Introduction to Neoplasia

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• Introduction to Neoplasia

Marcio Gomes, MD, PhD Surgical Pathologist, The
Ottawa Hospital Assistant Professor, The
University of Ottawa
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A NEOPLASM is an abnormal mass of cells
which Exhibits uncontrolled proliferation Per
sists in its growth after the stimulus which
originally produced the growth has stopped
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FEATURES OF NEOPLASIA

• An irreversible process
• Does not respond to normal growth controls
• The cell has undergone a fundamental and
  permanent modification (DNA damage)
• End result is uncontrolled (autonomous)cell
  growth

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• List two characteristics of benign and malignant
  neoplasms

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BENIGN

• A neoplasm which does not invade adjacent tissues
  or spread to distant sites.
• Usually not lethal.
• However, may be life-threatening if
• it forms in a critical location
• it grows to a large size
• it obstructs important channels in the body
• it ulcerates or bleeds
• it produces endocrine disturbances

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MALIGNANT

• A neoplasm which
• Invades normal adjacent tissues (including blood
  vessels or lymphatic)
• and
• may spread to distant sites (metastasize),
  setting up secondary neoplastic masses.
• Usually shows cytologic differences from the
  parent tissue
• Usually less functionally differentiated.

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• CARCINOMA
• A malignant neoplasm which arises from an
  epithelial cell.
• SARCOMA
• A malignant neoplasm which arises from a
  mesenchymal cell.

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CARCINOMA-IN-SITU

• Morphologically malignant cells have fully
  occupied a site (usually an epithelium) but have
  not yet invaded into the underlying or adjacent
  tissue.
• Often becomes an invasive carcinoma after a
  period of time (usually years).

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FIG 4.12
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Tubular Adenoma
Villous Adenoma
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MALIGNANT TRANSFORMATION

• A malignant neoplasm has arisen from within a
  pre-existing benign neoplasm.
• eg colon
• 3-5 of resected TAs contain foci of carcinoma
• 40 of resected VAs contain foci of carcinoma
• The risk of carcinoma increases with increasing
  size of the lesion and the amount villous
  component.

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INVASION

• A property of malignant cells
• Malignant cells break through their basement
  membrane and begin to grow within the connective
  tissue stroma of the tissue of origin.
• Malignant cells may then grow directly into
  adjacent tissues/organs OR grow through the wall
  of blood vessels/lymphatic channels
• When invasion occurs, the patient may experience
• obstruction of a body channel
• bleeding (invasion of blood vessels)
• pain(invasion of nerve roots)

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• Define metastasis
• Describe the different types of spread of
  neoplastic cells

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METASTASIS (secondary neoplasm)
PRIMARY NEOPLASM

• A neoplasm which has originated from the tissue
  at a given site.

• A secondary neoplasm
• A subpopulation of malignant cells which has
• detached from the primary (parent) neoplasm
• spread to a distant site
• formed a secondary neoplastic mass (which may
  then grow, invade adjacent normal tissue and
  spread

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METASTASIS (secondary neoplasm)

• A secondary neoplasm
• A subpopulation of malignant cells which has
• detached from the primary (parent) neoplasm
• spread to a distant site
• formed a secondary neoplastic mass (which may
  then grow, invade adjacent normal tissue and
  spread

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METASTASIS (secondary neoplasm)cont

• One of the defining features of a malignant
  neoplasm
• The transfer of malignant cells from one site to
  a distant site.
• Pathways of metastatic spread
• Via blood vessels (hematogeneous spread)
• Via lymphatic channels (lymphatic spread)
• Seeding across the body cavity (trans celomic
  spread)
• Metastases often (but not always) resemble the
  primary neoplasm histologically.

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NAMING (CLASSIFICATION) OF NEOPLASMS

• The word TUMOR is a non-specific term which
  originally meant swelling or local enlargement.
  Now the term is used almost exclusively to mean
  neoplasm.
• Neoplasms are generally named according to their
  cell of origin or by some characteristic of their
  growth.

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• Benign neoplasms end with the suffix oma.
  e.g. a benign neoplasm of smooth muscle is called
  a leiomyoma
• leio smooth
• my muscle
• oma benign

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• MALIGNANT NEOPLASMS
• Named according to cell of origin.
• ending
• carcinomadenotes epithelial origin
• or
• sarcomadenotes mesenchymal origin.
• Ex
• squamous carcinoma - malignant neoplasm arising
• from squamous epithelium
• chondrosarcoma - malignant neoplasm arising
• from cartilage.

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Exceptions to nomenclature rules

• Historically names for malignant
• neoplasms which have been carried over into
  current use BUT,end with the suffix oma.
• Ex
• Melanoma a malignant neoplasm arising from
  melanocytes in the skin
• lymphoma a malignant neoplasm arising in lymph
  nodes
• hepatoma a malignant neoplasm arising in the
  liver

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Steps involved in the formation of metastases

1. invasion of the basement membrane underlying the
   primary neoplasm
2. movement of neoplastic cells through the
   extracellular matrix
3. invasion of lymphatics or blood vessels (usually
   capillaries or venules) at the primary site
4. release of cells from the primary neoplasm into
   these thin-walled vascular channels
5. transport of the neoplastic cells in the
   circulation
6. cells lodge in the micro-circulation of a
   different tissue/organ
7. neoplastic cells penetrate from the vessel lumen
   into the parenchyma of the new tissue/organ
8. cells grow autonomously in the new site, to make
   secondary neoplasms

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Benign Malignant
Expansile growth C often encapsulated C well demarcated Invasive growth C non-encapsulated C poorly circumscribed
No metastases Metastases
Slow growth May have rapid growth
Necrosis, hemorrhage, ulceration not frequent Necrosis, hemorrhage, ulceration frequent
No systemic symptoms Systemic symptoms present cachexia, anemia, anorexia, etc.
If an endocrine neoplasm, may hyperfunction Rarely show hyperfunctioning
Tend to reproduce the architectural patterns of the parent tissue in their histology Less regular histologic appearance Diminished to complete loss of normal architectural pattern and cellular differentiation in histology Loss of polarity of cells Excess stratification of cells
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Benign Malignant
Nucleus Normal size, smooth contour of nuclear membrane, finely dispersed chromatin, normal staining reaction Nucleus Enlarged size, often irregular shape, contour of nuclear membrane indented or folded, coarse clumping of chromatin, hyperchromatic, one or more prominent nucleoli
Ratio of nuclear size/cytoplasmic size is normal Nuclear/cytoplasmic ratio often increased
Few or no mitoses Increased number of mitoses
Normally shaped mitoses Often abnormal configurations of mitoses
Normal chromosomes Cytogenetic, abnormalities translocations, deletions, etc.
Diploid chromosome number Often aneuploid chromosome number
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• For further reading on neoplasia, please see
  Robbins Pathologic Basis of Disease, 7th edition,
  2004