Marginal zone lymphoma-derived interfollicular diffuse large B-cell lymphoma harboring 20q12 chromosomal deletion and missense mutation of <Emphasis Type="Italic">BIRC3</Emphasis> gene: a case report

Background

Diffuse large B-cell lymphoma (DLBCL) typically leads to effacement of the nodal architecture by an infiltrate of malignant cells. Rarely (<1%), DLBCL can present with an interfollicular pattern (DLBCL-IF) preserving the lymphoid follicles. It has been postulated that DLBCL-IF is derived from marginal zone B cells and may represent a large-cell transformation of marginal zone lymphoma (MZL), however no direct evidence has been provided to date. Here we describe a rare case of a diagnostically challenging DLBCL-IF involving a lymph node in a patient with a prior history of lymphadenopathy for several years and MZL involving skin.

Case presentation

A 53-year old man presented to our Dermatology Clinic due to a 1-year history of generalized itching, fatigue of 2–3 month’s duration, nausea and mid back rash that was biopsied. PET (positron emission tomography)/CT (computed tomography) was performed and revealed inguinal, pelvic, retroperitoneal, axillary, and cervical lymphadenopathy. The patient was referred to surgery for excisional biopsy of a right inguinal lymph node.Diagnostic H&E stained slides and ancillary studies were reviewed for the lymph node and skin specimens. B-cell clonality by PCR and sequencing studies were performed on both specimens.We demonstrate that this patient’s MZL and DLBCL-IF are clonally related, strongly suggesting that transformation of MZL to DLBCL had occurred. Furthermore, we identified a novel deletion of the long arm of chromosome 20 (del(20q12)) and a missense mutation in BIRC3 (Baculoviral IAP repeat-containing protein 3) in this patient’s DLBCL that are absent from his MZL, suggesting that these genetic alterations contributed to the large cell transformation.

Conclusions

To our knowledge, this is the first report providing molecular evidence for a previously suspected link between MZL and DLBCL-IF. In addition, we describe for the first time del(20q12) and a missense mutation in BIRC3 in DLBCL. Our findings also raise awareness of DLBCL-IF and discuss the diagnostic pitfalls of this rare entity.

     

Macrophytes in tropical shallow lakes: An important food item to benthic entomofauna or an underused resource?

Although macrophytes are known to increase benthic diversity in lakes, the importance of this resource as food for the insects living at the bottom of these ecosystems are still poorly understood. This study assessed the diets of benthic Chironomidae and Campsurus (Ephemeroptera) in two environments: a lake with macrophytes (M+) and another without macrophytes (M?). We expected a differential use of food resources in M+, where plant tissue is particularly important for the aquatic insects’ diet. The diet of 734 individuals from 16 taxa were analyzed. Contrary to expectations, benthic insects consumed low amounts of plant tissue. This finding led us to investigate whether the presence of macrophytes in lakes would indirectly contribute to the benthic insects’ feeding, as more food resources were explored in M+ and a spatial variation of resources intake was observed in this lake, in contrast to the homogeneous feeding in M?. We highlight that macrophytes were responsible for the organic matter build‐up in the sediment, especially at the lake region dominated by these plants, and contributed to increase the deposition of high‐quality amorphous organic matter, which favored taxa in M+ that fed exclusively on this item. The lower diversity of food items exploited in M?, and the Tanypus alga‐based diet in this lake, indicates the low quality of organic resources in its sediment. Although macrophytes were indirectly beneficial for benthic insects’ feeding, we found that this is not an attractive resource for prompt ingestion by most benthic taxa.     

Gain-of-Function Mutations of SLC16A11 Contribute to the Pathogenesis of Type 2 Diabetes

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The sterol transporting heterodimer ABCG5/ABCG8 requires bile salts to mediate cholesterol efflux

The ATP binding cassette transporters ABCG5 and ABCG8 are indispensable for hepatobiliary cholesterol transport. In this study, we investigated the specificity of the heterodimer for cholesterol acceptors. Dog gallbladder epithelial cells were mono- or double-transfected with lentiviral mouse Abcg5 and Abcg8 vectors. Double-transfected cells showed increased efflux to different bile salt (BS) species, while mono-transfected cells did not show enhanced efflux. The efflux was initiated at micellar concentrations and addition of phosphatidylcholine increased efflux. Cholesterol secretion was highly BS dependent, whereas other cholesterol acceptors such as ApoAI, HDL or methyl-beta-cyclodextrin did not elicit Abcg5/g8 dependent cholesterol secretion.     

Towards a Case Definition for Devil Facial Tumour Disease: What Is It?

In the mid 1990s an emerging disease characterised by the development of proliferative lesions around the face of Tasmanian devils (Sarcophilus harrisii) was observed. A multi-disciplinary approach was adopted to define the condition. Histopathological and transmission electron microscopic examination combined with immunohistochemistry help define Devil Facial Tumour Disease (DFTD) as a neoplastic condition of cells of neuroendocrine origin. Cytogenetic analysis of neoplastic tissue revealed it to be markedly different from normal devil tissue and having a consistent karyotype across all tumours examined. Combined with evidence for Major histocompatability (MHC) gene analysis there is significant evidence to confirm the tumour is a transmissible neoplasm.     

Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model

Background

Availability of an ultra-short-course drug regimen capable of curing patients with tuberculosis in 2 to 3 mo would significantly improve global control efforts. Because immediate prospects for novel treatment-shortening drugs remain uncertain, we examined whether better use of existing drugs could shorten the duration of treatment. Rifapentine is a long-lived rifamycin derivative currently recommended only in once-weekly continuation-phase regimens. Moxifloxacin is an 8-methoxyfluoroquinolone currently used in second-line regimens.

Methods and Findings

Using a well-established mouse model with a high bacterial burden and human-equivalent drug dosing, we compared the efficacy of rifapentine- and moxifloxacin-containing regimens with that of the standard daily short-course regimen based on rifampin, isoniazid, and pyrazinamide. Bactericidal activity was assessed by lung colony-forming unit counts, and sterilizing activity was assessed by the proportion of mice with culture-positive relapse after 2, 3, 4, and 6 mo of treatment. Here, we demonstrate that replacing rifampin with rifapentine and isoniazid with moxifloxacin dramatically increased the activity of the standard daily regimen. After just 2 mo of treatment, mice receiving rifapentine- and moxifloxacin-containing regimens were found to have negative lung cultures, while those given the standard regimen still harbored 3.17 log₁₀ colony-forming units in the lungs (p < 0.01). No relapse was observed after just 3 mo of treatment with daily and thrice-weekly administered rifapentine- and moxifloxacin-containing regimens, whereas the standard daily regimen required 6 mo to prevent relapse in all mice.

Conclusions

Rifapentine should no longer be viewed solely as a rifamycin for once-weekly administration. Our results suggest that treatment regimens based on daily and thrice-weekly administration of rifapentine and moxifloxacin may permit shortening the current 6 mo duration of treatment to 3 mo or less. Such regimens warrant urgent clinical investigation.     

Genetic analysis of the Linnaean Ulva lactuca (Ulvales,Chlorophyta) holotype and related type specimens reveals name misapplications,unexpected origins,and new synonymies

Current usage of the name Ulva lactuca, the generitype of Ulva, remains uncertain. Genetic analyses were performed on the U. lactuca Linnaean holotype, the U. fasciata epitype, the U. fenestrata holotype, the U. lobata lectotype, and the U. stipitata lectotype. The U. lactuca holotype is nearly identical in rbcL sequence to the epitype of U. fasciata, a warm temperate to tropical species, rather than the cold temperate species to which the name U. lactuca has generally been applied. We hypothesize that the holotype specimen of U. lactuca came from the Indo‐Pacific rather than northern Europe. Our analyses indicate that U. fasciata and U. lobata are heterotypic synonyms of U. lactuca. Ulva fenestrata is the earliest name for northern hemisphere, cold temperate Atlantic and Pacific species, with U. stipitata a junior synonym. DNA sequencing of type specimens provides an unequivocal method for applying names to Ulva species.     

Contrasting patterns of genetic structure and phylogeography in the marine agarophytes Gelidiophycus divaricatus and G. freshwateri (Gelidiales,Rhodophyta) from East Asia

The evolutionary and population demographic history of marine red algae in East Asia is poorly understood. Here, we reconstructed the phylogeographies of two upper intertidal species endemic to East Asia, Gelidiophycus divaricatus and G. freshwateri. Phylogenetic and phylogeographic inferences of 393 mitochondrial cox1, 128 plastid rbcL, and 342 nuclear ITS2 sequences were complemented with ecological niche models. Gelidiophycus divaricatus, a southern species adapted to warm water, is characterized by a high genetic diversity and a strong geographical population structure, characteristic of stable population sizes and sudden reduction to recent expansion. In contrast, G. freshwateri, a northern species adapted to cold temperate conditions, is genetically relatively homogeneous with a shallow population structure resulting from steady population growth and recent equilibrium. The overlap zone of the two species roughly matches summer and winter isotherms, indicating that surface seawater temperature is a key feature influencing species range. Unidirectional genetic introgression was detected at two sites on Jeju Island where G. divaricatus was rare while G. freshwateri was common, suggesting the occurrence of asymmetric natural hybrids, a rarely reported event for rhodophytes. Our results illustrate that Quaternary climate oscillations have left strong imprints on the current day genetic structure and highlight the importance of seawater temperature and sea level change in driving speciation in upper intertidal seaweed species.     

Translating chemometric analysis into physiological insights from in vivo confocal Raman spectroscopy of the human stratum corneum

The superficial layer of the skin, the stratum corneum (SC), consists of corneocytes surrounded by lipid regions and acts as a protective barrier for the body against water loss, toxic agents and microorganisms. As most substances permeate the stratum corneum through the lipid regions, lipid organization is considered crucial for the skin barrier function. Here, we investigate the potential of in vivo confocal Raman spectroscopy to describe the composition and organization of the SC. Confocal Raman spectroscopy is finding increasing use in the characterization of skin in biomedical, pharmaceutical and cosmetic applications. In this work, we analyze the spectra using chemometric methods and obtain principal components that correspond to the primary skin constituents: protein (keratin), natural moisturizing factor (NMF), water and lipid contributions in both ordered (orthorhombic) and disordered structural organization. By identifying these important components of the SC, these results highlight the utility of this in vivo, non-invasive, and depth resolved tool at the forefront of skin research.