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 occurs through the following steps:
Detachment of tumor cells: Down-regulation of adhesion molecules (cadherins).
Attachment of cells to matrix components: Adhesion to laminin and fibronectin.
Degradation of extracellular matrix: Tumor-secreted enzymes like Type IV collagenase and cathepsin D degrade the basement membrane (BM) and connective tissue (CT).
Migration of tumor cells: Chemotactic factors guide the movement of tumor cells.
A. Local Spread
B. Distant Spread
Lymphatic
Hematogenous
Transcoelomic
Transluminal
Implantation
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.
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
More common in carcinoma than in sarcoma.
Two ways of lymphatic spread:
Lymphatic embolism
Lymphatic permeation
Lymphatic Embolism
Tumor invades the wall of a lymph vessel.
Tumor cells are carried as emboli in afferent lymphatics to the lymph node (LN).
Tumor emboli proliferate in the subcapsular sinus β invade the rest of the lymph node β destroy and replace it.
Spread to other nodes of the same group:
a. Via efferent lymphatics
b. Directly through the capsule
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:
Enlarged
Firm
Initially discrete β matted
Initially mobile β fixed
Microscopic: Metastatic tumor resembles the primary tumor.
Two routes exist for hematogenous spread.
Mechanism of Hematogenous Spread
Invasion of extracellular matrix by metastatic tumor cells.
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
Tumors of organs drained by systemic veins:
Lung is the primary site.
Bone and kidney as primary sites.
Tumors from organs drained via the portal vein:
1st: Hepatic vein
2nd: Liver
3rd: Other organs via portal blood
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.
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.
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.
Surgical implantation: Instruments contaminated by tumor cells during removal of the tumor β implantation of malignant cells in the surgical wound β secondary deposits.
Secondary tumor in the upper lip from the tumor of the lower lip.
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 |
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 |
Neoplasia 2
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 |
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 |