BCL3 rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases.

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively.

Distinct molecular profile of IRF4-rearranged large B-cell lymphoma.

Pediatric large B-cell lymphomas (LBCLs) share morphological and phenotypic features with adult types but have better prognosis. The higher frequency of some subtypes such as LBCL with IRF4 rearrangement (LBCL-IRF4) in children suggests that some age-related biological differences may exist. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse LBCLs (DLBCLs), not otherwise specified (NOS); 20 LBCL-IRF4 cases; and 12 cases of high-grade B-cell lymphoma (HGBCL), NOS in patients ≤25 years using an integrated approach, including targeted gene sequencing, copy-number arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12.3-q25, whereas DLBCL, NOS was predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (eg, SOCS1 and KMT2D), gains of 2p16/REL, and losses of 19p13/CD70. A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma-related genes such as MYC, ID3, and DDX3X and homozygous deletions of 9p21/CDKN2A, whereas other cases were genetically closer to GCB DLBCL. Factors related to unfavorable outcome were age >18 years; activated B-cell (ABC) DLBCL profile, HGBCL, NOS, high genetic complexity, 1q21-q44 gains, 2p16/REL gains/amplifications, 19p13/CD70 homozygous deletions, and TP53 and MYC mutations. In conclusion, these findings further unravel the molecular heterogeneity of pediatric and young adult LBCL, improve the classification of this group of tumors, and provide new parameters for risk stratification.

Genetic and phenotypic characterisation of HIV-associated aggressive B-cell non-Hodgkin lymphomas, which do not occur specifically in this population: diagnostic and prognostic implications.

The frequency of aggressive subtypes of B-cell non-Hodgkin lymphoma (B-NHL), such as high-grade B-cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) or Burkitt-like lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV-associated aggressive B-NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy-five HIV-associated aggressive B-NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV-encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell-of-origin classification of diffuse large B-cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV-negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL-DH/TH and BL-like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV-associated aggressive B-NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM-1 expression in BL, have a negative prognostic impact on HIV-infected individuals.

Cytokeratin expression in plasmablastic lymphoma - a possible diagnostic pitfall in the routine work-up of tumours.

AIMS: Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoma that frequently arises at extranodal sites in the setting of immunosuppression. The diagnosis of PBL is complex, owing to a frequent solid or cohesive growth pattern, and an often unusual immunophenotype. Several case reports have described cytokeratin (CK) expression in PBL, introducing a diagnostic pitfall. The aim of this study was to determine the frequency of CK expression in PBL in the largest series available to date. METHODS AND RESULTS: By using immunohistochemistry in a cohort of 72 PBLs, we identified CK8/18 positivity in 11 of 72 cases (15%) and AE1/3 positivity in six of 65 cases (9%), clearly contrasting with a control series of non-PBL aggressive B-cell lymphomas (one of 96 diffuse large B-cell lymphomas), as well as with data in the literature describing only occasional CK expression in haematological neoplasms. CONCLUSIONS: Our data indicate CK expression in a substantial number (15%) of PBLs. In view of the particular morphological features of PBL and its frequent negativity for the common leukocyte antigen and B-cell markers, this feature represents a pitfall in the routine diagnostic work-up of PBL, and requires more extensive immunohistochemical and molecular characterisation of cases entering the differential diagnosis.

Flow cytometric expression of CD71, CD81, CD44 and CD39 in B cell lymphoma.

Flow cytometry is a useful ancillary tool for the diagnosis of nodal B cell lymphomas. Well-established antigens have diagnostic limitations. This study aimed to assess the expression of CD71, CD81, CD44 and CD39 by flow cytometry in B cell lymphomas. Expression of these 4 antigens was queried in 185 samples with a diagnosis of a B cell lymphoma according to a histological examination of the lymph node and the World Health Organization (WHO) classification (follicular lymphoma [FL, n = 96], diffuse large B cell lymphoma/High grade B cell lymphoma [DLBCL/HGBH, n = 48], marginal zone lymphoma/lymphoplasmacytic lymphoma [MZL/LPL, n = 14], chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL, n = 10], mantle cell lymphoma [MCL, n = 11], Burkitt lymphoma [BL, n = 4] and other [n = 2]). CD81 was bright and CD44 was dim in germinal center-derived malignancies, particularly aggressive lymphomas (BL and CD10-positive DLBCL/HGBL). CD81 was very dim in CLL. CD71 was bright in aggressive lymphomas (DLBCL/HGBL and BL). CD39 was bright in CD10-negative DLBCL. CD71 appeared valuable in the differential diagnosis between indolent and aggressive lymphomas, CD39 between CD10-negative DLBCL and MZL/LPL and CD81 between MCL and CLL. To conclude, we report the expression of CD71, CD81, CD44 and CD39 by FC in B cell lymphomas. Further studies will have to determine the value they add to specific FC panels.

Long-term outcome comparing histological grades of follicular lymphoma patients treated with immunochemotherapy as first-line therapy: A retrospective analysis from two institutions.

OBJECTIVES: To clarify the impact of histological grades in follicular lymphoma. METHODS: We retrospectively analysed 250 patients diagnosed with FL treated with chemoimmunotherapy: 188 patients were grades 1-2 and 62 grade 3A. RESULTS: In our series, grade 3A FL patients were older, higher proportion of localised disease and lower bone marrow infiltration at diagnosis comparing grades 1-2 FL patients. Estimated six-year progression-free survival and time to progression showed no differences between both groups [grade 3A: 56% (95%CI: 39%-73%) and 51% (95%CI: 41%-61%) vs grades 1-2:55% (95%CI: 46%-63%) and 57% (95%CI: 49%-65%), P = .782 and P = .521, respectively]. Estimated six-year overall survival was lower, 76% (95%CI: 64%-88%) for the grade 3A group than grades 1-2 83% (95%CI: 77%-89%); P = .044. In addition to that, cumulative incidence curves of death not related to lymphoma at 10 years between groups were as follows: [0.26 (95%CI: 0.25-0.27) and 0.05 (95%CI: 0.04-0.06) for G3AFL and G1-2FL, respectively], P = .010. Grade 3A FL showed in PFS curve no relapses after 6 years. These results were absolutely reproduced in 199 patients receiving R-CHOP regimen as induction. CONCLUSIONS: Our results indicate similar long-term outcomes in terms of progression-free survival and time to progression in grades 1-2 and 3A. No relapses were observed in G3AFL group after 6 years.

Clinicopathologic features and prognostic significance of CD30 expression in de novo diffuse large B-cell lymphoma (DLBCL): results in a homogeneous series from a single institution.

Introduction: The present study evaluates CD30 expression by immunohistochemistry (IHQ) in 216 patients with de novo DLBCL.Methods: CD30 expression was assessed retrospectively in all cases by IHQ. More than >0% and >20% of CD30 expression in the malignant cells were used as a cut-off for positivity. Survival was analysed in 176 patients treated with R-CHOP/R-CHOP-like regimens.Results: CD30 expression >0% was found in 66 (31%) patients, and >20% in 41 (19%). Younger patients <60 years (p = 0.03), good performance status (p = 0.04), and non-GCB subtype (p = 0.004) correlated with CD30 expression. No significant differences were found in overall survival and progression-free survival (PFS), although there was a trend towards better PFS in CD30-positive patients (p = 0.07). Among 7 patients with Epstein-Barr virus (EBV)-positive-DLBCL, CD30 was expressed in 71%, and 2-year PFS significantly inferior compared with CD30-positive EBV-negative-DLBCL patients (p = 0.01).Conclusion: CD30 is expressed in 30% of DLBCL patients, in whom targeted therapy with an anti-CD30 monoclonal antibody could be explored. CD30 is expressed more frequently younger patients, with better performance status and in the non-GCB subtype and its expression trends towards a better PFS. No significant differences regarding characteristics at diagnosis or prognosis were found between groups with different cut-off for positivity.

Plasma Epstein-Barr Virus Load as an Early Biomarker and Prognostic Factor of Human Immunodeficiency Virus-related Lymphomas.

BACKGROUND: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis and can be found infecting tumor cells and in plasma at lymphoma diagnosis, especially in human immunodeficiency virus (HIV)-infected patients. Our aim was to evaluate the usefulness of plasma EBV load as biomarker and prognostic factor in HIV-positive patients with lymphomas. METHODS: EBV loads were measured by polymerase chain reaction in plasma samples of 81 HIV-positive patients' lymphomas at different moments: within 1 year before lymphoma diagnosis, at diagnosis, and at complete response (CR). Control samples included HIV-negative patients with lymphomas and HIV-positive patients without neoplasia or opportunistic infections. RESULTS: HIV-positive patients with lymphomas had more frequently-detectable EBV load at lymphoma diagnosis (53%) than either HIV-negative patients with the same lymphoma type (16%; P < .001) or HIV-positive individuals without neoplasia or opportunistic infection (1.2%; P < .001). HIV-positive lymphoma patients with detectable EBV load in plasma at lymphoma diagnosis had statistically significant decrease of EBV load at CR. High EBV load (>5000 copies/mL) at lymphoma diagnosis was an independent negative prognostic factor for overall survival and progression-free survival in HIV-positive patients with lymphomas. Detectable plasma EBV loads identified HIV-positive subjects that would eventually develop lymphoma (area under the curve, 82%; 95% CI: 0.67-0.96). CONCLUSIONS: Plasma EBV load can be used as a biomarker and as a prognostic factor in HIV-positive patients with lymphomas. The presence of the EBV load in the plasma of an HIV-positive patient can be an early predictor of lymphoma development.

m7FLIPI and targeted sequencing in high-risk follicular lymphoma.

Patients with follicular lymphoma (FL) refractory to front-line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high-risk FL. Twenty-five patients with FL refractory to front-line ICT and 10 non-refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three-year progression-free survival (PFS) and OS probabilities were 25% (95% CI, 13%-41%) and 53% (34%-69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0-3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non-refractory). In conclusion, in this study, patients with high-risk follicular lymphoma were genetically heterogeneous.

Experiences and lessons learned for planning and supply of micronutrient powders interventions.

Realistic planning for a nutrition intervention is a critical component of implementation, yet effective approaches have been poorly documented. Under the auspices of "The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance," 3 working groups were formed to summarize experiences and lessons across countries regarding micronutrient powders (MNP) interventions for young children. This paper focuses on programmatic experiences in the planning stages of an MNP intervention, encompassing assessment, enabling environment and adaptation, as well as considerations for supply. Methods included a review of published and grey literature, key informant interviews, and deliberations throughout the consultation process. We found that assessments helped justify adopting an MNP intervention, but these assessments were often limited by their narrow scope and inadequate data. Establishing coordinating bodies and integrating MNP into existing policies and programmes have helped foster an enabling environment and support programme stability. Formative research and pilots have been used to adapt MNP interventions to specific contexts, but they have been insufficient to inform scale-up. In terms of supply, most countries have opted to procure MNP through international suppliers, but this still requires understanding and navigating the local regulatory environment at the earliest stages of an intervention. Overall, these findings indicate that although some key planning and supply activities are generally undertaken, improvements are needed to plan for effective scale-up. Much still needs to be learned on MNP planning, and we propose a set of research questions that require further investigation.

Intravascular (blood vessel) histiocytosis with haemophagocytosis.

AIMS: Many types of intravascular lymphohistiocytic proliferation have been described recently; this was previously an unnoticed or misinterpreted phenomenon. Intralymphatic lymphohistiocytic aggregates are relatively common, and include benign, malignant and indeterminate conditions. In contrast, all non-endothelial proliferations in the lumina of blood vessels have been interpreted so far as malignant. Herein, we present three cases of histiocytic proliferations in the lumen of blood vessels associated with intracytoplasmic granulocyte debris (haemophagocytosis), a previously undescribed entity. METHODS AND RESULTS: We identified three patients from two institutions with similar cutaneous lesions, both clinically and microscopically. Information regarding clinical history, histological features and immunoprofiles were obtained. The three cases presented intravascular histiocytosis with haemophagocytosis involving blood vessels of the dermis, a process that may be representative of a new entity. The patients were two women and one man who presented a symmetrical reticulated erythema with a tendency to involve the skin of the breasts. The lesions were indolent, did not ulcerate and followed a benign course. CONCLUSION: This seemingly novel condition is characterized by the presence of histiocytic cells inside blood vessels, where they have not been described previously as an entity. The most reasonable explanation for this process is an origin from the non-classical subset of monocytes that 'patrol' the inner face of blood vessels acting as macrophages. The existence of this entity should be kept in mind to avoid overdiagnosis of malignancy.

Role of miR-200 family members in survival of colorectal cancer patients treated with fluoropyrimidines.

BACKGROUND AND OBJECTIVES: Surgery is the standard treatment for colorectal cancer (CRC), and adjuvant chemotherapy has been shown to be effective in stage III but less so in stage II. We have analyzed the expression of the miR-200 family in tissue samples from resected CRC patients and correlated our findings with survival to adjuvant treatment with fluoropyrimidines. METHODS: Tumor tissue samples were obtained from 127 surgically resected patients with stage I-III CRC. miRNA detection was performed using TaqMan MicroRNA assays. RESULTS: High levels of miR-200a and miR-200c were associated with longer overall survival, while high levels of miR-429 correlated with longer overall and disease-free survival (DFS). In the subgroup of 56 patients treated with fluoropyrimidines and in the smaller subgroup of 32 stage II patients treated with fluoropyrimidines, those with high levels of miR-200a, miR-200c, miR-141, or miR-429 had significantly longer overall and DFS. Low miR-429 levels were identified as an independent prognostic marker. High levels of miR-429 combined with 5-fluorouracil inhibited cell invasion in LOVO cells. CONCLUSIONS: miR-200a, miR-200c, miR-141, and miR-429 expression levels may identify CRC patients, including those with stage II disease, who are most likely to benefit from adjuvant chemotherapy.

Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

MYC status determination in aggressive B-cell lymphoma: the impact of FISH probe selection.

AIMS: To assess how hybridization probe design may affect MYC status determination in Burkitt lymphoma and diffuse large B-cell lymphoma. METHODS AND RESULTS: We compared the results obtained with one dual-fusion and two break-apart commercial probes in a retrospective series of 91 aggressive B-cell lymphomas. All three probes were able to detect the IGH-MYC translocation in every case bearing it (13/13). However, seven of 13 (54%) non-IGH-MYC (light-chain immunoglobulin or non-immunoglobulin-MYC) rearrangements were unambiguously detected by just one of the probes tested. On the other hand, when the IGH-MYC dual-fusion probe was used, nine of 15 (60%) cases with a hybridization pattern suggestive of a non-IGH-MYC translocation were attributable to MYC copy gain rather than MYC rearrangement, as demonstrated by both break-apart probes. CONCLUSIONS: Taking into account the prognostic and therapeutic implications of the MYC translocation, probe design and limitations should be particularly kept in mind when MYC hybridization patterns are interpreted. In our experience, detection of 8q24 abnormalities could be optimized by a two-probe approach involving the application of both IGH-MYC dual-fusion and MYC break-apart selected kits.

Cutaneous presentation of chronic lymphocytic leukemia as unique extramedullar involvement in a patient with normal peripheral blood lymphocyte count (monoclonal B-cell lymphocytosis).

Skin infiltration by chronic lymphocytic leukemia (CLL) is very rare and almost all reported cases occur in advanced stage. We report a patient with no relevant past medical history who presented with cutaneous erythematous plaques. A punch biopsy showed typical CLL morphologic and immunophenotypic features. Subsequent studies revealed a normal lymphocyte count in peripheral blood, and there was no evidence of lymphadenopathy or organomegaly. Flow cytometry demonstrated a clonal B-cell population both in the bone marrow and peripheral blood (1.60 × 10(9)/l) with a CLL phenotype, but it did not fulfill required criteria for CLL diagnosis. Without cutaneous involvement, this case should be classified as monoclonal B-cell lymphocytosis.

Diffuse Large B-Cell Lymphoma in the HIV Setting.

Despite the widespread use of combined antiretroviral therapy (cART) and the subsequent decrease in AIDS-defining cancers, HIV-related lymphomas remain a leading cause of morbidity and mortality in people with HIV (PWH). Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype in PWH. This lymphoma is a heterogeneous disease including morphological variants and molecular subtypes according to the cell of origin or the mutation profile. In the pre-cART era, treatment with standard-dose chemotherapy induced high rates of toxicity and outcomes were very poor. The introduction of cART and the incorporation of infection prophylaxis allowed the use of conventional intensive chemotherapy regimens used in the general population, such as R-CHOP or R-EPOCH. The use of cART during chemotherapy treatment was initially controversial due to the potential risk of adverse drug-drug interactions. However, the availability of current cART regimens with less potential to cause drug interactions and evidence that cART improves survival rates in NHL strongly support the use of cART in PWH with DLBCL. Consequently, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PWH with NHL.

Pre- and Post-Neoadjuvant Clinicopathological Parameters Can Help in the Prognosis and the Prediction of Response in HER2+ and Triple Negative Breast Cancer.

Neoadjuvant treatment (NAT) is one of the most widely used options for HER2+ and triple negative (TN) early breast cancer (BC). Since around half of the patients treated with NAT do not achieve a pathologically complete response (pCR), biomarkers to predict resistance are urgently needed. The correlation of clinicopathological factors with pCR was studied in 150 patients (HER2 = 81; TN = 69) and pre- and post-NAT differences in tumour biomarkers were compared. Low estrogen receptor (ER) expression, high tumour-infiltrating lymphocytes (TILs) and low cT-stage were associated with pCR in HER2+ tumours (p = 0.022; p = 0.032 and p = 0.005, respectively). Furthermore, ER expression was also associated with residual cancer burden (RCB; p = 0.046) in the HER2+ subtype. Similarly, pre-NAT, low progesterone receptor expression (PR; 1-10%) was associated with higher RCB (p < 0.001) in TN tumours. Only clinical and pathological T-stage (cpT-stage) had prognostic capacity in HER2+ tumours, whereas pre-NAT cpT-stage and post-NAT TILs had this capacity for the prognosis of TN tumours. We conclude that ER and PR expression may help predict response to NAT in HER2 and TN BC and should be taken into account in residual tumours. Also, changes observed in the phenotype after NAT suggest the need to reevaluate biomarkers in surviving residual tumour cells.

Round-robin testing for LMO2 and MYC as immunohistochemical markers to screen MYC rearrangements in aggressive large B-cell lymphoma.

Aggressive large B-cell lymphomas (aLBCL) include a heterogeneous group of lymphomas with diverse biological features. One of the approaches to the diagnosis of aLBCL is based on the identification of MYC rearrangements (MYC-R), in addition to BCL2 and BCL6 rearrangements by genetic techniques, mainly fluorescent in situ hybridization (FISH). Because of the low incidence of MYC-R, the identification of useful immunohistochemistry markers to select cases for MYC FISH testing may be useful in daily practice. In a previous work, we identified a strong association between the profile CD10 positive/LMO2 negative expression and the presence of MYC-R in aLBCL and obtained good intralaboratory reproducibility. In this study, we wanted to evaluate external reproducibility. To evaluate whether LMO2 can be a reproducible marker between observers 50 aLBCL cases were circulated among 7 hematopathologists of 5 hospitals. Fleiss' kappa index for LMO2 and MYC were 0.87 and 0.70, respectively, indicating high agreement between observers. In addition, during 2021-2022, the enrolled centers included LMO2 in their diagnostic panels to evaluate prospectively the utility of the marker, and 213 cases were analyzed. Comparing LMO2 with MYC, the group of CD10 positive cases showed higher specificity (86% vs 79%), positive predictive value (66% vs 58%), likelihood positive value (5.47 vs 3.78), and accuracy (83% vs 79%), whereas the negative predictive values remained similar (90% vs 91%). These findings place LMO2 as a useful and reproducible marker to screen MYC-R in aLBCL.

HHV8 and EBV-negative primary effusion-based lymphoma: A case report of a new provisional entity and review of literature.

Key Clinical Message: HHV8- and EBV-negative primary effusion lymphoma is an extremely rare neoplasm involving body cavities without detectable tumor mass. It usually presents in elderly patients without known immunodeficiency. Compared to primary effusion lymphoma, it has a better prognosis.Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma confined exclusively to body cavities without detectable tumor masses. The term PEL-like is an entity similar to PEL in clinical presentation but without relation to human herpesvirus 8 (HHV8). We report a case of HHV8- and EBV-negative primary effusion-based lymphoma.