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U N I T 1
Cell and Tissue Function
Malignant Neoplasms
In contrast to benign tumors, malignant neoplasms tend
to grow rapidly, invade and infiltrate nearby tissue, and
spread to other parts of the body. They lack a well-defined
capsule and their margins are not clearly separated from
the normal surrounding tissue.
2,3
Because of their rapid
rate of growth, malignant tumors may compress blood
vessels and outgrow their blood supply, causing ischemia
and tissue injury. Some malignancies secrete hormones
and/or cytokines, liberate enzymes and toxins, and/or
induce an inflammatory response that injures normal tis-
sue as well as the tumor itself.
There are two categories of malignant neoplasms—
solid tumors and hematologic cancers. Solid tumors
initially are confined to a specific tissue or organ. As
the growth of the primary solid tumor progresses, cells
detach from the original tumor mass, invade the sur-
rounding tissue, and enter the blood and lymph system
to spread to distant sites, a process termed
metasta-
sis
. Hematologic cancers involve cells normally found
within the blood and lymph, thereby making them dis-
seminated diseases from the beginning.
Cancer in situ
is a localized preinvasive lesion. For
example, in ductal carcinoma in situ of the breast, the
malignant cells have not crossed the basement mem-
brane. Depending on its location, an in situ lesion usu-
ally can be removed surgically or treated so that the
chances of recurrence are small. For example, cancer in
situ of the cervix is essentially 100% curable.
Tumor Cell Characteristics
Whether a tumor is benign or malignant is determined by
an examination of its cells. Typically, such an examination
includes macroscopic (naked eye) inspection to determine
the presence or absence of a tumor capsule and inva-
sion of the surrounding tissue, supplemented by micro-
scopic examination of histologic sections of the tumor.
Additional information may be obtained from electron
microscopy, immunochemistry techniques, chromosomal
studies, and DNA analysis. The growth and behavior of
tumor cells may be studied using culture techniques.
Differentiation and Anaplasia.
Differentiation refers
to the extent to which the parenchymal (specific organ
versus supportive tissue) cells of a tumor resemble their
normal forbearers morphologically and functionally.
2,3
Malignant neoplasms that are composed of poorly dif-
ferentiated or undifferentiated cells are described as
being
anaplastic, anaplasia
literally means to “form
backward” to an earlier dedifferentiated state. On histo-
logic examination, benign tumors are composed of cells
that resemble the tissue from which they have arisen.
By contrast, the cells of malignant tumors are character-
ized by wide changes of parenchymal cell differentiation
from well differentiated to completely undifferentiated.
Undifferentiated cancer cells are marked by a number
of morphologic changes. Both the cells and nuclei dis-
play variations in size and shape, a condition referred to
as
pleomorphism
.
2,3
Their nuclei are variable in size and
bizarre in shape, their chromatin is coarse and clumped,
and their nucleoli are often considerably larger than
normal (Fig. 7-2A). Characteristically, the nuclei con-
tain an abundance of DNA and are extremely dark
staining. The cells of undifferentiated tumors usually
display a large number of mitoses, reflecting a higher
rate of proliferation. They also display atypical, bizarre
mitotic figures, sometimes producing tripolar, tetrapo-
lar, or multipolar spindles (Fig. 7-2B). Highly anaplas-
tic cancer cells, whatever their tissue of origin, begin to
resemble undifferentiated or embryonic cells more than
they do their tissue of origin.
Some cancers display only slight anaplasia and others
marked anaplasia. The cytologic/histologic grading of
tumors is based on the degree of differentiation and the
number of proliferating cells. The closer the tumor cells
resemble comparable normal tissue cells, both morpho-
logically (structurally) and functionally, the lower the
FIGURE 7-2.
Anaplastic features of malignant tumors.
(A)
The cells of this anaplastic carcinoma are
highly pleomorphic (i.e., they vary in size and shape).The nuclei are hyperchromatic and are large
relative to the cytoplasm. Multinucleated tumor giant cells are present (arrows).
(B)
A malignant cell
in metaphase exhibits an abnormal mitotic figure. (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; 2012:162.)
A
B
