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Introduction

3. Frisch B. & Bartl R, (1990) Primary and secondary myelodysplastic syndromes. In Atlas of Bone Marrow Pathology (Frisch B. & Bartl R., Eds), pp. 67-80. Kluwer Academic Publishers, London. 4. List A. F., Garewal H. S. & Sandberg A. A. (1990) The myelodysplastic syndromes: biology and implications for management. J. clin. Oncol. 8, 1424. 5. Bartl R., Frisch B. & Baumgart R. (1991) Morphologic classification of the myelodysplastic syndromes (MDS). Combined utilisation of bone marrow aspirates and trephine biopsies. Leukemia Res. 16, 15-33. 6. Bain B. J. (1990) Leukaemia Diagnosis, a Guide to the FAB Classification. Lippincott, London. 7. Catovsky D. (1991) The leukemic cell. Methods in Hematology, 2nd edition. Churchill Livingstone, Edinburgh. 8. Frisch B. & Bartl R. (1986) Bone marrow histology in myelodysplastic syndromes. Scand. J. Haemat. 45 (Suppl. 36), 21.

9. Third MIC Cooperative Study Group (1988) Recommendations for a morphologic, immunologic and cytogenetic (MIC) working classification of the primary and therapy-related myelodysplastic disorders. Cancer Genet. Cytogenet. 32, 1. B. FRISCrl Institute of Haematology Ichilov Hospital University of Tel-Aviv Israel and R. BARTL Bone Marrow Diagnosis University of Munich F.R.G.

MINIMAL DIAGNOSTIC CRITERIA FOR THE MYELODYSPLASTIC SYNDROME IN CLINICAL PRACTICE MYELODYSPLASTIC syndromes (MDS) comprise a heterogeneous group of haematological stem cell disorders of clonal origin, that are characterized by bone marrow dysmaturation with signs of ineffective haematopoiesis in one to three cell lines, and accompanied by various degrees of anaemia and peripheral blood cytopenia [1]. There is no single pathognomonic test for MDS. Instead a diagnosis of MDS should be founded on a careful clinical and haematological observation, sometimes requiring repeated bone marrow examinations, and the use of special investigations. In the following we have tried to summarise what we consider to be main diagnostic features of MDS. CLINICAL FINDINGS MDS usually affects the elderly, and is quite rare before the age of 50, unless therapy induced, i.e. secondary to previously given mutagenic treatment. Main symptoms are as a rule related to anaemia, and often combined with signs of infections and/or increased bleeding tendency. The anaemia may have proven refractory to vitamin B12, folic acid or iron therapy.

of MDS, usually in connection with increased numbers of abnormal megakaryocytes. Erythropoiesis

Signs of dyserythropoiesis include megaloblastoid changes and nuclear abnormalities. Other important findings are increased numbers of ring sideroblasts and erythroid hyperplasia with a decreased M/E (myeloid/erythroid) ratio. Granulopoiesis

Cytologic dysplastic changes include abnormal monocytoid precursors and decreased granulation of myeloid cells. Usually a left shift of the granulocytopoiesis is seen, with a relative overweigh of immature myeloid cells with or without an increased percentage of blast cells. The identification of abnormal localisation of immature precursors (ALIP [2]) is helpful. Megakaryocytopoiesis

Typically there are increased numbers of abnormal lookil~g megakaryocytes, i.e. micromegakaryocytes, hypolobated large megakaryocytes or megakaryocytes with multiple small separated nuclei. P E R I P H E R A L B L O O D FINDINGS

BONE M A R R O W FINDINGS Cellularity

The bone marrow in MDS is usually hyper- or normocellular. Hypoplastic bone marrow is rare and should evoke suspicion of aplastic anaemia. Bone marrow fibrosis is becoming recognised as a feature

Red cells

Macrocytic anaemia with moderately increased MCV. The reticulocyte count is low or normal, never increased. A double erythrocyte population with both normo- and hypochromic red cells can be seen in ring sideroblastic anaemia.

Introduction WBC

Quantitative changes include granulocytopenia and/or absolute monocytosis, with monocyte counts above 1.0 x 109/1. Dysplastic changes in neutrophilic granulocytes, i.e. nuclear abnormalities and cytoplasmatic hypogranulation, can be estimated by the percentage of pelgeroid polymorphs (ppp), and the use of a granulation scoring system (G-score), respectively [3].

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states or toxic exposures. MDS should also be separated from myeloproliferative disorders and de novo acute myeloid leukaemia. Even though most cases of MDS are diagnosed during its chronic anaemic phase, it is evident that many patients pass this stage unnoticed and are diagnosed only when presenting with an acute myeloid leukaemia. In these cases the identification of bone marrow tri-lineage dysplasia [5] or peripheral blood polymorph dysplasia [6] could suggest a diagnosis of MDS.

Platelets

Thrombocytopenia, particularly in the presence of large abnormal platelets with balloon-like features [4]. SPECIAL INVESTIGATIONS Cytogenetics

Identification of an abnormal chromosomal clone in the bone marrow is a significant finding in MDS, especially if chromosomes Nos. 5, 7, and 11 are involved. Complex clones with multiple chromosomal aberrations would indicate imminent transformation to acute myeloid leukaemia. Bone marrow in vitro colony growth

Abnormal in vitro growth of haematopoietic stem cells is a characteristic of MDS, best documented for the granulocyte-macrophage lineage (CFU-GM), but also found within erythroid and megakaryocytic lineages. However, normal growth patterns or cytogenetics, do not rule out a diagnosis of MDS.

REFERENCES 1. Bennett J. M., Catovsky D., Daniel M. T., Flandrin G., Galton D. A. G., Gralnick H. R. & Sultan C. (1982) Proposals for the classification of myelodysplastic syndromes. Br. J. Haemat. 51, 189. 2. Tricot G., Vlietinck R., Boogaerts M. A., et al. (1985) Prognostic factors in the myelodysplastic syndromes: importance of initial data on peripheral blood counts, bone marrow cytology, trephine biopsy and chromosomal analysis. Br. J. Haemat. 60,..10. 3. Hast R., Nilsson I., Widell S. & Ost/~. (1989) Diagnostic significance of dysplastic features of peripheral blood polymorphs in myelodysplastic syndromes. Leukemia Res. 13, 173-i78. 4. Widell S. & Hast R. (1987) Balioon-platelets in myelodysplastic syndrome a feature of dysmegakaryopoiesis? Leukemia Res. 11,747-752. 5. Brito-Babapulle F., Catovsky D. & Galton D. A. G. (1987) Clinical and laboratory features of de novo acute myeloid leukemia with trilineage myelodysplasia. Br. J. Haemat. 66, 445-450. 6. Hast R. & Widell S. (1991) Dysplastic peripheral blood polymorphs link acute myeloblastic leukemia in elderly to the myelodysplastic syndromes. (Submitted for publication.) ROBERT HAST

DIFFERENTIAL DIAGNOSIS Differential diagnoses that should be eliminated include hereditary or reversible causes of bone marrow dysmaturation, like vitamin or mineral deficiencies, immunological disorders, haemolytic

MINIMAL

DIAGNOSTIC

MYELODYSPLASTIC TrIE possibility to establish a reliable diagnosis of MDS is increasingly important because MDS is a prevalent disease. In most cases it is a slowly progressing disease and therefore, in clinical practice, one finds patients with the entire spectrum of findings from those giving only a vague suspicion of MDS to a classical full-blown picture of MDS. Diagnoses require criteria sensitive enough to include the majority of patients suffering from a

PER BERNELL Division of Hematology Department of Medicine Danderyd Hospital and Karolinska Institute Stockholm, Sweden

CRITERIA

FOR THE

SYNDROME certain disease, but also specific enough to exclude patients suffering from other diseases with similar features. A high degree of sensitivity usually results in a rather low degree of specificity and vice versa. It is difficult to find the ideal balance between sensitivity and specificity for the diagnosis of MDS and especially concerning the differential diagnosis against some intimately related disorders, i.e. aplastic anaemia, paroxysmal nocturnal haemoglobinuria,

Minimal diagnostic criteria for the myelodysplastic syndrome in clinical practice.

8 Introduction 3. Frisch B. & Bartl R, (1990) Primary and secondary myelodysplastic syndromes. In Atlas of Bone Marrow Pathology (Frisch B. & Bartl...
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