Neoplasia

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Neoplasia

• Dr. Bruce F. Burns
• Anatomical Pathology
• Ottawa Hospital

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Overview

• Characteristics of neoplasms compared to normal
  tissues
• Types of neoplasms
• Benign vs malignant
• Cellular differentiation
• Classification schemes
• Genetic basis for neoplasia

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What is a neoplasm?

• Lay term of tumor conveys usual connotations
  ie a new growth or mass
• Definition revolves around these features
• Monoclonal proliferation of cells with specific
  mutations
• Excessive and unregulated growth of these cells,
  often at the expense of surrounding normal tissue

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Biology of tumor growth
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Terms to know about when discussing neoplasia

• Metastasis - spread of a malignant tumor from
  one site to another via blood or lymph
• Benign typically refers to those tumors
  incapable of metastasis and having a good
  clinical outcome (prognosis)
• Malignant those tumors capable of invasive
  growth and/or metastasis, often fatal if not
  treated effectively

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More terms.

• Parenchyma these are the tumor cells
  themselves, usually referring to epithelial cells
  in organs.
• Stroma connective tissue cells that support the
  parenchymal cells not actually tumor cells, but
  are stimulated to grow by the tumor via growth
  factors, eg angiogenesis

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Cellular differentiation

• Tumors are often graded as to how closely they
  resemble the normal parent tissue that they are
  derived from.
• Well-differentiated means the cells are very
  similar in appearance and architectural
  arrangement to normal tissue of that organ

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Normal cervical Pap smear
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Malignant cervical Pap smear
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Colonic adenoma illustrating a
well-differentiated neoplasm similar to normal
colon mucosa
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Differentiation

• Poorly-differentiated refers to tumors that
  show only minimal resemblance to the normal
  parent tissue they are derived from.
• Anaplastic means the tumor shows no obvious
  similarity to its parent tissue, usually
  associated with aggressive behavior

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So what??????

• Differentiation often provides clues as to the
  clinical aggressiveness of the tumor
• Tumors often lose differentiation features over
  time as they become more malignant and as they
  acquire more cumulative genetic mutations
• Differentiation often predicts responsiveness to
  certain therapies, eg estrogen receptors and
  Tamoxifen in breast cancers

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Gross (macroscopic) features of two breast
neoplasms
Benign circumscribed, often encapsulated,
pushes normal tissue aside
Malignant infiltrative growth, no capsule,
destructive of normal tissues
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Classification of neoplasms

• Epithelial tumors
• Benign forms adenoma , papilloma
• Malignant forms carcinoma, eg adenocarcinoma,
  squamous cell carcinoma
• Mesenchymal tumors
• Benign forms fibroma, leiomyoma,
• Malignant forms sarcoma, eg fibrosarcoma,
  leiomyosarcoma

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Classification continued

• Tumors of lymphocytes are always malignant
  called lymphoma
• Tumors of melanocytes
• Benign nevus
• Malignant - melanoma

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Microscopic features of tumors

• Loss of normal architectural arrangement

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Microscopic features of tumors

• Pleomorphism variation in size and shape of
  cells within the neoplasm

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Microscopic features of tumors

• Mitotic activity - Increased in more malignant
  tumors and often abnormal in shape

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Precursors of neoplasia

• Hyperplasia
• Metaplasia
• Chronic inflammation
• dysplasia

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Metaplasia, dysplasia, neoplasia

• Metaplasia an adaptive change in
  differentiation, reversible, no mutations
  necessary.
• Eg- change of esophageal mucosa from squamous to
  gastric type in the setting of acid reflux
  (heartburn). Better able to withstand the
  corrosive effects of the acid.
• Metaplasia is fertile ground for development of
  dysplasia (disordered growth)

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Metaplasia, dysplasia, neoplasia

• Dysplasia refers to recognizable morphologic
  changes in cells that indicate the presence of
  genetic mutations beginning the development of a
  neoplasm
• Often graded, eg PAP smears for uterine cervical
  cancer are low and high grade

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Causes of Cancer

• Most cancer arises as the result of somatic
  mutations in the genome resulting from
• Chance (ie, we dont know)
• Environmental factors chemical, radiation,
  viruses
• Ageing
• Inherited cancer syndromes- defect in germline
  DNA

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Environmental carcinogens

• Chemicals capable of DNA damage
• Initiators vs Promoters
• Common denominator is electrophilic
  intermediates forming adducts with DNA
• Some are direct acting, others are activated in
  the body, usually in the liver by cytochrome
  P-450 enzymes

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Radiation

• Ionizing radiation x-rays, gamma rays,
  radioactive materials such as Radon gas all
  cause a variety of defects to DNA
• UV light (non-ionizing) primarily sun-exposure
  and T-T dimerization skin cancers

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Common features of viral carcinogenesis

• Oncogenic viruses typically integrate their
  genomes into host cells and enter a period of
  latency
• May be of DNA or RNA type
• DNA viruses include EBV, HPV and Hepatitis B
  virus
• RNA viruses include retroviruses like HTLV-1 and
  indirectly HIV

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Viral carcinogenesis

• Human papilloma virus (HPV) prototype
• Cause warts
• Some types have stronger cancer causing
  associations, esp 16 and 18 with uterine cervix
  cancer - Pap smears of cervix can detect
  precursor lesions of infection Rx
• Viral genes interact with human genes concerned
  with cell division

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How does HPV cause cancer?

• Gene products of certain sub-type (eg 16 and 18)
  interfere with normal cellular proteins
• Early viral proteins E6 and E7 bind p53 and RB
  proteins respectively

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Other oncogenic viruses

• Epstein-Barr virus (EBV) associated with some
  lymphomas and nasopharyngeal carcinoma
• Hepatitis B virus associated with malignant liver
  tumors