C h a p t e r 7
Neoplasia
135
The
seeding
of cancer cells into body cavities occurs
when a tumor erodes and sheds cells into these spaces.
2,3
Most often, the peritoneal cavity is involved, but other
spaces such as the pleural cavity, pericardial cavity, and
joint spaces may be involved. Seeding into the perito-
neal cavity is particularly common with ovarian can-
cers. Similar to tissue culture, tumors in these sites grow
in masses and often produce fluid (e.g., ascites, pleural
effusion).
2
The seeding of cancers is often a concern dur-
ing the surgical removal of cancers, where it is possible
to inadvertently introduce free cancer cells into a body
cavity such as the peritoneal cavity.
8
Metastatic Spread
The term
metastasis
is used to describe the development
of a secondary tumor in a location distant from the pri-
mary tumor.
2,3
Metastatic tumors frequently retain many
of the microscopic characteristics of the primary tumor
from which they were derived. Because of this, it usually
is possible to determine the site of the primary tumor
from the cellular characteristics of the metastatic tumor.
Some tumors tend to metastasize early in their devel-
opmental course, while others do not metastasize until
later. Occasionally, a metastatic tumor will be found far
advanced before the primary tumor becomes clinically
detectable.
Malignant tumors disseminate by one of two path-
ways: lymph channels (lymphatic spread) or blood ves-
sels (hematogenous spread).
2
Lymphatic spread is more
typical of carcinomas, whereas hematogenous spread is
favored by sarcomas.
Lymphatic Spread.
In many types of cancer, the first
evidence of disseminated disease is the presence of
tumor cells in the lymph nodes that drain the tumor
area.
9
When metastasis occurs by way of the lymphatic
channels, the tumor cells lodge first in the initial lymph
node that receives drainage from the tumor site. Once
in this lymph node, the cells may die because of the lack
of a proper environment, remain dormant for unknown
reasons, or grow into a discernible mass (Fig. 7-4). If
they survive and grow, the cancer cells may spread from
more distant lymph nodes to the thoracic duct, and then
gain access to the blood vasculature. Furthermore, can-
cer cells may gain access to the blood vasculature from
the initial node and more distant lymph nodes by way
of tumor-associated blood vessels that may infiltrate the
tumor mass.
The term
sentinel node
is used to describe the ini-
tial lymph node to which the primary tumor drains.
10
Because the initial metastasis in breast cancer is almost
always lymphatic, lymphatic spread and, therefore,
extent of disease may be determined through lymphatic
mapping and sentinel lymph node biopsy. This is done
by injecting a radioactive tracer and blue dye into the
tumor to determine the first lymph node in the route
of lymph drainage from the cancer. Once the sentinel
lymph node is identified, it is examined to determine
the presence or absence of cancer cells. The procedure
is also used to map the spread of melanoma and other
cancers that have their initial metastatic spread through
the lymphatic system.
Hematogenous Spread.
With hematogenous spread,
cancer cells commonly invade capillaries and venules,
whereas thicker-walled arterioles and arteries are rela-
tively resistant. With venous invasion, blood-borne neo-
plastic cells follow the venous flow draining the site of
the neoplasm, often stopping in the first capillary bed
they encounter. Since venous blood from the gastroin-
testinal tract, pancreas, and spleen is routed through the
portal vein to the liver, and all vena caval blood flows
to the lungs, the liver and lungs are the most frequent
metastatic sites for hematogenous spread.
2,3
Although the site of hematologic spread usually is
related to vascular drainage of the primary tumor, some
tumors metastasize to distant and unrelated sites. For
example, prostatic cancer preferably spreads to bone,
bronchogenic cancer to the adrenals and brain, and neu-
roblastomas to the liver and bones. The selective nature
of hematologic spread indicates that metastasis is a finely
orchestrated and multistep process, in which only a
small, select clone of cancer cells has the right combina-
tion of gene products to perform all of the steps needed
for establishment of a secondary tumor (Fig. 7-5). To
metastasize, a cancer cell must be able to break loose
from the primary tumor, invade the surrounding extra-
cellular matrix, gain access to a blood vessel, survive
its passage in the bloodstream, emerge from the blood-
stream at a favorable location, invade the surrounding
tissue, and begin to grow and establish a blood supply.
Considerable evidence suggests that cancer cells
capable of metastasis secrete enzymes that break down
the surrounding extracellular matrix, allowing them to
FIGURE 7-4.
Metastatic carcinoma in periaortic lymph nodes.
Aorta has been opened and nodes bisected. (From Strayer
DS, Rubin E. Neoplasia. In: Rubin R, Strayer DS, eds. Rubin’s
Pathology: Clinicopathologic Foundations of Medicine. 6th ed.
Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &
Wilkins; 2012:167.)
