Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification.

BACKGROUND: All peripheral T-cell lymphomas (PTCLs) diagnosed at a single institution were evaluated to determine the unique clinical features and outcome of specific entities and test the predictive validity of the International Prognostic Index (IPI). PATIENTS AND METHODS: Cases of PTCL seen at the British Columbia Cancer Agency between 1981 and 2000 were identified. Pathologic material was re-assessed and classified according to the WHO classification, and patients were staged and treated uniformly according to era-specific guidelines. In total, there were 199 patients with PTCL and the most common subtypes were peripheral T-cell lymphoma unspecified (PTCL-US) (59%), anaplastic large-cell lymphoma, systemic type (ALCL) (17%) and extranodal NK/T-cell lymphoma, nasal and nasal-type (NASAL) (9%). Most patients were treated with CHOP-type chemotherapy. RESULTS: Three distinct prognostic subgroups were notable on survival analysis: favorable (cutaneous ALCL), 5-year overall survival (OS) 78%; intermediate [PTCL, ALCL and angioimmunoblastic lymphoma (AILT)], 5-year OS 35-43%; unfavorable [NASAL and enteropathy-type T-cell lymphoma (ETTL)], 5-year OS 22-24%. Furthermore, in PTCL-US and ALCL clinical separation of patients into good risk (IPI 0,1) and poor risk (IPI > or =2) subsets was demonstrated. CONCLUSIONS: A large proportion of PTCL patients have poor risk disease and/or a histologically aggressive subtype with frequent relapse and unfavorable outcome. For these patients, treatment with CHOP chemotherapy is only minimally effective and new strategies need to be developed, an effort that will require a multi-institution international collaboration due to the rarity of most subtypes.     

FDG-PET in T-cell and NK-cell neoplasms.

BACKGROUND: A growing number of studies demonstrate the utility of (18)fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in the management of malignant lymphoma. The results of FDG-PET, however, have not been studied extensively for T-cell and natural killer (NK)-cell neoplasms. PATIENTS AND METHODS: We retrospectively evaluated pretreatment FDG-PET scans in 41 patients with T/NK-cell neoplasms diagnosed according to the World Health Organization (WHO) classification. Histological subtypes frequently included were peripheral T-cell lymphoma, unspecified (PTCLu, n = 11), extranodal NK/T-cell lymphoma, nasal type (ENKL, n = 8), primary cutaneous anaplastic large cell lymphoma (C-ALCL, n = 5), and angioimmunoblastic T-cell lymphoma (AILT, n = 4). RESULTS: FDG-PET detected a lymphoma lesion in at least one site in 36 out of 41 patients. The positive rate was equally high in most histological subtypes except for cutaneous lymphomas: PTCLu 91%, ENKL 100%, C-ALCL 60%, AILT 100%. All the patients without an FDG-avid lesion had lesions restricted to skin. Among patients who had cutaneous lesions, only 50% had FDG-avid cutaneous lesions, all of which were tumorous. The positive rate of FDG-PET for bone marrow involvement was only 20%. CONCLUSION: T/NK-cell neoplasms incorporated in this study were generally FDG-avid except for cutaneous lesions and bone marrow involvement.     

A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome

BackgroundThe prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome.Patients and methodsThis study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other.ResultsMedian follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II–IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P = 0.016). Overall survival at 3 years was 41% for all patients.ConclusionAllogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies.     

原发结内外周T细胞淋巴瘤19例临床特征及预后分析

 目的　分析原发结内外周T细胞淋巴瘤（PTCL）的临床特点、治疗和预后。方法　回顾性分析19例原发结内PTCL患者的临床资料、治疗反应以及预后因素。结果　19例患者中位发病年龄54岁,男女比例2.17∶1,其中94.7 %（18／19）为Ⅲ～Ⅳ期,84.2 %（16／19）有B症状,84.2 %（16／19）有结外器官受累,57.9 %（11／19）有骨髓浸润。化疗完全缓解（CR）率36.8 %（7／19）,2年总生存（OS）率47.4 %,2年无进展生存（PFS）率25 %。预后分析显示,结外侵犯数量（EN）≥2个、美国东部肿瘤协作组（ECOG）体能状态评分≥2分、国际预后指数（IPI）评分＞2分以及β2-微球蛋白（β2-MG）升高为不良预后因素。结论　原发结内PTCL是一类高度侵袭的异质性T细胞淋巴瘤,化疗效果差,多项因素提示不良预后。     

Classification of distinct subtypes of peripheral T-cell lymphoma unspecified, identified by chemokine and chemokine receptor expression: Analysis of prognosis

WHO classification for malignant lymphoma was recently proposed. However, PTCL is heterogeneous. Chemokines and its receptors are closely associated with the T-cell subtypes. To clarify the T-cell subtype in PTCL, we conducted DNA chips of chemokine, its receptor (R) and cytokines. Angioimmunoblastic T-cell lymphoma (AILD, n=4), anaplastic large cell lymphoma (ALCL, n=4), adult T-cell leukemia lymphoma (ATLL, n=7), NK-cell lymphoma (NKL, n=2) and PTCL, unspecified (PTCL-U, n=6) were analyzed using DNA chips. In addition, immunological stainings were performed in 280 cases. In DNA chip, AILD, ALCL, NKL and ATLL showed a tendency for respective clusters, otherwise, PTCL-U clustered with AILD, ALCL and ATLL. From the gene expression profiling, CCR4, CCR3, MIG, CXCR3 and BLC were selected for immunohistochemistry. ATLL (n=48) expressed CCR4. ALCL (n=26) expressed CCR3, NKL (n=20) expressed MIG, and AILD (n=29) expressed CXCR3 and/or BLC. From the expression patterns, PTCL-U (n=134) were classified into three groups; CCR4 type (CCR4(+), n=42), CCR3 type (CCR3(+), n=31) and CXCR3 type (CXCR3(+) BLC(+/-), n=54). The prognosis was poor for ATLL, intermediate for AILD and favorable for ALCL (P=0.0014). Among PTCL-U, CCR4 type, CXCR3 type and CCR3 type had prognoses equivalent to ATLL, AILD and ALCL, respectively (P<0.0001).     

Peripheral T-cell lymphomas: Initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. Classification

Background: Peripheral T-cell lymphomas (PTCL) account for about 10% of all lymphomas in Western countries. The aim of the present study is to analyze the initial characteristics and prognostic factors in a large series of PTCL patients.Patients and methods: 174 patients (105 male/69 female; median age 61 years) were diagnosed with PTCL according to the R.E.A.L. Classification in nine Spanish institutions between 1985 and 1996. Cutaneous lymphomas and T-cell chronic lymphocytic/prolymphocytic leukemia were excluded from the study. Univariate and multivariate analyses were used to assess the prognostic value of the main initial variables.Results: The distribution according to histology subgroup was: PTCL unspecified, 95 cases (54.4%); anaplastic large-cell Ki-1-positive (ALCL), 30 cases (17%); angioimmunoblastic T cell, 22 cases (13%); angiocentric, 14 cases (8%); intestinal T cell, 12 cases (7%), and hepatosplenic T cell, one case (0.6%). As compared to the other types, ALCL presented more frequently in ambulatory performance status, without extranodal involvement, in early stage, normal serum 2-microglobulin (B2M) level and low-risk international prognostic index (IPI). Most patients were treated with adriamycin-containing regimens. The overall CR rate was 49% (69% for ALCL vs. 45% for other PTCL; P < 0.02). The risk of relapse was 48% at four years. Median survival of the series was 22 months (65 months for ALCL vs. 20 months for other PTCL; P = 0.03), with a four-year probability of survival of 38% (95% confidence intervals (95% CI): 28–48). In the univariate analysis, in addition to the histology, older age, poor performance status, presence of B-symptoms, extranodal involvement, bone marrow infiltration, advanced Ann Arbor stage, high serum LDH, high serum B2M, and intermediate- or high-risk IPI were related to poor survival. In the multivariate analysis the histologic subgroup (ALCL vs. other PTCL) (P = 0.02; response rate (RR): 4.3), the presence of B-symptoms (P = 0.02, RR: 2.2), and the IPI (low vs. high) (P = 0.04, RR: 2) maintained independent predictive value. When the analysis was restricted to the unspecified subtype, only IPI had independent prognostic value (P = 0.003; RR: 3.5).Conclusions: PTCL have adverse prognostic features at diagnosis, respond poorly to therapy and have short survival, with no sustained remission. ALCL constitutes a subgroup which responds better to therapy and has a longer survival.     

Primary cutaneous non-Hodgkin's lymphoma with aggressive histology: inferior outcome is associated with peripheral T-cell type and elevated lactate dehydrogenase, but not extent of cutaneous involvement.

BACKGROUND: The aim of this study was to explore the association between extent of cutaneous involvement, presenting features and progression-free survival (PFS) in patients with primary cutaneous non-Hodgkin's lymphoma (PCNHL) of aggressive histology. METHODS: Previously untreated patients with localized or extensive PCNHL of aggressive histology, treated with combination chemotherapy, but excluding lymphoblastic lymphoma and mycosis fungoides and its variants, were reviewed retrospectively. RESULTS: We identified 53 patients, of whom 52 (35 males, 17 females) were treated with doxorubicin-based regimens. Median age was 52 years (range 25-81 years), and disease was localized and extensive in 37 and 16 patients, respectively. Twenty-four patients had diffuse large B-cell lymphoma, nine had grade 3 follicular lymphoma, 13 had peripheral T-cell lymphoma (PTCL; not otherwise specified) and seven had anaplastic large cell lymphoma (WHO classification). With a median follow-up of 101 months (range 2-237 months) for survivors, the 10-year PFS was 65 +/- 7% and overall survival was 72 +/- 8%. The first failure involved the skin in 33% of B-cell and 91% of relapsing T-cell lymphomas. Univariate analysis revealed that PTCL (P = 0.005), lymphopenia (P = 0.01) and high serum levels of beta(2)-microglobulin (P = 0.0006) and LDH (P = 0.002), but not extent of skin involvement, were associated with inferior PFS. Multivariate analysis revealed that only PTCL and high serum lactate dehydrogenase (LDH) were independently associated with inferior PFS. CONCLUSIONS: PTCL and elevated serum LDH level, but not extent of cutaneous involvement are associated with inferior PFS in aggressive PCNHL treated with combination chemotherapy.     

Anaplastic large cell lymphoma--a rare disorder in southern Taiwan

Anaplastic large cell lymphoma (ALCL) is a subgroup of non-Hodgkin's lymphomas with large lymphoma cells expressing CD30 antigen. This entity has rarely been reported in Taiwan. We performed a retrospective clinicopathologic study in a medical center in southern Taiwan during a 13-year period and identified 13 cases. There were 10 males and 3 females with a median age of 49 years old. Seven presented with pure nodal disease and 5 had bony involvement. The staging results were stage I (5 patients), II (1), III (1), and IV (4). The pathologic subtypes were common variant (10), lymphohistiocytic variant (2), and small cell variant (1). Eleven tumors were of T-cell lineage; 2, null-cell. Immunohistochemically, 5 tumors (38.5%) expressed cytotoxic markers, T-cell intracellular antigen-1 and/or granzyme B. Two tumors (15.4%) expressed anaplastic lymphoma kinase (ALK). Long-term follow-up information was available in 8 patients. The 2 patients with ALK-expressing tumors (37 and 49 years old) were free of disease for 61 and 54 months, respectively. The other 6 patients were either died of disease (5 patients) or experienced relapse with progressive disease (1). In conclusion, we reported the largest series of ALCL in Taiwan. We confirmed ALK-expressing ALCL carries favorable prognosis and ALK-negative ALCL has similar poor prognosis as non-anaplastic T-cell lymphoma. As compared to the previous reports from the West, our ALK positive rate was lower and the age of our ALK-positive patients was older. A larger national or multi-institutional study is needed for further characterization of ALCL in Taiwan.     

Adjuvant chemotherapy for stage I and II non-Hodgkin's lymphoma--a seven-year follow up

From 1975 to 1983, 51 patients of stage I (30) and II (21) of non-Hodgkin's lymphoma were treated with a combination chemotherapy consisting of vincristine, cyclophosphamide and prednisolone as an adjuvant therapy after radiation or operation. The following results were obtained. 1) Nine patients in stage I and 7 in stage II relapsed, so that 10 year-relapse free survival rates were 68% in stage I and 67% in stage II, respectively. 2) Three patients in nodal lymphomas, 7 in Waldeyer's ring lymphomas and 6 in extranodal lymphomas relapsed, so that 10 year-relapse free survival rates were 80%, 48% and 72%, respectively. 3) Ten year-survival rates were 86% in stage I and 70% in stage II. 4) Ten year-survival rates were 82% in nodal lymphomas, 62% in Waldeyer's ring lymphomas and 86% in extranodal lymphomas. 5) Ten patients relapsed within 1 year, 4 between 1-5 years and 2 after 5 years. Relapses occurred in other than primary sites in most patients. These results suggest that an adjuvant chemotherapy is useful for localized non-Hodgkin's lymphoma, but more intensive chemotherapy before local treatments is necessary.     

Peripheral T-cell lymphomas: clinical features and prognostic factors of 92 cases defined by the revised European American lymphoma classification

The purpose of this study was to better define the clinical features and natural history of peripheral T-cell lymphomas (PTCL) entities included in the Revised European American lymphoma (REAL) classification. Cases of PTCL were retrieved from the records of the Department of Pathology and classified according to the REAL classification. In addition, cases of anaplastic large cell lymphoma (ALCL) were divided into classical, small cell, and primary cutaneous subtypes, and immunostaining for the anaplastic large-cell kinase (ALK) protein was performed on all cases of ALCL. Clinical features, response to therapy and survival were abstracted. Ninety-two cases of PTCL with adequate clinical information were retrieved. There were 40 cases of ALCL (30 classical, 7 small cell variant, 3 primary cutaneous), 28 PTCL, unspecified, 13 angioimmunoblastic T-cell lymphoma and 11 with other entities. The patients had a median age of 48 years with a range of 6-84 and had an estimated overall survival (OS) of 49% and progression-free survival (PFS) of 22% at 5 years. The International Prognostic Index (IPI) was a significant prognostic factor for both progression-free and OS. Histology was a significant predictor of PFS with anaplastic large cell having the best prognosis. ALK expression was not associated with an improved progression-free or overall-survival in patients with systemic T-cell ALCL. In conclusion, the REAL classification describes distinct PTCL entities. The IPI is the most important predictor of progression-free and OS in patients with PTCL. ALK expression may not provide prognostic information for systemic ALCL.     

Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy

BackgroundOptimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear.Patients and methodsWe examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses.ResultsPTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I–II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34–0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22–0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14–0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17–0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission.ConclusionsThis analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed.     

Large-cell lymphomas: clinical and prognostic features

We reviewed the clinical and pathologic features in 186 patients with large-cell lymphomas seen at Vanderbilt University Hospital between 1970 and 1986. Ninety-two cases (49%) were large noncleaved-cell lymphoma (LNCCL), 61 cases (33%) were large-cleaved-cell lymphoma (LCCL), 17 cases (9%) were peripheral T-cell lymphoma (PTCL), and 16 cases (9%) were immunoblastic sarcoma of B cells (IBS-B). These subsets of large-cell lymphoma did not differ with respect to median age, distribution by stage, or incidence of bone marrow involvement. Significant differences between groups were noted with regard to male:female ratio, incidence of symptoms, incidence of extranodal disease, and pattern of adenopathy. However, when LCCL was excluded from the analysis, none of these differences were significant. By univariate analysis, age, stage, marrow involvement, extranodal disease, B symptoms, elevated serum lactic dehydrogenase (LDH), and diffuse pattern were unfavorable prognostic features in large-cell lymphoma. However, when cases were stratified by cell of origin, nodular versus diffuse pattern was of no prognostic significance. Nodularity was favorable only because 71% of nodular and nodular-diffuse cases were LCCL, while the majority of diffuse cases were LNCCL. Although IBS-B is considered a "high-grade" lymphoma, we found no evidence for inferior survival in these patients compared with LNCCL or LCCL. In fact, survival was better in IBS-B than in LNCCL or LCCL, although this difference was not significant. However, survival was significantly inferior in PTCL (median, 11 months) compared with the other subsets of large-cell lymphoma (median, 46 months; P = .038, log-rank test). Since the association of PTCL and an inferior survival has most often been noted in the context of "second-generation" chemotherapy, we believe that this association may be therapy-dependent and may be minimized by the use of more aggressive chemotherapy regimens.     

Phase 2 trial of combined cisplatin,etoposide, gemcitabine,and methylprednisolone (PEGS) in peripheral T‐cell non‐Hodgkin lymphoma

BACKGROUND:

Patients with peripheral T‐cell lymphomas (PTCLs) have inferior progression‐free survival (PFS) and overall survival (OS) compared with patients who have aggressive B‐cell non‐Hodgkin lymphoma. Because PTCLs over express multidrug resistance gene 1/P‐glycoprotein (MDR‐1/P‐gp), we devised platinum, etoposide, gemcitabine, and methylprednisolone (PEGS) with agents that are not substrates of the efflux pump. Gemcitabine was included because of its excellent single‐agent activity in PTCL.

METHODS:

Patients who had PTCL with stage II bulky disease, stage III or IV disease with extra‐nodal, nodal, and transformed cutaneous presentations were eligible. Patients received intravenous cisplatin 25 mg/m² on days 1 through 4, etoposide 40 mg/m² on days 1 through 4, gemcitabine 1000 mg/m² on day 1, and methylprednisolone 250 mg on days 1 through 4 of a 21‐day cycle for 6 cycles.

RESULTS:

In total, 34 patients were enrolled, 33 were eligible, and 79% were newly diagnosed. Histologic types were PTCL not otherwise specified (n = 15), anaplastic lymphoma kinase (ALK)‐negative anaplastic large cell lymphoma (n = 4), angioimmunoblastic T‐cell lymphoma (n = 6), or other T‐cell non‐Hodgkin lymphomas (n = 8). Adverse events included 1 grade 5 infection with grade 3 or 4 neutropenia and 9 grade 4 hematologic toxicities. The overall response rate was 39% (47% in PTCL not otherwise specified, 33% in angioimmunoblastic T‐cell lymphoma, 25% in ALK‐negative and 38% in other T‐cell non‐Hodgkin lymphomas). The PFS rate at 2 years was 12% (95% confidence interval, 0.1%‐31%), and the median PFS was 7 months. The OS rate at 2 years was 30% (95% confidence interval, 8%‐54%), and the median OS was 17 months. Immunohistochemical analysis of P‐gp expression revealed strong positivity in a subset of lymphoma cells (n = 6) and tumor endothelium (n = 25).

CONCLUSIONS:

Overall, PEGS was well tolerated, but OS was not considered promising given the design‐specified targets. These results may serve as a benchmark for future comparisons for non‐CHOP regimens. Cancer 2013. © 2012 American Cancer Society.     

CD30 expression in extranodal natural killer/T-cell lymphoma,nasal type among 622cases of mature T-cell and natural killer-cell lymphoma at a single institution in South China

Background: Mature T-cell and natural killer (NK)-cell lymphomas compose a heterogeneous group of non-Hodgkinlymphomas, and extranodal NK/T-cell lymphoma, nasal type (ENKTL) is an aggressive subtype with sporadic CD30expression. However, the significance of CD30 expression in ENKTL is controversial. We aimed to classify a large cohortof patients with mature T-cell and NK-cell lymphomas according to the 2016 World Health Organization (WHO) classificationguidelines and to study the association between CD30 expression and prognosis of patients with ENKTL.Methods: We selected consecutive patients with mature T-cell and NK-cell lymphomas who attended our institutionbetween September 1, 2009 and August 31, 2013. We classified the lymphomas according to the 2016 revision of theWHO classification of lymphoid neoplasms, analyzed the associations between CD30 expression and clinicopathologicfeatures of ENKTL patients, and evaluated the prognostic implications of CD30 expression.Results: We identified 622 consecutive patients with mature T-cell and NK-cell lymphomas, including 317 (51.0%)patients with ENKTL. In addition, CD30 expression was detected in 43 (47.3%) of a subset of 91 patients with ENKTL.No clinicopathologic features were associated with CD30 expression, and CD30 positivity showed no prognosticsignificance in patients with ENKTL.Conclusions: ENKTL is the most common type of mature T-cell and NK-cell lymphoma diagnosed at our institution.CD30 is frequently expressed in ENKTL and represents a therapeutic target; however, it may not be a prognosticmarker.     

Natural killer-cell malignancies: diagnosis and treatment.

Natural killer (NK)-cell malignancies are uncommon diseases. Previously known as polymorphic reticulosis or angiocentric T-cell lymphomas, they are classified by the World Health Organization as NK/T-cell lymphoma, nasal type and aggressive NK-cell leukemia. They are prevalent in Asia and South America, but exceptionally rare in western countries. Pathologically, NK-cell lymphomas show a polymorphic neoplastic infiltrate with an angioinvasive and angiodestructive pattern. Lymphoma cells are characteristically CD2+, CD56+ and cytoplasmic CD3epsilon+. T-cell receptor gene is germline, and clonal Epstein-Barr virus (EBV) infection is almost invariably. Clinically, they can be divided into nasal, non-nasal, and aggressive lymphoma/leukemia subtypes. Most nasal NK-cell lymphomas present with stage I/II disease, and frontline radiotherapy is the most important key to successful treatment. Many stage I/II patients treated with radiotherapy fail systemically, implying that concomitant chemotherapy may be needed. Chemotherapy is indicated for advanced nasal NK-cell lymphoma, and the non-nasal and aggressive subtypes. However, treatment results are unsatisfactory. High-dose chemotherapy with hematopoietic stem cell transplantation may be beneficial to selected patients. The International Prognostic Index and presentation EBV DNA load is of prognostic significance and may be useful in the stratification of patients for various treatment modalities.     

High-dose therapy and autologous stem cell transplantation in Korean patients with aggressive T/NK-cell lymphoma

The proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma. This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT). Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases. Twenty-eight patients from 6 centers were reviewed retrospectively. The M : F ratio was 20:8, and median age was 36 years (range 16--60 years). Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas. Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively. A complete response (CR) after HDT comprised 20 patients, including 16 with continued CR. Absolute neutrophil count ( > 500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients. Two therapy-related mortalities occurred. Estimated 3-year event-free survival and overall survival (OS) (+/- SE) were 24+/- 9 and 42+/- 10 months, respectively. Only CR status after HDT influenced OS (P=0.000). Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.     

Primary Extra Nodal Non Hodgkin Lymphoma: A 5 Year Retrospective Analysis

Background and Aim: The incidence of extra nodal non Hodgkin lymphoma (ENL) is rising throughoutthe world. However, data regarding ENL as a group is limited. The aim was to study the epidemiological andhistomorphological trends of primary ENL (pENL) in India. Material and Methods: The biopsy materials fromsixty eight patients with pENL (45 male, 23 female, M:F= 1.9:1), diagnosed over a five year period (2005-2009),were analysed and pathologically reclassified according to the World Health Organization (WHO) classification,2008 criteria. Results: Primary extra nodal non Hodgkin lymphomas constituted 22.0% (68/308) of all nonHodgkin lymphomas (NHL). The mean age at presentation for pENL and primary nodal NHL was 43 years and58 years, respectively with a male predilection (M: F=2:1). Central nervous system (CNS) constituted the mostcommon extranodal site (20/68, 29.5%) followed by gastrointestinal tract (17/68, 25%), and nose/nasopharynx(8/68, 11.8%). Diffuse large B-cell lymphoma (DLBCL, not otherwise specified), extranodal marginal lymphomaof mucosa associated lymphoid tissue (MALT) type, and B cell NHL unclassified (U) were the three most commonhistological types observed. T-cell phenotype was rarely noted (4%). Follicular lymphomas and anaplastic largecell lymphoma, seen among nodal NHL, were absent at extra nodal sites. Majority (41/68, 60%) of the patientswith pENL were immunocompetent and 55% were in stage I-II with favorable prognosis. Conclusion: Centralnervous system was the most common site of ENL, followed by gastrointestinal tract. Majority of pENL occurredin immunocompetent hosts with a favorable prognosis.     

Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin's Lymphoma Classification Project.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is rare in most parts of the world. Therefore, we have evaluated the 96 cases of PTCL diagnosed within the Non-Hodgkin's Lymphoma Classification Project (NHLCP) (1378 cases) for their geographical distribution, pathologic features and diagnostic reliability, as well as clinical presentation and outcome. MATERIALS AND METHODS: Diagnoses of all cases were rendered independently by five experienced hematopathologists based on morphology only, and after introduction of the immunophenotype and clinical data. Divergent diagnoses were jointly discussed and a final consensus diagnosis was established in each case. Reliability of the diagnoses was evaluated statistically, and the clinical features and outcome were analyzed according to the consensus diagnoses. RESULTS: Seven per cent of all non-Hodgkin's lymphoma (NHL) cases reviewed were classified as PTCL and the frequency varied from 1.5% to 18.3% in different countries. The interobserver agreement with the consensus diagnosis of PTCL was 86% in the Revised European-American Lymphoma (REAL) classification, but the designation of subtypes was less reliable. Diagnostic reliability improved from 41% to 86% after immunophenotyping, but did not improve further with the addition of detailed clinical data. Clinically, angiocentric nasal lymphoma presented in young females (median age 49 years) at extranodal sites, but with few adverse risk factors, whereas angioimmunoblastic lymphoma presented most often in older males (median age 65 years) at nodal and extranodal sites with numerous risk factors. The 5-year overall and failure-free survivals for patients with PTCL treated with doxorubicin (Adriamycin)-containing regimens were only 26% and 20%, respectively. Both failure-free and overall survival were strongly correlated with the performance status and International Prognostic Index scores at presentation, but differences in survival were not observed between the major histological types. However, within the PTCL 'not otherwise specified' category, but not angioimmunoblastic lymphoma, the number of transformed blasts was prognostically relevant. CONCLUSIONS: PTCLs can be diagnosed reliably by experienced hematopathologists, but immunophenotyping is absolutely necessary. Currently, all types of PTCL should be considered high-grade lymphomas. An increased ability to distinguish T-lymphocyte subsets is needed in order to better subclassify the PTCLs for therapeutic and prognostic purposes.     

Expression of cytotoxic proteins in peripheral T-cell and natural killer-cell (NK) lymphomas: association with extranodal site, NK or Tgammadelta phenotype, anaplastic morphology and CD30 expression

Most peripheral T-cell lymphomas (PTCL) express the alphabeta T-cell receptor (TCR) whereas rare PTCL express the gammadelta TCR. Most if not all gammadelta PTCL are extranodal lymphomas and among them, hepatosplenic gammadelta PTCL constitute a distinct clinicopathological entity. Besides alphabeta and gammadelta PTCL, there is a recently recognized group of extranodal, mainly nasal tumours, which display, in most instances, phenotypic and genotypic features of Natural-Killer cell non-Hodgkin's lymphomas (NK-NHL). Cytotoxic cells, including NK cells and cytotoxic alphabeta and gammadelta T lymphocytes may induce lysis of the target by using granule-associated cytotoxic proteins such as the T-cell intracellular antigen-1 (TIA-1), perforin and granzyme B. Expression of TIA-1 can be detected in all cytotoxic cells whereas granzyme B and perforin expression can be detected in high levels only in activated cytotoxic cells. Recently, several studies showed that the expression of these cytotoxic proteins in tumour cells of PTCL and NK-NHL is associated with a) extranodal site of clinicopathological presentation b) NK or Tgammadelta-cell phenotype c) CD30 expression in cutaneous T-cell lymphoproliferations and d) anaplastic morphology in nodal PTCL. This latter finding contrasts with the data that only rare Hodgkin lymphomas (HL) express cytotoxic proteins in Hodgkin and Reed-Sternberg cells. Altogether the data of the literature indicate that most extranodal T and NK-NHL are activated cytotoxic lymphomas with the notable exception of hepatosplenic gammadelta PTCL which represent tumours of non-activated cytotoxic cells. On this basis, it is suggested that the expression of cytotoxic proteins may be useful for the identification and classification of extranodal T and NK-cell lymphomas and, to some extent, for the differential diagnosis between HL and CD30+ anaplastic large cell lymphomas. Cytotoxic lymphomas are preferentially localized in extranodal sites such as skin, lung, upper respiratory and gastrointestinal tracts, which are continuously exposed to various antigens. Since cytotoxic T and NK cells are regarded as first line of defense in these sites, and some cytotoxic tumours such as nasal lymphomas and enteropathy-type intestinal lymphomas are associated with EBV and gliadin, respectively, it is likely that chronic antigen exposure may play a role in the pathogenesis of cytotoxic lymphomas occurring in mucosa and/or skin. Besides chronic antigenic stimulation, chronic immunosuppression may also have pathogenetic significance in cytotoxic lymphomas in view of their increased incidence in immunocompromised patients.     

CD56+ hematological neoplasms presenting in the skin: a retrospective analysis of 23 new cases and 130 cases from the literature.

BACKGROUND: The aim of this study was to define prognostic parameters and guidelines for diagnosis and treatment for CD56+ hematological neoplasms with first presentation in the skin. PATIENTS AND METHODS: The study group included 153 cases (23 new and 130 from the literature). According to the World Health Organization classification, the group included 15 nasal and 38 nasal-type natural killer (NK)/T-cell lymphomas, 63 blastic NK-cell lymphomas, 14 cutaneous CD30+ lymphoproliferations, 10 cases of myeloid leukemia, six cases of subcutaneous panniculitis-like T-cell lymphoma (SCPLTCL) and seven peripheral T-cell lymphomas, unspecified. RESULTS: In general, these CD56+ hematological neoplasms had a poor prognosis, with only 27% of patients alive after a median follow-up of 12 months. The median survival was 13 months. Nasal and nasal-type NK/T-cell lymphomas and CD56+ SCPLTCL had the worst prognosis, with a median survival of 5, 6 and 5 months, respectively. Only nasal-type NK/T-cell lymphomas presenting with only skin lesions had a somewhat better prognosis (median survival 27 months). In blastic NK-cell lymphomas (median survival 14 months), age 相似文献