Case Report: Large Granular Lymphocyte Leukemia (LGLL)—A Case Series of Challenging Presentations

Large granular lymphocyte leukemia (LGLL) represents a rare group of diseases with considerable difficulties in their correct diagnostic workup and therapy. The major challenges lie in their distinction from reactive (including autoimmune) lymphoproliferations. Moreover, monoclonal LGL proliferative diseases are in fact a heterogeneous group of disorders, as recognized by the three subtypes in the current WHO classification. It distinguishes two chronic forms (the focus of this case series), namely T-LGLL and chronic lymphoproliferative disorders of Natural Killer cells (CLPD-NK) as well as aggressive NK-cell leukemia. In the clinical routine, the variable presentations and phenotypes of T-LGLL and CLPD-NK are underappreciated. The relevant differential diagnoses range from benign reactive T-cell expansions to other mature T-cell leukemias to highly aggressive γδ-lymphomas. T-LGLL or CLPD-NK patients suffer from a wide variety of symptoms often including, but not limited to, cytopenias or classical autoimmune phenomena. They receive treatments ranging from mere supportive measures (e.g. antibiotics, growth factors, transfusions) over strategies of immunosuppression up to anti-leukemic therapies. The diagnostic pitfalls range from recognition of the subtle T-cell proliferation, repeated establishment of monoclonality, assignment to a descript immunophenotypic pattern, and interpretations of molecular aberrancies. Here, we report a series of selected cases to represent the spectrum of LGLL. The purpose is to raise awareness among the scientifically or practically interested readers of the wide variety of clinical, immunological, and phenotypic features of the various forms of LGLL, e.g. of T-cell type, including its γδ forms or those of NK-lineage. We highlight the characteristics and courses of four unique cases from two academic centers, including those from a prospective nationwide LGLL registry. Each case of this instructive catalogue serves to transport a key message from the areas of (chronic inflammatory) contexts in which LGLL can arise as well as from the fields of differential diagnostics and of various treatment options. Implications for optimization in these areas are discussed.

A rare case of asymptomatic solitary cutaneous mastocytoma in a child

Mastocytosis is a rare group of disorders occurring when mast cells diffusely infiltrate the skin or internal organs. It has two forms: Cutaneous and systemic mastocytosis. We present a case of a 12-year-old male child presenting with a reddish-brown cutaneous nodule on the anterior chest wall for 1 month. No other similar lesions were noted elsewhere. Routine hematological and radiological investigations did not reveal any abnormality. The lesion was excised, and a diagnosis of solitary cutaneous mastocytoma was made based on the clinical, histopathological, and immunohistochemical features. This case highlights the importance of diagnosing this rare tumor which can present as an asymptomatic cutaneous lesion in a young child.

Opportunities of MRI in the early diagnosis of the progression of muscular dystrophies

Progressive muscular dystrophies are a genetically heterogeneous group of disorders characterized by progressive muscle weakness, muscle atrophy, and movement disorders. This is a rare group of pathologies that presents a diagnostic problem in the practice of a neurologist. The combination of clinical, radiological, and laboratory methods of examination plays an important role in making the correct diagnosis. Magnetic resonance imaging of muscles is used to diagnose primary muscle damage based on specific patterns of muscle damage. In this article, we will briefly discuss the opportunities of early diagnosis of muscular dystrophies and note the role of MRI of muscles as a highly informative diagnostic method in progressive muscle diseases.

Myelodysplastic syndromes (MDS)

MDS in children is a rare group of hematopoietic stem cell clonal disorder. Allogeneic HSCT is the only curative treatment. HLA typing and the search for a compatible donor must be carried out upon diagnosis, for all patients. However, patients with refractory cytopenia of childhood without an unfavorable karyotype can keep the disease stable for a long time. Thus, in the absence of transfusion dependence or severe neutropenia, a careful observation strategy without treatment is recommended. The treatment of children diagnosed with MDS with excess blasts remains a major challenge. Allogeneic HSCT is the only curative treatment, although the data published in the literature generally include a small number of patients, heterogeneously transplanted. For children with MDS secondary to therapy, despite HSCT, the evolution is generally unfavorable.

Biochemical markers of ovarian stromal cell tumors

Ovarian stromal cell tumors are a rare group of neoplasms that characterized by an ambiguous prognosis and biological activity associated with the hypersecretion of a number of substances. The review presents the latest data on the biochemical diagnosis of tumors of the stroma of sex cord, including granulosa cell tumor of the ovary. The importance of hormones,

In Silico Prediction of Steroids and Triterpenoids as Potential Regulators of Lipid Metabolism

This review focuses on a rare group of steroids and triterpenoids that share common properties as regulators of lipid metabolism. This group of compounds is divided by the type of chemical structure, and they represent: aromatic steroids, steroid phosphate esters, highly oxygenated steroids such as steroid endoperoxides and hydroperoxides, α,β-epoxy steroids, and secosteroids. In addition, subgroups of carbon-bridged steroids, neo steroids, miscellaneous steroids, as well as synthetic steroids containing heteroatoms S (epithio steroids), Se (selena steroids), Te (tellura steroids), and At (astatosteroids) were presented. Natural steroids and triterpenoids have been found and identified from various sources such as marine sponges, soft corals, starfish, and other marine invertebrates. In addition, this group of rare lipids is found in fungi, fungal endophytes, and plants. The pharmacological profile of the presented steroids and triterpenoids was determined using the well-known computer program PASS, which is currently available online for all interested scientists and pharmacologists and is currently used by research teams from more than 130 countries of the world. Our attention has been focused on the biological activities of steroids and triterpenoids associated with the regulation of cholesterol metabolism and related processes such as anti-hyperlipoproteinemic activity, as well as the treatment of atherosclerosis, lipoprotein disorders, or inhibitors of cholesterol synthesis. In addition, individual steroids and triterpenoids were identified that demonstrated rare or unique biological activities such as treating neurodegenerative diseases, Alzheimer’s, and Parkinson’s diseases with a high degree of certainty over 95 percent. For individual steroids or triterpenoids or a group of compounds, 3D drawings of their predicted biological activities are presented.

Single cell genomics reveals plastid-lacking Picozoa are close relatives of red algae

The endosymbiotic origin of plastids from cyanobacteria gave eukaryotes photosynthetic capabilities and launched the diversification of countless forms of algae. These primary plastids are found in members of the eukaryotic supergroup Archaeplastida. All known archaeplastids still retain some form of primary plastids, which are widely assumed to have a single origin. Here, we use single-cell genomics from natural samples combined with phylogenomics to infer the evolutionary origin of the phylum Picozoa, a globally distributed but seemingly rare group of marine microbial heterotrophic eukaryotes. Strikingly, the analysis of 43 single-cell genomes shows that Picozoa belong to Archaeplastida, specifically related to red algae and the phagotrophic rhodelphids. These picozoan genomes support the hypothesis that Picozoa lack a plastid, and further reveal no evidence of an early cryptic endosymbiosis with cyanobacteria. These findings change our understanding of plastid evolution as they either represent the first complete plastid loss in a free-living taxon, or indicate that red algae and rhodelphids obtained their plastids independently of other archaeplastids.

THE LATE ANTIQUITY VAULT FROM THE KURGAN IN THE SOUTHERN NECROPOLIS IN PHANAGORIA

Позднеантичный некрополь столицы Азиатского Боспора преимущественно состоит из погребений второй половиной IV - первой половиной V в. н. э. Что может быть обусловлено раскопками локальных участков кладбища. В этом контексте интересна находка грунтового склепа под курганом Южного некрополя Фанагории, которому и посвящена эта публикация. Однокамерный грунтовый склеп состоял из дромоса и камеры, в которой стоял единственный гроб с погребением пожилого мужчины. С ним найдены: амфора, ремень с железной пряжкой, нож в деревянных ножнах, кремень и статер боспорского царя Фофорса 303/304 гг. н. э. Монета могла быть использована в качестве «обола Харона». Гробница появилась в начале IV в. - после 303 г. н. э. Она относится к редкой группе склепов, построенных для погребения одного мужчины, в то время как подавляющее большинство подобных гробниц являются семейными усыпальницами. Традиция индивидуальных погребений в склепах существовала у жителей Фанагории на протяжении всей позднеантичной эпохи. Не исключено, что так хоронили некоторых заслуженных граждан, возможно воинов. Нельзя исключать связи этой традиции с утверждением новой христианской погребальной обрядности на Боспоре Киммерийском. The late Antiquity necropolis in the capital of the Asian Bosporan Kingdom predominantly consists of graves from the second half of 4th - first half of the 5 centuries AD, which may be explained by the excavations of the cemetery local sections. In this context, of interest is the discovery of an in-ground vault under the kurgan of the Southern Necropolis in Phanagoria which is described in this paper. The one-chamber in-ground vault consisted of a dromos and a burial chamber that contained only one coffin with a buried elderly male. Other finds include an amphora, a belt with an iron buckle, a knife in a wooden scabbard, a firestone and a stater of Fophors, king of the Bosporan Kingdom, dating 303/304. The coin was probably used as the Charon's obol. The tomb was made early in the 4th century, i. e. after 303. It is referred to a rare group of vaults built to bury only one male whereas most similar tombs are family vaults. It is quite possible that some distinguished citizens, maybe, warriors were buried individually like this. We cannot exclude a link between this tradition and development of a new Christian funerary rite in Cimmerian Bosporus.

Two distinct mechanisms leading to loss of virological control in the rare group of antiretroviral therapy-naïve, transiently aviraemic children living with HIV

HIV-specific CD8+ T-cells play a central role in immune control of adult HIV, but their contribution in paediatric infection is less well-characterised. Previously, we identified a group of ART-naïve children with persistently undetectable plasma viraemia, termed ‘elite controllers’, and a second group who achieved aviraemia only transiently. To investigate the mechanisms of failure to maintain aviraemia, we characterized in three transient aviraemics (TAs), each of whom expressed the disease-protective HLA-B*81:01, longitudinal HIV-specific T-cell activity and viral sequences. In two TAs, a CD8+ T-cell response targeting the immunodominant epitope TPQDLNTML (‘Gag-TL9’) was associated with viral control, followed by viral rebound and the emergence of escape variants with lower replicative capacity. Both TAs mounted variant-specific responses, but only at low functional avidity, resulting in immunological progression. By contrast, in TA-3, intermittent viraemic episodes followed aviraemia without virus escape or a diminished CD4+ T-cell count. High quality and magnitude of the CD8+ T-cell response was associated with aviraemia. We therefore identify two distinct mechanisms of loss of viral control. In one scenario, CD8+ T-cell responses initially cornered low replicative capacity escape variants, but with insufficient avidity to prevent viraemia and disease progression. In the other, loss of viral control was associated neither with virus escape nor progression, but with a decrease in the quality of the CD8+ T-cell response, followed by recovery of viral control in association with improved antiviral response. These data suggest the potential for a consistently strong and polyfunctional antiviral response to achieve long-term viral control without escape. IMPORTANCE Very early initiation of antiretroviral therapy (ART) in paediatric HIV infection offers a unique opportunity to limit the size and diversity of the viral reservoir. However, only exceptionally is ART alone sufficient to achieve remission. Additional interventions are therefore required that likely include contributions from host immunity. The HIV-specific T-cell response plays a central role in immune control of adult HIV, often mediated through protective alleles such as HLA-B*57/58:01/81:01. However, due to the tolerogenic and type 2 biased immune response in early life, HLA-I-mediated immune suppression of viraemia is seldom observed in children. We describe a rare group of HLA-B*81:01-positive, ART-naïve children who achieved aviraemia, albeit only transiently, and investigate the role of the CD8+ T-cell response in the establishment and loss of viral control. We identify a mechanism by which the HIV-specific response can achieve viraemic control without viral escape, that can be explored in strategies to achieve remission.

Finnish Variant of Late Infantile Ceroid Neuronal Lipofuscinosis (fvLINCL); Atypical Finding on Magnetic Resonance Imaging

Ceroid neuronal lipofuscinosis (CLN) is a rare group of autosomal recessive neurodegenerative diseases that cause developmental delay and seizures. Herein, we present a case of a 7-year-old girl who referred for magnetic resonance imaging (MRI) following cognitive impairment and seizures. MRI was performed demonstrating some usual findings, and, surprisingly, a normal-sized cerebellum. This case draws attention to not hold to just the classical imaging presentation in order to suspect some leukodystrophy.