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Age, PS, LDH serum level, CSF protein concentration, and involvement of deep structures of the brain were independent predictors of survival. A prognostic score including these five parameters seems advisable in distinguishing different risk groups in PCNSL patients. The proposed score and its relevance in therapeutic decision deserve to be validated in further studies.

The molecular alterations underlying the pathogenesis of angioimmunoblastic Tcell lymphoma (AITL) and peripheral Tcell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n ‫؍‬ 18) and PTCLs-u (n ‫؍‬ 16) was analyzed using gene expression profiling.

• Diagnostic signatures for PTCL subtypes and 2 novel subgroups with distinct oncogenic pathway and prognostic importance in PTCL-NOS were identified. • Demonstrated that ALK(-) ALCL is a distinct molecular entity and the tumor microenvironment has prognostic significance in AITL patients.Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P 5 .01). High expression of cytotoxic genesignature within the TBX21 subgroup also showed poor clinical outcome (P 5 .05). In AITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P 5

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was toanalyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (> 10 cm), thrombocytopenia (< 150 ؋ 10 9 /L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies. (Blood. 2011;117(12):3402-3408) IntroductionPeripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are an uncommon and heterogeneous group of disorders that compose 5% to 20% of all non-Hodgkin lymphomas (NHLs) in different parts of the world. 1,2 In recent years, the incidence of PTCL and NKTCL in the United States has increased by almost 3-fold with an annual increase of 3.8%, whereas the incidence of B-cell lymphoma and Hodgkin lymphoma has been relatively stable. 3,4 One of the most common subtypes of PTCL is a heterogeneous group of nodal and extranodal mature T-cell lymphomas that do not correspond to any of the specifically defined T-cell entities in the World Health Organization classification, 1 and are therefore called PTCL, not otherwise specified (NOS). Uncommon variants of PTCL-NOS include lymphoepithelioid (Lennert) lymphoma, and cases with a follicular or T-zone pattern of growth. 1 Over the last 12 years, several clinical studies have attempted to identify the clinical and pathologic features of prognostic importance in PTCL-NOS, but the number of cases in these studies was generally small and the findings have been inconsistent or unconfirmed. [5][6][7][8][9][10][11][12][13] The International Peripheral T-cell Lymphoma Project was undertaken as a large retrospective study of PTCL and NKTCL in North America, Europe, and Asia with the goal of better characterizing this group of NHL. One objective of was to analyze the clinical and pathologic features of the 340 cases of PTCL-NOS in the study, and to determine the important prognostic factors for this uncommon entity. MethodsTwenty-two institutions in North America, Europe, and Asia partici...

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Few large, international series of enteropathy-associated T-cell lymphoma (EATL) have been reported. We studied a cohort of 62 patients with EATL among 1153 patients with peripheral T-cell or natural killer (NK)-cell lymphoma from 22 centers worldwide. The diagnosis was made by a consensus panel of 4 expert hematopathologists using World Health Organization (WHO) criteria. Clinical correlations and survival analyses were performed. EATL comprised 5.4% of all lymphomas in the study and was most common in Europe (9.1%), followed by North America (5.8%) and Asia (1.9%). EATL type 1 was more common (66%) than type 2 (34%), and was especially frequent in Europe (79%). A clinical diagnosis of celiac sprue was made in 32.2% of the patients and was associated with both EATL type 1 and type 2. The median overall survival was only 10 months, and the median failure-free survival was only 6 months. The International Prognostic Index (IPI) was not as good a predictor of survival as the Prognostic Index for Peripheral T-Cell Lymphoma (PIT). Clinical sprue predicted for adverse survival independently of the PIT. Neither EATL subtype nor other biologic parameters accurately predicted survival. Our study confirms the poor prognosis of patients with EATL and the need for improved treatment options.

Since the initial description of splenic marginal zone lymphoma (SMZL) in 1992, an increasing number of publications have dealt with multiple aspects of SMZL diagnosis, molecular pathogenesis and treatment. This process has identified multiple inconsistencies in the diagnostic criteria and lack of clear guidelines for the staging and treatment. The authors of this review have held several meetings and exchanged series of cases with the objective of agreeing on the main diagnostic, staging and therapeutic guidelines for patients with this condition. Specific working groups were created for diagnostic criteria, immunophenotype, staging and treatment. As results of this work, guidelines are proposed for diagnosis, differential diagnosis, staging, prognostic factors, treatment and response criteria. The guidelines proposed here are intended to contribute to the standardization of the diagnosis and treatment of these patients, and should facilitate the future development of clinical trials that could define more precisely predictive markers for histological progression or lack of response, and evaluate new drugs or treatments.