Teaching Cases from the Royal Marsden and St Mary’sHospitals. Case 23: An Unexpected Finding During
Investigation of Thrombocytopenia
KETAN C. PATELa, BARBARA J. BAINa,b,* and BRIDGET S. WILKINSc
aDepartment of Haematology, St Mary’s Hospital, Praed Street, Paddington, London W2 1NY, UK; bSt Mary’s Hospital, Campus of Imperial College,Faculty of Medicine and cDepartment of Histopathology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
(Received 20 September 2001)
Keywords: Myelodysplastic syndrome; MDS; Gaucher’s disease
CASE REPORT
A 69-year-old retired Ashkenazi-Jewish man presented to
our Chest and Allergy clinic with a history of rhinitis.
Apart from hypertension (for which he was taking
bendrofluazide and losartan) he was in good health.
There was no family history of note. FBC showed a WBC
7.8 £ 109/l, Hb 15.7 g dl21, MCV 83 fl and platelet count
of 29 £ 109 l21; which led to a haematology referral. The
blood film showed anisopoikilocytosis with occasional
acanthocytes and irregularly contracted cells, platelet
anisocytosis with some giant hypogranular forms,
neutrophils with borderline hypogranularity and increased
nuclear projections and an occasional blast cell (Fig. 1).
There was no history of easy bruising or bleeding and he
had undergone an adenoidectomy as a child without
incident. Physical examination was unremarkable with no
lymphadenopathy or hepatosplenomegaly; abdominal
ultrasound confirmed the lack of organomegaly. Further
blood tests, which included a coagulation screen, liver
function tests, assays of serum vitamin B12, red cell folate
and serum ferritin, and an autoimmune profile were all
normal.
A bone marrow aspiration and trephine biopsy were
performed. The aspirate was normocellular and normo-
blastic with some hypolobated megakaryocytes (Fig. 2),
hypogranular neutrophil precursors, dysplastic neutrophils
(as in the peripheral blood) and large abnormal
macrophages (Fig. 2). Iron stores were increased but
there were no ring sideroblasts. The trephine biopsy
showed large focal aggregates of abnormal macrophages
(Fig. 3) and small hypolobated megakaryocytes. Further
ISSN 1042-8194 print/ISSN 1029-2403 online q 2002 Taylor & Francis Ltd
DOI: 10.1080/10428190290021407
FIGURE 1 Peripheral blood film showing thrombocytopenia and a blastcell.
FIGURE 2 Bone marrow aspirate showing a large hypolobatedmegakaryocyte (left) and an abnormal macrophage (right).
*Corresponding author. Address: Department of Haematology, St Mary’s Hospital, Praed Street, Paddington, London W2 1NY, UK. E-mail:[email protected]
Leukemia and Lymphoma, 2002 Vol. 43 (5), pp. 1155–1157
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tests were performed to confirm the morphological
diagnoses.
FOLLOW UP AND FURTHER INVESTIGATIONS
The large abnormal macrophages observed in the bone
marrow aspirate and trephine biopsy sections had the
features of Gaucher cells.
Immunohistochemistry of the trephine biopsy speci-
men, using antibodies directed against CD61 and CD42b,
confirmed the presence of a large number of dysplastic
megakaryocytes including numerous micromegakaryo-
cytes (Fig. 4). Cytogenetic analysis was normal. In view of
the unexpected observation of Gaucher cells, leucocyte b-
glucocerebrosidase was assayed and was found to be
markedly reduced at 0.15 nmol h21 mg ptn21 (normal
range 5.4–16.8). This result is indicative of Gaucher’s
disease. Subsequent molecular genetic analysis revealed
the patient to be homozygous for the N370S mutation,
confirming type 1 Gaucher’s disease.
The patient therefore had both a myelodysplastic
syndrome (MDS), refractory anaemia (FAB classifi-
cation), and type 1 Gaucher’s disease. It is likely that
both conditions are contributing to his cytopenia.
DISCUSSION
Gaucher’s disease is the most common lysosomal storage
disorder, characterized by accumulation of glucocerebro-
side in cells of the reticuloendothelial system throughout
the body. It is caused by an autosomally inherited
deficiency of the lysosomal enzyme, glucocerebrosidase.
Of the three forms of the disease, type 1 is the most
common, characterized by splenomegaly, hepatomegaly,
pancytopenia and both osteolytic and osteopenic degener-
ation of the bones with sparing of the central nervous
system. Type 1 Gaucher’s disease can affect all ethnic
groups but it is especially common in the Ashkenazi-
Jewish population. The clinical expression of type 1
disease is variable; it can be apparent during the first
week of life or can remain undetected until as late as
the eighth decade. The gene locus for glucocerebrosi-
dase has been mapped to chromosome 1q21. Several
point mutations have been described, the most common
being N370S, causing substitution of asparagine by
serine at position 370. This occurs in about 45% of
patients with Gaucher’s disease. Cytopenias in Gau-
cher’s disease, of which thrombocytopenia is the most
common, are mainly a consequence of hypersplenism
but may also be a consequence of extensive marrow
infiltration.
Pseudo-Gaucher cells are observed in various haema-
tological disorders including acute leukaemias, chronic
granulocytic leukaemia, type II congenital dyserythro-
poietic anaemia and b thalassaemia major [1]. To our
knowledge, they have not been reported in MDS but
nevertheless we considered it important to assay b-
glucocerebrosidase to confirm our suspicion that the
patient had two unrelated conditions.
Gaucher’s disease has been reported in patients with
various myeloid neoplasms including acute myeloid
leukaemia [2] and MDS [3,4]. The occurrence of
Gaucher’s disease with diverse myeloid neoplasms may
well be coincidental although Ruchlemer et al. [4] found
Gaucher’s disease in three of approximately 400 patients
with MDS, a much higher prevalence of the disease than is
found in the general Jewish population (prevalence of one
in 2500 among Ashkenazi Jews). The possible role of
Gaucher’s disease in predisposing to MDS remains to be
determined.
Myelodysplastic syndrome; MDS; Gaucher’s disease
References
[1] Bain, B.J., Clark, D.C., Lampert, I.A. and Wilkins, B.S. (2001) BoneMarrow Pathology, 3rd ed. (Blackwell Science, Oxford).
[2] Mehta, A.B. and Richfield, L. (2001) “Gaucher’s disease: theimpact of enzyme replacement therapy”, Br. J. Haematol. 113(Suppl.1), 47.
FIGURE 3 Section of trephine biopsy specimen showing an abnormalinfiltrate of altered macrophages (periodic acid–Schiff stain, £ 50objective).
FIGURE 4 Section of trephine biopsy specimen showing numerousmegakaryocytes including micromegakaryocytes (immunoperoxidasewith CD42b monoclonal antibody, £ 40 objective).
K.C. PATEL et al.1156
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[3] Saito, H., Uemura, K., Muruyana, T., Kawakami, H., Iijima, Y.,
Kitano, K., Kaji, R. and Furata, S. (1987) “Gaucher’s disease (type 1)
with clinical picture like a myelodysplastic syndrome: difference
between this Gaucher’s cell with CML pseudo-Gaucher’s cell”, Jap.
J. Clin. Hematol. 28(8), 1449–1455.
[4] Ruchlemer, R., Elstein, D., Meytes, D., Rachmilewitz, E., Mittelman,M. and Zimran, A. (2000) “Myelodysplastic syndrome in type 1Gaucher disease”, Blood 96, 263b.
[5] Smith, W.C., Kaneshiro, M.M., Goldstein, B.D., Parket, J.W. andLukes, R.T. (1968) “Gaucher’s cells in chronic granulocyticleukaemia”, Lancet 2, 780–781.
TEACHING CASES FROM ROYAL MARSDEN—ST MARY’S HOSPITALS 1157
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