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Disorders of growth

  • Decreased cell growth
    • Atrophy: shrinkage of a tissue; due to apoptosis or autophagy
    • Agenesis or hypoplasia: primary failure of an organ/tissue to grow; or decreased growth
  • Increased cell growth
    • Hypertrophy
    • Hyperplasia
  • Autonomous cell growth - 'Neoplasia

Note that hyperplasia/hypertrophy are in response toa stimulus that, if removed, will result in the growth stopping. This is different to neoplasia

The cell cycle

  • Most epithelial cells are continually cycling
  • Other cells (e.g. liver) are quiescent but can regenerate by hyperplasia
  • Cardiac myocytes don't have the capacity to go back into the cell cycle (terminally differentiated); therefore there can be no hyperplasia, but there can be hypertrophy
  • Hyperplasia and hypertrophy often occur together
  • Population of a cell depends on 1) proliferation 2) cell death 3) differentiation and 4) the extent to which stem cells differentiate into this population
    • Only the cells in the basal area of the skin can proliferate (once terminally differentiated, can't divide any more)

The normal breast

  • Acini lined by lobular epithelium (cuboidal), CT surrounding lobules
  • Lactating breast: hyperplasia. Lobule has grown greatly. Increased cell division made it larger, and the acinar cells became bigger because their cytoplasms are filled with mother's milk
    • Both hypertrophy and hyperplasia reflecting the function of the breast, due to hormones of pregnancy
    • Note that hyperplasia and hypertrophy are normal phenomena brought upon by normal physiology; reversible

Cardiac hypertrophy

  • LV
  • Increase in size (not number) of myocytes, in response to aortic stenosis

Nodular prostatic hyperplasia

  • Example of pathological hyperplasia
  • Very common disease
  • Enlargement of prostate with age
  • Can result in obstruction of urinary flow
  • AKA benign prostatic hyperplasia
  • Androgen-dependent proliferation of epithelium and stroma of prostate
  • Zones of prostate: central zone, TZ, PZ
  • CZ is particularly susceptible to hyperplasia in response to androgens
  • Proliferating masses of tissue = nodule blobs in prostate
    • Forms cysts as well
    • Obstructs outflow of urine
  • Histo: capsule outside, hypertrophic and hyperplastic tissue lining acini
    • Too many of them (crowding; forming fingerlike projections): hyperplasia
    • Long and columnar: hypertrophic; due to this, they're producing too much mucin

Neoplasm

  • A cellular phenomenon seen in complex organisms, in which altered cells show autonomous growth, and form clonal and multicellular masses
  • Occurs within an individual cell and its offspring
  • Only occurs in complex organisms - only these complex organisms have elaborate mechanisms for growth control, which can go awry to produce neoplasia
  • The mass of cells produced is clonal (all from one parent cell)

Tumour nomenclature

Tumours are according to:

  • 1) Histogenesis/differentiation/cell type (tissue of origin)
  • 2) Behaviour (benign vs malignant)
    • Just by recording how things that look a certain way will behave

Naming convents for tumours

  • Prefix reflects nature of tissue of origin
  • Benign = oma
  • Note adipocytes: lipoma/liposarcoma and lymphoid: lymphoma and myeloma
  • Sarcoma = malignant tumour of mesenchymal origin
  • Lymphoma, myeloma and melanoma are stupidly malignant (naming fail)

Epidemiology of malignant neoplasms

Benign neoplasms are very common, most are harmless. Each of us is riddled with them. SCC (skin cancers) are so common that no-one counts them. Just burn them off or cut them out. All malignancies other than these SCC are reported to government for them to keep track.

  • Overall incidence
  • Common malignancies
  • Commonly fatal malignancies
  • Lifetime risk of cancer in NSW is 1/3.5

Cancer incidence and mortality

  • People get older, so cancer is increasing. But even with age-standardisation, there is an increasing prevalence of cancers. Males' spike is due to PSA screening for prostate cancer.
  • Lung cancer is commonest cause of death by cancer (preventable by not smoking). If you get lung cancer, the chances of dying are high (only beaten by pancreatic cancer)
  • Brackets = percentage of deaths. Outside brackets = incidence

Biological basis of neoplasia

  • Mnemonic: SESLIT
    • Sustained angiogenesis
    • Evading apoptosis
    • Self-sufficiency in growth signals
    • Limitless replicative potential
    • Insensitivity to anti-growth signals
    • Tissue invasion and metastasis
  • Key features of neoplasms
    • Clonality
    • Heterogeneity
  • Subsequent selection of phenotypes that characterise neoplasia
    • Altered cell growth
    • Altered cell differentiation
    • Change in relationship to surrounding cells and tissues
  • Clonality - all derived from same cell; but the cancer cells are actually heterogeneous
  • By Darwin's theory, there will be evolutionary changes (predictable based on the past) within the clone to get the characteristics needed to outstrip its competitor cells
  • Tumours are heterogenous because underlying the tumour phenomenon is instability in the genome and the epigenetics of the tumour
    • Therefore the process of natural selection can be sped up tremendously within tumour cells
    • Selection characteristics = the list of things in the mnemonic above; e.g. enter the cell cycle more rapidly (appears less differentiated because it's not making structural proteins, just to be able to replicate), metastasise (spread away from home), induce blood supply, evade apoptosis, evade immune system, etc

Growth of tumours

Alterations in cell growth

  • It can take 10-30 years to transfer from transformed cell to a detectable mass
  • Then from the small mass to a large mass, it doesn't take very long (relatively small increase in number of cells)

Altered cell differentiation

  • More energy put into reproduction, less energy put into creating structural proteins
  • Very common appearance in histopathology

Morphological changes in neoplastic cells

  • Changes in the appearance of individual cells because of loss of normal differentiation is _____

Cervical epithelium

  • Can see through histo that the cervix is neoplastic and how neoplastic it is
    • Irregular, increased N:C ratio
    • Cell overall gets smaller (not making keratin, just dividing)
    • Most severe state (CIN III): nearly all of the cell is nucleus

3. Changes in relationship to surrounding cells and tissues

  • Changes in epithelial organisation
    • Eg secretory
    • Individiual cells show some of the things we talked about above, but also the glands themselves are distorted, don't behave as normal
    • Degree to which the cells are organising themselves is used to estimate how well differentiated the neoplasm is (and how bad it is)
    • Undifferentiated carcinoma: sheets of cells, unorganised
    • Pictures: note the different levels of organisation of the colonic epithelium, first with irregular glands, then to sheets of cells
  • Induction of stroma
    • Ingrowth of blood vessels
    • Blood vessels supported by connective tissue
    • The body often responds to invasive tumour by forming scar tissue (desmoplasia).
      • This gives cancers their hard feel, and also are tethered to neighbouring material (cancer the crab, grabs onto surrounding tissues)
  • Tissue invasion and distant spread
    • Separates benign and malignant tumours
    • Compare adenoma to adenocarcinoma
    • Around adenocarcinoma, note surrounding adenoma, and the invasive carcinoma. The invasive cell randomly mutated and continued to sap surrounding tissues; proliferated beyond its peers due to this adaptation allowing it to have its own private nutrient supply
  • Ultimate adaptation of a tumour cell is to be in its own environment where it can proliferate (due to natural selection, not because it's nasty)