Idiopathic cytopenias of undetermined significance (ICUS), clonal hematopoiesis of indeterminate potential (CHIP), and clonal cytopenias of undetermined significance (CCUS)
- David P Steensma, MD
David P Steensma, MD
- Associate Professor of Medicine
- Harvard Medical School
Peripheral blood cytopenias are common in adults, especially the elderly, and can either be inconsequential or a sign of serious disease. A specific cause for anemia, neutropenia, or thrombocytopenia can be identified in most cases after a careful medical history, targeted physical examination, and appropriate laboratory and imaging tests, supplemented in some circumstances by a bone marrow aspirate and biopsy. (See "Approach to the adult patient with anemia" and "Approach to the adult with unexplained neutropenia" and "Approach to the adult with unexplained thrombocytopenia".)
However, diagnostic uncertainty persists in some patients and cytopenias may remain unexplained even after careful, thorough evaluation . Several terms are used to describe individuals who have cytopenias, clonal mutations in genes known to be associated with hematologic neoplasia, or both, yet who do not meet World Health Organization (WHO) diagnostic criteria for a specific disease entity. These terms are described further below (table 1).
The entities described below are not included in the current WHO classification of tumors of the hematopoietic system (4th edition, 2008), and will not be formal categories in the 5th edition (scheduled for publication in 2016 to 2017), since they are not clearly neoplastic [2,3].
DEFINITIONS AND DISTINCTION FROM MDS
Definitions — The following terms have been proposed to describe individuals who have cytopenias, clonal mutations in genes known to be associated with hematologic neoplasia, or both, yet who do not meet World Health Organization (WHO) diagnostic criteria for a specific disease entity (table 1) :
●Idiopathic cytopenia of undetermined significance (ICUS) – Single or multiple blood cytopenias that remain unexplained despite an appropriate evaluation including marrow examination. Excludes patients with a known clonal mutation. (See 'ICUS definition' below.)
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- DEFINITIONS AND DISTINCTION FROM MDS
- Distinction from MDS
- IDIOPATHIC CYTOPENIAS OF UNDETERMINED SIGNIFICANCE (ICUS)
- ICUS definition
- ICUS natural history
- Following patients with ICUS
- CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP)
- CHIP definition
- CHIP incidence
- CHIP natural history
- Following patients with CHIP
- CLONAL CYTOPENIAS OF UNDETERMINED SIGNIFICANCE (CCUS)
- CCUS definition
- CCUS natural history
- Following patients with CCUS
- SUMMARY AND RECOMMENDATIONS