Research Oncology

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Research Oncology

• Cures (target discovery and drug development)
• Management (induction of stasis, pain, cachexia,
  etc)
• Diagnostics (early detection, pharmacogenetics)
• Prediction (genetics)
• Epidemiology
• Prevention
• Drug delivery

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The Language of Oncology

• BYU Cancer Research Center

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Commonly Used Terms

• Tumor (literally means swelling Latin tumere,
  to swell). May be benign (e.g. relatively
  harmless) or malignant (bad or dangerous)
• Malignancy -- a malignant tumor
• Cancer a malignant tumor
• Malignant tumors differ dramatically in their
  properties. Cancer is not a single type of
  disease and different cancers dont necessarily
  have the same outcomes!

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What makes a neoplasm malignant ?

• The ability to invade and/or metastasize.
• Examples Basal cell carcinoma ( a skin neoplasm)
  invades but rarely metastasizes.
• Malignant melanoma of the skin invades and can
  widely metastasize.

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Language of Oncology

• Neoplasm (meaning new growth that is
  autonomous) scientific term for a tumor. May
  be malignant or benign
• Other plasias
• Hyperplasia an increase in cell number
• Hypertrophy an increase in cell size but not
  number
• Metaplasia a reversible process where one cell
  type changes into another cell type

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Dysplasia and Anaplasia

• Dysplasia is used by pathologists to refer to
  changes in the size or arrangements of cells or
  to abnormalities in the development of tissues
  not in malignant neoplasms.
• Anaplasia is a hallmark of malignant neoplasms
  (not in benign). Cytologic anaplasia results
  from increased or altered nucleic acid synthesis
  in the cells and in other processes resulting in
  a distortion of cellular architecture away from
  the terminally differentiated state. Positional
  anaplasia results in changes in normal
  positioning of cells in tissues.

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Cancer Histology and ICD Classification

• Linda B. Piller, MD, MPH
• Assistant Professor of Biological Sciences
• May 28, 2002

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Nomenclature Benign Tumors

• --oma---for tumors of mesenchymal origin
  (fibroma, chondroma, osteoma)
• More varied nomenclature for cells of epithelial
  origin
• Adenoma---tumors derived from glands or forming
  glandular patterns (epithelial)
• Papilloma---produce finger-like projections
  (epithelial)
• Exceptions to the rule (there are many)melanoma,
  seminoma

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Nomenclature-2

• Polyp---benign unless otherwise specified
• Benign tumors variously classified according to
  cells of origin, microscopic architecture,
  macroscopic appearance

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Adenomatous Polyps of the Colon
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Liver Adenoma
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Small Intestine Lipoma
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Uterine Leiomyoma
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Most Common Benign Tumor?
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Nomenclature Malignant Tumors

• Sarcoma--arising from mesenchyme (fibrosarcoma,
  liposarcoma, osteosarcoma, leiomyosarcoma,
  rhabdomyosarcoma)
• Carcinoma--epithelial origin (squamous cell
  carcinoma, adenocarcinoma)
• Undifferentiated or poorly differentiated
  malignant tumor

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Benign vs. Malignant

• Differentiation
• Rate of growth
• Local invasion
• Metastasis

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Benign Neoplasms

• Resemble cells of origin (well-differentiated)
• Slow growth usually
• Expansile growth without infiltration or distant
  spread (metastasis)
• Fibrous capsule
• Few mitoses, uniform cells, normal nuclear-
  to-cytoplasmic (n/c) ratio

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Malignant Neoplasms

• Some degree of failure of cellular
  differentiation
• More rapid growth (correlates with level of
  differentiation)
• Potentially expansive, invasive, metastatic
• Usually no true capsule
• Increased, sometimes abnormal, mitoses, high n/c
  ratio, cell pleomorphism

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Components of Malignant Tumors

• Proliferating unregulated neoplastic cells
  constitute the parenchyma
• Connective tissue and blood vessels constitute
  the supportive stroma angiogenesis factors
  secreted by tumor for development of vascular
  stroma
• If stromal response disproportionate to number of
  tumor cells, desmoplasia

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Differentiation and Anaplasia

• Extent to which parenchymal cells resemble normal
  cells morphologically, functionally
• Well, moderately, or poorly differentiated
• Undifferentiated---anaplastic (to form
  backward) but not due to dedifferentiation
• Anaplasia cell, nuclear pleomorphism
  hyperchromasia n/c increase nucleoli
  increased, atypical mitoses orientation lost

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Cell Differentiation
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Toward Anaplasia

• Large cells
• Increased nuclear/cytoplasmic ratios
• Hyperchromatic nucleus
• Cell and nuclear pleomorphism
• Prominent nucleolus
• Atypical and increased mitoses
• Poor cell orientation
• /- Ischemic necrosis

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Normal (left) thyroid versus anaplastic thyroid
neoplasm (right)
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In-Situ Neoplasm

• Basement membrane not crossed
• Full thickness dysplasia disorderly
  proliferation, loss in uniformity of cells, loss
  of orientation, abnormal mitoses, cell
  pleomorphism--cytologic features of malignancy
• Pre-invasive
• Occurs in epithelial cells

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Functional Differentiation of Neoplastic Cells

• Better differentiated--retain functional
  capabilities
• Hormones, keratin, enzymes elaborated in more
  differentiated tumors
• The less differentiated, the less specialization
  retained
• Unanticipated functions may appear AFP, HCG,
  hormones

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Melanoma, Skin
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Malignant Melanoma ABCs

• Asymmetry
• Border irregularity
• Color variability
• Diameter gt 6 mm
• Elevation (usually but not always present)

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Squamous CellCarcinomaof the Cervix
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Hepatocellular Carcinoma
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Metastases to Liver
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Grade versus Stage of neoplastic disease

• Grade refers to the degree of anaplasia in the
  tumor. Low grade lower degree of anaplasia
  High grade highly anaplastic.
• Stage measures the degree to which the neoplasm
  has spread. The higher the number the more
  spread.