Blood, 15 August 2001, Vol. 98, No. 4, pp. 1273-1275
CORRESPONDENCE
To the editor:
Pseudo Pelger-Huët anomaly in myelodysplastic syndrome:
hyposegmented or apoptotic neutrophil?
Huët first observed an abnormal hyposegmented neutrophil
granulocyte in 1928, and a year later Pelger reported an additional case. Such a cell later became known as Pelger-Huët anomaly. In
1932 Huët pointed out its hereditary and systemic
character.1 The Pelger-Huët anomaly is a familial
anomaly that is transmitted as a Mendelian dominant trait but that is
unaccompanied by any pathologic phenomenon.2 It is found
in a heterozygous state in about one of every 5000 individuals. It is
characterized by hyposegmentation of the granulocyte nuclei. Almost all
nuclei are rod-shaped or have only 2 lobes, and their chromatin
structure is coarser than that of a normal neutrophil.
Anomalies resembling Pelger-Huët anomaly that are
acquired rather than familial have been described as pseudo
Pelger-Huët anomaly.3,4 The morphologic
characteristic seen in pseudo Pelger-Huët anomaly is similar to
Pelger-Huët anomaly. The acquired pseudo Pelger-Huët
anomaly has been associated with pathologic conditions including
myelodysplastic syndromes (MDS).
MDS are a closely related group of bone marrow disorders seen in
elderly populations characterized by peripheral cytopenias and
dysplastic hematopoiesis. But dysplastic hematopoiesis is a feature not
confined only to MDS: this feature is also seen during the
administration of certain drugs and in megaloblastic anemia.5 On the other hand, some abnormalities such as
pseudo Pelger-Huët anomaly and micromegakaryocytes are considered
to be highly characteristic and highly pathognomonic of MDS. One or the
other of these abnormalities occurs in a high percentage of MDS
patients. From its first recognition until now, the presence of pseudo
Pelger-Huët anomaly is considered to be the most specific dysplastic marker for the diagnosis of MDS without any
bias.6 Recent studies have also included this morphologic
abnormality as a prognostic marker in MDS.7,8 In the past
our group has reported excessive intramedullary apoptosis of
hematopoietic cells in MDS.9 Apoptosis was found to be
pronounced in maturing/matured cells in the high-density fraction of
the bone marrow (BM) aspirate and biopsy.10
In light of the above findings in MDS and the current knowledge of
morphology of apoptotic cells, we decided to evaluate whether the
Pelger-Huët cells are apoptotic. BM aspirates and peripheral blood (PB) specimens from 56 MDS patients were examined for apoptosis using light microscopy (LM), electron microscopy (EM), and in situ end
labeling (ISEL) of DNA, as described earlier.10 Of these,
25 patients had refractory anemia (RA), 12 were RA with ring
sideroblasts (RARS), 13 were RA with excessive blasts (RAEB), 4 were RAEB in tranformation (RAEB-t), and 2 were chronic myelomonocytic leukemia (CMMoL). The patient population consisted of 34 males and
22 females, and the median age was 68 years (range, 26-85 years).
On examining the BM aspirate and PB of the MDS patients, 78% (44 of
56) of patients belonging to different FAB types showed the presence of
characteristic Pelger-Huët anomaly by LM and EM (Figure
1). They were seen in both the PB and the
BM aspirates of these patients. The median frequency of the pseudo
Pelger-Huët cells was 3.8% (range, 1-34) in the PB and 4.6%
(range, 2-38) in the BM aspirate. The incidence of these cells reported
in this study was comparable to those reported earlier.6
Interestingly, both the high density (HD) and the low density (LD)
fractions of the PB and BM aspirate compartments showed the presence of pseudo Pelger-Huët anomaly. In addition, a higher number of these cells were seen in the HD fraction than in the LD fraction (9.6% versus 4.2%; P = .0001). Morphologically, 98% of these
cells looked like mature granulocytes undergoing apoptosis. The
electron microscopic morphology showed that both unilobed and bilobed
cells were undergoing apoptosis. The cells showed characteristic
apoptotic features in both the nucleus and the cytoplasm. The nucleus
showed compact and segregated chromatin sharply delineated toward the
periphery of the nucleus. Marked condensation of the cytoplasm with
distorted organelles and mild convolution of the cellular outlines were noted. These findings were further confirmed by ISEL (Figure 1).
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| Figure 1.
Pseudo Pelger-Huët
anomaly forms.
Panels A through E depict the Stodtmeister, or unilobed, form.
Early granulocyte with coarse chromatin segregated toward the periphery
of the nucleus. (A) PB Giemsa from an MDS patient (magnification
× 100). (B) ISEL showing a pseudo Pelger-Huët cell undergoing
apoptosis (magnification × 100). (C-E) Electron micrographs showing
the classical apoptotic features (uranyl acetate and lead citrate
staining; original magnifications, × 6600, × 10 000, and × 6600,
respectively). Panels F through J depict the bilobed form. Mature
neutrophil showing bilobed nucleus with marked chromatin condensation
and altered cytoplasm. (F) PB Giemsa from an MDS patient (magnification
× 100). (G) ISEL showing a pseudo Pelger-Huët cell undergoing
apoptosis (magnification × 100). (H- J) Electron micrographs showing
the classical apoptotic features (uranyl acetate and lead citrate
staining; original magnifications, × 8300, × 6600, and × 6600,
respectively).
|
|
The above finding raises the question whether the pseudo
Pelger-Huët cell is an anomaly or a manifestation of apoptosis. A
normal neutrophil attains its matured multilobulated nuclear morphology
subsequent to the mononuclear (pro/meta/myelocyte) and band-form
stages. The mononuclear pseudo Pelger-Huët cells shown by
different techniques in the figure thus may resemble an early
myeloid cell undergoing apoptosis. Similarly, it is possible that the
bilobulated pseudo Pelger-Huët cells may also be an apoptotic
manifestation of the band cells or later stages prior to culminating in
to multilobulated form. Pseudo Pelger-Huët cells thus may
represent different stages of neutrophil differentiation undergoing
apoptosis. The death of pseudo Pelger-Huët cells in the BM of MDS
patients may be inflicted by the BM microenvironment that has been
shown to have high amounts of proapoptotic cytokines such as tumor
necrosis factor alpha (TNF-
) and interferon gamma (IFN-
).
Vilasini T. Shetty, Suneel D. Mundle, and Azra Raza
Correspondence: Vilasini Shetty, Department of Medicine, Rush
Cancer Institute, 2242 West Harrison Street, Suite 108, Chicago, IL
60612-3515; vravanam{at}rush.edu
References
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