Overview & History of the VHA Electron Microscopy Program
Overview: The appropriate use of ultrastructural study adds a new dimension to diagnostic pathology. Its value in difficult diagnostic situations has been demonstrated repeatedly in VA hospitals, particularly when there is close coordination between pathologists and clinicians.
Ultrastructural study may be applied to a variety of substances including biological materials. By examination of specially prepared tissue sections, changes not perceived by light microscopy can be identified leading to improved diagnostic interpretations. For instance, in certain kidney diseases, the correct diagnosis can be made only by these means and this in turn affects the prognosis and selection of therapy. Similarly, certain neoplasms can be identified definitively only through ultrastructural study with obvious implications for prognosis and selection of therapy. Many other examples include studies of diseases of the liver, muscle, nervous and gastrointestinal systems. Another area of growing importance is the identification of viral particles in biological material. In some instances, ultrastructural study is the only way to establish the presence of a viral infection and in other instances a diagnosis may be made earlier than by serological methods. The use of electron microscopy is a vital part of the modern diagnostic armamentarium. The costs of diagnostic EM are relatively small in light of the benefits to patient care.
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The role of electron microscopy in diagnostic pathology was reviewed by Rosai and Erlandson (American Journal of Surgical Pathology, 19: 247-250, 1995). They concluded that electron microscopy remains “... an important and sometimes essential tool in diagnostic pathology.” In this article they compared electron microscopy with immunohistochemistry: “...The techniques of electron microscopy and immunohistochemistry should be viewed not as competing with each other but rather as complementary methods for achieving the same goal (i.e., the recognition of diagnostic structures, features of differentiation in neoplasms, or microorganisms). When comparing these procedures, it becomes apparent that the detailed fine structure of cellular and extracellular constituents can be resolved only by high resolution transmission electron microscopy. Examples of such diagnostic structures include ciliary abnormalities in immotile cilia syndrome, bands of Bungner (rows of Schwann cell processes) in axonal atrophy, Weibel-Palade bodies in endothelial cells, Birbeck granules in Langerhans cells, melanosomes in amelanotic malignant melanoma, and myosin/ribosome complexes or rudimentary sarcomeres in poorly differentiated rhabdomyosarcoma. Using immunohistochemical stains, we can only assume the presence of these potentially diagnostic structures in neoplasms......... as with all other techniques, there are pitfalls and limitations associated with immunohistochemistry. These include the failure of attempts to standardize methodology and institute quality control; the paucity of absolute tissue- or tumor-specific antibodies; the lack of a distinct diagnostic immunophenotype in many tumors; the occurrence of anomalous (aberrant or unexpected) immunostaining; and the fact that small amounts of antigens may not be detectable by immunostaining methods, notably in neuroendocrine carcinomas. A false diagnostic impression by the pathologist may also result in the selection of an inappropriate panel of antibodies. These limitations sometimes require extensive (and expensive) panels of antibodies for the evaluation of a given neoplasm. Similar considerations apply to other special techniques such as cytogenetics and molecular analysis.......
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“Only the most appropriate and cost-effective ancillary diagnostic procedure should be employed in the evaluation of cases that cannot be resolved using routine methods. The choice of the initial procedure should be based on the specific problem and the resources available to the laboratory. For instance, the first approach for the elucidation and subclassification of hematopoietic neoplasms should be immunohistochemical. Conversely, whenever possible, the initial approach to the adenocarcinoma versus epithelial mesothelioma (not sarcomatoid variants) diagnostic dilemma should be electron microscopy, in view of the fact that long, thin, nonrigid, nonintestinal-type microvilli devoid of a glycocalyx and actin rootlets are diagnostic for epithelial mesotheliomas, whereas none of the antibodies presently advocated for this differential diagnosis is specific. Ultrastructural studies also may be preferable to immunophenotyping for the evaluation of percutaneous fine-needle aspiration specimens. Electron microscopy should also be used as a first approach or conjointly with other procedures for the diagnosis of a select number of nonneoplastic diseases. Examples include glomerular diseases (currently the most widely used diagnostic application of electron microscopy), notably the idiopathic nephrotic syndrome, benign familial recurrent hematuria (thin basement membrane syndrome), and hereditary nephropathy [i.e., Alport's syndrome]; bullous skin disorders such as epidermolysis bullosa; diseases due to ciliary dysmorphology; and the rapid diagnosis of viral diseases.” Another excellent review article on the role of electron microscopy in diagnostic pathology is by Dr. Andra R. Frost, et al at the Department of Pathology, The George Washington University Medical Center, Washington, DC. (Archives of Pathology & Laboratory Medicine, 1994;118:922-926).
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VHA Background: Diagnostic electron microscopy originated as one of the VA's approximately twenty-three designated Special Medical Services which also included such modalities as renal dialysis, renal transplant and cardio-pulmonary by-pass surgery. These Services were supported by specific appropriations and were present only in selected hospitals. The former office of the Assistant Chief Medical Director for Professional Services had the responsibility for the nurture, planning, site selection, management and evaluation of all the Special Services, and this duty was delegated to the appropriate professional service. For example, diagnostic electron microscopy was delegated to the Pathology Service in the VA's Central Office. Inherent in the establishment of electron microscopy units is the concept that teaching and research are legitimate and important activities. In the hospitals, the diagnostic EM units are organizationally part of the Pathology and Laboratory Medicine Services. In some instances, the Chief of the Laboratory Service may also be the director of the local EM program, but more frequently the responsibility is assigned to another pathologist with particular interest and skill in this field. Monitoring of Electron Microscopy units occurs by periodic evaluation of workload productivity and annual quality assurance assessment by a national committee of VA and non-VA pathologists.
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FUNDING - background (under Specialized Medical Services Program) The EM programs received their basic funding from the appropriation that supported the Special Medical Services. The support for each approved program was specifically identified and provided for both the initial and the recurring costs. Initial costs include such items as the purchase of the EM and other necessary equipment and the construction or remodeling of space to accommodate the unit. Recurring costs consist of the salaries for the staff, the supplies and the service contract for maintenance of the EM. The indirect costs were supported from the general operating budget of the Medical Center. The selection of the electron microscope and other equipment is made locally, although the decision may be reviewed and approved in National Headquarters. In general, only high resolution transmission electron microscopes are acquired, but a few instruments that may be used also for scanning have been purchased. The salary allocation was sufficient to support on a full-time basis one pathologist and two technologists. This level of staffing is considered satisfactory for a diagnostic EM unit examining at least 250 specimens annually. Replacement of existing equipment, acquisition of new capital equipment and salaries for additional personnel including secretarial support must be provided by the hospital through regular budgetary procedures. Funding support consisted of 1.0 FTE physician calculated at Chief Grade, Step 3; 2 technologists calculated at GS 7/5; appropriate annual budget for supplies and service contract; electron microscope and related equipment, averaging $150,000; and necessary installation costs (renovation or construction). Starting in FY 1987, specialized medical care funding was no longer provided from Central Office sources. Individual Medical Centers provide the required funding to operate the EM program at that Medical Center. However, those EM funds previously targeted were included in the recurring funding base allocated annually to each EM program medical center but were not specifically targeted or identified for EM activities.
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Another topic that requires brief description is the VA's extensive affiliations with medical schools (there are also affiliations with schools for dentistry and many allied health professions and occupations). There are now affiliate relations with more than 152 medical and dental schools. More than half of the U.S. practicing physicians have trained in VA facilities. Most of the pathology residency training in VA hospitals is conducted through integrated programs with the affiliated medical schools. The diagnostic EM units are all located in hospitals which are affiliated and provide pathology graduate medical education. The VA has statutory authority to enter into agreements with affiliated medical schools and other hospitals to share specialized and scarce patient-care services. These agreements are established most frequently for the sharing of the Special Medical Services. Sharing agreements for diagnostic electron microscopy are discussed later in more detail. An important component of those sharing agreements is that billing must be computed to recover actual cost of providing those services.
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There are also in certain VA hospitals EM facilities that are part of the research and not the pathology program, The research facilities are funded separately from the diagnostic units and their selection and evaluation is handled through different channels. A limited number of diagnostic EM studies are carried out on research equipment in some hospitals that do not have diagnostic units, but information about such examinations is not collected by the Pathology & Laboratory Medicine Service in National Headquarters. In addition, some specimens are referred elsewhere, frequently to an affiliated medical school, from VA hospitals lacking EM resources.
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