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41


Leukemic mantle cell lymphoma and chronic lymphocytic leukemia: a rare composite lymphoma and literature review [Review]

Marks, Etan; Liu, Cynthia; Raphael, Bruce; Arbini, Arnaldo
Composite lymphomas are rare entities that either represent a collision of two separate lymphomas, or one lymphoma that expresses two distinct phenotypes. Mantle cell lymphoma has been reported in some composite lymphomas, but when combined with chronic lymphocytic leukemia, it can be difficult to recognize because of the phenotypic overlap of these two entities. We report a case of a 75-year-old male with a slowly progressing lymphocytosis, but who was otherwise asymptomatic. Flow cytometry revealed two different populations, one showing bright Lambda positivity and CD5(+), while the other was positive for both lambda and kappa and was CD5(+). Subsequently, cytogenetics revealed two different populations, one with a trisomy 12 and the other with a t(11;14). Additionally, immunohistochemistry on a bone marrow biopsy showed SOX-11 to be negative and cyclin D1 to be positive on scattered lymphocytes. This was consistent with a composite lymphoma of leukemic mantle cell lymphoma and chronic lymphocytic lymphoma.
ISI:000433986000006
ISSN: 1868-9256
CID: 3161812

Usefulness of an Online Risk Estimator for Bronchopulmonary Dysplasia in Predicting Corticosteroid Treatment in Infants Born Preterm

Cuna, Alain; Liu, Cynthia; Govindarajan, Shree; Queen, Margaret; Dai, Hongying; Truog, William E
OBJECTIVE:To assess the usefulness of a bronchopulmonary dysplasia (BPD) outcome estimator developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in identifying high-risk preterm infants treated with steroids. STUDY DESIGN:This was a single-center retrospective study of infants born ≤30 weeks of gestational age. The NICHD BPD outcome estimator was used to retrospectively calculate BPD risk at various postnatal ages. The best combination of risk estimates for identifying steroid treatment was identified using stepwise model selection. A cut-off value with the best combination of sensitivity and specificity was identified using receiver operating characteristic analysis. RESULTS:A total of 165 infants born preterm (mean gestational age 26 ± 1.6 weeks, mean birth weight 837 ± 171 g) were included. Of these, 61 were treated with steroids for BPD and 104 were not. Risk estimates for BPD or death were significantly greater in infants treated with steroids compared with controls. Both combined risk for severe BPD or death and single risk of no BPD were identified as factors with the best predictive power for identifying treatment with steroids, with accurate prediction possible as early as the second week of life. A greater than 37% risk for severe BPD or death or a less than 3% risk of no BPD on day of life 14 had 84%-92% sensitivity and 77%-80% specificity for predicting steroid treatment. CONCLUSION:The NICHD BPD outcome estimator can be a useful objective tool for identifying infants at high risk for BPD who may benefit from postnatal steroids.
PMID: 29551313
ISSN: 1097-6833
CID: 5430782

Role of dysregulated cytokine signaling and bacterial triggers in the pathogenesis of Cutaneous T Cell Lymphoma

Fanok, Melania H; Sun, Amy; Fogli, Laura K; Narendran, Vijay; Eckstein, Miriam; Kannan, Kasthuri; Dolgalev, Igor; Lazaris, Charalampos; Heguy, Adriana; Laird, Mary E; Sundrud, Mark S; Liu, Cynthia; Kutok, Jeff; Lacruz, Rodrigo S; Latkowski, Jo-Ann; Aifantis, Iannis; Odum, Niels; Hymes, Kenneth B; Goel, Swati; Koralov, Sergei B
Cutaneous T cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome revealed a highly heterogeneous landscape of genetic perturbations and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease. Nonetheless, using data harvested from high-throughput transcriptional profiling allowed us to develop a reliable signature of this malignancy. Focusing on a key cytokine signaling pathway, previously implicated in CTCL pathogenesis, JAK/STAT signaling, we used conditional gene targeting to develop a fully penetrant small animal model of this disease that recapitulates many key features of mycosis fungoides, a common variant of CTCL. Using this mouse model, we demonstrate that T cell receptor engagement is critical for malignant transformation of the T lymphocytes and that progression of the disease is dependent on microbiota.
PMCID:5912980
PMID: 29128259
ISSN: 1523-1747
CID: 2785082

A Rare Case of Composite Dural Extranodal Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Bustoros, Mark; Liechty, Benjamin; Zagzag, David; Liu, Cynthia; Shepherd, Timothy; Gruber, Deborah; Raphael, Bruce; Placantonakis, Dimitris G
Background/UNASSIGNED:Primary extranodal marginal zone lymphoma (MZL) of the dura is a rare neoplastic entity in the central nervous system (CNS). Methods/UNASSIGNED:We used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Results/UNASSIGNED:We identified 104 cases of dural MZL in the literature. None of them presented concurrently with another type of non-Hodgkin lymphoma. This is the first report of composite lymphoma consisting of dural MZL and CLL/SLL in the bone marrow and lymph nodes. Conclusion/UNASSIGNED:Primary dural MZL is a rare, indolent low-grade CNS lymphoma, with a relatively good prognosis. Its treatment is multidisciplinary and often requires surgical intervention due to brain compression, along with low to moderate doses of radiotherapy and/or systemic chemotherapy.
PMCID:5928293
PMID: 29740389
ISSN: 1664-2295
CID: 3085002

TET1 is a tumor suppressor of hematopoietic malignancy

Cimmino, Luisa; Dawlaty, Meelad M; Ndiaye-Lobry, Delphine; Yap, Yoon Sing; Bakogianni, Sofia; Yu, Yiting; Bhattacharyya, Sanchari; Shaknovich, Rita; Geng, Huimin; Lobry, Camille; Mullenders, Jasper; King, Bryan; Trimarchi, Thomas; Aranda-Orgilles, Beatriz; Liu, Cynthia; Shen, Steven; Verma, Amit K; Jaenisch, Rudolf; Aifantis, Iannis
The methylcytosine dioxygenase TET1 ('ten-eleven translocation 1') is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. The diminished expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we found that deletion of Tet1 promoted the development of B cell lymphoma in mice. TET1 was required for maintenance of the normal abundance and distribution of 5hmC, which prevented hypermethylation of DNA, and for regulation of the B cell lineage and of genes encoding molecules involved in chromosome maintenance and DNA repair. Whole-exome sequencing of TET1-deficient tumors revealed mutations frequently found in non-Hodgkin B cell lymphoma (B-NHL), in which TET1 was hypermethylated and transcriptionally silenced. Our findings provide in vivo evidence of a function for TET1 as a tumor suppressor of hematopoietic malignancy.
PMCID:4545281
PMID: 25867473
ISSN: 1529-2916
CID: 1532762

Limited miR-17-92 overexpression drives hematologic malignancies

Danielson, Laura S; Reavie, Linsey; Coussens, Marc; Davalos, Veronica; Castillo-Martin, Mireia; Guijarro, Maria V; Coffre, Maryaline; Cordon-Cardo, Carlos; Aifantis, Iannis; Ibrahim, Sherif; Liu, Cynthia; Koralov, Sergei B; Hernando, Eva
The overexpression of microRNA cluster miR-17-92 has been implicated in development of solid tumors and hematological malignancies. The role of miR-17-92 in lymphomagenesis has been extensively investigated; however, because of the developmental defects caused by miR-17-92 dysregulation, its ability to drive tumorigenesis has remained undetermined until recently. Here we demonstrate that overexpression of miR-17-92 in a limited number of hematopoietic cells is sufficient to cause B cell malignancies. In sum, our study provides a novel and physiologically relevant model that exposes the potent ability of miR-17-92 to act as a driver of tumorigenesis.
PMCID:4376677
PMID: 25597017
ISSN: 0145-2126
CID: 1439872

Synchronous Gastric and Diffuse Colonic MALT Lymphoma in a Patient With Strongyliodes Infection: A Causal or Incidental Association [Meeting Abstract]

Subei, Obada; Zahir, Ismail; Liu, Cynthia; Gandhi, Soren
ISI:000363715900323
ISSN: 1572-0241
CID: 1854252

Expression of c-MYC and MMP9 in Alternatively Activated Macrophages (M2) of Classical Hodgkin Lymphoma [Meeting Abstract]

Yang, Long; Harris, Jonathan A; Ibrahim, Sherif; Liu, Cynthia
ISI:000349233802204
ISSN: 1528-0020
CID: 1497532

Extranodal natural killer/T-cell lymphoma masquerading as conjunctivitis [Letter]

Charles, Norman C; Liu, Cynthia Z; Belinsky, Irina; Patel, Payal
PMID: 25103666
ISSN: 0008-4182
CID: 1252272

C-kit (CD117) expression in mucosal melanomas of head and neck-42 cases of eastern Chinese patients [Meeting Abstract]

Chen, G.; Wu, L.; Li, P.; Kong, M. X.; Liu, C.; Sun, W.; Wang, B. Y.
ISI:000308126900424
ISSN: 0309-0167
CID: 178291