Secondary Breast Burkitt Lymphoma Involving the Stomach, Ovary, Pancreas, and Bones: A Case Report.

Breast lymphomas are rare, malignant breast neoplasms with a heterogeneous pattern of clinical symptoms. Burkitt's lymphoma is a rare, highly aggressive, and rapidly growing B-cell non-Hodgkin lymphoma. We report about a 27-year-old woman diagnosed as having secondary breast Burkitt's lymphoma, probably originating from the stomach, with multiple distant metastases. Breast ultrasonography revealed multiple, variable sized, heterogeneous masses with posterior acoustic enhancement and echogenic rims. These imaging findings may sometimes overlap with those of other breast malignancies. However, unlike other breast malignancies, lymphoma can be diagnosed by biopsy and does not require surgical excision. To avoid unnecessary treatment, radiologists and clinicians should be aware of the characteristic imaging features of breast lymphomas.

NK Cell Degranulation Triggered by Rituximab Identifies Potential Markers of Subpopulations with Enhanced Cytotoxicity toward Malignant B Cells.

A promising strategy in cancer immunotherapy is to restore or enhance the cytotoxicity of NK cells, among others, by activating the mechanism of antibody-dependent cellular cytotoxicity (ADCC). Monoclonal antibodies targeting tumor antigens, such as rituximab (targeting CD20), induce NK cell-mediated ADCC and have been used to treat B cell malignancies, such as non-Hodgkin lymphoma, but not always successfully. The aim of this study was to analyze the gene expression profile of the NK cells involved in the cytolytic response stimulated by rituximab. NK cells were co-cultured with rituximab-opsonized Raji cells. Sorting into responder and non-responder groups was based on the presence of CD107a, which is a degranulation marker. RNA-seq results showed that the KIT and TNFSF4 genes were strongly down-regulated in the degranulating population of NK cells (responders); this was further confirmed by qRT-PCR. Both genes encode surface proteins with cellular signaling abilities, namely c-KIT and the OX40 ligand. Consistent with our findings, c-KIT was previously reported to correlate inversely with cytokine production by activated NK cells. The significance of these findings for cancer immunotherapy seems essential, as the pharmacological inhibition of c-KIT and OX40L, or gene ablation, could be further tested for the enhancement of the anti-tumor activity of NK cells in response to rituximab.

Primary CNS Burkitt Lymphoma Presenting as Sudden Bilateral Blindness in a Patient With Underlying Kabuki Syndrome: A Case Report.

Burkitt lymphoma is an aggressive B-cell non-Hodgkin lymphoma (NHL). Primary CNS lymphoma (PCNSL) is a rare disease, and the subtype of Burkitt lymphoma presenting as a sole CNS lesion is an even rarer diagnosis. Acute sudden blindness is a rare presenting symptom of PCNSL or NHL in general. We present an interesting case of a four-year-old boy with dysmorphic features whose visual examination showed a sudden bilateral loss of vision. There was bilateral eye proptosis and complete ptosis. Extraocular muscles were fixed straight. The pupils were fixed and mid dilated bilaterally and there was grade 3/4 papilledema in both eyes. Neuroimaging showed a mass in the base of the skull, extending to orbits and sinuses. A cervical biopsy of the enlarged lymph nodes was taken and a histopathological diagnosis of Burkitt lymphoma was made. Genetic analysis showed a GNB1 mutation, and the patient was diagnosed with Kabuki syndrome by a pediatrician, based on characteristic dysmorphic features. Treatment with steroids and chemotherapy was initiated.

Very late relapse of Burkitt's lymphoma in an EBV-negative patient after 20 years of complete remission.

Burkitt's lymphoma (BL) is an aggressive B-cell lymphoma that occurs in children and adults. It is a chemosensitive lymphoma with very exceptional cases of late relapse. We report the case of a 32-year-old male, originally from a nonendemic area for BL, who was successfully treated for abdominal BL 20 years ago. He described a two-month history of cervical swelling and a one-week history of dyspnea. Physical examination was unremarkable except for a left submandibular mass that extended to the collarbone. An ultrasound of the neck revealed cervical lymphadenopathy. The patient was submitted to a lymph node biopsy with an immunohistochemical analysis, which concluded to the diagnosis of BL. Screening for recent Epstein-Barr-Virus (EBV) infection was negative. We considered this a very late relapse (VLR) of the original disease, and the patient was treated according to the same initial protocol. Unfortunately, he suffered a second relapse and died. We report an unusual case of a VLR of nonendemic BL in an EBV-negative patient, occurring 20 years after achieving complete remission following the initial chemotherapy.

Colo-colonic intussusception secondary to Burkitt lymphoma with concurrent malignant small bowel mesh adhesion.

Intussusception is a rare presentation in adult population and usually occurs secondary to an underlying pathology. We report an unusual case of a 28-year-old female who developed a colo-colonic intussusception secondary to Burkitt lymphoma which was managed with an extended right hemicolectomy. The case was further complicated by a segment of small bowel with malignant adhesion to a prosthetic mesh requiring resection of the involved segment of small bowel. We have discussed the significance of this case as well as general considerations in the surgical management of adult intussusception.

Burkitt's lymphoma revealed by intestinal obstruction: A case report.

Intestinal obstruction is a surgical emergency frequently encountered in routine practice, usually caused by abdominal adhesions. Although extra nodal lymphoma is most often localized in the gastrointestinal tract and may be responsible for intestinal obstruction, Burkitt's lymphoma is a very rare cause in adults. We report a case of Burkitt's lymphoma mimicking an intestinal obstruction in a 48-year-old adult who presented with an obstructive syndrome and altered general condition. Imaging and anatomopathological examination after immunohistochemical analysis concluded to a multi-systemic Burkitt's lymphoma. Chemotherapy was immediately started with complete remission.

Composite Burkitt Lymphoma and Classical Hodgkin Lymphoma in an Human Immunodeficiency Virus (HIV)-Positive Patient.

Lymphoma, a term encompassing tumor masses in the lymph nodes, is often classified into Hodgkin and non-Hodgkin lymphomas, each with distinct subtypes. We present the unique case of an HIV-positive patient diagnosed with Burkitt lymphoma and classical Hodgkin lymphoma simultaneously as a composite lymphoma. Over the course of five years, a variety of dose-adjusted chemotherapy regimens were used that ultimately proved highly effective. The successful management of this rare case reinforces the significance of considering unexpected combinations of neoplastic processes during diagnosis and treatment planning.

Plasma metabolites in childhood Burkitt lymphoma cases and cancer-free controls in Uganda.

INTRODUCTION: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma associated with Plasmodium falciparum and Epstein-Barr virus, both of which affect metabolic pathways. The metabolomic patterns of BL is unknown. MATERIALS AND METHODS: We measured 627 metabolites in pre-chemotherapy treatment plasma samples from 25 male children (6-11 years) with BL and 25 cancer-free area- and age-frequency-matched male controls from the Epidemiology of Burkitt Lymphoma in East African Children and Minors study in Uganda using liquid chromatography-tandem mass spectrometry. Unconditional, age-adjusted logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for the BL association with 1-standard deviation increase in the log-metabolite concentration, adjusting for multiple comparisons using false discovery rate (FDR) thresholds and Bonferroni correction. RESULTS: Compared to controls, levels for 42 metabolite concentrations differed in BL cases (FDR < 0.001), including triacylglyceride (18:0_38:6), alpha-aminobutyric acid (AABA), ceramide (d18:1/20:0), phosphatidylcholine ae C40:6 and phosphatidylcholine C38:6 as the top signals associated with BL (ORs = 6.9 to 14.7, P < 2.4✕10- 4). Two metabolites (triacylglyceride (18:0_38:6) and AABA) selected using stepwise logistic regression discriminated BL cases from controls with an area under the curve of 0.97 (95% CI: 0.94, 1.00). CONCLUSION: Our findings warrant further examination of plasma metabolites as potential biomarkers for BL risk/diagnosis.

Non-Hodgkin lymphoma mortality disparities across different sexes, races, and geographic locations.

Non-Hodgkin lymphoma (NHL) is one of the most common hematological cancers in the United States. The mortality rate of NHL in the United States is the sixth highest among all cancers. Our cross-sectional study aims to examine the trends and disparity in NHL mortality. We analyzed death certificate data from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) United States to determine the NHL mortality trends among the U.S. population aged ≥15 years. NHL (ICD-10 C82-85) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and joinpoint trend analysis were performed to determine the average annual percent change (AAPC) in AAMR trends. From 1999 to 2020, NHL accounted for 457,143 deaths in the United States, of which 54% are men and 46% are women. The NHL AAMR decreased significantly from 10.59 to 6.21 per 100,000 individuals with an AAPC of -2.55. Men had a higher AAMR than women (10.10 vs 6.29 per 100,000 individuals). Whites recorded the highest AAMR (8.43 per 100,000 individuals), followed by Hispanics (6.32 per 100,000 individuals), Blacks (5.71 per 100,000 individuals), American Indians (5.31 per 100,000 individuals), and Asians (5.10 per 100,000 individuals). Those who lived in the Midwest and the rural areas had the highest AAMR at 8.60 and 8.35 per 100,000 individuals respectively. Despite the declining NHL mortality rate, this study calls for targeted intervention to improve outcomes for susceptible individuals affected by NHL.

Burkitt lymphoma in a scalp region: a case report of it's recurrence in a 13-year-old child.

Introduction: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma characterized by chromosome 8 MYC gene translocation. It manifests in three clinical types: immunodeficiency-related, sporadic (nonendemic), and endemic (African), each differing in epidemiology and clinical behavior. Treatment typically involves enrollment in clinical trials or intensive chemotherapy regimens like R-CODOX-M/IVAC. The authors present a case of recurrent BL following treatment. Case report: A 13-year-old female presented with a gradually progressive swelling in the left parieto-occipital region. Examination revealed normal vital signs and a Glasgow coma scale, with seronegative findings on investigations. An excision of a subganglion soft tissue tumor was performed, revealing histopathological features suggestive of a small round blue cell tumor. After chemotherapy, the patient experienced a recurrence in the scalp region, diagnosed as BL. Discussion: While scarce reports exist on BL in the scalp region, cases have been documented in various body locations. Treatment strategies, including chemotherapy and surgery, have shown promising results in managing the disease and improving symptoms. Conclusion: The recurrence of BL is rare, highlighting the importance of vigilance in monitoring patients post-treatment. The authors report a case of recurrent BL in a 13-year-old female, emphasizing the need for continued research and surveillance in managing this aggressive malignancy.

Severe Lactic Acidosis and Hypoglycemia Associated With Burkitt Lymphoma and the Warburg Effect.

Type B lactic acidosis secondary to the Warburg effect is a rare metabolic complication associated with hematological malignancies. Type B lactic acidosis occurs without tissue dysoxia due to increased aerobic glycolysis and excess lactic acid formation, commonly known as the Warburg effect. Here, we present a case of Burkitt lymphoma in a 69-year-old female with severe type B lactic acidosis and hypoglycemia that was effectively treated by the prompt initiation of chemotherapy. Type B lactic acidosis has been mostly described with hematological malignancies and rarely with solid malignancies. It is considered one of the oncological emergencies, and initiation of chemotherapy as soon as possible has been beneficial compared to alkali therapy. Lactic acidosis associated with malignancies carries a poor prognosis and high mortality.

Treatment Cost and Psychological Impact of Burkitt Lymphoma on Ghanaian Families and Caregivers.

OBJECTIVE: Before June 2022, the treatment cost of Burkitt lymphoma (BL) in Ghana was mainly borne by the child's family or caregiver. We determined the treatment cost of BL in children and its psychological impact on parents and caregivers. METHOD: This prospective observational study assessed the direct medical and nonmedical costs (US dollars [USD]) incurred during the treatment of a child with BL for 6 consecutive months using a cost diary. Productivity losses and the psychological impact on parents and caregivers were assessed using a self-administered questionnaire and the Caregiver Quality of Life Index-Cancer (CQOLC). RESULTS: Of the 25 participants, 7 abandoned the treatment of their children, and 4 withdrew because the children passed away. The median (Q1, Q3) cost for treating BL per child for caregivers/parents (N = 12) was USD 947.42 (USD 763.03, USD 1953.05). Direct medical costs formed 71% (USD 11 458.97) of total treatment costs. Working hours of parents before the child's cancer diagnosis decreased from a median (Q1, Q3) of 44.00 (20.00, 66.00) hours to 1.50 (0, 20.00) hours after the diagnosis. The mean (SD) CQOLC score was 107.92 (15.89), with higher scores in men (111.00 [17.26]), married participants (111.26 [17.29]), Higher National Diploma certificate holders (113.00 [1.41]), and participants earning a monthly income more than USD 84.60. CONCLUSION: Treatment costs reduced the overall household income of 5 families. Parents and caregivers experienced reduced work hours and loss of employment. CQOLC scores were higher in married participants, those with a higher educational background, and those with higher income.

An AI based, open access screening tool for early diagnosis of Burkitt lymphoma.

Burkitt Lymphoma (BL) is a highly treatable cancer. However, delayed diagnosis of BL contributes to high mortality in BL endemic regions of Africa. Lack of enough pathologists in the region is a major reason for delayed diagnosis. The work described in this paper is a proof-of-concept study to develop a targeted, open access AI tool for screening of histopathology slides in suspected BL cases. Slides were obtained from a total of 90 BL patients. 70 Tonsillectomy samples were used as controls. We fine-tuned 6 pre-trained models and evaluated the performance of all 6 models across different configurations. An ensemble-based consensus approach ensured a balanced and robust classification. The tool applies novel features to BL diagnosis including use of multiple image magnifications, thus enabling use of different magnifications of images based on the microscope/scanner available in remote clinics, composite scoring of multiple models and utilizing MIL with weak labeling and image augmentation, enabling use of relatively low sample size to achieve good performance on the inference set. The open access model allows free access to the AI tool from anywhere with an internet connection. The ultimate aim of this work is making pathology services accessible, efficient and timely in remote clinics in regions where BL is endemic. New generation of low-cost slide scanners/microscopes is expected to make slide images available immediately for the AI tool for screening and thus accelerate diagnosis by pathologists available locally or online.

Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.

Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in two B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis.

Retrospective analysis of pediatric patients with Burkitt lymphoma treated in Tanzania following the implementation of the 2016 National Treatment Guidelines: Poor outcomes to current standard-of-care therapy.

BACKGROUND: Despite the excellent outcomes achieved in the treatment of pediatric Burkitt lymphoma (BL) in high-income countries (HICs), outcomes remain poor in low- and middle-income countries (LMICs). Efforts to improve BL outcomes in Tanzania included the creation of National Treatment Guidelines in 2016. However, disease outcomes in Tanzania following the creation of these guidelines have not been reported to date. PROCEDURE: Historical records from 2016 to 2021 for patients 0-18 years of age with a diagnosis of BL and seen at Bugando Medical Centre (BMC), in Mwanza, Tanzania, were curated into an electronic database and analyzed descriptively. Patients in this cohort were treated per the Tanzanian National Treatment Guidelines, which include six cycles of cyclophosphamide, vincristine, and methotrexate (COM) chemotherapy with intrathecal methotrexate and cytarabine. RESULTS: In total, 92 BL patients' records were eligible for analysis. Patients in this cohort were most commonly Murphy stage II (28%) or stage III (34%). Nearly all, 91%, met International Network for Cancer Treatment and Research (INCTR) high-risk criteria at presentation. Forty-two percent of patients did not receive a biopsy and were treated with a presumed diagnosis of BL alone. A 1-year event-free survival of 29.6% (95% confidence interval [CI]: 20.3%-39.5%) and a 1-year overall survival of 38.5% (95% CI: 28%-48.9%) were observed. A high rate of treatment abandonment (34%) was also observed. CONCLUSION: In a historical cohort of pediatric patients with BL treated per the 2016 Tanzanian National Treatment Guidelines, we observed poor outcomes and a high rate of abandonment. These outcomes appear inferior to those achieved in the INCTR clinical trial that informed the guidelines' creation, and highlights the importance of "real-world" outcomes data in LMICs. These data reinforce the idea that continued clinical research and capacity building efforts are necessary to improve BL outcomes in LMICs.

Ciwujianoside E inhibits Burkitt lymphoma cell proliferation and invasion by blocking ENO1-plasminogen interaction and TGF-ß1 activation.

Burkitt's lymphoma (BL) is a rare and highly aggressive B-cell non-Hodgkin lymphoma. Although the outcomes of patients with BL have greatly improved, options for patients with relapsed and refractory BL are limited. Therefore, there is an urgent need to improve BL therapeutics and to develop novel drugs with reduced toxicity. In this study, we demonstrated that enolase 1 (ENO1) is a potential novel drug target for BL treatment. We determined that ENO1 was aberrantly upregulated in BL, which was closely related to its invasiveness and poor clinical outcomes. Furthermore, using RNA interference, we demonstrated that ENO1 depletion significantly inhibited cell proliferation and invasion both in vitro and in vivo. Mechanistically, we established that ENO1 knockdown suppressed the PI3K-AKT and epithelial-mesenchymal transition (EMT) signaling pathways by reducing plasminogen (PLG) recruitment, plasmin (PL) generation, and TGF-ß1 activation. Addition of activated TGF-ß1 protein to the culture medium of shENO1 cells reversed the inhibitory effects on cell proliferation and invasion, as well as those on the PI3K-AKT and EMT signaling pathways. Notably, our research led to the discovery of a novel ENO1-PLG interaction inhibitor, Ciwujianoside E (L-06). L-06 effectively disrupts the interaction between ENO1 and PLG, consequently reducing PL generation and suppressing TGF-ß1 activation. In both in vitro and in vivo experiments, L-06 exerted impressive antitumor effects. In summary, our study elucidated the critical role of ENO1 in BL cell proliferation and invasion and introduced a novel ENO1 inhibitor, which holds promise for improving the treatment of patients with BL in the future.

Disseminated tuberculosis after Polatuzumab-Vedotin based chemoimmunotherapy in a patient with Burkitt's lymphoma.

This report highlights the risk of latent tuberculosis (TB) reactivation after treatment with Polatuzumab Vedotin (PV), Rituximab, and Bendamustine (PBR protocol) despite appropriate chemoprophylaxis. A 48-year-old male with refractory Burkitt's lymphoma (BKL) was treated with PBR protocol. At baseline, the patient had a negative QuantiFERON test result, which turned out to be positive prior to starting PBR. He received chemoprophylaxis for 9 months and was compliant with treatment. One year later, he was admitted with COVID-19 pneumonia and was treated according to the protocol. His symptoms persisted for 1 month. Investigations yielded disseminated TB-infiltrated bone marrow and pleura. Downstream B-cell and T-cell depletion secondary to CD20 and CD79b antagonism may potentially explain the increased risk of TB reactivation associated with the combination of PV and rituximab. Further research is necessary to monitor the risk of TB reactivation among patients receiving a combination of PV and rituximab, especially in endemic areas with high prevalence and incidence of TB.

Recent advancements in 18F-FDG PET/CT for the diagnosis, staging, and treatment management of HIV-related lymphoma.

Infection with the Human Immunodeficiency Virus (HIV) is one of the most pressing issues facing public health on a worldwide scale. Currently, HIV-related lymphoma is the most common cause of death among people living with HIV, and warrants more attention. The unique challenges associated with HIV-related lymphoma management derive from the underlying HIV infection and its immunosuppressive effects. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has gained significant prominence in the past few years as a valuable diagnostic and therapeutic instrument for the treatment of HIV-related lymphoma. This review will start with an overview of the subtypes, risk factors, and therapeutic choices for individuals with HIV-related lymphoma. We will then briefly discuss the current application of 18F-FDG PET/CT in the medical management of HIV-related lymphoma patients, followed by the initial staging of the disease, the evaluation of therapeutic response, the prediction of prognostic outcomes, the decision-making process for radiotherapy guided by PET findings, and the distinguishing of various diagnoses.