Benign tumors of soft parts are fairly common and most of them can be identified from their appearance in routine light microscopic sections. Soft tissue sarcomas make up fewer than 1% of all malignancies, but it is often difficult to recognize the cell type by light microscopy: while a number of immunohistochemical procedures are helpful, in many instances the only way to clarify the type of tumor is by ultrastructural study. Since precise subclassification of a soft tissue sarcoma often does not influence management of the patient, a clinician or pathologist will generally feel that the expense of diagnostic electron microscopy for confirmation of the diagnosis of sarcoma or for subclassification is not warranted, and the inducement to study soft tissue neoplasms with the electron microscope is as a rule academic interest. Such studies are to be encouraged, however, since they may be the only means whereby correlation of sarcoma type and biologic behavior or response to therapy is possible.
Because of the limited time available, only a brief review of this extensive field can be attempted. A selection of cases will be used to illustrate how transmission electron microscopy can complement light microscopy and immunohistochemistry in the study and diagnosis of tumors with fibroblastic, lipoblastic, vasoformative, myogenic and neural differentiation and some tumors of uncertain histogenesis.
Tumors of
fibroblasts.
Fibroblasts are the most ubiquitous of soft tissue cells, and
they are among the most structurally pliable with the result that
a broad range of appearances can be encountered at the
ultrastructural level among their tumors. Some sarcomas are
widely accepted as falling within this category while ascription
of fibroblastic derivation to others is controversial. Electron
microscopy will not always serve to identify neoplastic cells as
fibroblasts, in part because of the spectrum of morphology they
display, and also since it can be difficult when studying a tumor
with the electron microscopy to distinguish between fibroblasts
and some other neoplastic soft tissue cells, or even cells of
sarcomatoid carcinomas. It must be kept in mind that fibroblasts,
often showing pronounced reactive features, are a common
component of sarcomas of other types, and some dedifferentiated
sarcoma cells closely resemble fibroblasts. Despite these
limitations, electron microscopy is the most useful tool for the
identification of neoplastic fibroblasts, particularly when they
are displaying myofibroblastic differentiation.
Tumors of
fat cells.
The hallmark of lipogenic cells is the presence within the
cytoplasm of lipid droplets, and they tend to coalesce,
ultimately forming a single large vacuole that compresses the
nucleus and organelles into a thin peripheral rim of cytoplasm.
Lipid droplets can also be numerous in other sarcoma cells,
notably malignant fibrous histiocytomas, but they generally
remain small and discrete. Lipid is not always evident in
liposarcoma cells: many cells of a myxoid liposarcoma may have
few or no lipid droplets. Dedifferentiation in a liposarcoma is
an example of how sarcoma cells can lose their distinctive
features and come to resemble fibroblasts.
Tumors of
vasoformative cells.
There is no specific ultrastructural feature that will serve to
identify a neoplastic cell as having vasoformative potential, but
a number are seen with some frequency. The tendency to form
vascular channels is sometimes expressed in angiosarcomas and
Kaposi's sarcoma, and erythrocytes are admixed with the tumor
cells. Intracellular lumens can be seen in an epithelioid
hemangioendothelioma and pinocytotic vesicles, cytoplasmic
filaments and pericytic cells may also be evident.
Tumors
with myogenic differentiation.
Myofilaments are readily identified with the electron microscope.
They appear to varying degrees within neoplastic cells in
sarcomas, their frequency often paralleling the degree of
differentiation seen by light microscopy. Skeletal muscle
myofilaments can be recognized from their components of thin and
thick filaments in characteristic spatial array, often with
interspersed Z-band formation. Variations on the sarcomere theme
are common in rhabdomyomas and rhabdomyosarcomas and they are
occasionally encountered in sarcomas of other types. Smooth
muscle myofilaments can be plentiful in leiomyosarcomas but when
they are sparse, distinction from myofibroblasts may be
difficult. A minority of malignant gastrointestinal stromal
tumors possess smooth muscle myofilaments. They are not usually
present when the cells have undergone epithelioid transformation.
Tumors
with neural differentiation.
The ability of neoplastic neurogenic cells to form long
cytoplasmic extensions is particularly well seen in schwannomas
and perineuriomas, and other neural features are basal lamina,
microtubules, neurofilaments, and mesaxon formation. While they
are not usually well defined in sarcomas, electron microscopy can
sometimes serve to identify a malignant neural tumor. In a small
cell sarcoma of the soft tissues resembling Ewing's sarcoma of
bone, neural differentiation is indicated by the presence of
short, slender dendritic processes which may contain a few small
dense-core granules.
Tumors of
uncertain histogenesis.
A number of soft
tissue tumors can be recognized from their light microscopic
morphology and electron microscopy is only required for their
diagnosis when the features are not well defined. The
ultrastructural features may elucidate appearances seen in
hematoxylin/eosin-stained sections and provide clues to the
histogenesis. A monophasic synovial sarcoma of the spindle-cell
type resembles a fibrosarcoma but some subtle differences between
the cells can be detected at the ultrastructural level. Cells of
the epithelial component of this tumor are indistinguishable from
those of an adenocarcinoma. Abundant cytoplasmic filaments are
responsible for the homogeneous cytoplasm of epithelioid sarcoma
cells and nucleus and organelles are often compressed into an
eccentric location. The filaments can suggest vimentin or
cytokeratin. The profusion of Iysosomes in granular cell tumors
is well known, but subdivision of the cells into multiple
compartments in the benign tumors is only revealed by electron
microscopy. Cytoplasmic crystals are uncommon in neoplasms but
they are seen to good advantage in cells of an alveolar soft part
sarcoma. They are not always found, but the presence of small
densities around an extensive Golgi complex is compatible with
the diagnosis.
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