Non-Alcohol-Related Wernicke Encephalopathy

Acute Cognitive Dysfunction in a Patient With Traumatic Brain Injury: A Clinical Vignette.

Comparison of TP53 Alterations in Hematological Malignancies

Challenges in the Management of Burkitt's Lymphoma

HIV-Associated Burkitt Lymphoma: Case Report and Literature Review

Second Primary Malignancies in Patients with Non-Hodgkin Lymphoma

Wernicke's encephalopathy (WE) is a neurological disorder caused by thiamine deficiency. This condition is characterized by impaired consciousness, eye movement disorders, and gait ataxia. Early diagnosis and thiamine treatment are critical owing to the condition's high mortality rate and risk of progression to Korsakoff syndrome. However, WE is often underdiagnosed, and treatment guidelines remain limited. In this case study, we report the case of a patient diagnosed with WE shortly after improvement from alcohol withdrawal delirium. High-dose thiamine administration for approximately nine weeks resulted in a marked improvement in consciousness. This case underscores the importance of considering WE in patients with alcohol use disorder who exhibit episodes of impaired consciousness and poor food intake, specifically when guided by Caine's criteria. It also highlights the potential benefit of high-dose intravenous thiamine administration, particularly in the early stages of treatment, and suggests that prolonged treatment may still yield improvements, even in cases with delayed recovery.

Introduction: BCL6 is a key oncogene in lymphoma pathogenesis. Malignant lymphoid cells exploit several mechanisms to deregulate the expression of BCL6, including chromosomal translocations, somatic mutations in the promoter regulatory regions, or inactivation of the pathway that controls its degradation. FBXO11 was recently identified as a major ubiquitin ligase involved in the degradation of BCL6 and was found to be frequently inactivated by mutations or deletion in diffuse large B cell lymphoma (DLBCL). Thus, FBXO11 acts as an oncosuppressor in DLBCL by promoting the accumulation of BCL6. Given the prominent role of FBXO11 in regulating BCL6 stability, we searched for FBXO11 mutations in BCL6-positive lymphomas, other than DLBCL, and we investigated its role in lymphoma development in vivo. Methods: We sequenced the entire FBXO11 coding sequence by classical Sanger sequencing in 100 cases of follicular lymphoma (FL), 36 cases of Burkitt lymphoma (BL), 8 BL cell lines and 8 anaplastic large cell lymphoma cell lines, all BCL6-positive lymphomas. Moreover, we sequenced 50 cases of marginal zone B cell lymphoma (MZL), which show variable expression of BCL6. We functionally validated the FBXO11 mutations by developing mutant constructs and testing their ability to induce BCL6 and SNAIL degradation. We then applied the CRISPR/Cas9 system to disrupt the endogenous FBXO11 gene in BL cells and evaluated its effect on BCL6 stability. To dissect the in vivo role of FBXO11 in lymphomagenesis we generated conditional FBXO11 knock-out (KO) mice (FBXO11fl/fl) to delete protein expression in CD19-positive B cells. To investigate whether FBXO11 inactivation cooperates with c-myc in lymphomagenesis we crossed CD19/Cre-FBXO11fl/fl mice with Eμ-myc transgenic mice. Results: We identified FBXO11 mutations in BL cases and cell lines (10/44, 22.7%), one case of FL (1/100) and one case of MZL (1/50). In FL and MZL, the mutational analysis of tissue collected by microdissection showed that the mutation was specifically acquired by the high-grade component. The frequency of FBXO11 mutation in BL was further validated on an independent cohort of 51 BL cases (6/51, 11.7%), obtained from published data of a previous whole-exome sequencing study (Love et al. Nat Genet 2012). BL mutations were mostly missense mutations located in the functional CASH domains and also splice-site mutations that were never described before and that induced alternative splicing, as confirmed on the mRNA extracted from the tumor samples. All mutations produced a mutant FBXO11 with impaired ability to induce BCL6 and SNAIL degradation. CRISPR/Cas9 mediated KO of FBXO11 in BL cells resulted in an almost complete stabilization of BCL6, thus suggesting that FBXO11 is the main, if not unique, ubiquitin ligase that controls BCL6 stability in BL. Finally, we observed an acceleration of lymphoma development in the CD19/Cre-FBXO11fl/fl mice crossed with Eμ-myc transgenic mice. The lymphomas showed histologic features of high-grade disease with a more mature B-cell phenotype than the Eμ-myc tumors alone. Conclusions: Overall our results demonstrate that FBXO11 is frequently mutated in BL. All mutants identified impair the ability of FBXO11 to regulate the degradation of BCL6. Together with our previous findings (Duan et al. Nature 2012), this study shows that FBXO11 is mostly mutated in aggressive lymphomas such as DLBCL and BL, and suggests that FBXO11 mutations could contribute to their aggressiveness. In fact, we show that FBXO11 inactivation cooperates with c-myc in accelerating lymphomagenesis. We have established a novel murine lymphoma model that resembles more closely the human BL, providing a novel promising tool for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches with BCL6 and/or c-myc inhibitors. This abstract is also being presented as Poster 32. Citation Format: Chiara Pighi, Mara Compagno, Taek-Chin Cheong, Teresa Poggio, Qi Wang, Fernanda Langellotto, Anoop Sendamarai, Kyriacos Markianos, Paola Francia di Celle, Alberto Zamò, Roberto Chiarle. FBXO11 is recurrently mutated in Burkitt lymphoma and its inactivation accelerates lymphomagenesis in Eμ-myc mice [abstract]. In: Proceedings of the Second AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; May 6-9, 2017; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(24_Suppl):Abstract nr PR10.

Palliative Outpatient Care in Children with Hematologic Malignancies Compared to Solid Tumors

Analysis of BRCA1 and BRCA2 Mutations and Gene Expression in Hematological Malignancies - Implications for Differential Involvement in Pathogenesis of Lymphoid Neoplasms

Paraneoplastic neurological syndromes (PNS) are mostly immune-mediated, tumor-associated disorders that can develop years before detection of any malignancy. Their prevalence varies among different tumor types. Diagnostic criteria for PNS include the presence of a classical or nonclassical clinical syndrome in association with antineuronal antibodies and the presence of any malignancy [1]. We report the case of a 32-year-old male, who presented with a 2-year history of progressing neurological deficits starting with headaches, muscle pain and weight loss. Nine months later, the patient had developed two generalized epileptic seizures, optic and acoustic hallucinations, oculomotor disturbances, gait ataxia and signs of polyneuropathy. Over time, investigations in external hospitals had led to the assumption of an autoimmune encephalitis according to the following findings: a T2-sequence hyperintense alteration of the right hippocampus in the magnetic resonance imaging (MRI), positive oligoclonal bands but normal cell count in the cerebrospinal fluid, and positive serum tests for Anti-Huand N-Methyl-D-aspartic acid-receptor (NMDA-R) antibodies. Serum antibodies against acetycholine receptors and repeated tumor search remained negative. Treatments with prednisolone, intravenous immunglobuline and plasmapheresis were not effective. On clinical examination we saw a 32-year-old, cachectic and wheelchair bound patient with complex oculomotor disturbances including an anisocoric, converged right pupil with disturbed abduction and a dysfunction of horizontal movements of both eyes. There were signs of dysphagia and dysphonia. Severe generalized muscle atrophy and muscle pain were accompanied by pareses focused on the muscles of the neck causing a dropped head, but pareses were also found in the muscles of the proximal upper limb region and the distal lower limbs. Severe gait and limb ataxia and signs of polyneuropathy predominantly of the lower limbs including pallhypaesthesia and arreflexia made it impossible for the patient to stand or walk. Considering the fast progression of symptoms several diagnostics were repeated: cerebral MRI (1.5 T) showed an unchanged T2-hyperintense, non-contrast enhancing signal alteration of the right hippocampal area (Fig. 1). The patient’s serum was again tested positive (Indirect immunofluorescence test [2], Euroimmun Medical Laboratory Diagnostics, Luebeck, Germany) for anti-Hu-antibodies (titre 1:1,000, reference \1:10) and NMDA-R antibodies (titre 1:320, reference\1:10). The patient denied repetition of lumbar puncture at this point. Electroneurography demonstrated a mostly demyelinating sensorimotor I. Pohley M. Wittstock R. Benecke A. Wolters Department of Neurology, University of Rostock, Rostock, Germany

Unusual case of metachronous EBV‐associated B‐cell and NK/T‐cell lymphoma mimicking polymyositis‐diagnostic challenges and pitfalls

Performance of a Liquid Biopsy Diagnostic Prediction Model for EBV-Positive Burkitt Lymphoma in Sub-Saharan Africa

To assess the effect of high-dose oral thiamine supplements on glucose tolerance in patients with impaired glucose metabolism. Twelve hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes) completed this randomized, double-blind trial, where all participants received both placebo and thiamine capsules (3×100mg/day) for 6weeks in a cross-over manner. The main endpoint was changes in 2-h plasma glucose. Fasting plasma glucose and insulin, 2-h plasma insulin, the hemostatic model assessment of insulin resistance (HOMA-IR), renal function measurement and thiamin status were also evaluated at the commencement and completion of each treatment period. Thiamine supplementation resulted in significant decrease in 2-h plasma glucose relative to baseline (8.78±2.20 vs. 9.89±2.50mmol/l, p=0.004), with no significant change in the placebo arm. Fasting plasma glucose and insulin, and HOMA-IR increased significantly from baseline after 6weeks in the placebo arm (p=0.003, p=0.04 and p=0.02, respectively). These variables did not change with thiamine supplementation. There were no significant changes in 2-h plasma insulin or renal function marker, within or between arms. Supplementation with high-dose thiamine may prevent deterioration in fasting glucose and insulin, andimprove glucose tolerance in patients with hyperglycemia. High-dose thiamine supplementation may prevent or slow the progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose regulation.

ObjectivesPatients with systemic lupus erythematosus (SLE) are at higher risk of haematological malignancies (HMs) than the general population. Most reports have focused on HM diagnosed after SLE, and have excluded...

Categorizing Molecular Mutations in MDS and AML