12 research outputs found
A case of primary extranodal natural killer/T-cell lymphoma in the orbit and intraocular tissues with cerebrospinal fluid involvement
Purpose: To report a rare case of primary orbital natural killer (NK)/T-cell lymphoma without nasal lesions but with cerebrospinal fluid involvement. Observations: A 73-year-old woman was referred to the uveitis clinic with suspected unilateral acute uveitis in her right eye and a right orbital tumor. EpsteināBarr virus DNA was detected in the aqueous humor in her right eye, and orbital biopsy revealed the presence of extranodal NK/T-cell lymphoma (ENKTL), nasal type. Positron emission tomography showed significant 18F-fluorodeoxyglucose uptake in the right orbit, with no other signs of systemic involvement. Cerebrospinal fluid analysis demonstrated lymphoma cell infiltration. She was diagnosed with stage IV ENKTL and treated with orbital radiotherapy and systemic chemotherapy, with subsequent remission. However, the lymphoma relapsed in her left vitreous at 10 months after therapy, suggesting metastasis of lymphoma cells to the contralateral eye via the vitreous and cerebrospinal fluid. Conclusions and importance: A few cases of ocular-tissue ENKTL have been reported, mostly involving invasion or dissemination of primary nasal lesions; in contrast, primary orbital and intraocular ENKTL has rarely been reported. To the best of our knowledge, this is the first report of a primary orbital ENKTL metastasizing to the vitreous of the contralateral eye. Although ENKTL is rare in the orbit and intraocular tissues, it should be considered as a possible differential diagnosis in patients with orbital tumors or intraocular inflammation resistant to steroid therapy because ENKTL has a very poor prognosis in the advanced stage. Keywords: Malignant lymphoma, Natural killer/T-cell lymphoma, Uveitis, EpsteināBarr viru
Clinical Significance of sIL-2R Levels in B-Cell Lymphomas
<div><p>Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R Ī± chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas.</p></div
Model of sIL-2R elevation in B-cell lymphomas.
<p>MMP-9 released from tumor associated macrophages (especially CD68-positive) cleaves the IL-2R Ī± chain on bystander T-cells and B-lymphoma cells, if they express CD25 (IL-2RĪ±). This mechanism may be involved in elevation of sIL-2R levels in patients with B-cell lymphomas.</p
Characteristics of analyzed patients and results of immunohistochemical study.
<p>Abbreviations: sIL-2R; Soluble Interleukin-2 Receptor, DLBCL; Diffuse large B-cell lymphoma, FL; Follicular lymphoma, RLH; reactive lymph node hyperplasia.</p
Production of MMP-9 by tumor-associated macrophages.
<p>(A) Positive correlations between sIL-2R and MMP-9 levels were observed in patients with FL (Ļā=ā0.585, p-valueā=ā0.028), but not in DLBCL. (B) Immunohistochemical staining with anti-MMP-9 antibody in DLBCL, FL and RLH. MMP-9-positive cells were mainly macrophages in each sample, and lymphoma cells were negative for MMP-9 in DLBCL and FL. *Significant correlation was observed.</p
Effects of MMP-9 on cleavage of IL-2RĪ±.
<p>(A) The ATL cell line, MT4, in which MMP-9 expression was not detected by RT-PCR, was treated with rMMP-9 (1 Āµg/ml or 3 Āµg/ml). After 6 h of incubation, analysis of CD25 expression was performed by flow cytometry. (B) MT4 was treated with rMMP-9 (400 ng/ml) or MMP-9 inhibitor (0.1 mM), and cultured in FCS-free medium. After 6 h of culture, experiments were performed in triplicate. P-values of <0.05 were considered to be statistically significant.</p
Overall survival based on sIL-2R levels (ā¤1500 vs. >1500) in DLBCL (A) and FL (B).
<p>Serum sIL-2R levels were analyzed in previously untreated patients with DLBCL (nā=ā104) or FL (nā=ā30). The 5-year OS rates for patients with sIL-2R levels of ā¤1500 U/ml and >1500 U/ml were 76% and 62%, respectively (p<0.05) in DLBCL, and 100% and 79.3%, respectively (pā=ā0.189) in FL.</p
Relationship between sIL-2R concentrations and expressions of CD25.
*<p>FLIPI1 was used in patients with FL.</p><p>Abbreviations: sIL-2R; soluble interleukin-2 receptors, LDH; lactate dehydrogenase, CS; clinical stage, IPI; international prognostic index, DLBCL; diffuse large B-cell lymphoma, FL; follicular lymphoma, MCL; mantle cell lymphoma, RLH; reactive lymph node hyperplasia, NA; not available.</p><p>Normal range: sIL-2R; 145ā518 U/ml, LDH; 119ā229 IU/l.</p