Thursday, May 2, 2013

Mechanisms of Invasion and Metastases

Local Invasion:
  • Almost all benign tumors grow as cohesive expansile masses
  • Remain localized to their site of origin
  • Do not have the capacity to infiltrate, invade, or metastasize to distant sites
  • Usually have rim of fibrous capsule that separates them from host tissue
  • Rim is composed of stroma of the native tissues as its parenchymal cells atrophy under the pressure of expanding tumor
  • Tends to be contained as a discrete, readily palpable, and easily movable mass
  • Some benign tumors can be encapsulated (example = hemangiomas)
  • The growth of malignant tumors is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue
  • Poorly separated from surrounding normal tissue
  • Slowly expanding malignant tumors may develop an apparently enclosing fibrous capsule; capsule has breaks along its margin
  • Invasiveness is one of most reliable features (next to metastases) to differentiates malignant from benign tumors
  • Carcinoma in situ – displays the cytologic features of malignancy w/out invasion of the basement membrane
  • Example = carcinoma of the uterine cervix
  • Can be considered one step removed from invasive cancer
  • In time, most become invasive

Example of Disturbance of Growth:

  • Progression in cervix from normal squamous epithelium to squamous cell carcinoma in situ
  • Mild dysplasia is present when abnormal organization and cellular atypia is confined to the lower one third of the epithel layer
  • Moderate dysplasia – 1/3 to 2/3 of epithelium is involved
  • Severe dysplasia – indistinguishable from CIS since the full thickness of the epithelium is involved
  • In each of these situations the basement membrane is intact
  • Abnormal process is confined to the epith layer
Continuum:
  • Progression of cellular dysplasia to carcinoma-in-situ- to locally invasive carcinoma followed by metastases
Metastases:
  • Tumor implants discontinuous with the primary tumor
  • Unequivocally marks a tumor as malignant b/c benign neoplasms do not metastasize
  •  With few exceptions, all cancers can metastasize
  •  Exceptions are gliomas and basal cell carcinomas of the skin – both are highly invasive but rarely metastasize
  • More aggressive, more rapidly growing, and the larger the primary neoplasm, the greater the likelihood that it will metastasize
  • Strongly reduces the possibility of cure
  • About 30% of newly dx pts w/ solid tumors have metastases

Mechanisms of Invasion and Metastases:
1.      Clonal Expansion, growth, diversification, and angiogenesis
2.      Metastatic subclone adheres to and invades basement membrane
3.      Passes t/ ECM
4.      Intravasation
5.      Interaction w/ host lymphoid cells
6.      Tumor cell embolus
7.      Adhesion to basement membrane
8.      Extravasation
9.      Metastatic deposit
10.  Angiogenesis
11.  Growth

Factors in Invasion and Metastases:



Pathways of Spread:
1.      Direct seeding of body cavities or surfaces
2.      Lymphatic spread
3.      Hematogenous spread

Direct seeding of body cavities or surfaces:

  • May occur whenever a malignant neoplasm penetrates into an open field
  • Most often is the peritoneal cavity, but also can be any other cavity
  • Esp common of carcinomas arising from ovaries à coats all peritoneal surfaces w/ cancerous glaze
  • Pseudomyxoma peritonei – mucus secreting ovary and appendiceal carcinomas fill peritoneal cavity w/ gelatinous neoplastic mass

Lymphatic Spread:

  • Most common p’way for initial dissemination of carcinomas
  • Sarcomas also use this p’way
  • Pattern of lymph node involvement follows the natural routes of drainage
  • Local lymph nodes may be bypassed b/c of venous-lymphatic anastomoses, or b/c inflamm or radiation has obliterated channels
  • Regional nodes serve as effective barriers to further dissemination, at least for a while
  • Tumor-specific immune response may participate
  • Enlargement of lymph nodes may be caused by:
1.      Spread and growth of cancer cells
2.      Reactive hyperplasia

  • Nodal enlargement in proximity to a cancer does not necessarily mean dissemination of the primary lesion

Hematogenous Spread:
  1. Typical of sarcomas, but also used by carcinoma
  2.  Arteries have thicker walls, are less readily penetrated than are veins
  3. Arterial spread may occur when tumor cells pass t/ pulmonary capillary beds or pulmonary arteriovenous shunts, or pulmonary metastases give rise to tumor emboli
  4. Venous invasion: blood-borne cells follow the venous flow, draining the site of the neoplasm
  5.  Liver and lungs are most frequently involved secondarily in venous dissemination
  • All portal area drainage flows to liver
  • All caval blood flows to lungs

Grading and staging of cancer

Grading criteria
  • Degree of differentiation (e.g., low, intermediate, or high grade)
  • Nuclear features, invasiveness
Staging criteria
  •  Most important prognostic factor
TNM system
  • Universal system
  • Progresses from the least to the most important prognostic factor
  • T refers to tumor size
  •  ≥2cm correlates with metastatic ability.
  • N refers to whether lymph nodes are involved.
  •  M refers to extranodal metastases (e.g., liver, lung).
Other systems
  • For individual cancers
  •  Duke staging for intestinal cancer

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