Idiopathic cytopenia of undetermined significance (ICUS) and idiopathic dysplasia of uncertain significance (IDUS), and their distinction from low risk MDS

Abstract

It is now generally appreciated that hematologic neoplasms can develop over many years if not decades, often being initially occult or showing minimal (subdiagnostic) abnormalities. However, whereas such early neoplastic conditions have been defined in some detail in lymphoproliferative neoplasms, little is known about minimal lesions preceding the manifestation of an overt myeloid neoplasm, about underlying mechanisms, the clinical course and outcome, and the prognostic significance of such conditions. Members of several groups have recently described two 'premalignant' myeloid conditions, namely idiopathic cytopenia of undetermined significance (ICUS) and idiopathic bone marrow dysplasia of uncertain significance (IDUS). At least in some patients these are neoplastic conditions. Both conditions may progress to an overt myelodysplastic syndrome (MDS), but may also progress to another myeloid neoplasm such as acute myeloid leukemia, a myeloproliferative neoplasm (MPN), or a mast cell disorder (mastocytosis). In ICUS the dysplasia is mild and does not fulfill the WHO criteria for MDS but cytopenias can be severe. In IDUS the dysplasia is prominent but cytopenias, if detectable, are mild. In both conditions it is possible that a neoplastic clone has already replaced most or all of normal bone marrow cells when ICUS or IDUS is detected, but evidence to support this possibility is not necessarily available. For both groups of patients we recommend a thorough hematologic follow up because of the potential of disease-manifestation and the unpredictable form and time of progression. In the present review, we discuss current concepts relating to ICUS and IDUS as well as diagnostic approaches and available criteria.