Page 219 - Textbook of Pathology, 6th Edition

fragments or clusters of tumour cells break off to be carried 203
in the coelomic fluid and are implanted elsewhere in the body
cavity. Peritoneal cavity is involved most often, but
occasionally pleural and pericardial cavities are also affected.
A few examples of transcoelomic spread are as follows:
a) Carcinoma of the stomach seeding to both ovaries CHAPTER 8
(Krukenberg tumour).
b) Carcinoma of the ovary spreading to the entire peritoneal
cavity without infiltrating the underlying organs.
c) Pseudomyxoma peritonei is the gelatinous coating of the
peritoneum from mucin-secreting carcinoma of the ovary or
apppendix.
d) Carcinoma of the bronchus and breast seeding to the pleura Neoplasia
and pericardium.
ii) Spread along epithelium-lined surfaces. It is unusual
for a malignant tumour to spread along the epithelium-lined
surfaces because intact epithelium and mucus coat are quite
resistant to penetration by tumour cells. However,
exceptionally a malignant tumour may spread through:
a) the fallopian tube from the endometrium to the ovaries or
vice-versa;
b) through the bronchus into alveoli; and
c) through the ureters from the kidneys into lower urinary
tract.
iii) Spread via cerebrospinal fluid. Malignant tumour of the
ependyma and leptomeninges may spread by release of
tumour fragments and tumour cells into the CSF and produce
metastases at other sites in the central nervous system.
iv) Implantation. Rarely, a tumour may spread by
implantation by surgeon’s scalpel, needles, sutures, or may
be implanted by direct contact such as transfer of cancer of
the lower lip to the apposing upper lip.

MECHANISM AND BIOLOGY OF
INVASION AND METASTASIS

The process of local invasion and distant spread by lymphatic
and haematogenous routes discussed above involves passage
through barriers before gaining access to the vascular lumen.
This includes making the passage by the cancer cells by
dissolution of extracellular matrix (ECM) at three levels— at
the basement membrane of tumour itself, at the level of
interstitial connective tissue, and at the basement membrane Figure 8.15 Mechanism and biology of local invasion and
metastasis. The serial numbers in the figure correspond to their
of microvasculature. The following steps are involved at the description in the text.
molecular level which are schematically illustrated in
Fig. 8.15. 2. Tumour cell loosening. Normal cells remain glued to
each other due to presence of cell adhesion molecules (CAMs)
1. Aggressive clonal proliferation and angiogenesis. The i.e.E (epithelial)-cadherin. In epithelial cancers, there is either
first step in the spread of cancer cells is the development of loss or inactivation of E-cadherin and also other CAMs of
rapidly proliferating clone of cancer cells. This is explained immunoglobulin superfamily, all of which results in
on the basis of tumour heterogeneity, i.e. in the population of loosening of cancer cells.
monoclonal tumour cells, a subpopulation or clone of tumour
cells has the right biologic characteristics to complete the 3. Tumour cell-ECM interaction. Loosened cancer cells are
steps involved in the development of metastasis. Tumour now attached to ECM proteins, mainly laminin and fibronectin.
angiogenesis plays a very significant role in metastasis since This attachment is facilitated due to profoundness of
the new vessels formed as part of growing tumour are more receptors on the cancer cells for both these proteins. There is
vulnerable to invasion as these evolving vessels are directly also loss of integrins, the transmembrane receptors, further
in contact with cancer cells. favouring invasion.