Comprehensive morphologic characterization of bone marrow biopsy findings in a large cohort of patients with VEXAS syndrome: A single-institution longitudinal study of 111 bone marrow samples from 52 patients.

OBJECTIVES: VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable. METHODS: To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review. RESULTS: Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases. CONCLUSIONS: Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context.

Aggressive B-cell non-Hodgkin lymphomas: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Aggressive B-cell non-Hodgkin lymphomas are a heterogeneous group of diseases and our concepts are evolving as we learn more about their clinical, pathologic, molecular genetic features. Session IV of the 2020 EAHP Workshop covered aggressive, predominantly high-grade B-cell lymphomas, many that were difficult to classify. In this manuscript, we summarize the features of the submitted cases and highlight differential diagnostic difficulties. We specifically review issues related to high-grade B-cell lymphomas (HGBCLs) with MYC and BCL2 and/or BCL6 rearrangements including TdT expression in these cases, HGBCL, not otherwise specified, large B-cell lymphomas with IRF4 rearrangement, high-grade/large B-cell lymphomas with 11q aberration, Burkitt lymphoma, and pleomorphic mantle cell lymphoma. Since the workshop, the 5th edition of the WHO Classification for Haematolymphoid Tumours (WHO-HAEM5) and International Consensus Classification (ICC) 2022 were published. We endeavor to use the updated terminology.

The spectrum of nodular lymphocyte predominant Hodgkin lymphoma: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Session 4 of the 2021 European Association of Haematopathology/Society for Hematopathology Workshop focused on nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). First, the spectrum of immunophenotypic variations in NLPHL and the defining criteria for classic Hodgkin Lymphoma (CHL) were discussed. The added value of further immunophenotypic characterization of both tumor cells and microenvironment to support the differential diagnosis was presented. Next, unusual cases with combined growth patterns and evolution of morphological features over time were presented to explore the clinicopathological impact of presumed high-risk patterns. Based on a large collection of cases, the defining morphological, immunophenotypical, and gene expression features of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and THRLBCL-like NLPHL (pattern E) were reviewed to explore this challenging differential diagnosis and critically evaluate whether aggressive behavior and transformation of NLPHL can be predicted in practice.

Mediastinal large B cell lymphoma and surrounding gray areas: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Session 3 of the 2021 European Association for Haematopathology/Society for Hematopathology Workshop focused on mediastinal large B cell lymphomas and surrounding gray areas. One half of the session was dedicated to primary mediastinal large B cell lymphoma (PMBL) and included cases with classic clinicopathologic features, as well as cases with either morphologic or immunophenotypic variation, and PMBL-like cases with primary extramediastinal disease. The role of additional immunophenotyping and/or molecular testing to aid in the diagnosis of PMBL was discussed. The second half of the session focused on mediastinal and non-mediastinal gray zone lymphomas (GZL) with features intermediate between diffuse large B cell lymphoma (DLBCL) and classic Hodgkin lymphoma (CHL). Several cases illustrating the current challenges in separating this entity from PMBL/DLBCL and CHL were presented. There was discussion regarding the clinical and genetic differences between mediastinal and non-mediastinal GZLs. Rare cases of PMBL and GZL associated with EBV or follicular lymphoma were reviewed. Finally, several cases included in the session highlighted composite or sequential CHL and PMBL/DLBCL and/or GZL, highlighting challenges in separating such cases from GZL.

Lymphomas with plasmablastic features: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Lymphomas with plasmablastic features are a heterogeneous group of aggressive and mostly uncommon neoplasms of varied aetiologies, presenting in immunocompetent individuals as well as in immunodeficiency, associated with EBV and Kaposi sarcoma virus infections, and some as progression from indolent B-cell lymphomas. They show overlapping diagnostic features and pose a differential diagnosis with other aggressive B-cell lymphomas that can downregulate the B-cell expression programme. The spectrum of rare reactive proliferations and all lymphomas defined by plasmablastic features, together with an expanding range of poorly characterised, uncommon conditions at the interface between reactive lymphoid proliferations and neoplasia submitted to the session V of the 20th European Association for Haematopathology/Society for Hematopathology lymphoma workshop are summarised and discussed in this paper.

Transformation of FL into DLBCL with a PMBL gene expression signature.

We investigated the clinicopathologic features of 5 follicular lymphomas (FLs) that transformed (tFL) morphologically to diffuse large B-cell lymphomas (DLBCLs) and had a primary mediastinal large B-cell lymphoma (PMBL)-like gene expression profile (tFL-PMBLsig-pos). None of the tFL-PMBLsig-pos cases arose in the mediastinum, all cases tested had a germinal center B-cell phenotype, 20% were CD30+, 60% CD23+, 80% MAL+, 20% CD200+, and 0% CD273/PDL2+. Whole-exome sequencing detected alterations in genes associated with both FL/DLBCL (CREBBP, KMT2C, KMT2D, ARID1A, HIST1 members, and TNFRSF14) and PMBL (JAK-STAT pathway genes, B2M, and CD58). Copy number (CN) analysis detected gains/amplification of REL and STAT6 in 60%, gains of SOCS1 in 40%, and gains of chromosome 16, including IL4R, in 40% of the cases. CN gains/amplification of BCL6 and MYC and loss of TNFRSF14 and TNFAIP3 were identified in 20% of the cases. Three of 5 cases lacked a BCL2 rearrangement. Despite having some features that are less common in DLBCL (MAL and CD23 expression and JAK-STAT activation), these tFL-PMBLsig-pos cases lack the most characteristic CN alteration seen in PMBL (9p24.1 gain/amplification). This cohort expands the biologic heterogeneity of tFL, illustrating a subset with gene expression and some genetic features reminiscent of PMBL, with potential treatment implications that include the use of novel targeted therapies.

Primary Effusion Lymphoma: A Clinicopathologic Perspective.

Primary effusion lymphoma (PEL) is a rare, aggressive B-cell lymphoma that usually localizes to serous body cavities to subsequently form effusions in the absence of a discrete mass. Although some tumors can develop in extracavitary locations, the areas most often affected include the peritoneum, pleural space, and the pericardium. PEL is associated with the presence of human herpesvirus 8 (HHV8), also called the Kaposi sarcoma-associated herpesvirus (KSHV), with some variability in transformation potential suggested by frequent coinfection with the Epstein-Barr virus (EBV) (~80%), although the nature of the oncogenesis is unclear. Most patients suffering with this disease are to some degree immunocompromised (e.g., Human immunodeficiency virus (HIV) infection or post-solid organ transplantation) and, even with aggressive treatment, prognosis remains poor. There is no definitive guideline for the treatment of PEL, although CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone) are frequently prescribed and, given the rarity of this disease, therapeutic focus is being redirected to personalized and targeted approaches in the experimental realm. Current clinical trials include the combination of lenalidomide and rituximab into the EPOCH regimen and the treatment of individuals with relapsed/refractory EBV-associated disease with tabelecleucel.

Histopathologic, immunophenotypic, and mutational landscape of follicular lymphomas with plasmacytic differentiation.

Follicular lymphomas with plasmacytic differentiation (FL-PCD) include two major subtypes: one with predominantly interfollicular PCD that usually harbors a BCL2 rearrangement (BCL2-R), and a second that has predominantly intrafollicular PCD and the frequent absence of a BCL2-R. It is proposed that these latter cases share some features with marginal zone lymphomas (MZL). To further explore this hypothesis in an expanded cohort of FL-PCD, a clinicopathologic investigation of 25 such cases was undertaken including an analysis of their mutational landscape. The 10 interfollicular FL-PCDs exhibited typical intrafollicular centrocytes/centroblasts (90%), CD10 expression (90%), full PCD including expression of CD138 by the plasma cells (PC) (100%), and PCs with class-switched immunoglobulin heavy chains (70%). These cases were BCL2-R positive (100%), BCL6-R positive in 30%, lacked extra BCL2 copies, and only 22% had extra copies of BCL6. Similar to classic FLs, 80% of interfollicular FL-PCDs harbored mutations in epigenetic regulators KMT2D (70%), CREBBP (40%), and/or EZH2 (30%). In contrast, only 45% of 11 intrafollicular FL-PCDs demonstrated typical intrafollicular centrocytes/centroblasts, 55% were CD10(-), 80% contained IgM+ PCs, and only 27% harbored BCL2-Rs. BCL6-Rs were identified in 27% of intrafollicular FL-PCD, while 60% showed extra copies of BCL2 and 50% extra copies of BCL6, consistent with complete or partial trisomies of chromosomes 18 and 3, respectively. Only 54% of intrafollicular FL-PCDs showed mutations in epigenetic regulators. Both subtypes showed mutational differences compared to classic FL, but only the interfollicular subtype showed differences from what is reported for nodal MZL. Four additional cases showed mixed intra- and interfollicular PCD. These results suggest that FL-PCD has some distinctive features and supports the existence of two major subtypes. The interfollicular PCD subtype shares many features with classic FL. The intrafollicular FL-PCDs are more heterogeneous, have differences from classic FL, and have a greater morphologic, immunophenotypic, and genetic overlap with MZL.

Mutational Landscape of TdT+ Large B-cell Lymphomas Supports Their Distinction From B-lymphoblastic Neoplasms: A Multiparameter Study of a Rare and Aggressive Entity.

In the current World Health Organization classification, terminal deoxynucleotidyl transferase (TdT) expression in a high grade/large cell B-cell lymphoma (LBCL) indicates a B-lymphoblastic lymphoma/leukemia (B-LBL), although TdT expression in what appear to be mature LBCL or following mature B-cell neoplasms is reported. The frequency of TdT+ LBCL, how to best categorize these cases, and their clinicopathologic features, molecular landscape, and relationship to classic B-LBL remain to be better defined. TdT expression was therefore assessed in 258 LBCL and the results correlated with the cytologic, phenotypic, and cytogenetic findings. Targeted mutational analysis, review of prior biopsies, and assessment of clinical associations was performed in the 6 cases with >10% TdT+ cells. All 6 TdT+ LBCL were blastoid-appearing, CD34-, MYC+, BCL2+, and had MYC rearrangements (R) (5/6 with BCL2 and/or BCL6-R). 5/6 had a prior TdT- LBCL and/or follicular lymphoma and all had an aggressive course. Fifteen nonsynonymous variants in 11 genes were seen in the 4/5 tested cases with mutations. TdT+ and TdT- areas in 1 case showed identical mutations. The mutational profiles were more like those reported in germinal center B-cell type-diffuse LBCL rather than B-LBL. Evolution from preceding TdT- lymphomas was nondivergent in 1/3 tested cases and partially divergent in 2. The clinicopathologic and cytogenetic features of these 6 cases were similar to those found in a meta-analysis that included additional cases of TdT+ LBCL or B-LBL following follicular lymphoma. Thus, TdT+, CD34- large B-cell neoplasms with MYC rearrangements and often a "double hit" are rare, frequently a transformational event and aggressive but are distinct from classic B-LBL.

Genomic landscape of Epstein-Barr virus-positive extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue.

Epstein-Barr virus (EBV)-positive extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) were initially described in solid organ transplant recipients, and, more recently, in other immunodeficiency settings. The overall prevalence of EBV-positive MALT lymphomas has not been established, and little is known with respect to their genomic characteristics. Eight EBV-positive MALT lymphomas were identified, including 1 case found after screening a series of 88 consecutive MALT lymphomas with EBER in situ hybridization (1%). The genomic landscape was assessed in 7 of the 8 cases with a targeted high throughput sequencing panel and array comparative genomic hybridization. Results were compared to published data for MALT lymphomas. Of the 8 cases, 6 occurred post-transplant, 1 in the setting of primary immunodeficiency, and 1 case was age-related. Single pathogenic/likely pathogenic mutations were identified in 4 of 7 cases, including mutations in IRF8, BRAF, TNFAIP3, and SMARCA4. Other than TNFAIP3, these genes are mutated in <3% of EBV-negative MALT lymphomas. Copy number abnormalities were identified in 6 of 7 cases with a median of 6 gains and 2 losses per case, including 4 cases with gains in regions encompassing several IRF family or interacting genes (IRF2BP2, IRF2, and IRF4). There was no evidence of trisomies of chromosomes 3 or 18. In summary, EBV-positive MALT lymphomas are rare and, like other MALT lymphomas, are usually genetically non-complex. Conversely, while EBV-negative MALT lymphomas typically show mutational abnormalities in the NF-κB pathway, other than the 1 TNFAIP3-mutated case, no other NF-κB pathway mutations were identified in the EBV-positive cases. EBV-positive MALT lymphomas often have either mutations or copy number abnormalities in IRF family or interacting genes, suggesting that this pathway may play a role in these lymphomas.

How I Diagnose Primary Cutaneous Marginal Zone Lymphoma.

OBJECTIVES: Primary cutaneous marginal zone lymphoma (PCMZL) is 1 of the 3 major subtypes of primary cutaneous B-cell lymphoma. The diagnosis of PCMZL may be challenging, as the differential diagnosis includes benign cutaneous lymphoproliferations as well as other primary or secondary cutaneous B-cell or T-cell lymphomas. This review describes our approach to the diagnosis of PCMZL. METHODS: Two cases are presented that illustrate how we diagnose each of the 2 subtypes of PCMZL. The clinicopathologic features of PCMZL and the ways in which these cases can be distinguished from both benign and other neoplastic entities are emphasized. RESULTS: A definitive diagnosis of PCMZL requires the incorporation of histologic and immunophenotypic features, molecular genetic studies in some cases, and just as importantly, clinical findings. Emerging data suggest that the heavy chain class-switched cases may be more like a clonal chronic lymphoproliferative disorder. CONCLUSIONS: The 2 subtypes of PCMZL create different diagnostic challenges and require the use of a multiparameter approach. Although very indolent, it is important to distinguish PCMZLs from reactive proliferations, because they frequently recur and may require antineoplastic therapies. It is also critical to distinguish PCMZLs from other B- or T-cell lymphomas so that patients are properly evaluated and not overtreated.

Class-switched Primary Cutaneous Marginal Zone Lymphomas Are Frequently IgG4-positive and Have Features Distinct From IgM-positive Cases.

Primary cutaneous marginal zone lymphoma (PCMZL) can be subdivided into 2 groups based on immunoglobulin (Ig) heavy chain usage: IgM-positive cases that constitute a less common and more T-helper type 1-driven process, and more common heavy chain class-switched cases that are predominantly T-helper type 2-driven. Although some report a significant IgG4-positive subset, others have found a much smaller proportion. To further evaluate the proportion of IgG4-positive PCMZL, to address whether IgG4-positive cases have any distinctive characteristics, and to assess whether additional features separating IgM-positive and class-switched cases could be identified, the clinicopathologic features of 26 PCMZL obtained from 19 patients were investigated. Twenty of 26 (77%) PCMZL were heavy chain class-switched (19 IgG-positive, 1 IgA-positive), including 9 that were IgG4-positive (35%). IgG4-positive and other class-switched PCMZL were morphologically similar. IgM-positive cases occurred in older individuals (median: 69 vs. 46.5 y; P=0.0001), more often involved the subcutis (P=0.002), demonstrated plasma cells diffusely scattered versus at the periphery of the lymphoid infiltrate (P=0.005), uniformly showed follicular colonization (P=0.0001), contained more numerous B cells (P=0.0004), and were more likely to have a T-cell CD4:CD8 ratio of <3:1 (P=0.03). None of the IgM-positive PCMZL harbored a MYD88 L265P mutation. No significant differences in clinical outcome were documented. These results highlight the high frequency of IgG4-positive PCMZL, which are otherwise similar to other class-switched cases, provide additional evidence supporting the distinction between class-switched and IgM-positive cases, and emphasize the indolent nature of at least the class-switched PCMZL, which may warrant their categorization as a clonal chronic lymphoproliferative disorder.

Molecular and Cytogenetic Education in Hematopathology Fellowship.

OBJECTIVES: Given the increased complexity of molecular and cytogenetic testing (MOL-CG), the Society for Hematopathology Education Committee (SH-EC) was interested in determining what the current expectations are for MOL-CG education in hematopathology (HP) fellowship training. METHODS: The SH-EC sent a questionnaire to HP fellowship program directors (HP-PDs) covering MOL-CG training curricula, test menus, faculty background, teaching, and sign-out roles. These findings were explored via a panel-based discussion at the 2018 SH-EC meeting for HP-PDs. RESULTS: HP fellows are expected to understand basic principles, nomenclature, and indications for and limitations of testing. Interpretation of common assays is within that scope, but not necessarily proficiency in technical troubleshooting of testing or analysis of complex raw data. CONCLUSIONS: The consensus was that HP fellows should understand the components of MOL-CG testing necessary to incorporate those results into an accurate, clinically relevant, and integrated HP report.

Hematolymphoid neoplasms are common in bone marrow biopsies performed for non-specific, diffuse marrow signal alterations on magnetic resonance imaging.

AIMS: MRI is an imaging modality used for a wide range of clinical indications. Occasionally, non-specific, diffuse T1 marrow signal alterations are identified, which may prompt a bone marrow biopsy (BM). However, there is little data on the clinicopathologic significance of this signal alteration. This study evaluated the frequency and nature of pathologic findings in BM performed to evaluate diffuse MRI T1 marrow signal alterations. METHODS: Records from January 2003 to May 2015 were searched for BM performed to evaluate abnormal MRIs. 179 cases were identified. Patients with nodular/destructive bone lesions on MRI or other imaging studies, or a previous diagnosed metastatic tumor or hematologic malignancy were excluded, resulting in 45 cases. RESULTS: The patients included 22 males and 23 females with a median age of 56 years. The location of the MRI T1 marrow signal alterations included spine, pelvis, knee, skull, femur, and arm. 19/45 patients had neoplasms identified in the BM. The remaining 26 patients had benign BM findings. There was a significant difference in hemoglobin values in patients with neoplastic versus benign BM findings (p = 0.037, unpaired Student's t-test). CONCLUSIONS: Diffuse T1 marrow signal alterations on MRI should warrant a BM evaluation, as 42% of cases showed an underlying hematolymphoid neoplasm or metastatic tumor, even when patients with a known history of malignancy were excluded. When faced with a BM from a patient with a non-specific, diffuse MRI signal alteration, a pathologist should have a high index of suspicion for a malignant neoplasm, most often of hematopoietic/lymphoid type.

Comparison of Myocyte Enhancer Factor 2B Versus Other Germinal Center-associated Antigens in the Differential Diagnosis of B-Cell Non-Hodgkin Lymphomas.

Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Limited data exists concerning its expression in B-cell lymphomas, and comparison with other GC-associated antigens is lacking. Its role in the differential diagnosis of B-cell lymphomas, particularly in the distinction of follicular lymphoma (FL) versus marginal zone lymphoma (MZL), remains to be determined. We evaluated MEF2B expression, in comparison with additional GC markers, LIM domain-only transcription factor 2 (LMO2), and human GC-associated lymphoma (HGAL), in a variety of B-cell lymphomas, with particular emphasis on their utility in differentiating FL from MZL. MEF2B was positive in all FL and Burkitt lymphomas, 8/9 mantle cell lymphomas, 2/24 splenic MZL, 1/10 chronic lymphocytic leukemia/small lymphocytic lymphomas, and 38/44 diffuse large B-cell lymphoma (DLBCL), but was negative in all extranodal MZL of mucosa-associated lymphoid tissue, nodal MZL, and B-lymphoblastic lymphomas. Focusing on low-grade FL versus MZL, MEF2B was 100% sensitive and 95% specific for FL, which was similar to BCL6, but superior to LMO2 (sensitivity 87%, specificity 86%) and HGAL (sensitivity 97%, specificity 86%). Importantly, MEF2B was positive in 4/4 FL with plasmacytoid differentiation, which were CD10, only weakly BCL6, and included 1 case that lacked both LMO2 and HGAL expression. MEF2B was positive in 22/25 (88%) GC-type DLBCL, but was also positive in 16/19 (61%) non-GC-type DLBCL. MEF2B shows superior sensitivity and specificity than LMO2 and HGAL in the differential diagnosis of FL versus MZL and is particularly useful in FL with plasmacytoid differentiation, which may have morphologic and immunophenotypic overlap with MZL. MEF2B, however, is not specific for GC-derived B-cell lymphomas as it is also apparently positive in most mantle cell lymphoma and many non-GC-type DLBCL.

Solar prominences: theory and models: Fleshing out the magnetic skeleton.

Magnetic fields suspend the relatively cool material of solar prominences in an otherwise hot corona. A comprehensive understanding of solar prominences ultimately requires complex and dynamic models, constrained and validated by observations spanning the solar atmosphere. We obtain the core of this understanding from observations that give us information about the structure of the "magnetic skeleton" that supports and surrounds the prominence. Energetically-sophisticated magnetohydrodynamic simulations then add flesh and blood to the skeleton, demonstrating how a thermally varying plasma may pulse through to form the prominence, and how the plasma and magnetic fields dynamically interact.

J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas.

Magnetic Nulls and Super-radial Expansion in the Solar Corona.

Magnetic fields in the Sun's outer atmosphere-the corona-control both solar-wind acceleration and the dynamics of solar eruptions. We present the first clear observational evidence of coronal magnetic nulls in off-limb linearly polarized observations of pseudostreamers, taken by the Coronal Multichannel Polarimeter (CoMP) telescope. These nulls represent regions where magnetic reconnection is likely to act as a catalyst for solar activity. CoMP linear-polarization observations also provide an independent, coronal proxy for magnetic expansion into the solar wind, a quantity often used to parameterize and predict the solar wind speed at Earth. We introduce a new method for explicitly calculating expansion factors from CoMP coronal linear-polarization observations, which does not require photospheric extrapolations. We conclude that linearly polarized light is a powerful new diagnostic of critical coronal magnetic topologies and the expanding magnetic flux tubes that channel the solar wind.