Mapping carbon accumulation potential from global natural forest regrowth.

To constrain global warming, we must strongly curtail greenhouse gas emissions and capture excess atmospheric carbon dioxide1,2. Regrowing natural forests is a prominent strategy for capturing additional carbon3, but accurate assessments of its potential are limited by uncertainty and variability in carbon accumulation rates2,3. To assess why and where rates differ, here we compile 13,112 georeferenced measurements of carbon accumulation. Climatic factors explain variation in rates better than land-use history, so we combine the field measurements with 66 environmental covariate layers to create a global, one-kilometre-resolution map of potential aboveground carbon accumulation rates for the first 30 years of natural forest regrowth. This map shows over 100-fold variation in rates across the globe, and indicates that default rates from the Intergovernmental Panel on Climate Change (IPCC)4,5 may underestimate aboveground carbon accumulation rates by 32 per cent on average and do not capture eight-fold variation within ecozones. Conversely, we conclude that maximum climate mitigation potential from natural forest regrowth is 11 per cent lower than previously reported3 owing to the use of overly high rates for the location of potential new forest. Although our data compilation includes more studies and sites than previous efforts, our results depend on data availability, which is concentrated in ten countries, and data quality, which varies across studies. However, the plots cover most of the environmental conditions across the areas for which we predicted carbon accumulation rates (except for northern Africa and northeast Asia). We therefore provide a robust and globally consistent tool for assessing natural forest regrowth as a climate mitigation strategy.

Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma.

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

A targeted mutational landscape of angioimmunoblastic T-cell lymphoma.

The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6 (n = 3), CCND3 (n = 2), and EP300 (n = 5), as well as gain-of-function mutations in JAK2 (n = 2) and STAT3 (n = 4). TET2 was mutated in 65 (76%) AITLs, including 43 that harbored 2 or 3 TET2 mutations. DNMT3A mutations occurred in 28 (33%) AITLs; 100% of these also harbored TET2 mutations (P < .0001). Seventeen AITLs harbored IDH2 R172 substitutions, including 15 with TET2 mutations. In summary, AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers and targetable mutations in a subset of cases.

Can carbon emissions from tropical deforestation drop by 50% in 5 years?

Halving carbon emissions from tropical deforestation by 2020 could help bring the international community closer to the agreed goal of <2 degree increase in global average temperature change and is consistent with a target set last year by the governments, corporations, indigenous peoples' organizations and non-governmental organizations that signed the New York Declaration on Forests (NYDF). We assemble and refine a robust dataset to establish a 2001-2013 benchmark for average annual carbon emissions from gross tropical deforestation at 2.270 Gt CO2 yr(-1). Brazil did not sign the NYDF, yet from 2001 to 2013, Brazil ranks first for both carbon emissions from gross tropical deforestation and reductions in those emissions - its share of the total declined from a peak of 69% in 2003 to a low of 20% in 2012. Indonesia, an NYDF signatory, is the second highest emitter, peaking in 2012 at 0.362 Gt CO2 yr(-1) before declining to 0.205 Gt CO2 yr(-1) in 2013. The other 14 NYDF tropical country signatories were responsible for a combined average of 0.317 Gt CO2 yr(-1) , while the other 86 tropical country non-signatories were responsible for a combined average of 0.688 Gt CO2 yr(-1). We outline two scenarios for achieving the 50% emission reduction target by 2020, both emphasizing the critical role of Brazil and the need to reverse the trends of increasing carbon emissions from gross tropical deforestation in many other tropical countries that, from 2001 to 2013, have largely offset Brazil's reductions. Achieving the target will therefore be challenging, even though it is in the self-interest of the international community. Conserving rather than cutting down tropical forests requires shifting economic development away from a dependence on natural resource depletion toward recognition of the dependence of human societies on the natural capital that tropical forests represent and the goods and services they provide.

CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma.

Cyclin D1(-) mantle cell lymphomas (MCLs) are not well characterized, in part because of the difficulties in their recognition. SOX11 has been identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1(-) variant. We investigated 40 lymphomas with MCL morphology and immunophenotype that were negative for cyclin D1 expression/t(11;14)(q13;q32) but positive for SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and poor outcome (5-year overall survival, 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18 of 22, in particular with light chains (10 IGK@ and 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1(-) SOX11(+) MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1/SOX11 MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome for the patients. This comprehensive characterization of a large series of cyclin D1(-) MCL patients indicates that these tumors are clinically and biologically similar to the conventional cyclin D1(+) MCL and provides a basis for the proper identification and clinical management of these patients.

Contribution of longitudinal follow up and clinical pathological correlation in the diagnosis CD30-positive skin infiltrates.

The diagnosis of a CD30+ cutaneous infiltrate is often difficult and requires clinicopathologic correlation. To further evaluate this challenge, initial clinical and histopathologic diagnoses were correlated with final clinicopathologic diagnosis in 44 cases with CD30 immunopositivity. Dermatopathologic evaluation confirmed the initial clinical diagnosis in 65% of the suspected benign cases, all cases of suspected lymphomatoid papulosis (LyP), and 72% of clinically malignant cases. In the 25 patients with clinical suspicion for lymphoma, the histopathologic diagnoses included lymphoma in 18, LyP in 2, CD30+ lymphoproliferative disorder (CD30 LPD) in 3 and hypersensitivity reaction in 2 patients. Clinicopathologic correlation led to a change in three cases diagnosed histopathologically as anaplastic large cell lymphoma (ALCL) reclassified as LyP type C, and one patient diagnosed as CD30 LPD clinically evolved as herpes virus infection. Furthermore, five cases reported as CD30 LPD received more specific diagnoses after clinicopathologic correlation (LyP type C in three, and ALCL in two patients). Clinicopathologic correlation is essential in establishing the correct diagnosis of CD30 LPD, in particular the distinction of ALCL from LyP type C. In this setting, the histopathologic diagnosis of CD30 LPD is advisable in the absence of clinical data.

PD-1, S-100 and CD1a expression in pseudolymphomatous folliculitis, primary cutaneous marginal zone B-cell lymphoma (MALT lymphoma) and cutaneous lymphoid hyperplasia.

BACKGROUND: Pseudolymphomatous folliculitis is a lymphoid proliferation that clinically and histopathologically mimics primary cutaneous extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In this study, we assessed the diagnostic value of three immunohistochemical markers, programmed death-1 (PD-1), CD1a and S100. METHODS: We evaluated 25 cases of cutaneous lymphoid proliferations with established diagnoses, including 9 patients with pseudolymphomatous folliculitis, 11 with MALT lymphoma, and 5 with cutaneous lymphoid hyperplasia (CLH). The clinical, histopathologic and immunohistochemical characteristics were reviewed and three major characteristics assessed: (a) proportion of T cells expressing PD-1, (b) pattern of expression of CD1a by dendritic cells and (c) pattern of expression of S100 by dendritic cells. RESULTS: We found pseudolymphomatous folliculitis to have a significant increase in PD-1+ T cells compared with MALT lymphoma (p < 0.0001). The pattern of CD1a staining is also informative: MALT lymphoma is significantly more likely to demonstrate a peripheral concentration of CD1a+ dendritic cells around lymphoid nodules than pseudolymphomatous folliculitis (p < 0.0003) or CLH (p < 0.05). Pseudolymphomatous folliculitis demonstrates an interstitial distribution of CD1a+ cells more often than MALT lymphoma (p < 0.04). S100 staining was not a helpful discriminator. CONCLUSIONS: Histopathologic factors including PD-1 and CD1a staining patterns may allow for more certainty in distinguishing lymphoid hyperplasia, including pseudolymphomatous folliculitis, from MALT lymphoma.

Benchmark map of forest carbon stocks in tropical regions across three continents.

Developing countries are required to produce robust estimates of forest carbon stocks for successful implementation of climate change mitigation policies related to reducing emissions from deforestation and degradation (REDD). Here we present a "benchmark" map of biomass carbon stocks over 2.5 billion ha of forests on three continents, encompassing all tropical forests, for the early 2000s, which will be invaluable for REDD assessments at both project and national scales. We mapped the total carbon stock in live biomass (above- and belowground), using a combination of data from 4,079 in situ inventory plots and satellite light detection and ranging (Lidar) samples of forest structure to estimate carbon storage, plus optical and microwave imagery (1-km resolution) to extrapolate over the landscape. The total biomass carbon stock of forests in the study region is estimated to be 247 Gt C, with 193 Gt C stored aboveground and 54 Gt C stored belowground in roots. Forests in Latin America, sub-Saharan Africa, and Southeast Asia accounted for 49%, 25%, and 26% of the total stock, respectively. By analyzing the errors propagated through the estimation process, uncertainty at the pixel level (100 ha) ranged from ± 6% to ± 53%, but was constrained at the typical project (10,000 ha) and national (>1,000,000 ha) scales at ca. ± 5% and ca. ± 1%, respectively. The benchmark map illustrates regional patterns and provides methodologically comparable estimates of carbon stocks for 75 developing countries where previous assessments were either poor or incomplete.

Shades of gray between large B-cell lymphomas and Hodgkin lymphomas: differential diagnosis and biological implications.

Hodgkin lymphomas (HLs) are neoplasms of large B cells. Two types are recognized: nodular lymphocyte predominant HL (NLPHL) and classical HL (CHL). In both types, there may be morphological and possibly biological overlap with large B-cell lymphomas (LBCLs) of non-HL types. These include nodular sclerosis CHL and primary mediastinal large B-cell lymphoma; CHL rich in lymphocytes and NLPHL; and NLPHL and T-cell/histiocyte-rich LBCL. This review covers the defining features of each of these diseases, the borderlines between them, and strategies for differential diagnosis.

The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications.

The World Health Organization classification of lymphoid neoplasms updated in 2008 represents a worldwide consensus on the diagnosis of these tumors and is based on the recognition of distinct diseases, using a multidisciplinary approach. The updated classification refined the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. However, some questions were unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors, and the status of provisional entities, categories for which the World Health Organization working groups felt there was insufficient evidence to recognize as distinct diseases at this time. In addition, since its publication, new findings and ideas have been generated. This review summarizes the scientific rationale for the classification, emphasizing changes that have had an effect on practice guidelines. The authors address the criteria and significance of early or precursor lesions and the identification of certain lymphoid neoplasms largely associated with particular age groups, such as children and the elderly. The issue of borderline categories having overlapping features with large B-cell lymphomas, as well as several provisional entities, is reviewed. These new observations chart a course for future research in the field.

Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project.

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.

Spatial database of planted forests in East Asia.

Planted forests are critical to climate change mitigation and constitute a major supplier of timber/non-timber products and other ecosystem services. Globally, approximately 36% of planted forest area is located in East Asia. However, reliable records of the geographic distribution and tree species composition of these planted forests remain very limited. Here, based on extensive in situ and remote sensing data, as well as an ensemble modeling approach, we present the first spatial database of planted forests for East Asia, which consists of maps of the geographic distribution of planted forests and associated dominant tree genera. Of the predicted planted forest areas in East Asia (948,863 km2), China contributed 87%, most of which is located in the lowland tropical/subtropical regions, and Sichuan Basin. With 95% accuracy and an F1 score of 0.77, our spatially-continuous maps of planted forests enable accurate quantification of the role of planted forests in climate change mitigation. Our findings inform effective decision-making in forest conservation, management, and global restoration projects.

Infectious mononucleosis mimicking lymphoma: distinguishing morphological and immunophenotypic features.

The diagnosis of infectious mononucleosis (acute Epstein-Barr virus (EBV) infection) is usually made on the basis of clinical and laboratory findings. However, an atypical clinical presentation occasionally results in a lymph node or tonsillar biopsy. The morphological features of EBV-infected lymphoid tissue can easily mimic lymphoma. Furthermore, the immunophenotype of the immunoblasts has not been well characterized. To assess the morphological spectrum of acute EBV infection and the utility of immunohistochemistry in diagnosing difficult cases that resemble lymphoma, we reviewed 18 cases of acute EBV infection submitted in consultation to our institution with an initial diagnosis of/or suspicion for lymphoma. Patients included nine male and nine female individuals with a median age of 18 years (range 9-69). Biopsies were obtained from lymph nodes (3/18) or Waldeyer's ring (15/18). Infectious mononucleosis was confirmed by monospot or serological assays in 72% of cases (13/18). All cases featured architectural distortion by a polymorphous infiltrate with an immunoblastic proliferation, sometimes forming sheets. Reed-Sternberg-like cells were present in 8/18 (44%) of the cases. Infiltrates were often accompanied by necrosis (10/18) and mucosal ulceration (6/15). The majority of immunoblasts in all cases were CD20+ B cells with a post-germinal center immunophenotype (strongly positive for MUM1/IRF4 (18/18), CD10- (18/18 negative) and BCL-6- (16/18 negative; 2/18 faint BCL-6 expression in <10% of immunoblasts)). Immunoblasts showed variable weak expression of BCL-2 and polyclonal expression of κ and λ immunoglobulin light chains in 81% cases. Reed-Sternberg-like cells in 8/8 cases were CD30+, CD15-, BOB.1+ and OCT-2+. In conclusion, an atypical lymphoid infiltrate with numerous MUM1+, CD10-, BCL-6- immunoblasts should raise the suspicion of a reactive process, such as infectious mononucleosis, and warrants additional consideration before a diagnosis of lymphoma is made.

Rates and drivers of aboveground carbon accumulation in global monoculture plantation forests.

Restoring forest cover is a key action for mitigating climate change. Although monoculture plantations dominate existing commitments to restore forest cover, we lack a synthetic view of how carbon accumulates in these systems. Here, we assemble a global database of 4756 field-plot measurements from monoculture plantations across all forested continents. With these data, we model carbon accumulation in aboveground live tree biomass and examine the biological, environmental, and human drivers that influence this growth. Our results identify four-fold variation in carbon accumulation rates across tree genera, plant functional types, and biomes, as well as the key mediators (e.g., genus of tree, endemism of species, prior land use) of variation in these rates. Our nonlinear growth models advance our understanding of carbon accumulation in forests relative to mean annual rates, particularly during the next few decades that are critical for mitigating climate change.

HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma and HHV8-positive intravascular large B-cell lymphoma.

Human herpesvirus type 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus, is a human gamma herpesvirus that underlies the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. We recently encountered two cases of HHV8-positive large B-cell lymphoma with features not previously described. The first patient was a 61-year-old immunocompetent man with an enlarged cervical lymph node containing scattered large, bizarre cells in a reactive background of lymphocytes, plasma cells and scattered regressed follicles resembling those of hyaline-vascular Castleman's disease. The appearance suggested classical Hodgkin's lymphoma, but the large cells were negative for CD15, CD30, CD20 and CD3, and positive for MUM1/IRF4, EMA, HHV8, EBER and dim IgM lambda. The second patient was a 59-year-old HIV-positive man who died after several weeks of fever, night sweats, anemia, thrombocytopenia, hepatosplenomegaly and multiorgan failure. At autopsy an intravascular large B-cell lymphoma that was positive for MUM1/IRF4, HHV8 and IgM lambda, and negative for CD20 and EBER involved multiple organs, including lung, heart, kidney, liver and spleen. On the basis of the histologic features in these two cases, the presence of HHV8 was unexpected. These cases expand the spectrum of lymphoproliferative disorders that can be associated with HHV8.

Immunomodulator agent-related lymphoproliferative disorders.

The recent development of inhibitors of key immune response proteins has revolutionized the therapy of autoimmune diseases; these immunomodulator agents include monoclonal antibodies and receptor antagonists. However, as with all therapies, these new agents are not without side effects and complications. In particular, anti-tumor necrosis factor alpha (TNFalpha) agents have been reported to be associated with an increased incidence of lymphoproliferative disorders, infections, and vasculitis. We evaluated the clinicopathological features of 18 cases of immunomodulator agent-related lymphoproliferative disorders (IAR-LPD) from several institutions. These included 6 cases of B-cell lymphoma, 2 cases of T-cell lymphoma, 3 cases of classical Hodgkin lymphoma, and 7 atypical lymphoid proliferations that did not fulfill diagnostic criteria for lymphoma; two of the latter regressed after discontinuation of the immunomodulator agent therapy. All eight lymphoma patients with available information had also received prior chemotherapy (methotrexate or 6-mercaptopurine). EBV was strongly associated with the B-cell and classical Hodgkin lymphomas. This case series illustrates that a broad range of lymphoid proliferations can occur after immunomodulator agent therapy and that these immunomodulator agent-related lymphoproliferative disorders have considerable overlap with other well-defined lymphoproliferative diseases associated with iatrogenic immunosuppression. Further study is warranted to evaluate how these therapies interact with other immunosuppressive agents and the underlying abnormal immune system to enhance the development of lymphomas and atypical lymphoid proliferations.

Classifying drivers of global forest loss.

Global maps of forest loss depict the scale and magnitude of forest disturbance, yet companies, governments, and nongovernmental organizations need to distinguish permanent conversion (i.e., deforestation) from temporary loss from forestry or wildfire. Using satellite imagery, we developed a forest loss classification model to determine a spatial attribution of forest disturbance to the dominant drivers of land cover and land use change over the period 2001 to 2015. Our results indicate that 27% of global forest loss can be attributed to deforestation through permanent land use change for commodity production. The remaining areas maintained the same land use over 15 years; in those areas, loss was attributed to forestry (26%), shifting agriculture (24%), and wildfire (23%). Despite corporate commitments, the rate of commodity-driven deforestation has not declined. To end deforestation, companies must eliminate 5 million hectares of conversion from supply chains each year.

HHV-8+, EBV+ multicentric plasmablastic microlymphoma in an HIV+ Man: the spectrum of HHV-8+ lymphoproliferative disorders expands.

Human herpesvirus-8 (HHV-8) is associated with several distinct lymphoproliferative disorders: primary effusion lymphoma, multicentric Castleman disease (MCD), MCD-associated plasmablastic lymphoma and HHV-8+, Epstein-Barr virus (EBV)+ germinotropic lymphoproliferative disorder. We report the case of a human immunodeficiency virus (HIV)+ male with fever, generalized lymphadenopathy, and splenomegaly. Two peripheral lymph nodes were excised and showed features of MCD and a prominent proliferation of HHV-8+, EBV+, CD20, CD138, MUM1+, lambda dim+, Ig heavy chain plasmablasts and immunoblasts replacing some follicles. Subsequently, a splenectomy and biopsy of retroperitoneal lymph nodes were performed; the retroperitoneal and splenic hilar lymph nodes showed changes similar to those in the peripheral lymph nodes while the markedly enlarged spleen showed replacement of occasional white pulp by the HHV-8+, EBV+ large cells. The histologic features and coinfection by EBV and HHV-8 suggested a diagnosis of HHV-8+ germinotropic lymphoproliferative disorder. However, the occurrence in an HIV+ individual, the background of MCD, the widespread anatomic distribution and the aggressive clinical course tended to exclude germinotropic lymphoproliferative disorder, and to favor multifocal plasmablastic microlymphoma. The patient died shortly after surgery; postmortem examination showed progression to overt lymphoma. The marrow showed extensive hemophagocytosis, consistent with development of a hemophagocytic syndrome. This unique case has clinical features compatible with a MCD-associated plasmablastic lymphoproliferative disorder, with pathologic features intermediate between HHV-8+ plasmablastic microlymphoma, and HHV-8+ germinotropic lymphoproliferative disorder, although in contrast to both of these, in our case, light chain expression was dim and heavy chain was not detected.

Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma.

Primary mediastinal large B-cell lymphoma (PMLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that is difficult to distinguish from other types of DLBCL on the basis of histologic features alone. We recently identified a molecular signature of PMLBCL that is distinct from other forms of DLBCL but shares features with classical Hodgkin lymphoma. This signature includes activation of the nuclear factor kappaB (NFkappaB) signaling pathway, which in part, acts through nuclear translocation of c-Rel containing NFkappaB transcriptional complexes, and subsequent expression of NFkappaB target genes such as tumor necrosis factor receptor-associated factor-1 (TRAF1). Using standard immunohistochemical techniques, we examined 251 large B-cell lymphomas (78 cases of PMLBCL and 173 cases of other types of DLBCL) to determine whether the expression patterns of c-Rel and TRAF1 could reliably distinguish between PMLBCL and other types of DLBCL. Robust nuclear c-Rel was present in 31 of 48 (65%) cases of PMLBCL and 28 of 160 (18%) cases of DLBCL. In addition, cytoplasmic TRAF1 expression was seen in 48 of 78 (62%) cases of PMLBCL, but only 20 of 173 (12%) cases of DLBCL. Finally, the combined expression of nuclear c-Rel and TRAF1 was seen in 24 of 45 cases (53%) of PMLBCL, but in only 3 of 156 cases (2%) of other types of DLBCL. Thus, the combined nuclear localization of c-Rel and the cellular expression of TRAF1 is a highly specific (specificity=98%) means to distinguish PMLBCL from DLBCL that is readily applicable to routine surgical pathology practice.