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:b.bain@ic.ac.uk

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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