Immunohistochemical Characterization of H3K4Me3 in Reactive Lymph Nodes and Follicular Lymphoma

Introduction/Objective Genes involved in histone methylation are frequently mutated in non-Hodgkin’s lymphomas. For instance, frequent mutations in genes encoding histone methytransferases MML2 and EZH2 are present in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). The aim of this study was to characterize the immunohistochemical expression of H3K4Me3 in benign/reactive lymph nodes (LNs) with comparison to follicular lymphoma (FL). Methods/Case Report Immunohistochemical staining with an anti-H3K4Me3 antibody was performed on FFPE whole slide section from patients with benign/reactive LNs (n=21), low grade (grade 1-2) FL (n=21). H3K4Me3 reactivity was scored for staining intensity and percentage of lymphocytes showing reactivity. Results (if a Case Study enter NA) The majority of the reactive LN sections (15 out of 21 cases) showed a distinct distribution of H3K4Me3 staining, with the majority of cells in the mantle zone and the interfollicular zones showing moderate-strong staining, whereas reactive germinal centers (GCs) showed significantly decreased or close to negative staining. Neoplastic follicles in all the FL cases contained positive cells with significantly stronger staining compared to that in the germinal centers in benign lymph nodes. The interfollicular zones, while diminished in FL due to expanded neoplastic follicles, showed retained H3K4Me3 staining. The difference in staining intensity between follicles and mantle/interfollicular zones became indistinct in FL. Conclusion H3K4Me3 expression in benign/reactive LNs is characterized by positive expression in lymphocytes in interfollicular and mantle zones and significantly decreased in GCs. However, the expression pattern is different in FL, which showed significantly increased expression in the follicles compared to that in reactive GCs. In FL, the expression in GCs is similar to that in the interfollicular and mantle zone lymphocytes. It is reported that about 90% of FL have MLL2 mutation and MLL2 is the enzyme responsible for the methylation of H3K4. So far, it is unclear whether the mutation of MLL2 in FL affects the overall methylation activity of the enzyme. In our study, there is increased methylation of H3K4 in the follicles of FL, which raises the possibility that MLL2 mutation somehow increases H3K4 methylation.

Robo2 Receptor Gates the Anatomical Divergence of Neurons Derived From a Common Precursor Origin

Sensory information relayed to the brain is dependent on complex, yet precise spatial organization of neurons. This anatomical complexity is generated during development from a surprisingly small number of neural stem cell domains. This raises the question of how neurons derived from a common precursor domain respond uniquely to their environment to elaborate correct spatial organization and connectivity. We addressed this question by exploiting genetically labeled mouse embryonic dorsal interneuron 1 (dI1) neurons that are derived from a common precursor domain and give rise to spinal projection neurons with distinct organization of cell bodies with axons projecting either commissurally (dI1c) or ipsilaterally (dI1i). In this study, we examined how the guidance receptor, Robo2, which is a canonical Robo receptor, influenced dI1 guidance during embryonic development. Robo2 was enriched in embryonic dI1i neurons, and loss of Robo2 resulted in misguidance of dI1i axons, whereas dI1c axons remained unperturbed within the mantle zone and ventral commissure. Further, Robo2 profoundly influenced dI1 cell body migration, a feature that was partly dependent on Slit2 signaling. These data suggest that dI1 neurons are dependent on Robo2 for their organization. This work integrated with the field support of a model whereby canonical Robo2 vs. non-canonical Robo3 receptor expression facilitates projection neurons derived from a common precursor domain to read out the tissue environment uniquely giving rise to correct anatomical organization.

HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of Lzts1

ABSTRACTDifferential Hox gene expression is central for specification of axial neuronal diversity in the spinal cord. Here, we uncover an additional function of Hox proteins in the developing spinal cord, restricted to B cluster Hox genes. We found that members of the HoxB cluster are expressed in the trunk neural tube of chicken embryo earlier than Hox from the other clusters, with poor antero-posterior axial specificity and with overlapping expression in the intermediate zone (IZ). Gain-of-function experiments of HoxB4, HoxB8 and HoxB9, respectively, representative of anterior, central and posterior HoxB genes, resulted in ectopic progenitor cells in the mantle zone. The search for HoxB8 downstream targets in the early neural tube identified the leucine zipper tumor suppressor 1 gene (Lzts1), the expression of which is also activated by HoxB4 and HoxB9. Gain- and loss-of-function experiments showed that Lzts1, which is expressed endogenously in the IZ, controls neuronal delamination. These data collectively indicate that HoxB genes have a generic function in the developing spinal cord, controlling the expression of Lzts1 and neuronal delamination.

Functional zones of Peyer’s patch (PPs) in rabbits’ caecum

A feature of rabbit gut-associated lymphoid tissue is that its structure is more developed than in other animal species. In rabbits it is composed of sacculus rotundus, vermiform appendix and Peyer’s patches. These immune formations contain an organized component of lymphoid tissue – lymphoid nodules (B-cell zone) and interfollicular region (T-cell). Secondary lymphoid nodules with germinal centers presented in them are formed due to antigen stimulation. The caecum of Hyplus rabbits at the age of 30 -, 60 - and 90-days was investigated. Each age group consisted of 5 rabbits. Experimental rabbits are clinically healthy, unvaccinated and untreated against ecto- and endoparasites. Peyer’s patches of the caecum were selected for the study and fixed in 10% of formalin. Subsequently, the specimens stained with hematoxylin-eosin were prepared from the obtained samples. On the 30th day of life, Peyer’s patches in the cecum were detected by gross examination. On the histological level, they had formed interfollicular region and lymphoid nodules. In turn, lymphoid nodules were divided into primary and secondary ones. A well-defined mantle zone and germinal centers were observed in the secondary lymphoid nodules. The regularities of their area indicators increase (mean value, median and interquartile range (IQR)) and their correlation were studied. The most intensive growth of the mantle area and the germinal center was observed from the 30th to the 60th day. The relative area of the mantle zone and the germinal center as part of the secondary lymphoid nodule was determined. Its value did not change during the experimental period.

Geological Prospection of Placer Chromium Deposits in the Waropen Regency—Indonesia (New Guinea) Using the Method of Indicator Minerals

Indicator minerals (IM) have been used in the research of gemstone and base metals for over 100 years. IMs are a main source of information about the occurrence of deposits, hydrothermal and weathering changes, as well as bedrock source and type. Since 2013, base metal mineral exploration has taken place on New Guinea Island (the Indonesian part). The analysis of chromian spinels as IM in beach and river sediments led to the discovery of rich chromian-bearing deposits in the Botawa River sediments. The dominant detrital minerals include chromian spinels, olivine, pyroxenes and serpentine. The source of chromian spinels, olivine and pyroxenes are most likely peridotites from the Earth’s mantle zone of the ophiolite series, generated under supra-subduction conditions. The terrigenous deposits contain metamorphic minerals, such as staurolites, andalusites, epidotes, amphiboles and fragments of micas, quartz and chlorite schists. Using ICP-MS analysis of the beach sands, the concentration of Cr2O3 was determined to be at the level of 1.17%, while in the heavy minerals concentrate from the Botawa River sediment, the content of Cr2O3 amounts to 24.83%. The authors conclude that the west parts of the Van Rees Mountains are the probable parent rocks for chromium-bearing sediments.

A 62-Year-Old African American Woman With Stable Lymphadenopathy Over 5 Years

The patient is a 62-year-old African American female with medical history of Plummer Vinson syndrome and CT scan in 2014 showing lymphadenopathy of the porta hepatis. Needle core biopsy of enlarged lymph nodes revealed sheets of polytypic plasma cells with no aberrant B or T cells or granulomas or hyaline-like depositions identified. The findings were suspicious for unicentric Castleman disease. In 2019, the patient presented with chronic fatigue without other systemic symptoms. Contrast CT revealed persistent retroperitoneal lymphadenopathy and calcified granulomas in the liver, spleen, and lung. Excision of portal and celiac nodes showed preserved nodal architecture with mild mantle zone expansion and marked hyaline-like deposition in the follicles. Sheets of mature plasma cells and focally increased vasculatures were seen in the interfollicular areas. Focally frequent nonnecrotizing granulomas were noted. Occasional giant cells and rare asteroid bodies were identified in the granulomas. Immunohistochemistry stain workup revealed normal distribution of the B and T lymphocytes. CD138 stain highlighted marked increased plasma cells and HHV8 was negative. Immunofluorescence microscopy for kappa and lambda did not show monoclonality; IgA was positive in <10% of plasma cells; special stain for Congo red and serum amyloid associated protein (SSA) IHC stain were strongly positive in the follicles. The overall findings are consistent with reactive lymphadenopathy with interfollicular polytypic plasmacytosis, noncaseating granuloma formation, and reactive amyloidosis. The features of mantle zone hyperplasia and polytypic plasmacytosis are suggestive of HHV8-negative/idiopathic unicentric Castleman disease. This case possibly represents an example of concurrent amyloidosis, sarcoidosis, and idiopathic unicentric Castleman disease. Given that SSA was recently reported to have a pathogenic role in granulomatous inflammation of sarcoidosis through sustained inflammatory reaction, the possibility of increased SSA triggering sarcoidoisis in this patient can be considered. However, the exact pathogenesis of these concurrent findings needs further investigation and clarification.

Mantle Cell Lymphoma With Mantle Zone Growth Pattern

ObjectivesTo characterize the clinical and pathologic features of mantle cell lymphoma with mantle zone growth pattern (MCL-MZGP).MethodsThe clinicopathologic data from 35 cases of MCL-MZGP obtained in 12 centers were analyzed.ResultsThe patients with MCL-MZGP typically sought treatment at high clinical stages (81%). Intriguingly, 40% (14/35) of cases were incidentally noted. The lymph nodes with MCL-MZGP showed preserved architecture and expanded mantles containing lymphoma cells with classic or small cell cytology. MCL-MZGP was positive for BCL2 (96%, bright), CD5 (82%, moderate), cyclin D1 (100%), and SOX11 (89%). Clinically, our study revealed no significant difference in the overall survival between patients managed with observation alone and those who received chemotherapy.ConclusionsMCL-MZGP was often incidentally identified and resembled reactive mantles. Therefore, recognition of this unusual morphology emphasizes the utility of cyclin D1 immunostain in the cases with suspicious morphology. However, the clinical significance of these findings is still unclear.

Hydrothermal fluid circulations in the western Pyrenees: new data on stable isotopes, in-situ gas analysis and fluid inclusions

Several fluid circulation events are recorded in the Aquitaine Basin and the Chaînons Béarnais in the Pyrenean belt of southwestern France. Different fluid types are found in all locations studied. The main difference comes from the thermal peak event (rifting), which was more intense in the Chaînons Béarnais close to the exhumed mantle zone. In situ gas analysis associated of fluid inclusions and isotopic (C, O, H, S) analyses show that similar fluids are generated in both systems, although separated by deep structures, e.g. the North Pyrenean Frontal Thrust (NPFT). The Pyrenean tectonic history leads to the compartmentalization of fluid circulations.