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Minimal diagnostic criteria for the myelodysplastic syndrome in clinical practice
Leukemia Research Vol. 16, No. 1, pp. 3-11, 1992.
0145-2126/92 $5.00 + .00 PergamonPressplc
Printed in Great Britain.
INTRODUCTION WHAT IS MDS? It has recently become obvious that, while the diagnosis of MDS is uncontroversial in many 'typical' cases, there is considerable disagreement regarding the minimal diagnostic criteria. Several experienced MDS-researchers were therefore invited to attempt a brief definition of these criteria. Six proposals follow. It is obvious that, while they have much in
common they are also dissimilar, and that some kind of a consensus is urgently required. Criteria should not consist of pathophysiological reasoning, but should be useful for the young and inexperienced practising haematologists. PETER REIZENSTEIN AKE OST
MINIMAL DIAGNOSTIC CRITERIA FOR THE MYELODYSPLASTIC SYNDROME IN CLINICAL PRACTICE THE myelodysplastic syndromes (MDS) are clonal proliferations of multipotent bone marrow stem cells which retain the capacity to differentiate to mature blood cells but do so in a disordered and inefficient manner, so that daughter cells are reduced in number, deficient in function and abnormal in morphology. With time there is a tendency for the capacity to differentiate to be lost so that an acute leukaemia evolves. This tendency is not absolute, indeed in the majority of patients death from cytopenia or incidental cause supervenes before leukaemia. In the typical case diagnosis is not difficult. Pancytopenia is associated with a hyperplastic bone marrow which shows some of the characteristic morphological abnormalities in all lineages: in the erythroid series, macrocytosis, anisopoikilocytosis, hypochromic fragments, basophilic stippling, multinucleate normoblasts, megaloblastoid change, dyskaryorrhexis, cytoplasmic vacuoles and ring sideroblasts; in the granulocytic series, hypogranular neutrophils, metamyelocytes, myelocytes and promyelocytes, Pelger cells, grossly hypersegmented neutrophils, and increased small agranular or sparsely granular blasts in the bone marrow; in the monocytic series, agranularity, abnormal nuclear lobulation and circulating promonocytes, and in the megakaryocytic series, giant and agranular platelets, micromegakaryocytes, large mononuclear megakaryocytes and large polyploid megakaryocytes with dispersed nuclei. These dysplastic features are not only seen in MDS, and other causes such as B12 or folate deficiency, the effects of alcohol or cytotoxic drugs, and AIDS must be excluded.
It is when such florid features are not present that diagnosis becomes difficult. The marrow may be hypocellular or heavily infiltrated with fibrous tissue, dysplastic features may be minor seen in only one or two lineages, there may be a single cytopenia only, or just macrocytosis without anaemia. In such cases we may need to fall back on the acronyms NQMDS (not quite MDS) or NYMDS (not yet MDS) and watch and wait with MDS as the working diagnosis waiting to be confirmed. In these cases diagnosis may be helped by marrow histology which is disorganised or by bone marrow culture, although it is often in the diagnostically difficult cases that this technique is least helpful. Peripheral blood progenitor assays may be more helpful. It is often helpful to establish clonality, either by demonstrating characteristic chromosomal abnormalities or, in women, using one of the assays for X-linked polymorphisms. However, clonality alone does not confirm MDS. A further element of confusion arises when there is a proliferative component to the blood dyscrasia, as, for example, with the neutrophils and granulocytes in chronic myelomonocytic leukaemia, or with the platelets in the 5q-syndrome or in some cases of sideroblastic anaemia. In my view the confusion here is largely semantic; such syndromes may be thought of as both myelodysplastic and myeloproliferative. Finally, it should be noted that my initial definition is principally a biological one. Any blood disease that fulfils that definition is MDS whether or not the artefact of Romanowsky staining endorses the diagnosis. TERRY HAMBLIN
Royal Bournemouth Hospital Bournemouth, U.K.
0145-2126/92 $5.00 + .00 PergamonPressplc
Printed in Great Britain.
INTRODUCTION WHAT IS MDS? It has recently become obvious that, while the diagnosis of MDS is uncontroversial in many 'typical' cases, there is considerable disagreement regarding the minimal diagnostic criteria. Several experienced MDS-researchers were therefore invited to attempt a brief definition of these criteria. Six proposals follow. It is obvious that, while they have much in
common they are also dissimilar, and that some kind of a consensus is urgently required. Criteria should not consist of pathophysiological reasoning, but should be useful for the young and inexperienced practising haematologists. PETER REIZENSTEIN AKE OST
MINIMAL DIAGNOSTIC CRITERIA FOR THE MYELODYSPLASTIC SYNDROME IN CLINICAL PRACTICE THE myelodysplastic syndromes (MDS) are clonal proliferations of multipotent bone marrow stem cells which retain the capacity to differentiate to mature blood cells but do so in a disordered and inefficient manner, so that daughter cells are reduced in number, deficient in function and abnormal in morphology. With time there is a tendency for the capacity to differentiate to be lost so that an acute leukaemia evolves. This tendency is not absolute, indeed in the majority of patients death from cytopenia or incidental cause supervenes before leukaemia. In the typical case diagnosis is not difficult. Pancytopenia is associated with a hyperplastic bone marrow which shows some of the characteristic morphological abnormalities in all lineages: in the erythroid series, macrocytosis, anisopoikilocytosis, hypochromic fragments, basophilic stippling, multinucleate normoblasts, megaloblastoid change, dyskaryorrhexis, cytoplasmic vacuoles and ring sideroblasts; in the granulocytic series, hypogranular neutrophils, metamyelocytes, myelocytes and promyelocytes, Pelger cells, grossly hypersegmented neutrophils, and increased small agranular or sparsely granular blasts in the bone marrow; in the monocytic series, agranularity, abnormal nuclear lobulation and circulating promonocytes, and in the megakaryocytic series, giant and agranular platelets, micromegakaryocytes, large mononuclear megakaryocytes and large polyploid megakaryocytes with dispersed nuclei. These dysplastic features are not only seen in MDS, and other causes such as B12 or folate deficiency, the effects of alcohol or cytotoxic drugs, and AIDS must be excluded.
It is when such florid features are not present that diagnosis becomes difficult. The marrow may be hypocellular or heavily infiltrated with fibrous tissue, dysplastic features may be minor seen in only one or two lineages, there may be a single cytopenia only, or just macrocytosis without anaemia. In such cases we may need to fall back on the acronyms NQMDS (not quite MDS) or NYMDS (not yet MDS) and watch and wait with MDS as the working diagnosis waiting to be confirmed. In these cases diagnosis may be helped by marrow histology which is disorganised or by bone marrow culture, although it is often in the diagnostically difficult cases that this technique is least helpful. Peripheral blood progenitor assays may be more helpful. It is often helpful to establish clonality, either by demonstrating characteristic chromosomal abnormalities or, in women, using one of the assays for X-linked polymorphisms. However, clonality alone does not confirm MDS. A further element of confusion arises when there is a proliferative component to the blood dyscrasia, as, for example, with the neutrophils and granulocytes in chronic myelomonocytic leukaemia, or with the platelets in the 5q-syndrome or in some cases of sideroblastic anaemia. In my view the confusion here is largely semantic; such syndromes may be thought of as both myelodysplastic and myeloproliferative. Finally, it should be noted that my initial definition is principally a biological one. Any blood disease that fulfils that definition is MDS whether or not the artefact of Romanowsky staining endorses the diagnosis. TERRY HAMBLIN
Royal Bournemouth Hospital Bournemouth, U.K.