Neoplasia Flashcards

1
Q

What is Neoplasia?

A

A disorder of cell growth that is triggered by a series of aquired mutations affecting a single cell and its clonal progeny.,

Excessive and unregulated proliferation that becomes autonomous

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2
Q

Are these neoplasms?

A
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3
Q

Most Neoplasms will fall into one of three categories, what are they?

A
  • Round Cell Neoplasms
  • Mesenchymal Neoplasms
  • Epithelial Neoplasms
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4
Q

What properties do round cell neoplasms have?

A
  • Well-defined cell borders (obvious where cells starts and stops)
  • Generally round to ovoid in shape (but can have variable shapes)
  • Do not adhere to one another
  • Form sheets in histology and separate into loose, non-adherent, evenly distributed sheets of cells in cytology.
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5
Q

What properties do Mesenchymal cell neoplasms have?

A
  • Generally poorly-defined cell borders (not clear where cell starts and stops)
  • Spindle shaped - generally elongate
  • Mild to moderate adherence to one another
  • Form streams and whols in histology and loose, uneven clumps in cytology
  • Generally produce matrix (and the matrix helps us decide what type of cell it is)
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6
Q

What properties do Epithelial cell neoplasms have?

A
  • Sometime well-defined sometimes poorly defined cell borders (depends on exact cell)
  • Polygonal, cuboidal, columnar shaped cells
  • Strong adherence to one another - can sometimes see adherence molecules eg. desmosomes in keratinocytes (this can be lost in malignant transformation.)
  • Form nests, islands, clusters, lobules, ducts and acinar structures on histology and uneven, variably dense clusters on cytology
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7
Q

Explain the difference between Benign and Malignant neoplasms.

A
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8
Q

Where do Round Cell Neoplasms Origin

A
  • Mast cells (top middle) ** really important to note that mast cell granules attract eosinophils and so you will generally have mast cells and eosinophils mixed in together in a mast cell neoplasm **
  • Histiocytes/macrophages (bottom right)
  • Plasma cells (bottom left)
  • Lymphocytes (top left)
  • Melanocytes (top right) – important to note that melanocytes are a slightly odd cell. Sometimes they are round, sometimes they are spindyloid sometimes they are epithelioid. They really can do whatever they want.
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9
Q

Where to Mesenchymal Cell Neoplams originate from?

A

Arise from cells of embryonic mesodermal origin – there are many but here are some of the most common

  • Fibroblasts – produce collagen (top left)
  • Osteoblasts – produce osteoid matrix that becomes mineralised and turns into bone (top middle)
  • Chondrocytes – produce chondroid matrix (top right)
  • Endothelial cells – line blood vessel lumens (bottom left)
  • Adipocytes – contain lipid within their cytoplasm (bottom middle)
  • Skeletal muscle cells – don’t produce a matrix but characteristic morphology
  • Schwann cells
  • Smooth muscle cells
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10
Q

Where do Epithelial Cell Neoplasms originate from?

A

Arise from endodermal and ectodermal embryonic layers – there are many but here are some of the most common

  • Epidermal keratinocytes (top right)
  • Gastric mucosal epithelial cells or mucosal epithelium of any part of the alimentary tract (top middle)
  • Hepatocytes (top left)
  • Renal tubular epithelial cells (bottom left)
  • Mammary glandular epithelium (bottom middle)
  • Sebocytes - sebaceous glands in the skin
  • Prostatic epithelial cells
  • Thyroid follicular cells
  • Parathyroid follicular cells
  • Adrenal cortical cells
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11
Q

How do we name Neoplasms?

  • What is the name for Benign and Malignant neoplasms arrising from :-
  • Epithelial
  • Mesenchymal
  • Round

Give some examples

A
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12
Q

What are some local effects of neoplasias

A
  • Local organ/tissue erosion, replacement or compression
  • Obstruction
  • Hindrance of movement
  • Organ torsion/stangulation
  • Invasion/Erosion of blood vessels –> Haemorrhage
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13
Q

What is Cancer Cachexia?

A

Refers to a loss of body mass (including lean mass and fat in a disease state.

Cancer cachexia

  • Characterised by anorexia, anaemia, weight loss
  • Not associated with neoplastic demands
  • Cytokine mediated e.g. TNF-a, IL-1, IFN-y
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14
Q

What can cause Neoplasia?

A
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15
Q

Exposure to a carcinogenic substance alone will not give you cancer, what is required?

A

Initiation and several exposures to promotion.

Initiation - The initiating event involves a permanent change in DNA. For example, cells exposed to a carcinogenic initiator (such as a polycyclic hydrocarbon) sustained unrepaired DNA damage, which is fixed during replication (a rapid and irreversible change). This, alone, did not cancer, but required subsequent promotion. Initiated cells often appear normal and may remain in quiescence for an extended period of time. Given the right conditions, mutations in the initiated cells can impart cell survival and growth advantages.

Promotion – Promoters, such as croton oil (a phorbol ester from Euphorbia, that resembles diacylglycerol (DAG) and so activates protein kinase C), oestrogen and testosterone can induce tumours in initiated cells, but are non-tumorigenic by themselves or if applied before initiation. Promoters as the ones described above are not typically mutagenic and t heir effects are generally reversible once withdrawn. Essentially, a promoter causes cell growth and so provides a background of cellular proliferation against which initiated cells with enhanced proliferative ability can outgrow their neighbours.

Progression – Progression is a complex and poorly understood process that involves genetic and epigenetic changes in tumour cells. The autonomously proliferating cells can progressively undergo further accumulation of mutations and altered phenotype independently of initiation and promotion. This progression is a sort of evolution which selects those cells which are genetically unstable and so able to accumulate further growth-enhancing mutations, and outgrow their neighbours. Hallmarks of progression include karyotypic instability and increasing tumour cell heterogenecity.

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16
Q

What do Carcinogenic agents do?

A

They cause damage to the DNA (Initation)

17
Q

What are some Carcinogenic DNA viruses?

A
  • Human Papilloma virus
  • Ebstein-Barr Virus
  • Hepatitis B Virus
  • Marek’s disease (Gallid herpesvirus 2)
  • Poluoma virus
18
Q

Name some Virus and their associated Tumours in different species

A
19
Q

What is an oncogene?

A

Cancer Causing Gene

20
Q
  • Name a Tumour Suppressor
  • What does it do?
A
  • P53 (Guardian of the genome)
  • This protien acts to detect DNA damage and upon detection of such damage directs the cell cycle to halt for DNA repair or it repair cannot be undertaken the cell is sent into programmed cell death by apoptosis.
21
Q

What is one of the roes of P53 upon detecting DNA damage?

A

Is to upregulate p21 activity. P21 then inhibits cyclin-dependant kinses which, act to phosphorylate pRb, which would release the transcription factor E2F and allow cell cycle progression.

22
Q

What happens when p53 function is lost

A
  • DNA damage goes unrepaired
  • Mutations accumulate in dividing cells
  • Malignant progression
  • Loss of p21 or p16 prevents negative regulation of the cell cycle.
23
Q

Describe the Tumour Grading System

A

The most widely used staging scheme is the TNM system. This system allows for assessment of the likely course for the neoplasm, and the impact/effect of particular treatment modalities.

T – size of the primary tumour: T0 – carcinoma in situ, T1-T4 for all other carcinomas

N – Lymph node involvement: N0 – no detectable involvement. N1-N3 indicates progressive involvement

M – metastasis: M0 – no detectable metastasis, M1-M2 indicates metastasis to one and two organs.