73d ago

Neoplasia 2

Modes of Spread of Malignant Tumours

  • Malignant tumors are characterized by invasion and spread.

  • Normal cells transform into cancer cells with abnormal nuclei.

  • Cancer cells invade local tissues and can break off from the primary tumor.

  • New blood vessels are stimulated to grow to supply cancer cells.

  • Cancer cells spread to other areas of the body via blood vessels or lymph channels.

Invasion (Infiltration)

  • Invasion occurs through the following steps:

    1. Detachment of tumor cells: Down-regulation of adhesion molecules (cadherins).

    2. Attachment of cells to matrix components: Adhesion to laminin and fibronectin.

    3. Degradation of extracellular matrix: Tumor-secreted enzymes like Type IV collagenase and cathepsin D degrade the basement membrane (BM) and connective tissue (CT).

    4. Migration of tumor cells: Chemotactic factors guide the movement of tumor cells.

Mechanisms of Spread of Malignant Tumors

  • A. Local Spread

  • B. Distant Spread

    1. Lymphatic

    2. Hematogenous

    3. Transcoelomic

    4. Transluminal

    5. Implantation

A. Local Spread
  • Occurs along lines of least resistance.

  • Periosteum, bone, cartilage, elastic tissue, and fibrous tissue delay direct spread.

  • Spread to skin and mucous membranes leads to ulceration.

  • Perineural spread: Spread along perineural space causes nerve compression and severe pain.

B. Distant Spread (Metastasis)
  • Metastasis: Development of secondary malignant implants not continuous with the primary tumor.

  • Note: All malignant tumors undergo local spread, but some do not give distant metastasis β†’ LOCALLY MALIGNANT TUMOURS

1. Lymphatic Spread
  • More common in carcinoma than in sarcoma.

  • Two ways of lymphatic spread:

    1. Lymphatic embolism

    2. Lymphatic permeation

Lymphatic Embolism

  1. Tumor invades the wall of a lymph vessel.

  2. Tumor cells are carried as emboli in afferent lymphatics to the lymph node (LN).

  3. Tumor emboli proliferate in the subcapsular sinus β†’ invade the rest of the lymph node β†’ destroy and replace it.

  4. Spread to other nodes of the same group:

    • a. Via efferent lymphatics

    • b. Directly through the capsule

  5. Distant groups of LNs are then infiltrated β†’ thoracic duct β†’ tumor cells enter general circulation.

Lymphatic Permeation

  • Tumor grows as solid cords within lymph vessels, causing obstruction of lymph flow β†’ localized edema.

  • Common sites: Breast, Prostate, Bronchogenic carcinoma.

Lymph Node Metastasis

  • Gross:

    1. Enlarged

    2. Firm

    3. Initially discrete β†’ matted

    4. Initially mobile β†’ fixed

  • Microscopic: Metastatic tumor resembles the primary tumor.

2. Hematogenous (Blood) Spread
  • Two routes exist for hematogenous spread.

Mechanism of Hematogenous Spread

  1. Invasion of extracellular matrix by metastatic tumor cells.

  2. Vascular dissemination and homing of tumor cells:

    • Intravasation by crossing the vascular basement membrane.

    • Aggregated tumor cells adhere to leukocytes and platelets.

    • Emboli adhere to vascular endothelium, cross BM, and become extravasated.

    • Settle in new sites β†’ release tumor-associated angiogenic factors β†’ development of a metastatic growth.

Course of Tumor Emboli

  1. Tumors of organs drained by systemic veins:

    • Lung is the primary site.

    • Bone and kidney as primary sites.

  2. Tumors from organs drained via the portal vein:

    • 1st: Hepatic vein

    • 2nd: Liver

    • 3rd: Other organs via portal blood

  3. Emboli reaching the vertebral system from thoracic, abdominal, or pelvic tumors:

    • Metastasis to the brain, spinal cord, or vertebrae WITHOUT AFFECTING THE LUNGS.

Metastasis (Secondary Deposits)

  • Gross: Multiple, well-defined, non-encapsulated nodules.

  • Cut section: Grayish-white nodules.

  • Microscopic: Resembles the primary tumor.

3. Trans-coelomic Spread (Spread Through Body Cavities)
  • Tumors of organs having a serosal covering β†’ infiltration of serosa β†’ tumor cells separate and fall into the related serous sac β†’ tumor cells are implanted on the surface of another organ β†’ proliferate to form metastasis.

  • Primary tumor (e.g., stomach) can implant on the surface of the ovary.

Examples of Trans-coelomic Spread

  • Trans-peritoneal spread:

    • Gastric carcinoma β†’ metastatic omental nodules & hemorrhagic ascites.

    • Krukenberg tumor: Bilateral ovarian metastatic deposits with associated gastric carcinoma.

  • Trans-pleural & trans-pericardial spread:

    • Lung carcinoma β†’ metastatic deposits on the diaphragm, hemorrhagic pleural & pericardial effusion.

  • Malignant brain tumors:

    • If reaching the surface β†’ malignant cells get within cerebrospinal fluid β†’ metastasis on the lining of ventricles, base of brain & spinal cord.

4. Metastasis by Trans-luminal Spread
  • Through natural passages

  • Transitional cell carcinoma of the renal pelvis β†’ Cells detach β†’ pass through the ureter β†’ get implanted on the mucosa of the urinary bladder forming a metastatic nodule.

5. Direct Implantation
  1. Surgical implantation: Instruments contaminated by tumor cells during removal of the tumor β†’ implantation of malignant cells in the surgical wound β†’ secondary deposits.

  2. Secondary tumor in the upper lip from the tumor of the lower lip.

Differences Between Carcinomas and Sarcomas

Feature

Carcinoma

Sarcoma

Origin

Malignant tumor of epithelial origin

Malignant tumor of mesenchymal origin

Incidence

More common

Less common

Age

Mostly above 40

Mostly below 40

Mode of Growth

Mainly by infiltration

By expansion

Spread

Relatively slower, early lymphatic, later by blood

Faster, early by blood, rarely lymphatic

Gross Features of Carcinoma and Sarcoma

Feature

Carcinoma

Sarcoma

Size

Large, but generally smaller than sarcoma

Much larger than carcinoma

Boundaries

Usually ill-defined

Much more defined

Consistency

Usually hard

Usually soft and fleshy

Cut Section

Grey with areas of hemorrhage and necrosis

Pink [highly vascular]: usually with hemorrhage & marked necrosis

Site

Infiltrating ill-defined mass

Irregular mass

Shape

Fungating, ulcerating, or infiltrating

Arises from sub-epithelial tissues, giving an irregular mass


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Neoplasia 2

Modes of Spread of Malignant Tumours

  • Malignant tumors are characterized by invasion and spread.
  • Normal cells transform into cancer cells with abnormal nuclei.
  • Cancer cells invade local tissues and can break off from the primary tumor.
  • New blood vessels are stimulated to grow to supply cancer cells.
  • Cancer cells spread to other areas of the body via blood vessels or lymph channels.

Invasion (Infiltration)

  • Invasion occurs through the following steps:
    1. Detachment of tumor cells: Down-regulation of adhesion molecules (cadherins).
    2. Attachment of cells to matrix components: Adhesion to laminin and fibronectin.
    3. Degradation of extracellular matrix: Tumor-secreted enzymes like Type IV collagenase and cathepsin D degrade the basement membrane (BM) and connective tissue (CT).
    4. Migration of tumor cells: Chemotactic factors guide the movement of tumor cells.

Mechanisms of Spread of Malignant Tumors

  • A. Local Spread
  • B. Distant Spread
    1. Lymphatic
    2. Hematogenous
    3. Transcoelomic
    4. Transluminal
    5. Implantation

A. Local Spread

  • Occurs along lines of least resistance.
  • Periosteum, bone, cartilage, elastic tissue, and fibrous tissue delay direct spread.
  • Spread to skin and mucous membranes leads to ulceration.
  • Perineural spread: Spread along perineural space causes nerve compression and severe pain.

B. Distant Spread (Metastasis)

  • Metastasis: Development of secondary malignant implants not continuous with the primary tumor.
  • Note: All malignant tumors undergo local spread, but some do not give distant metastasis β†’ LOCALLY MALIGNANT TUMOURS
1. Lymphatic Spread
  • More common in carcinoma than in sarcoma.
  • Two ways of lymphatic spread:
    1. Lymphatic embolism
    2. Lymphatic permeation
Lymphatic Embolism
  1. Tumor invades the wall of a lymph vessel.
  2. Tumor cells are carried as emboli in afferent lymphatics to the lymph node (LN).
  3. Tumor emboli proliferate in the subcapsular sinus β†’ invade the rest of the lymph node β†’ destroy and replace it.
  4. Spread to other nodes of the same group:
    • a. Via efferent lymphatics
    • b. Directly through the capsule
  5. Distant groups of LNs are then infiltrated β†’ thoracic duct β†’ tumor cells enter general circulation.
Lymphatic Permeation
  • Tumor grows as solid cords within lymph vessels, causing obstruction of lymph flow β†’ localized edema.
  • Common sites: Breast, Prostate, Bronchogenic carcinoma.
Lymph Node Metastasis
  • Gross:
    1. Enlarged
    2. Firm
    3. Initially discrete β†’ matted
    4. Initially mobile β†’ fixed
  • Microscopic: Metastatic tumor resembles the primary tumor.
2. Hematogenous (Blood) Spread
  • Two routes exist for hematogenous spread.
Mechanism of Hematogenous Spread
  1. Invasion of extracellular matrix by metastatic tumor cells.
  2. Vascular dissemination and homing of tumor cells:
    • Intravasation by crossing the vascular basement membrane.
    • Aggregated tumor cells adhere to leukocytes and platelets.
    • Emboli adhere to vascular endothelium, cross BM, and become extravasated.
    • Settle in new sites β†’ release tumor-associated angiogenic factors β†’ development of a metastatic growth.
Course of Tumor Emboli
  1. Tumors of organs drained by systemic veins:
    • Lung is the primary site.
    • Bone and kidney as primary sites.
  2. Tumors from organs drained via the portal vein:
    • 1st: Hepatic vein
    • 2nd: Liver
    • 3rd: Other organs via portal blood
  3. Emboli reaching the vertebral system from thoracic, abdominal, or pelvic tumors:
    • Metastasis to the brain, spinal cord, or vertebrae WITHOUT AFFECTING THE LUNGS.
Metastasis (Secondary Deposits)
  • Gross: Multiple, well-defined, non-encapsulated nodules.
  • Cut section: Grayish-white nodules.
  • Microscopic: Resembles the primary tumor.
3. Trans-coelomic Spread (Spread Through Body Cavities)
  • Tumors of organs having a serosal covering β†’ infiltration of serosa β†’ tumor cells separate and fall into the related serous sac β†’ tumor cells are implanted on the surface of another organ β†’ proliferate to form metastasis.
  • Primary tumor (e.g., stomach) can implant on the surface of the ovary.
Examples of Trans-coelomic Spread
  • Trans-peritoneal spread:
    • Gastric carcinoma β†’ metastatic omental nodules & hemorrhagic ascites.
    • Krukenberg tumor: Bilateral ovarian metastatic deposits with associated gastric carcinoma.
  • Trans-pleural & trans-pericardial spread:
    • Lung carcinoma β†’ metastatic deposits on the diaphragm, hemorrhagic pleural & pericardial effusion.
  • Malignant brain tumors:
    • If reaching the surface β†’ malignant cells get within cerebrospinal fluid β†’ metastasis on the lining of ventricles, base of brain & spinal cord.
4. Metastasis by Trans-luminal Spread
  • Through natural passages
  • Transitional cell carcinoma of the renal pelvis β†’ Cells detach β†’ pass through the ureter β†’ get implanted on the mucosa of the urinary bladder forming a metastatic nodule.
5. Direct Implantation
  1. Surgical implantation: Instruments contaminated by tumor cells during removal of the tumor β†’ implantation of malignant cells in the surgical wound β†’ secondary deposits.
  2. Secondary tumor in the upper lip from the tumor of the lower lip.

Differences Between Carcinomas and Sarcomas

FeatureCarcinomaSarcoma
OriginMalignant tumor of epithelial originMalignant tumor of mesenchymal origin
IncidenceMore commonLess common
AgeMostly above 40Mostly below 40
Mode of GrowthMainly by infiltrationBy expansion
SpreadRelatively slower, early lymphatic, later by bloodFaster, early by blood, rarely lymphatic

Gross Features of Carcinoma and Sarcoma

FeatureCarcinomaSarcoma
SizeLarge, but generally smaller than sarcomaMuch larger than carcinoma
BoundariesUsually ill-definedMuch more defined
ConsistencyUsually hardUsually soft and fleshy
Cut SectionGrey with areas of hemorrhage and necrosisPink [highly vascular]: usually with hemorrhage & marked necrosis
SiteInfiltrating ill-defined massIrregular mass
ShapeFungating, ulcerating, or infiltratingArises from sub-epithelial tissues, giving an irregular mass