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Current Hematologic Malignancy Reports Dec 2016Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with... (Review)
Review
PURPOSE OF REVIEW
Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the United States. Data on epidemiology, disease presentation, and outcome for European and North American ("Western") cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience.
RECENT FINDINGS
We highlight key observations in its epidemiology, natural history, and trends in clinical management. In the USA, ENKTL-NT is more common among Asian Pacific Islanders (API) and Hispanics compared to non-Hispanic whites. Published studies indicate less heterogeneity in clinical presentation in Western ENKTL-NT compared to Asian patients. While there is variation in age at diagnosis, presence of antecedent lymphoproliferative disorders, and outcomes among racial/ethnic groups, the universal association of ENKTL-NT with EBV and the poor response of this neoplasm to anthracycline-based therapy is consistent across all geographic areas. Data on epidemiology, disease presentation, and clinical outcomes in mature T cell and NK cell (T/NK cell) neoplasms, including ENKTL-NT, in Europe and North America are very limited. As the classification and diagnostic characterization of the currently recognized T/NK cell lymphoma disease entities continue to evolve, gaps and inconsistencies in data reporting across different studies are being recognized. Despite these limitations, several studies from the USA suggest that the incidence of ENKTL-NT is higher in Asian Pacific Islanders (API) and non-white Hispanics and that outcomes may be worse in non-whites. However, the universal association of ENKTL-NT with Epstein-Barr virus (EBV) across all ethnic groups suggests a common pathogenesis. Given the overlap between the entities included in the category of T/NK cell neoplasms, there is a need to further define biological and clinical differences that may affect diagnosis, treatment, and outcome.
Topics: Antineoplastic Agents; Asparaginase; Biomarkers; DNA, Viral; Europe; Herpesvirus 4, Human; Humans; Lymphoma, Extranodal NK-T-Cell; North America
PubMed: 27778143
DOI: 10.1007/s11899-016-0355-9 -
Journal of Immunology Research 2023Many studies have demonstrated that PD-L1/PD-1 signaling is an immune evasion mechanism in tumors. PD-L1/PD-1 coexpression with CXCR3/CD36 in peripheral lymphocytes in...
Many studies have demonstrated that PD-L1/PD-1 signaling is an immune evasion mechanism in tumors. PD-L1/PD-1 coexpression with CXCR3/CD36 in peripheral lymphocytes in lymphoma still needs to be clarified. The current study investigated PD-L1/PD-1 coexpression with CXCR3/CD36 in circulating lymphocytes, serum IL-19 levels, and their correlation with clinical outcome and extranodal involvement in lymphoma. . The coexpression of PD-L1/PD-1 with CXCR3/CD36 on circulating lymphocytes was analyzed by flow cytometry in 78 lymphoma patients before and after therapy and in 50 healthy controls. The concentration levels of IL-19 in serum were assessed by an ELISA. . PD-L1 and PD-1 were expressed on circulating CXCR3+ and CD36+ lymphocytes in lymphoma and were significantly higher in patients with extranodal involvement than in lymphoma patients without extranodal involvement ( < 0.001). Elevated IL-19 levels were observed in lymphoma patients and increased significantly in extranodal involvement ( < 0.001). High percentages of PD-L1+CXCR3+ and PD-1+CXCR3+ lymphocytes were associated with high LDH levels, hepatomegaly, lymphedema, advanced tumor stage, and recurrence. Furthermore, patients with splenomegaly and generalized lymphadenopathy had high percentages of PD-L1+CXCR3+ lymphocytes. In addition, levels of PD-L1/PD-1 coexpression with CXCR3 and IL-19 were significantly associated with bone marrow, lung, and lymph vessel involvement. Further analysis revealed that high percentages of PD-L1+CD36+ and PD-1+CD36+ lymphocytes were associated with lung and bone marrow involvement. Patients with high levels of PD-L1/PD-1 coexpression with CXCR3 and IL-19 had inferior event-free survival (EFS) compared with that in lymphoma patients with low levels. EFS was decreased in patients with high percentages of PD-L1+CD36+ and PD-1+CD36+ lymphocytes. When using the receiver operating characteristic (ROC) curve, the superiority of IL-19 (area under the curve (AUC): 0.993) and PD-L1+CXCR3+% (AUC: 0.961) to PD-1+CXCR3+% (AUC: 0.805), PD-L1+CD36+% (AUC: 0.694), and PD-1+CD36+% (AUC 0.769) was evident in the diagnosis of extranodal involvement, identifying lymphoma patients with extranodal involvement from patients without extranodal involvement. . Coexpression of PD-L1/PD-1 with CXCR3/CD36 in circulating lymphocytes and serum IL-19 levels contributes to poor prognosis and might be potential markers for extranodal involvement in lymphoma.
Topics: Humans; B7-H1 Antigen; Biomarkers, Tumor; Lymphocytes; Prognosis; Programmed Cell Death 1 Receptor; Receptors, CXCR3; Lymphoma
PubMed: 36726488
DOI: 10.1155/2023/4556586 -
OncoTargets and Therapy 2018Extranodal NK/T-cell lymphoma is closely associated with Epstein-Barr virus (EBV) infection. However, the prognostic value of EBV-DNA in extranodal NK/T-cell lymphoma... (Review)
Review
Extranodal NK/T-cell lymphoma is closely associated with Epstein-Barr virus (EBV) infection. However, the prognostic value of EBV-DNA in extranodal NK/T-cell lymphoma remains unclear. Thus, we conducted a meta-analysis to estimate its prognostic significance. PubMed, EMBASE, and Web of Science were used to search for studies conducted until June 12, 2017. The pooled hazard ratio (HR) and its 95% confidence interval (CI) were calculated to evaluate the prognostic value of pretreatment EBV-DNA on the overall survival of extranodal NK/T-cell lymphoma. Seven eligible studies on 356 patients with extranodal NK/T-cell lymphoma were pooled for this meta-analysis. Results suggested that the pretreatment EBV-DNA positivity was significantly correlated with the overall survival of extranodal NK/T-cell lymphoma (pooled HR =3.78, 95% CI: 1.52-9.40, =0.004; heterogeneity test: =52%, =0.05). Subgroup analyses stratified by sample type, survival analysis mode, and HR origin showed that patients with positive pretreatment EBV-DNA had poorer prognosis than those with negative pretreatment EBV-DNA. Moreover, the cut-off value (HR =1.66; 95% CI: 0.73-3.73; =0.22) might account for the heterogeneity. No significant publication bias was observed. Pretreatment EBV-DNA positivity can predict poor prognosis for patients with extranodal NK/T-cell lymphoma. Future large-scale studies based on prognostic significance of EBV-DNA for patients with extranodal NK/T-cell lymphoma are necessary.
PubMed: 29520150
DOI: 10.2147/OTT.S153942 -
Chinese Clinical Oncology Mar 2015Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a rare disease, which is much more prevalent in Asia. With the advent of L-asparaginase-based regimen,... (Review)
Review
Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a rare disease, which is much more prevalent in Asia. With the advent of L-asparaginase-based regimen, the outcome of ENKL was improved obviously. Sequential chemotherapy and radiotherapy is the standard treatment for early-stage ENKL. However, the outcome of advanced-stage diseases is not satisfactory. Therefore, risk-stratification is needed for ENKL. The prognostic factors include IPI, KIPI, plasma EBV-DNA, and interim-PET/CT. However, these parameters are not validated in the era of L-asparaginase. The role of high-dose chemotherapy and heamatopoietic stem cell transplantation require further investigation.
Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Chemoradiotherapy; Diagnostic Imaging; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Extranodal NK-T-Cell; Molecular Diagnostic Techniques; Neoplasm Staging; Predictive Value of Tests; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 25841719
DOI: 10.3978/j.issn.2304-3865.2015.03.07 -
Open Life Sciences Jan 2018To summarize the etiology, pathology, diagnosis, clinical features, and treatment of the rare extranodal Rosai-Dorfman disease (RDD).
OBJECT
To summarize the etiology, pathology, diagnosis, clinical features, and treatment of the rare extranodal Rosai-Dorfman disease (RDD).
METHODS
Clinical data of three cases of extranodal RDD who were admitted to the E. N. T. Department of the second hospital of Jilin University were analyzed retrospectively, and the literature was reviewed.
RESULTS
Three cases of extranodal RDD (maxillary sinus, nasal pharyngeal focus, and external auditory meatus) had a low fever and weight loss rather than painless enlarged lymph nodes. Surgical intervention was managed to clarify the diagnosis. All pathological diagnoses were extranodal RDD. Predisone for oral use was given to all patients postoperatively. There was no recurrence in the following 3 months, except case 1 was lost 2 months later.
CONCLUSIONS
RDD is a rare idiopathic histiocytic proliferative disorder defined by its unique histopathological features: a proliferation of huge histiocytic cells with emperipolesis and S-100(+), CD1a(-). RDD is characterized clinically by bilateral cervical painless enlarged lymph nodes, while extranodal RDD is rarer and its manifestations varied. A defined therapeutic regimen has not been elucidated. RDD in about 20% of patients is self-limited. Surgical intervention is the main management of treatment, with glucocorticoids used in initial medical therapy. More clinical trials are necessary before drawing conclusions.
PubMed: 33817092
DOI: 10.1515/biol-2018-0032 -
Frontiers in Oncology 2019DLBCL is the most commonly occurring type of non-Hodgkin's lymphoma, which may be found at various extranodal sites. But little is known about the particular trends of...
Incidence and Mortality Trends and Risk Prediction Nomogram for Extranodal Diffuse Large B-Cell Lymphoma: An Analysis of the Surveillance, Epidemiology, and End Results Database.
DLBCL is the most commonly occurring type of non-Hodgkin's lymphoma, which may be found at various extranodal sites. But little is known about the particular trends of extranodal DLBCL. A total of 15,882 extranodal DLBCL patients were included in incidence analysis from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2015). The joinpoint regression software was used to calculate the annual percent change (APC) in rates. Nomograms were established by R software to predict overall survival (OS). The extranodal DLBCL incidence continued to rise at a rate of 1.6% (95% CI, 0.4-2.8, < 0.001) per year over the study period, until it declined around 2003. The incidence-based mortality trend of extranodal DLBCL had a similar pattern, with a decrease happening around 1993. Five-year survival rates improved dramatically from the 1970s to 2010s (44.15 vs. 63.7%), and the most obvious increase occurred in DLBCL patients with primary site in the head/neck. The C-index showed a value for OS of 0.708, which validated the nomograms performed well and were able to forecast the prognosis of patients with extranodal DLBCL. The calibration curves showed satisfactory consistency between true values and predicted values for 1-, 5-, and 10-year overall survival, respectively. The incidence and incidence-based mortality of extranodal DLBCL had been increasing for decades, followed by a promising downward trend in recent years. These findings may help scientists identify disease-related risk factors and better manage the disease. The prediction signature cloud identifies high-risk patients who should receive effective therapies to prevent the fatal nature of this disease, and low-risk patients to reduce over-treatment.
PubMed: 31781500
DOI: 10.3389/fonc.2019.01198 -
European Annals of Otorhinolaryngology,... Jun 2013Nasal NK/T-cell lymphoma is a rare but well-known clinical entity. Thanks to improvements in anatomopathology and the development of routine immunohistochemistry, the...
INTRODUCTION
Nasal NK/T-cell lymphoma is a rare but well-known clinical entity. Thanks to improvements in anatomopathology and the development of routine immunohistochemistry, the diagnosis of nasal NK/T-cell lymphoma (NK for "natural killer") was recognized by the WHO in 2001. The main differential diagnosis is with Wegener's granulomatosis. Treatment is based on radiotherapy and chemotherapy. Prognosis is poor, with variable evolution and sometimes rapid progression.
CASE REPORT
The authors report the case of a 54-year-old man without known pathological history, who presented with bilateral nasal obstruction with purulent rhinorrhea. Diagnosis was made on the basis of immunohistochemical study of biopsy samples. The tumor was graded IE on the Ann Arbor classification. Treatment, comprising CHOP chemotherapy followed by radiotherapy, achieved total remission at 8 months' follow-up.
DISCUSSION/CONCLUSION
Sinonasal NK/T-cell lymphoma is rare. Diagnosis is based on immunophenotypic and molecular characteristics. It is an aggressive lymphoma, requiring multidisciplinary management. Prognosis is poor.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Chemotherapy, Adjuvant; Diagnosis, Differential; Follow-Up Studies; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Maxillary Sinus Neoplasms; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Nose Neoplasms; Prognosis; Radiotherapy, Adjuvant; Rare Diseases; Treatment Outcome
PubMed: 23273887
DOI: 10.1016/j.anorl.2012.01.005 -
British Journal of Haematology Oct 2009Extranodal natural killer (NK)/T-cell lymphoma, nasal type, has a unique geographic distribution. Its pathology is characterized by marked angio-invasion and tissue... (Review)
Review
Extranodal natural killer (NK)/T-cell lymphoma, nasal type, has a unique geographic distribution. Its pathology is characterized by marked angio-invasion and tissue necrosis. A typical NK-cell phenotype is usually present: CD2(+), CD3 epsilon+, CD56(+), cytotoxic molecules+ and Epstein-Barr virus (EBV)+. Magnetic Resonance Imaging helps to clearly define the local involvement. Positron Emission Tomography helps to demonstrate system spread. Various prognostic variables (International Prognostic Index or the Korean Prognostic Index) should be documented. This may include quantification of plasma EBV DNA. For localized nasal disease, radiotherapy is important, although chemotherapy is often added. Sustainable remission is observed in over half of these patients. For extra-nasal or disseminated disease, systemic chemotherapy becomes the mainstay and the prognosis is usually poor. Doxorubicin-containing regimens are not entirely satisfactory and L-asparaginase containing regimens are being investigated. Patients with poor prognostic features may be considered for an early autologous haematopoietic stem cell transplant. Allogeneic transplantation is efficacious but is associated with high transplant-related mortality.
Topics: Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Extranodal NK-T-Cell; Neoplasm Staging; Nose Neoplasms
PubMed: 19604234
DOI: 10.1111/j.1365-2141.2009.07802.x -
Annals of Oncology : Official Journal... Jan 2009Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are highly aggressive diseases with a poor outcome. (Review)
Review
BACKGROUND
Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are highly aggressive diseases with a poor outcome.
PATIENTS AND METHODS
We report a multicentric French retrospective study of 15 patients with relapsed, refractory, or disseminated disease, treated with L-asparaginase-containing regimens in seven French centers. Thirteen patients were in relapse and/or refractory and 10 patients were at stage IV.
RESULTS
All but two of the patients had an objective response to L-asparaginase-based treatment. Seven patients reached complete remission and only two relapsed.
CONCLUSION
These data, although retrospective, confirm the excellent activity of L-asparaginase-containing regimens in refractory extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia. Therefore, L-asparaginase-based regimen should be considered as a salvage treatment, especially for patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia should be tested in prospective trials.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Drug Resistance, Neoplasm; Female; Humans; Leukemia; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Recurrence; Retrospective Studies; Treatment Outcome; Western World
PubMed: 18701429
DOI: 10.1093/annonc/mdn542 -
Journal of Hematology & Oncology Jan 2017The difference in clinical features and treatment outcomes between localized sinonasal diffuse large B cell lymphoma (SN-DLBCL) and sinonasal extranodal NK/T cell...
The difference in clinical features and treatment outcomes between localized sinonasal diffuse large B cell lymphoma (SN-DLBCL) and sinonasal extranodal NK/T cell lymphoma (SN-ENKTL) is unclear. Therefore, we analyzed a total of 47 patients with localized SN-DLBCL and 211 patients with localized SN-ENKTL. The age distribution for these two subtypes is very distinct and the B symptoms were more common in SN-ENKTL. However, both SN-DLBCL and SN-ENKTL patients could achieve high overall response rate (ORR) and favorable prognoses. The 3-year overall survival (OS) rates for patients with SN-DLBCL and SN-ENKTL were 79.7 and 83.6% (pā=ā0.707), and the 3-year progression-free survival (PFS) rates were 61.4 and 70.1% (pā=ā0.294), respectively. For SN-DLBCL patients, chemotherapy followed by involved-field radiotherapy (IFRT) resulted in higher OS (83.7 vs 62.5%) and PFS (63.9 vs 50.0%) compared with chemotherapy alone, but the difference was not significant. No significant difference was found in the OS or PFS between radiotherapy alone and radiotherapy combined with chemotherapy for all patients with SN-ENKTL. But in extensive stage I and stage II SN-ENKTL patients, radiotherapy combined with chemotherapy could significantly improve the PFS (73.8 vs 50.0%) compared with radiotherapy alone. These results indicate that remarkable clinical disparities exist between localized SN-DLBCL and SN-ENKTL. However, different treatment strategies for them can result in similarly favorable prognoses.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Lymphoma, Extranodal NK-T-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Maxillary Sinus Neoplasms; Middle Aged; Survival Rate; Treatment Outcome; Young Adult
PubMed: 28057019
DOI: 10.1186/s13045-016-0368-9