transforms to simple columnar epithelium due to gastro-oesophageal reflux: Barrett’s oesophagus.
Simple columnar epithelium of stomach transforms to intestinal epithelium, in chronic gastritis due to Helicobacter pylori
Mesenchymal metaplasia is much less common than epithelial metaplasia. There are three main types:
Osseous metaplasia – in old scars such as tuberculous scars in the lungs, in atheromatous plaques and in chronically damaged muscle
Chondroid metaplasia – in similar conditions to osseous metaplasia
Myeloid metaplasia (also known as extramedullary haemopoiesis) – in the spleen, liver and lymph nodes in patients with myeloproliferative diseases
Dysplasia refers to cells of abnormal phenotype that are not yet neoplastic, but are predisposed to be.
Encountered primarily in the epitheli
It is a premalignant process.
It is often preceded by metaplasia.
It is usually irreversible.
There is disordered maturation: the phenotype of the abnormal cells approaches that of malignant cells. Loss in uniformity of the individual cells as well as a loss in their architectural orientation. It is characterised by increased cell division, atypical cell morphology and lack of differentiation.
Considerable architectural anarchy
Considerable pleomorphism
Hyperchromatic nuclei
Nuclei are too large for cell
Increase numbers of mitotic figures, but conform to normal patterns; may appear in abnormal location w/in the epithelium
Examples include:
in str sq epithelium, mitoses are not confined to basal layers, may occur in surface cells.
Colonic epithelial dysplasia in longstanding ulcerative colitis.
Cervical Intraepithelial Neoplasia (CIN).
Glandular dysplasia in Barrett’s oesophagus
Paget’s disease of bone.
Carcinoma in situ
When dysplastic changes are marked and involve the entire thickness of the epithelium
Epithelial dysplasia almost invariably comes before the appearance of cancer
Dysplasia does not necessarily progress to cancer.
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