Use of Electron Microscopy

Examination of ultrastructural features of cellular and extracellular structures is a powerful diagnostic tool. The introduction of the transmission electron microscope in the early decades of the twentieth century dramatically expanded the investigative and diagnostic capabilities to study the submicroscopic details of diseased tissue including bone tumors and tumor like condition.

Use of the transmission through a thin section of tissue impregnated with electrondense material and embedded in plastic material and embedded in plastic medium is the most applicable for diagnostic purposes.

The scanning electron microscope provides an opportunity to examine the cell surface and intracytoplasmic membranous structures, as well as the three-dimensional composition of extracellular components. The so-called scanning and analytical instruments have little use in routine diagnosis.

Even the most enthusiastic electron microscopist must admit that as far as diagnostic pathology is concerned, the immunohistochemistry era is now upon us. The emergence of immunohistochemistry has significantly changed the approach to the diagnosis of bone tumors, and many diagnostic questions that in the past required ultrastructural studies are now addressed with the use of antibodies.

However, electron microscopy continues to provide unique, diagnostically useful information and should be used in addition to, not instead of, immunohistochemistry.

Diagnostically useful information can be obtained from cytologic preparations such as fine-needle aspirates. Limited ultrastructural studies can also be performed on tissue retrieved from paraffin-embedded material.

In bone tumors, as in general tumor pathology, ultrastructural studies provide valuable information about tumor histogenesis and differentiation pathways. Unfortunately, like other special techniques, ultrastructural studies are not useful in the differential diagnosis of benign versus malignant tumors and reactive conditions.

The most frequent applications of this technique in bone tumor pathology are in the differential diagnosis of:

1. Spindle-cell neoplasms
2. Small blue-cell neoplasms
3. Vascular versus nonvascular neoplasm and
4. A wide range of metastatic tumors of bone.

These four main areas of electron microscopy have numerous specific applications. Ultrastructural features of potential diagnostic significance are described with the individual conditions in their respective chapters.

Generally, tumors that cannot be diagnosed by light microscopy and that also have an inconclusive immunohistochemical profile very likely are not diagnosable by electron microsopcy. Ultrastructural studies conducted without a definite list of differential diagnosis and specific questions are likely to provide disappointing results.

Such studies have the best chance of being useful if conducted along with light microscopy and other applicable special techniques, with the formulation of specific questions that need to be answered.

The major limitations of ultrastructural studies in the diagnosis of bone tumors are similarly to those listed in general pathology textbooks:

1. Only a small proportion of tissue can be sampled and examined.

2. Relatively few ultrastructural features are diagnostically specific; as with light microscopy, the entire picture is more informative.

3. It is occasionally difficult to distinguish neoplastic from nonneoplastic cells in ultrastructural studies. Therefore the entrapment of normal elements with specific ultrastructural features of cellular differentiation can be misleading. This pitfall can be largely eliminated by careful examination of the so-called semi-thin section.

Electron microscopy is informative if it is used by an individual experienced in surgical pathology who also examines the light microscopic sections and knows the specific differential diagnostic problems related to the case under investigation.