Outcome analysis for stage IE and IIE thyroid lymphoma

Previous reports have revealed modest results in the management of thyroid lymphoma with radiotherapy alone. This retrospective report evaluates the outcome of patients treated for thyroid lymphoma with radiotherapy alone and with combined modality therapy (chemotherapy and radiotherapy) at a single institution. Twenty-seven patients with stages IE and IIE non-Hodgkin's lymphoma of the thyroid gland were treated between 1960 and 1998 at Barnes-Jewish Hospital, of which 14 patients were stage IE and 13 patients were stage IIE. The median age at diagnosis was 67 years, and there were 21 females and 6 males evaluated. The median follow-up time was 38 months (range: 3-279 months). All patients had histologically proven non-Hodgkin's lymphoma, of which 22 patients (81%) were intermediate grade. Treatment consisted of radiotherapy alone in 19 patients and a combined modality therapy in 8 patients. The median radiation dose to the thyroid bed was 44 Gy, and most patients received a doxorubicin-containing regimen administered prior to radiotherapy. Patient, tumor, and treatment-related characteristics were evaluated using Cox regression analysis. Local-regional tumor control, disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Four patients had local relapse in this series, with a crude local tumor control rate of 85%. No factor was determined to be significant for local tumor control. The actuarial 5-year DFS and OS for the entire cohort were 57%, and 56%, respectively. In terms of DFS, both age and stage were statistically significant. The 5-year actuarial DFS for patients less than age 65 years was 83% versus 37% for those more than this age (p = 0.024). Furthermore, the 5-year actuarial DFS for patients with stage I and II disease was 69% and 45%, respectively (p = 0.022). In multivariate analysis, age continued to be significant for DFS (p = 0.049). Overall survival analysis revealed age, local tumor control, and stage to be significant in univariate analysis. Multivariate analysis was further carried out using Cox proportional hazard model, and it revealed age (p = 0.006) and local tumor control (p = 0.007) to be significant. Primary thyroid gland lymphomas have a favorable outcome with appropriate therapy, but prognosis depends on both clinical stage and age at presentation. Because of the risk of both local-regional and distant failure, combined modality approaches that use chemotherapy with radiotherapy are warranted for intermediate- and high grade thyroid lymphoma.     

Phase 2 trial of "sandwich" L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma

BACKGROUND:

Extranodal natural killer/T‐cell lymphoma (ENKTL), nasal‐type, is a distinct entity of lymphoid tissue. ENKTL is sensitive to radiotherapy (RT), but the prognosis is poorer than for other types of early lymphoma. The treatment schedule is controversial.

METHODS:

A phase 2 study was conducted of “sandwich” protocols, with earlier RT after an initial 2 to 3 cycles of LVP (L ‐asparaginase, vincristine, and prednisone), followed by further “consolidation” cycles. Patients aged 18 years and older who had previously untreated ENKTL and localized lesions in the upper aerodigestive tract were enrolled. The primary endpoints were objective response rate and complete remission rate. The secondary endpoints were 2‐year overall survival, 2‐year progression‐free survival, and toxicity. This study is registered with www.Chictr.org , number ChicTR‐TNC‐00000394, and is ongoing for long‐term follow‐up.

RESULTS:

Twenty‐six patients completed total therapy, which resulted in 88.5% response that included 21 patients (80.8%) with complete response (CR) and 2 patients (7.7%) with partial response. Three (11.5%) of 26 patients progressed during therapy. With a median follow‐up of 27 months (range, 4‐35 months), the 2‐year overall survival was 88.5%, and the 2‐year progression‐free survival was 80.6%. Patients with CR had better prognosis than patients without CR. Only 2 patients (7.7%) experienced grade 3 leukocytopenia. No grade 4 toxicity or treatment‐related deaths were observed.

CONCLUSIONS:

The research showed that the “sandwich” protocol of LVP combined with RT was a safe and effective treatment for localized nasal natural killer/T‐cell lymphoma, and the results warrant further investigation into this protocol. Cancer 2011. © 2011 American Cancer Society.     

Radiotherapy combined with chemotherapy versus radiotherapy alone for early stage nasal natural killer/T-cell lymphoma: a meta-analysis

Objective: To compare the efficacy of radiotherapy (RT) plus chemotherapy (CMT) versus RT alone for early stage nasal natural killer (NK)/T-cell lymphoma.

Methods: All the eligible studies were searched by PubMed, Medline, Embase and the Cochrane Library. The meta-analysis was performed to compare odds ratios (ORs) for overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS).

Results: Eight studies were included in the meta-analysis. Chemotherapy group did not significantly differ from RT group. The pooled OR and 95% confidence interval (CI) for 1-year, 3-year, 5-year and 10-year OS was 1.25 [0.84, 1.87], 1.10 [0.76, 1.58], 0.83 [0.59, 1.17] and 1.05 [0.70, 1.56]. In addition, the combined OR and 95% CI for 5-year DFS and PFS were 0.96 [0.53, 1.73] and 0.71 [0.45, 1.12].

Conclusions: The current evidence suggests that CMT was not superior to RT alone. Radiotherapy may be still the main method in the treatment of early stage nasal NK/T-cell lymphoma.     

Combined chemoradiation for the management of nasal natural killer (NK)/T-cell lymphoma: elucidating the significance of systemic chemotherapy

The objective of this analysis was to evaluate the efficacy and treatment outcome of CHOP and CHOP combined with nitrosourea chemotherapy in natural killer (NK)/T-cell lymphoma of the nasal cavity. Sixty-three patients with NK/T-cell lymphoma of the nasal cavity were treated with CHOP or CHOP combined with oral nitrosourea chemotherapy between January 1997 and June 2005. By the Ann Arbor Lymphoma Staging Classification, 57 patients (90%) had Stage IE or IIE disease and six patients (10%) had Stage III or IV disease. All patients with Stage IE or IIE disease were intended to be treated curatively with combined chemoradiation; and patients who had Stage III or IV disease were treated with chemotherapy alone with curative intention. Chemotherapy consisted of: (1) up to six cycles of the standard CHOP based regimen, or (2) up to six cycles of the standard CHOP based regimen with oral Semustine dosed at 120 mg (or Lomustine dosed at 100mg) on day 1 of each chemotherapy cycle. External beam radiation therapy was delivered by daily conventional fractionation by Co-60 or 6MVx linear accelerator for patients with Stage IE or IIE disease. The radiation dose to the tumor bed was between 36 and 50 Gy with a median dose of 45 Gy. Fifty-three patients received chemotherapy prior to radiation, and four patients were treated with involved field radiation before chemotherapy. The median follow up for all 44 surviving patients was 31 months (range: 6-104 months). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively. The PFS and OS of patients who were treated with or without oral nitrosourea in addition to CHOP were 73% vs. 44% (P=0.035) and 75% vs. 64% (P=0.276), respectively. Nine patients with Stage IE or IIE diseases developed disease progression during their planned treatment and died within 10 months after the initiation of treatment; Six patients who achieved complete response (CR) after planned chemoradiation developed systemic recurrence and died at 13-48 months despite salvage treatment; one patient died of Hemophagocytic Syndrome during radiotherapy after achieving CR from chemotherapy. Three patients with Stage III or IV disease died during chemotherapy or during salvage treatment at 2, 4, and 19 months, respectively. Among the 59 patients who received chemotherapy as their initial treatment, 29, 6, 12, and 12 patients had complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) respectively after chemotherapy. The 2-year overall survival rates for these four groups of patients were 100%, 75%, 60%, and 17%, respectively (P<0.0001). Multivariate analysis revealed that International Prognostic Index (IPI) for Lymphoma, perforation of nasal septum as a presenting symptom, "B" symptoms, ECOG performance, as well as response after chemotherapy, were significant independent prognostic factors for this group of patients. The extent of response after induction chemotherapy is significantly related to the treatment outcome of patients with nasal NK/T-cell lymphoma. CHOP based chemotherapy combined with oral nitrosourea followed by involved field radiotherapy may provide improved treatment results compared to conventional CHOP chemotherapy and radiation. This strategy needs to be optimized and tested in a prospective trial for its efficacy.     

Treatment outcome of radiotherapy alone versus radiochemotherapy in early stage nasal natural killer/T-cell lymphoma

This study aims to investigate the prognostic factors and long-term treatment outcome in patients with early stage nasal natural killer (NK)/T-cell lymphoma. Sixty-four patients were recruited in this study, whose clinical and laboratory data were collected from hospital records. Early stage (stage IE: 51, stage IIE: 13) nasal NK/T-cell lymphoma (NNTCL) was established according to Ann Arbor staging classification. Among these patients, 23 received radiotherapy (RT) alone, the remaining 41 cases were treated with radiochemotherapy (RCT) comprised of 1–6 cycles of anthracycline-based chemotherapeutic regimens. Results show that the median overall survival (OS) time was 41 months. The 5-year OS and progression-free survival rates were 59.2 and 52.3%, respectively. The 5-year OS rate for patients who received RT alone was 57.9%, whereas that for patients who received RCT was 61.5% (P = 0.47). There is no significant difference between two treatment modalities. Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (PS) score ≥ 2, local tumor invasion out of nasal cavity, and lower complete remission (CR) rates in the initial treatment were significant unfavorable independent prognostic factors. Taken together, our study suggests that RCT did not improve the survival rate of patients with early stage NNTCL. PS score before treatment, local tumor invasion out of nasal cavity, and CR rate of the primary treatment may be independent prognostic factors among the subtype lymphoma entity.     

Failure patterns and clinical implications in early stage nasal natural killer/T-cell lymphoma treated with primary radiotherapy

BACKGROUND:

This study aimed to evaluate the failure patterns and clinical implications in patients with early stage nasal natural killer (NK)/T‐cell lymphoma treated with primary radiotherapy.

METHODS:

Two‐hundred fourteen patients were included. There were 182 cases of stage I and 32 cases of stage II disease. Patients received radiotherapy alone (n = 96) or radiotherapy and chemotherapy (n = 118). The median dose was 50 grays, and most patients received doxorubicin‐based chemotherapy.

RESULTS:

The 5‐year overall survival (OS) and progression‐free survival rates for all patients were 72% and 65%, respectively. Sixty‐three patients experienced treatment failure. The 5‐year cumulative incidences of locoregional, systemic, and overall failures were 12.0%, 25.5%, and 32.9%, respectively. Stage and paranasal extension were significant predictors for systemic failure. The 5‐year cumulative incidence of systemic failure was 22.6% for stage I disease versus 42.7% for stage II disease (P < .001), and 16.9% for limited disease versus 30.4% for paranasal extension (P < .001), respectively. Adding chemotherapy to extended involved‐field radiotherapy did not significantly decrease the systemic failure rate nor improve survival. The cumulative incidence of systemic failure and OS rate at 5 years were 24.1% and 74.4% for combined modality therapy compared with 28.5% (P = 0.758) and 69.8% (P = 0.529) for radiotherapy alone. A very low incidence of cervical lymph node or central nervous system relapse was observed.

CONCLUSIONS:

Patients with early stage nasal NK/T‐cell lymphoma have excellent locoregional control and favorable prognosis with radiotherapy, but patients with stage II disease or paranasal extension are at high risk of systemic failure, emphasizing the importance of integration of optimal radiotherapy with innovative systemic therapy. Cancer 2011;. © 2011 American Cancer Society.     

鼻型结外NK/T细胞淋巴瘤治疗的研究进展

结外NK/T细胞淋巴瘤,鼻型(ENKTL)是一种侵袭性非霍奇金淋巴瘤.ENKTL目前尚无标准治疗方案,局限期患者可考虑单纯放疗或放化疗联合治疗,多药联合化疗为晚期患者主要治疗手段,以蒽环类药物为主的传统化疗方案对ENKTL的疗效欠佳.近年,一些新的治疗方案在ENKTL中显示出一定的疗效,文章就ENKTL治疗的进展进行综述.     

Extranodal natural killer/T-cell lymphoma, nasal type: epidemiology study

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL) is a rarely kind of non-Hodgkin lymphoma (NHL). It is much more frequent in Asian and Latin American countries than other part of the world. It typically affects nasal cavity. In China, one of its endemically places, ENKTCL accounts for 74%–96% of nasal NHL. Patients with ENKTCL usually show a highly aggressive clinical course, and its etiology is unclear. However, it is already proved that ENKTCL is associated with Epstein-Barr virus (EBV) infection, regardless patients’, ethnicity and areas. Some studies show that the risk will increase among several occupations, such as farmer, who are frequently exposure to pesticides and chemical solvent and risk can be cut down if taking some protective measures.     

鼻腔自然杀伤/T细胞淋巴瘤放射治疗的疗效和影响因素

 目的　回顾分析鼻腔自然杀伤（NK）／T细胞淋巴瘤的放射治疗效果,并分析其预后因素。方法　回顾分析9年间接受放射治疗的62例鼻腔NK／T细胞淋巴瘤的临床资料和疗效,单因素分析采用Kaplan-Meier法,多因素分析用COX比例风险模型。结果　全组中位生存时间69.7个月（95 % CI为63.0～78.0个月）,3、5年总生存率分别为66.1 %和46.8 %,远处转移导致治疗失败占61.8 %。T淋巴细胞CD3升高组和降低组的中位生存时间分别为72.6个月和39.6个月,两组比较差异有统计学意义（χ2＝4.9309,P＝0.0264）。多因素分析表明,修正后国际预后指数（IPI）为0～1（χ2＝7.5266,P＝0.0061）、CD3升高（χ2＝9.0912,P＝0.0266）和治疗结束达到CR（χ2＝9.0912,P＝0.0106）是影响鼻腔NK／T细胞淋巴瘤放疗总生存的有利预后因素。结论　放射治疗鼻腔NK／T细胞淋巴瘤疗效肯定,但远处转移治疗失败率高,全身治疗仍具有重要地位;修正后IPI为0～1、CD3升高、治疗结束达到CR是影响鼻腔NK／T细胞淋巴瘤放疗总生存的有利预后因素。     

Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed,stage IE to IIE,nasal, extranodal NK/T-Cell lymphoma

On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m² weekly, 3–5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m² intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1–4 and cisplatin 75 mg/m² i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n=1) or because they had an infection (n=3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.     

Clinicopathologic correlations of stage IE/IIE primary thyroid diffuse large B-cell lymphoma.

BACKGROUND: We studied the clinicopathological characteristics and prognoses of localized stage thyroid diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: This study included 32 patients with stage I/IIE thyroid DLBCL. Their median age was 66 years, the male/female ratio was 10/22. RESULTS: As to the cellular immunophenotype, CD20 was positive in 31/32, CD5 in 0/32, CD10 in 4/32, CD23 in 1/32, BCL2 in 14/30, and BCL6 in 24/32. Twelve cases showed abnormal karyotypes: two cases with t(8;14)(q24;q32), four cases with 3q27, two cases with 17p11, and four cases with other abnormal karyotypes. As for treatment, eight cases were treated with chemotherapy alone and 24 cases were treated with chemotherapy followed by radiotherapy. Complete response was achieved in 94%. The 5-year progression-free survival was 84% and the 5-year overall survival was 90% with a median follow-up period of 62 months. The germinal center B-cell (GCB) type had a significantly better prognosis than the non-GCB type. CONCLUSION: Localized stage thyroid DLBCL is a disease with a relatively good prognosis. It is, however, a heterogeneous disease with regard to histological type and pathological state. Localized stage thyroid DLBCL has a good prognosis and it is that there are more GCB-type DLBCL lymphomas.     

Concurrent Etoposide,Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma,nasal type

PurposeRadiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen.MethodsAn induction phase with two upfront courses of CCRT delivering a 40 Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2–3 cycles of ESHAP chemotherapy alone.ResultsThirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62 years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3–4 haematological toxicity. The main non-haematological grade 3–4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%.ConclusionsWith optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type.     

Updating targets for natural killer/T-cell lymphoma immunotherapy

Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The current treatment methods for NKTCL are associated with several drawbacks.For example,chemotherapy can lead to drug resistance,while treatment with radiotherapy alone is inadequate and results in frequent relapses.Moreover,hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts.In recent years,immunotherapy has shown good clinical results and has become a hot spot in cancer research.Clinical activity of targeted antibodies,such as daratumumab(anti-CD38 antibody)and brentuximab vedotin(anti-CD30 antibody),have been reported in NKTCL.Additionally,dacetuzumab and Campath-1 H have demonstrated promising results.Further encouraging data have been obtained using checkpoint inhibitors.The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL.Furthermore,anti-CCR4 monoclonal antibodies(m Abs)exert cytotoxic actions on both CCR4+tumor cells and regulatory T cells.Depletion of these cells and the long half-life of anti-CCR4 m Abs result in enhanced induction of antitumor effector T cells.The role of IL10 in NKTCL has also been investigated.It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies.Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission.Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease.The present review outlines the known immunotherapy targets for the treatment of NKTCL.     

结外NK/T细胞淋巴瘤治疗进展

结外NK/T细胞淋巴瘤（ENKTL）是非霍奇金淋巴瘤中较为罕见的亚型,东亚地区比西方国家多见。主要发生在鼻腔或鼻窦区,皮肤受累少见。基于ENKTL的发病机理,几乎所有患者的淋巴瘤细胞中都存在EB病毒。EBV-DNA拷贝数与肿瘤负荷密切相关,并能预测ENKTL预后。由于P-糖蛋白的表达,使细胞产生耐药性,ENKTL预后较差。近年来,新的治疗方法的研究延长了ENKTL患者的生存期。对于局限期ENKTL放疗联合化疗已取得良好的疗效。对于晚期复发难治ENKTL以L-门冬酰胺酶为基础的化疗方案显著提高治疗有效率。有文献报道,造血干细胞移植在ENKTL的治疗中取得了重要地位,而靶向药物的出现为晚期ENKTL提供了新选择。本文综述了ENKTL的治疗进展。     

Extranodal natural killer/T-cell lymphoma, nasal type: the significance of radiotherapeutic parameters

BACKGROUND: The objective of this study was to investigate the correlation between local recurrence and radiotherapeutic parameters, including dose and RT radiotherapy (RT) field. METHODS: The current study included 35 patients who were diagnosed with immunohistochemically confirmed nasal natural killer (NK)/T-cell lymphoma between 1976 and 2004. There were 21 males and 14 females, and they ranged in age from 18 years to 76 years (median, 51 yrs). The primary tumor originated in the nasal cavity in 28 patients, and 32 patients had Stage I disease. Seventeen patients received treatment solely with RT, and the remaining 18 patients received a combination of chemotherapy and RT. The median tumor dose was 50 grays (Gy) (range, 22-60 Gy). Twenty-seven patients received RT to include all macroscopic lesions, all paranasal sinuses, the palate, and the nasopharynx. Eight patients received RT to all macroscopic lesions with generous margins. RESULTS: A complete remission (CR) or a CR/unconfirmed was achieved in 28 patients (80%). The 5-year overall survival (OAS) rate, disease-free survival (DFS) rate, and local control probability (LCP) were 47.3%, 42.9%, and 65.2%, respectively. Patients who received RT only to macroscopic lesions fared less well in terms of LCP (LCP 5 years, 71.9% vs. 41.7%; P=0.007). The difference in RT field also affected both the OAS rate and the DFS rate. Patients who received RT doses>or=50 Gy tended to achieve favorable local control. CONCLUSIONS: In the management of nasal NK/T-cell lymphoma, the RT field affected treatment outcomes. RT doses>or=50 Gy resulted in favorable local control.     

Clinicopathologic and genotypic study of extranodal nasal-type natural killer/T-cell lymphoma and natural killer precursor lymphoma among Koreans

BACKGROUND: This study aimed to define genotypic profile and to describe the clinicopathologic features of nasal-type natural killer (NK)/T-cell lymphoma of nasal and extranasal origin and NK precursor lymphoma. METHODS: NK/T-cell lymphomas from the upper aerodigestive tract (n = 45), skin (n = 2), gastrointestinal tract (n = 3), and soft tissue (n = 2) and NK precursor neoplasms (n = 3) were studied. Immunophenotype was analyzed by immunohistochemistry and flow cytometry. In situ hybridization with EBER 1/2 RNA probes was performed. T-Cell Receptor (TCR)-gamma gene rearrangement was analyzed by seminested polymerase chain reaction with heteroduplex analysis. Overall survival rate was correlated with clinicopathologic parameters and compared by Wilcoxon test. RESULTS: Clonal TCR-gamma gene rearrangement was detected in 3 of 31 upper aerodigestive and 1 of 2 skin tumors. When immunostained using paraffin embedded tissue, 6 upper aerodigestive lymphomas were negative for CD56 in which 4 cases lacked clonal TCR gene rearrangement. Epstein-Barr virus (EBV) mRNA was detected in 33 upper aerodigestive tumors including 26 of 29 nasal tumors (90%), and 7 of 10 extranasal tumors (70%). There was no histologic, immunophenotypic, or genotypic differences according to the lineage and EBV association in upper aerodigestive lymphomas. Among the patients with upper aerodigestive tumors, overall 1-year survival rate was 41%, and correlated well with the stage (P < 0.05) but not with the size of tumor cells, EBV status, and lineage (P > 0.05). Median survival rate of lymphomas from other sites excluding upper aerodigestive tract was not significantly different from that of upper aerodigestive lymphomas with same stage (P > 0.05). Unlike nasal-type NK/T-cell lymphomas, NK precursor lymphoma involved the bone marrow and lymph nodes at initial presentation or in the course of disease. Tumor cells were positive for TdT in all and myeloid markers in two. TCR gene rearrangement was germ line. CONCLUSIONS: Most upper aerodigestive nasal-type NK/T-cell lymphomas among Koreans are genotypically of NK derivation and few belong to T lineage. Presence or absence of EBV has no significant correlation with the histologic changes and the lineage of these lymphomas.