ICUS/CCUS/CHIP: basics &amp; beyond

Jain, Mili; Tripathi, Anil Kumar

doi:10.1080/17474086.2017.1371588

Cited by 16 publications

(11 citation statements)

References 27 publications

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“…Case 4 also featured a nonsense mutation in DNMT3A c.2384G>A p.W795* (AF = 24%). Detection of mutations classically associated with myeloid neoplasms (or clonal haematopoiesis of indeterminate potential; Jain & Tripathi, ) in two cases raises the question of whether these mutations are restricted to the lesional RDD cells and/or present within admixed non‐lesional haematolymphoid cells. Despite attempts to maximize the percentage of lesional cells by macrodissection, abundant background inflammatory cells in intimate association with the lesional histiocytes cannot be excluded, precluding an ability to definitively distinguish these possibilities.…”

Section: Discussionmentioning

confidence: 99%

Cyclin D1 expression and novel mutational findings in Rosai‐Dorfman disease

et al. 2019

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Summary Rosai‐Dorfman disease (RDD) is an enigmatic histiocytic disorder classically diagnosed by a distinctive combination of pathological features: emperipolesis, or migration of intact haematological cells through the voluminous cytoplasm of lesional histiocytes, and expression of S100 by these histiocytes. The pathogenesis has long been elusive until the recent detection of recurrent and mutually exclusive mutations in several oncogenes in the mitogen‐activated protein kinase (MAPK) pathway. Based on these findings, we investigated a cohort of 21 RDD patients and found that the lesional histiocytes in 86% (18/21) of patients exhibited strong and diffuse nuclear Cyclin D1 expression, which not only may provide a diagnostic marker for this sometimes pathologically challenging disease, but also probably reflects constitutive MAPK pathway activation because we additionally identified phosphorylated‐ERK expression in 90% (19/21) of cases. Further, we performed massively parallel sequencing on a subset (6/18) of the CyclinD1 positive cases, identifying several mutations that have not been previously reported in RDD. Taken together, our findings bolster the concept of RDD as a disease of MAPK activation in a substantial percentage of cases and enhance the current understanding of the pathogenesis of RDD.

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Section: Discussionmentioning

confidence: 99%

Cyclin D1 expression and novel mutational findings in Rosai‐Dorfman disease

et al. 2019

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“…Idiopathic cytopenias, which do not meet WHO criteria for any specific disease especially MDS, are classified as ICUS, CCUS and clonal haematopoiesis of indeterminate potential 3…”

Section: Discussionmentioning

confidence: 99%

Unexplained chronic cytopenia: is it idiopathic cytopenia of undetermined significance or myelodysplastic syndrome

et al. 2019

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Idiopathic cytopenia is a condition where there is a decrease in peripheral blood counts causing either anaemia, leucopoenia and thrombocytopaenia. Most cases of cytopenia reveal a cause on further workup. But very rarely, in some cases, a definitive cause could not be identified. Unexplained cytopenia becomes challenging and poses difficulty in diagnosis and management. Discriminating these groups of bone marrow failure disorders from myelodysplastic syndrome (MDS) becomes an important clinical question. We describe a case of a middle-aged Hispanic woman who presented with pancytopenia and on extensive workup did not reveal any specific cause. Her bone marrow examination revealed severely reduced megakaryocytes but with normal haemopoiesis of other lineages. Cytogenetics, flow cytometry, comprehensive next-generation whole genomic analysis did not reveal any abnormalities. She fit the criteria for idiopathic cytopenia of undetermined significance rather than MDS. She remained asymptomatic and her counts never improved with immunosuppressives or thrombopoietin mimetics.

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“…The current study included patients with idiopathic cytopenia of undetermined significance (ICUS). The ICUS diagnosis was based on the consensus criteria [5, 6] and included three or more hematology specialists. In addition, the myelodysplastic syndrome (MDS) diagnosis was eliminated for the ICUS diagnosis [5, 7].…”

Section: Methodsmentioning

confidence: 99%

Nonclonal chromosomal alterations and poor survival in cytopenic patients without hematological malignancies

et al. 2019

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BackgroundClonal chromosomal alterations (CCAs) reflect recurrent genetic changes derived from a single evolving clone, whereas nonclonal chromosomal alterations (NCCAs) comprise a single or nonrecurrent chromosomal abnormality. CCAs and NCCAs in hematopoietic cells have been partially investigated in cytopenic patients without hematological malignancies.MethodsThis single-center retrospective study included 253 consecutive patients who underwent bone marrow aspiration to determine the cause of cytopenia between 2012 and 2015. Patients with hematological malignancies were excluded. CCA was defined as a chromosomal aberration detected in more than two cells, and NCCA was defined as a chromosomal aberration detected in a single cell.ResultsThe median age of the patients was 66 years. There were 135 patients without hematological malignancies (median age, 64 years; 69 females); of these, 27 patients (median age, 69 years; 8 females) harbored chromosomal abnormalities. CCAs were detected in 14 patients; the most common CCA was −Y in eight patients, followed by inv.(9) in three patients and mar1+, inv. (12), and t (19;21) in one patient each. NCCAs were detected in 13 patients; the most frequent NCCA was +Y in four patients, followed by del (20), + 8, inv. (2), − 8, and add (6) in one patient each. Moreover, nonclonal translocation abnormalities, including t (9;14), t (14;16), and t (13;21), were observed in three patients. One patient had a complex karyotype in a single cell. The remaining 106 patients with normal karyotypes comprised the control group (median age, 65 years; range, 1–92 years; 56 females). Further, follow-up analysis revealed that the overall survival of the NCCA group was worse than that of the CCA and the normal karyotype groups (P < 0.0001; log-rank test).The survival of the NCCA-harboring cytopenic patients was worse than that of the CCA-harboring cytopenic patients without hematological malignancies, suggesting that follow-up should be considered for both CCA- and NCCA-harboring cytopenic patients.

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ICUS/CCUS/CHIP: basics & beyond

Cited by 16 publications

References 27 publications

Cyclin D1 expression and novel mutational findings in Rosai‐Dorfman disease

Cyclin D1 expression and novel mutational findings in Rosai‐Dorfman disease

Unexplained chronic cytopenia: is it idiopathic cytopenia of undetermined significance or myelodysplastic syndrome

Nonclonal chromosomal alterations and poor survival in cytopenic patients without hematological malignancies

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