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SA Betz, K Foucar, DR Head, IM Chen and CL Willman
Department of Pathology, University of New Mexico School of Medicine,
Albuquerque.
Because neither morphologic nor routine cytochemical features are
pathognomonic, the diagnosis of acute megakaryoblastic leukemia (AML- M7)
is difficult, requiring either specialized ultrastructural or immunologic
techniques. Because the ultrastructural techniques are cumbersome,
immunologic assays for expression of several platelet- specific antigens,
such as CD41a (platelet glycoprotein IIb/IIIa), have become the primary
method used to detect megakaryoblastic differentiation. In our flow
cytometric analysis of the immunophenotypes of over 1,000 cases of AML from
patients registered to Southwest Oncology Group (SWOG) Treatment Protocols,
we found that 38% of cases demonstrated CD41a reactivity. Because this
frequency of CD41a expression by flow cytometry greatly exceeded the number
of morphologically defined cases of AML-M7, we postulated that the reaction
may be caused by platelets adherent to leukemic blasts. To investigate this
hypothesis, we performed a side-by-side comparison of flow cytometric and
cytospin immunofluorescence studies on 37 cases of adult de novo AML that
demonstrated a wide range of CD41a expression by flow cytometric analyses.
We found that the expression of CD41a detected by flow cytometric
techniques was secondary to adherent platelets or platelet fragments in 85%
of cases. Many of these cases also expressed the lineage-specific
carbohydrate, LNF III (CD15), which may mediate platelet adhesion to mature
monocytes and neutrophils. Only 15% of the CD41a flow cytometrically
positive cases demonstrated true diffuse membrane and cytoplasmic
positivity on cytospin slides indicative of megakaryoblastic
differentiation. Cytospin immunofluorescence for CD41a should be performed
on all cases of suspected AML-M7. If only flow cytometric techniques are
used, adherent platelets may result in the erroneous diagnosis of this AML
subtype.
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