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Primary myelodysplastic syndromes: diagnostic and prognostic significance
of immunohistochemical assessment of bone marrow biopsies
MH Mangi and GJ Mufti
Department of Haematological Medicine, King's College School of Medicine
and Dentistry, London, UK.
Material from 63 cases with primary myelodysplastic syndromes (P-MDS)
(French-American-British [FAB] types: refractory anemia [RA] = 21; RA with
ring sideroblasts [RARS] = 8; RA with excess of blasts (RAEB) = 10; RAEB in
transformation (RAEBt) = 6; chronic myelomonocytic leukemia [CMML] = 10 and
unclassifiable = 8, ie, bone marrow aspiration was inadequate and stringent
FAB criteria were not applicable) was analyzed for bone marrow histologic
and immunohistochemical patterns. Standard Giemsa, hematoxylin and eosin
(H&E) and reticulin stains were used for morphologic assessment. To
identify the cell lineage precisely, chloroacetate esterase staining and an
indirect immunoperoxidase technique using mouse monoclonal antibodies CD15,
CD68, HLA-DR, and rabbit polyclonal CD3 and UEA-1 (lectin) was developed on
formalin- fixed paraffin embedded bone marrow biopsies (BMB). The
immunohistochemical assessment permitted accurate identification of
dysplastic features such as mononuclear and binuclear megakaryocytes,
Pelger-Huet neutrophils, and binuclear erythroblasts. Additional bone
marrow histologic and immunohistochemical features observed were
heterogeneity of immunohistochemical staining in various cell lineages,
megakaryocytic emperipolesis, alteration of bone marrow microarchitecture,
intravascular clusters of hematopoietic cells, and the types of benign
lymphoid aggregates. The nature of abnormally localized immature precursors
(ALIP) was discerned. Three types of clusters of immature cells were found
that were difficult to distinguish on Giemsa and H&E morphology, these
were erythroid aggregates (n = 18); megakaryocytic aggregates (n = 4), and
immature granulocytic and monocytic aggregates (n = 32). The bone marrow
histologic and immunohistologic patterns permitted the identification of
four groups of clinical relevance: Group 1, cases with predominant
erythroid hyperplasia and without ALIP (n = 15); group 2, cases with
prominent myeloid hyperplasia and presence of ALIP (n = 32); group 3, cases
with hypoplastic MDS (n = 10); and group 4, cases with hyperfibrotic MDS (n
= 6). Statistical analysis showed a significant difference in survival and
leukemic transformation between groups 1, 2, 3, and 4, with cases in group
2 showing the worst prognosis with early death due to increased propensity
to leukemic transformation and cytopenia-related complications (P less than
.0001). We conclude that immunohistochemistry is feasible on routinely
processed BMB and the information obtained is of diagnostic and prognostic
importance in P- MDS. The phenotype of ALIP varies with the morphologic and
histologic subtypes of MDS and the term should be reserved for cases in
whom the clusters in the intertrabecular region are of myeloid
(granulocytic and monocytic) lineage on immunohistochemistry.
Volume 79,
Issue 1,
pp. 198-205,
01/01/1992
Copyright © 1992 by The American Society of Hematology
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