Society for
Ultrastructural Pathology
EDITORIAL: HUMAN
PATHOLOGY
The journal, Human Pathology,
will publish an issue largely devoted to the role of electron
microscopy in diagnostic pathology sometime in 1998. The
following is the editorial that will introduce this topic in the
symposium issue.
Diagnostic Electron
Microscopy of Neoplasms
With its popularization in the
1980s, and apparent practicality and relative ease of
establishment in virtually any laboratory, immunohistochemistry
rapidly assumed a dominant diagnostic role in both surgical
pathology and cytopathology. Indeed, at times immunohistochemical
results seemed to displace the venerable hematoxylin and
eosin-stained section as the primary diagnostic tool in complex
differential diagnostic problems. Caught in this scenario, many
centers relegated the seemingly more costly and diagnostically
more challenging ultrastructural examination of problem cases to
an increasingly limited role. This, and even wholesale
elimination of electron microscopy in some laboratories, failed
to recognize that there are certain indications where
ultrastructural review is superior to immunohistochemistry for
diagnostic purposes (1,2) and, in fact, may even be both cheaper
(1) and faster (3,4). As the series of articles dealing with
neoplasia in the symposium in this issue of Human Pathology
indicate, and as outlined in Table 1, a
considerable range of diagnostic situations exists where electron
microscopy can be applied with a high degree of likelihood that a
diagnostic dilemma will be resolved. Although the present
symposium focuses on the role of electron microscopy in
neoplastic conditions, its role in non-neoplastic disorders must
not be forgotten, most notably in renal pathology (5).
Publications are beginning to
appear that emphasize the problems associated with
immunohistochemistry (summarized in4). It is significant that
there is such a paucity of information quantitating the
diagnostic efficiency of immunohistochemistry or cost/benefit
data for this technique. Pathologists are all too aware that
despite an extensive battery of immunohistochemical stains many
diagnostic problems remain unresolved or even more dangerous is
the fact that immunohistochemistry may produce results that are
entirely convincing but incorrect. In the latter case, a need for
electron microscopy may never be appreciated (6). In many
hospital laboratories, little account of such practical aspects
are taken in balancing or directing application of
immunohistochemistry versus electron microscopy. To their credit,
a few pathology departments have begun to analyze the relative
role of immunohistochemistry and electron microscopy in surgical
pathology (2) and fine-needle aspiration biopsies of lung (7);
both reports showed the excellence of electron microscopy as the
diagnostic modality in these circumstances. Electron microscopy,
with its greater versatility and reliability and lesser risk of
producing an incorrect diagnosis (6), should be a more logical
choice as the initial investigative approach in many diagnostic
algorithms.
The value of electron
microscopy in surgical pathology and cytopathology is
substantial. Depending on the study, major influences on solving
diagnostic problems in surgical pathology occur in 18 to 57
percent of cases (8-11). The same applies to fine-needle
aspiration biopsies (12-14), since these often contain small
fragments of tissue up to 0.6 mm in diameter and are, therefore,
mini-surgical biopsies (15). No such data is available for
assessing the role of immunohistochemistry. Rapid embedding
techniques ensure that diagnoses can be available in as little as
4 or 5 hours and routinely should be available in 36 to 48 hours
(3,16,17). A case illustrates many of these aspects.
On a Friday
morning, a surgical biopsy was performed on a rapidly enlarging
mass on the posterior aspect of the distal end of the right upper
arm of a 61-year-old woman. A previous fine-needle aspirate had
revealed a malignant neoplasm, probably a sarcoma (Fig. 1A). A frozen section from the surgical
biopsy confirmed this diagnosis (Fig. 1B), and, at the request of the surgeon and
oncologist involved in the case, the electron microscopy unit was
immediately provided with tissue to see whether a specific
diagnosis could be available prior to the weekend. By
mid-afternoon, using a microwave technique to enhance fixation
and processing, sections were available for review and a report
issued. The findings were specific and not only ruled out such
possibilities as rhabdomyosarcoma, certain other sarcomas,
malignant melanoma and metastatic carcinoma, but established a
diagnosis of a malignant peripheral nerve sheath tumor (Fig. 1C and D). Immunocytochemistry (positive S100
protein, neuron-specific enolase and vimentin, and negative
desmin, actin and cytokeratins) a few days later only served to
support the ultrastructural diagnosis. Further examples of the
essential role of diagnostic electron microscopy in pathology are
available via the web site of the Society for Ultrastructural
Pathology (http://sup.ultrakohl.com).
With the capital costs
involved in establishing a diagnostic electron microscopy unit,
as well as ongoing maintenance expenses, what is the optimal way
to provide electron microscopy services? It is likely that
consolidation and regionalization will occur to still allow
patients access to this essential service. Examples of the
effectiveness of regionalization can be found in Veterans
Administration hospitals in the United States and the experience
of McMaster University in Hamilton, Ontario, Canada. Currently
the 171 Veterans Administration Medical Centers in the USA are
served by diagnostic electron microscopy laboratories based at 40
of these different medical centers, many of which also provide
diagnostic electron microscopy services to their affiliated
university medical centers and, in some cases, to local community
hospitals. Since its inception in 1979, the centralized electron
microscopy unit in Hamilton, Ontario serves four local teaching
hospitals and additional hospitals in the region resulting in the
effective processing and reporting of about 1200 specimens per
year. Pathologists practicing in hospitals without electron
microscopes, but wishing to avail themselves of ultrastructural
diagnosis, should remember that it is inexpensive to
prospectively prepare tissue in anticipation of that electron
microscopy might be required. For example, faced with a spindle
cell, poorly differentiated or undifferentiated appearing
neoplasm at frozen section, a small portion can be fixed in
glutaraldehyde or even buffered formalin and stored pending
examination of the hematoxylin and eosin-stained slides. If a
diagnosis is readily established, the vial can be discardedžthe
total investment a few dollars at most, but if the diagnosis
remains problematic, fixed tissue can be forwarded to an
appropriate center for consultation and ultrastructural
examination.
Budgetary constraints in
hospitals in the United States and the reluctance to charge
patients for both immunohistochemical and ultrastructural
investigations has resulted in diminished use or even elimination
of some diagnostic electron microscopy services. Perhaps the
experience in Canada serves as a better indicator of the use and
value of electron microscopy in pathology, Here, as long as
global budgets within electron microscopy units are adhered to,
there is little restriction as to the number of cases that can be
embedded and examined, Not only does this provide experience for
selecting electron microscopy over immunohistochemistry, but it
increases the frequency with which unexpected but definite
diagnoses occur. The latter is a distinct advantage of
ultrastructural investigation and probably occurs in 8 to 10
percent of cases.14 When embedding and sectioning cases on a
daily basis, adding two or three extra cases adds negligible cost
in terms of technical time and materials. Indeed, the fee
schedule for the government sponsored health insurance in the
Province of Ontario for an electron microscopy case (technical
charges at $116.00 and a professional fee of $136.00) emphasizes
the rather inflated charges for this service in many hospitals in
the United States. Noteworthy, is that reimbursement for electron
microscopy by most insurance carriers in the United States
averages $160.00 for professional services and $130.00 for the
technical component. In Ontario similar costs are incurred by
ordering five immunohistochemical tests, a number which is not
unusual for, and often exceeded in, difficult diagnostic
problems.
The series of articles in this
symposium issue of Human Pathology provide illustration of the
type of tumors and clinical situations where electron microscopy
can benefit pathologists faced with difficult diagnostic
problems. Balancing immunohistochemistry with electron microscopy
as diagnostic modalities in the daily surgical pathology and
cytopathology services, i.e., defining specific indications for
each technique, is also addressed. Some cases, however, will
still require evaluation by both techniques for a correct final
diagnosis. As a result of the complementary roles of electron
microscopy and immunohistochemistry (6), rather than applying
these sequentially, potential benefits and cost savings can
result from their simultaneous use. To ensure proper patient care
requires maintenance of electron microscopy services in
pathology. This essential service must not be jeopardized by
wholesale closure of hospital-based electron microscopy
laboratories. Budgetary restraints necessitate a cost-effective
plan for regionalization of specialized laboratory services.
Irving Dardick, MD, FRCPC
Professor of Pathology and Otolaryngology
University of Toronto
Toronto, Ontario
Guillermo Herrera, MD
Professor of Pathology
Louisiana State University Medical Center–Shreveport
Shreveport, Louisiana
References
1. Fisher C: The value of
electronmicroscopy and immunohistochemistry in the diagnosis
of soft tissue sarcomas: A study of 200 cases. Histopathology
1990;16:441-454.
2. Frost AR, Orenstein JM, Abraham AA, Silverberg SG: A
comparison of the usefulness of electron microscopy and
immunohistochemistry - one laboratory’s experience. Arch
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3. Nesland JM, Millonig G, Wilson A, Johannessen JV: Rapid
techniques in diagnostic electron microscopy. Ultrastruct
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comparative utility of immunohistochemistry and electron
microscopy in the diagnosis of childhood round cell tumors.
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7. O’Reilly PE, Bruecker J, Silverman JF: Value of
ancillary studies in fine needle aspiration cytology of the
lung. Acta Cytol 1994;38:144-150.
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diagnostic electron microscopy in surgical pathology: A study
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13. Dabbs DJ, Silverman JF: Selective use of electron
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14. Dardick I, Yazdi HM, Brosko C, Rippstein P, Hickey NM: A
quantitative comparison of light and electron microscopic
diagnoses in specimens obtained by fine needle aspiration
biopsy. Ultrastruct Pathol 1991;15:105-126.
15. Yazdi HM, Dardick I: Diagnostic Immunocytochemistry and
Electron Microscopy. Guidelines to Clinical Aspiration
Biopsy. Igaku-Shoin, New York, 1991.
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17. Kurtz SM: Rapid ultrastructural examination of FNAs in
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