A 65-year-old woman with intractable nasal congestion.
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Aged↗
Biomedical subjects
Sindhu Cherian
Publications and source records attributed to Sindhu Cherian.
The genetics of the myelodysplastic syndromes: classical cytogenetics and recent molecular insights.
Myelodysplastic syndromes (MDS) are a complex group of clonal hematopoietic disorders with an attendant diverse array of associated genetic changes. Conventional cytogenetics plays a prominent and well-established role in determining the contemporary diagnosis and prognosis of these disorders. More recently, molecular approaches have been useful in further characterizing this group of diseases, albeit in a largely experimental context, with the detection of changes at the single gene level including mutations, amplification and epigenetic phenomena. Nevertheless, we remain largely ignorant of the genetic underpinnings of MDS. Here we briefly review the established role of cytogenetics in MDS, and emphasize recent advances in unraveling the genetics of MDS, with a view towards how such findings might facilitate our ability to understand, diagnose and treat these disorders in a more rational manner.
Chromosome Aberrations↗
Interleukin 1 receptor antagonist to treat cytophagic histiocytic panniculitis with secondary hemophagocytic lymphohistiocytosis.
Cytophagic histiocytic panniculitis (CHP) is a rare, usually fatal disease of childhood; it typically presents with daily high spiking fevers and severe panniculitis. Hemophagocytosis from macrophage activation during a cytokine storm can result in pancytopenia and disseminated intravascular coagulopathy. We describe a 14-year-old girl with long-standing CHP who developed severe hemophagocytic lymphohistiocytosis, which responded to treatment with a combination of high dose corticosteroids, cyclosporine, and the interleukin 1 receptor antagonist, anakinra.
Adolescent↗
Flow-cytometric analysis of peripheral blood neutrophils: a simple, objective, independent and potentially clinically useful assay to facilitate the diagnosis of myelodysplastic syndromes.
The diagnosis of myelodysplastic syndromes (MDS) is based upon cytopenias, morphologic dysplasia, and cytogenetic abnormalities. Because morphologic dyspoiesis may be subtle, and many cases have normal cytogenetics, additional objective diagnostic tools are needed. We previously developed a novel peripheral blood neutrophil flow-cytometric (FCM) scoring system to identify patients with MDS. Here, in an analysis of 25 patients, we demonstrate that FCM abnormalities are independent of currently measured parameters in MDS, including cytopenias, marrow blast percent, and IPSS score. Importantly, FCM abnormalities were seen in 9/16 MDS patients with normal cytogenetics, suggesting that this simple, non-invasive assay could play a central role in the diagnosis of MDS.
Adult↗
Peripheral blood MDS score: a new flow cytometric tool for the diagnosis of myelodysplastic syndromes.
BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders diagnosed using morphologic and clinical findings supported by cytogenetics. Because abnormalities may be subtle, diagnosis using these approaches can be challenging. Flow cytometric (FCM) approaches have been described; however the value of bone marrow immunophenotyping in MDS remains unclear due to the variability in detected abnormalities. We sought to refine the FCM approach by using peripheral blood (PB) to create a clinically useful tool for the diagnosis of MDS. METHODS: PB from 15 patients with MDS was analyzed by multiparametric flow cytometry using an extensive panel of monoclonal antibodies. Patterns of neutrophil antigen expression were compared with those of normal controls (n = 16) to establish light scatter and/or immunophenotypic abnormalities that correlated with MDS. A scoring algorithm was developed and validated prospectively on a blinded patient set. RESULTS: PB neutrophils from patients with MDS had lower side scatter and higher expression of CD66 and CD11a than did controls. Some MDS PB neutrophils demonstrated abnormal CD116 and CD10 expression. Because none of these abnormalities proved consistently diagnostic, we sought to increase the power of the assay by devising a scoring system to allow the association of multiple abnormalities and account for phenotypic variations. The PB MDS score differentiated patients with MDS from controls (P < 0.0001) in the test set. In a prospective validation, the PB MDS score successfully identified patients with MDS (sensitivity 73%, specificity 90%). CONCLUSIONS: FCM analysis of side scatter and only four additional immunophenotypic parameters of PB neutrophils using the PB MDS score proved more sensitive than standard laboratory approaches and may provide an additional, more reliable diagnostic tool in the identification of MDS.
Aged↗
Regression of pulmonary MALT lymphoma after treatment with rituximab.
We describe a patient with extranodal (pulmonary) marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) who was refractory to treatment with cytotoxic chemotherapy. After a single four-week course of rituximab she had significant regression of pulmonary lesions and remains progression free 19 months after finishing her treatment. This case report demonstrates the potential efficacy of rituximab as a single therapeutic agent in patients with pulmonary MALT lymphoma.
Adult↗
Expanded populations of surface membrane immunoglobulin light chain-negative B cells in lymph nodes are not always indicative of B-cell lymphoma.
Immunophenotypic analysis is useful in distinguishing reactive from neoplastic lymphoproliferations, particularly when tissue is limited or histologic findings are equivocal. Surface membrane immunoglobulin (SmIg) light chain restriction in B cells is especially helpful in documenting clonality, and the loss of SmIg by B cells in extramedullary sites also has been used as a criterion to support the presence of lymphoma. However, we identified 3 cases of benign follicular hyperplasia (in 101 cases analyzed) with profound expansions (56%-88% of the B cells) of SmIg light chain-negative B cells without clonality by immunoglobulin heavy chain gene polymerase chain reaction. Thus, although uncommonly encountered, lack of SmIg light chain expression by B cells should not necessarily be interpreted as indicative of lymphoma. Interestingly, 2 of the 3 patients with these "aberrant" expansions were HIV+, and such patients are at heightened risk for the development of lymphoma. Therefore, there is the potential for misdiagnosing lymphoma if flow cytometric data are interpreted inappropriately in isolation.
Adult↗
Flow cytometric test for beryllium sensitivity.
BACKGROUND: Chronic beryllium disease (CBD) is an occupational granulomatous disorder characterized by hypersensitivity to beryllium, mediated by CD4+ T lymphocytes, and predominantly affects the lungs. In this disorder, lymphocyte proliferative responses to beryllium, measured by 3H thymidine incorporation, are used for diagnosis of CBD, for screening asymptomatic workers or former workers to detect unrecognized disease, and for surveillance as a bioassay to detect abnormal exposures. Problems with test variability and the use of radioactivity have recently led to the search for alternative methods. METHODS: We applied a 5,6-carboxyfluorescein diacetate succinimidyl ester flow cytometric technique for measurement of mitogen- and antigen-induced T-lymphocyte proliferation to a group of beryllium-exposed sensitized individuals and beryllium-unexposed controls. RESULTS: We detected mitogen and antigen proliferative responses in CD3+, CD4+, and CD8+ subpopulations. Phytohemagglutinin and Candida stimulated CD4+ and CD8+ T-cell responses, but beryllium appeared to stimulate only CD3+/CD4+ responses. CONCLUSIONS: This technique may provide a sensitive, nonradioactive alternative to the traditional proliferation tests that measure beryllium sensitivity. It offers the added specificity of enabling phenotypic description of the responding cell type and may prove to be easier to standardize for clinical use.
Air Pollutants, Occupational↗