Skull base plasmacytoma in young patients aged below 40 years: Radiological perspectives and clinical outcomes.

BACKGROUND: Plasmacytoma of the skull base is a rare manifestation of plasma cell neoplasm with only a few cases documented in literature involving young adults. Plasmacytoma can be an isolated solitary lesion or a secondary manifestation of multiple myeloma (MM). In this study, we report the clinical and radiological characteristics, management, and outcomes of patients under the age of 40 who presented with skull base plasmacytoma and associated neurological manifestations. Additionally, we share our experience in treating a rare case of skull base plasmacytoma diagnosed during pregnancy, in which the patient exhibited a favorable response to myeloma treatment initiated after delivery. CASE SERIES: Four patients were identified, comprising one pregnant female and three male patients, with a median age of 36 years (range 33-37 years). The main presenting symptoms were headache, dizziness, and cranial nerve palsy. All patients received underwent systemic myeloma therapy and radiotherapy with three patients also underwent autologous stem cell transplantation (ASCT). Notably, all patients achieved complete remission. CONCLUSION: Skull base plasmacytoma represents a rare manifestation of plasma cell neoplasms, underscoring the importance of considering it in the differential diagnosis of skull base lesions to ensure early intervention and avoid potential serious complications. Throughout our series, the cornerstone of therapy involved radiotherapy, systemic myeloma therapy, and ASCT, all of which elicited a favorable response in every case.

Real world evidence of epidemiological trends, clinical presentation, and prognostic outcomes of multiple myeloma (2007-2021).

Background: Multiple myeloma (MM) is one of the most common hematological malignancies globally, and it is projected to increase in the coming years. It occurs more frequently in males and affects older individuals. Presenting symptoms can range from being asymptomatic to severely debilitating. The objective of this study was to determine the epidemiology, clinical features, and prognostic outcomes of patients with MM in the only tertiary cancer hospital in Qatar. Methods: Patients with symptomatic myeloma diagnosed at the National Center for Cancer Care and Research in Qatar between 2007 and 2021 were included. Data on demographics, laboratory work, bone marrow analysis, radiology, and given treatment were collected. Descriptive statistics, survival curves, and multivariable cox regression were used to identify independent mortality risk factors. Results: During the study period of 15 years, a total of 192 patients were diagnosed with MM. The incident rate of myeloma cases in 2021 was 8 patients per million. The median age of patients was 57 years [range 22-88], with 68% being above the age of 50 years at diagnosis. The majority of patients were male (71%) and (85%) were expats. At the time of diagnosis, most patients [n = 169 (88%)] had bone lesions, and 27% had extramedullary plasmacytoma. Anemia, hypercalcemia, and spinal cord compression were reported in 53%, 28%, and 7% of patients, respectively, at presentation. The monoclonal immunoglobulin subtypes were IgG, IgA, and free light chain in 52%, 16%, and 26% of patients, respectively. The overall median survival was 103 months (95% CI 71-135 months). In a multivariate cox-regression analysis for risk factors, only high serum calcium (≥ 2.7 mmol/L) was associated with increased mortality (HR: 2.54, 95% C.I.: 1.40-4.63, p = 0.002). Patients who received an autologous stem cell transplant (ASCT) had significantly better overall survival. Conclusion: In this comprehensive study of patients with MM treated in a country with a small and young general population, centralized hematology care, and free cancer care, we found a low but increasing incidence of MM and a good overall survival. Hypercalcemia was confirmed as a negative risk factor. ASCT had a significant positive impact on survival and should be provided to all patients eligible for this treatment, even in the era of novel agents.

Dissecting bloodstream infections in febrile neutropenic patients with hematological malignancies, a decade-long single center retrospective observational study (2009-2019).

BACKGROUND: The use of ill-suited antibiotics is a significant risk factor behind the increase in the mortality, morbidity, and economic burden for patients who are under treatment for hematological malignancy (HM) and bloodstream infections (BSI). Such unfitting treatment choices intensify the evolution of resistant variants which is a public health concern due to possible healthcare-associated infection spread to the general population. Hence, this study aims to evaluate antibiograms of patients with BSI and risk factors associated with septicemia. METHODS: A total of 1166 febrile neutropenia episodes (FNE) among 513 patients with HM from the National Center for Cancer Care and Research (NCCCR), Qatar, during 2009-2019 were used for this study. The socio-demographic, clinical, microbial, and anti-microbial data retrieved from the patient's health records were used. RESULTS: We analyzed the sensitivity of gram-negative and gram-positive bacilli reported in HM-FN-BSI patients. Out of the total 512 microorganisms isolated, 416 (81%) were gram-negative bacteria (GNB), 76 (15%) were gram-positive bacteria (GPB) and 20 (4%) were fungi. Furthermore, in 416 GNB, 298 (71.6%) were Enterobacteriaceae sp. among which 121 (41%) were ESBL (Extended Spectrum Beta-Lactamase) resistant to Cephalosporine third generation and Piperacillin-Tazobactam, 54 (18%) were Carbapenem-resistant or multidrug-resistant organism (MDRO). It's noteworthy that the predominant infectious agents in our hospital include E. coli, Klebsiella species, and P. aeruginosa. Throughout the study period, the mortality rate due to BSI was 23%. Risk factors that show a significant correlation with death are age, disease status, mono or polymicrobial BSI and septic shock. CONCLUSION: Decision pertaining to the usage of antimicrobials for HM-FN-BSI patients is a critical task that relies on the latest pattern of prevalence, treatment resistance, and clinical outcomes. Analysis of the antibiogram of HM-FN-BSI patients in Qatar calls for a reconsideration of currently followed empirical antibiotic therapy towards better infection control and antimicrobial stewardship.

A Rare Case of Lambert-Eaton Myasthenia Syndrome Associated with Non-Hodgkin's Lymphoma: A Case Report and Review of the Literature.

Introduction: Lambert-Eaton myasthenia syndrome (LEMS) is a rare autoimmune disorder characterized by autoantibodies targeting presynaptic neuromuscular junctions. It results in muscle weakness and autonomic dysfunction. LEMS can be idiopathic or associated with neoplastic diseases, often small-cell lung cancer. This case report describes a rare instance of paraneoplastic LEMS in a man with non-Hodgkin lymphoma. Case Presentation: A 57-year-old male with non-Hodgkin lymphoma presented with progressive muscle weakness, diminished reflexes, and autonomic symptoms. Diagnosis revealed LEMS with autoantibodies against voltage-gated calcium channels. Immunosuppressive therapy and lymphoma treatment led to significant improvement in his condition. Conclusion: This case highlights the rare occurrence of paraneoplastic LEMS in a patient with non-Hodgkin lymphoma. Recognition and timely management of LEMS alongside lymphoma treatment can lead to significant clinical improvement, emphasizing the need for increased awareness of such complex associations.

Polatuzumab Vedotin in a Patient with Refractory Burkitt Lymphoma, a Case Report.

Although Burkitt lymphoma is considered a curable disease due to the progress made in choosing the most effective first-line therapy, relapsed or refractory Burkitt lymphoma (BL) has a very poor outcome. There is a lack of data supporting the treatment regimens. We report a 48-year-old male with stage II Burkitt's lymphoma with no response to the first line of high-intensity chemotherapy. However, treatment with polatuzumab vedotin led to complete clinical remission for more than one year.

Bibliometric analysis of cancer care operations management: current status, developments, and future directions.

Around the world, cancer care services are facing many operational challenges. Operations management research can provide important solutions to these challenges, from screening and diagnosis to treatment. In recent years, the growth in the number of papers published on cancer care operations management (CCOM) indicates that development has been fast. Within this context, the objective of this research was to understand the evolution of CCOM through a comprehensive study and an up-to-date bibliometric analysis of the literature. To achieve this aim, the Web of Science Core Collection database was used as the source of bibliographic records. The data-mining and quantitative tools in the software Biblioshiny were used to analyze CCOM articles published from 2010 to 2021. First, a historical analysis described CCOM research, the sources, and the subfields. Second, an analysis of keywords highlighted the significant developments in this field. Third, an analysis of research themes identified three main directions for future research in CCOM, which has 11 evolutionary paths. Finally, this paper discussed the gaps in CCOM research and the areas that require further investigation and development.

Aberrant Acquisition of T-cell Associated Markers in Plasma Cell Neoplasms: An Aggressive Disease with Extramedullary Involvement and Very Short Survival.

BACKGROUND: Plasma cell neoplasms can show aberrant expression of different lineage-related antigens; however, co-expression of T-cell-associated markers on malignant plasma cells is extremely rare. MATERIAL AND METHODS: This report describes clinicopathologic characteristics of three myeloma patients with emergent plasmablastic morphology and aberrant acquisition of T-cell-associated markers diagnosed in our center. An extensive literature search for similar cases was conducted, and the relevant pathologic, clinical, and prognostic characteristics were summarized. RESULTS: A total of 22 cases of plasma cell neoplasm (including the three cases reported here) showed aberrant co-expression of T-cell markers. We found an evident association between aberrant expression of T-cell markers on malignant plasma cells and extramedullary involvement, aggressive morphologic features, high proliferative index ki67 >90%, aggressive clinical course, an adverse outcome, and short survival. DISCUSSION & CONCLUSION: Due to the rarity of this aberrant phenotype and scarcity of the published data, the precise causative mechanism and its clinical implications have not yet been elucidated.

Characterization of complete lncRNAs transcriptome reveals the functional and clinical impact of lncRNAs in multiple myeloma.

Multiple myeloma (MM) is an incurable disease, whose clinical heterogeneity makes its management challenging, highlighting the need for biological features to guide improved therapies. Deregulation of specific long non-coding RNAs (lncRNAs) has been shown in MM, nevertheless, the complete lncRNA transcriptome has not yet been elucidated. In this work, we identified 40,511 novel lncRNAs in MM samples. lncRNAs accounted for 82% of the MM transcriptome and were more heterogeneously expressed than coding genes. A total of 10,351 overexpressed and 9,535 downregulated lncRNAs were identified in MM patients when compared with normal bone-marrow plasma cells. Transcriptional dynamics study of lncRNAs in the context of normal B-cell maturation revealed 989 lncRNAs with exclusive expression in MM, among which 89 showed de novo epigenomic activation. Knockdown studies on one of these lncRNAs, SMILO (specific myeloma intergenic long non-coding RNA), resulted in reduced proliferation and induction of apoptosis of MM cells, and activation of the interferon pathway. We also showed that the expression of lncRNAs, together with clinical and genetic risk alterations, stratified MM patients into several progression-free survival and overall survival groups. In summary, our global analysis of the lncRNAs transcriptome reveals the presence of specific lncRNAs associated with the biological and clinical behavior of the disease.

Downregulation of Lymphoid enhancer-binding factor 1 (LEF-1) expression (by immunohistochemistry and/ flow cytometry) in chronic Lymphocytic Leukemia with atypical immunophenotypic and cytologic features.

INTRODUCTION: Lymphoid enhancer-binding factor 1 (LEF-1) overexpression has been recently remarkably reported in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other B-cell lymphomas. CLL has a well-defined immunophenotype, yet, some cases of CLL demonstrate atypical morphology/ phenotype reflected by low Matutes score (atypical CLL). Till date, LEF1 expression has not been systematically studied in cases of CLL with atypical features. METHODS: In this study, LEF-1 expression was assessed by two different techniques, (immunohistochemistry and flow cytometry), to investigate the expression profile of LEF-1 in cases of CLL/SLL, in comparison with other low-grade B-lymphomas and CLL with atypical features, including atypical immunophenotype and CLL with increased prolymphocytes or morphologically atypical cells. RESULTS: We found that LEF-1 expression is downregulated in CLL with atypical immunophenotype/features compared to classic CLL; Chi-Square P < .0001. The ratio for LEF-1 expression in malignant B-cells/NK (by flow cytometry) in CLL/SLL with classic immunophenotype was higher than atypical CLL and is significantly higher in other small B-cell lymphomas (P < .01). Absence of LEF-1 expression in CLL/SLL is correlated (P < .05) with downregulation of CD5, CD23, CD200, expression of FMC7, brighter expression of CD79b, brighter expression of surface light chain, increased prolymphocytes and lower Matutes score. CONCLUSION: As downregulation of LEF-1 expression is well correlated with atypical CLL, we suggest adding LEF-1 to Matutes score as a beneficial marker to differentiate classic from atypical CLL LEF-1 could also serve as a potential prognostic indicator for CLL clinical course.

Chromatin activation as a unifying principle underlying pathogenic mechanisms in multiple myeloma.

Multiple myeloma (MM) is a plasma cell neoplasm associated with a broad variety of genetic lesions. In spite of this genetic heterogeneity, MMs share a characteristic malignant phenotype whose underlying molecular basis remains poorly characterized. In the present study, we examined plasma cells from MM using a multi-epigenomics approach and demonstrated that, when compared to normal B cells, malignant plasma cells showed an extensive activation of regulatory elements, in part affecting coregulated adjacent genes. Among target genes up-regulated by this process, we found members of the NOTCH, NF-kB, MTOR signaling, and TP53 signaling pathways. Other activated genes included sets involved in osteoblast differentiation and response to oxidative stress, all of which have been shown to be associated with the MM phenotype and clinical behavior. We functionally characterized MM-specific active distant enhancers controlling the expression of thioredoxin (TXN), a major regulator of cellular redox status and, in addition, identified PRDM5 as a novel essential gene for MM. Collectively, our data indicate that aberrant chromatin activation is a unifying feature underlying the malignant plasma cell phenotype.

Characterization of circulating myeloma tumor cells by next generation flowcytometry in scleromyxedema patient: a case report.

INTRODUCTION: Scleromyxedema (rare cutaneous mucinosis), is characterized by the formation of lichenoid papules and presence of Serum monoclonal IgG in most cases, or all; after repeated testing. PATIENT CONCERNS: The patient is a 51-year-old male presented with thick, disfiguring elephant-like erythematous skin folds over the forehead, papular shiny eruptions over ears and trunk and waxy erythematous papules over arms and hands without dysphagia or respiratory or neurologic symptoms DIAGNOSIS: : Skin biopsy from right arm was consistent with scleromyxedema. Serum cryoglobulin was reported negative. Complete blood count and routine blood biochemistry were normal. Thyroid function tests were normal. Serum protein electrophoresis and immunofixation showed monoclonal band of 14.5 g/L typed as IgG lambda. INTERVENTIONS: Our patient was refractory to lenalidomide however improved clinically on immunoglobulins infusions on monthly basis without change in the MGUS level. OUTCOMES: NGF analysis revealed approximately 0.25% Lambda monotypic plasma cells in the bone marrow expressing CD38, CD138, and CD27 with aberrant expression of CD56 and were negative for CD45, CD19, CD117, and CD81. We also detected 0.002% circulating plasma cells (PCs) in peripheral blood. CONCLUSION: The immunophenotype of circulating tumor cells (CTCs) remain close to the malignant PCs phenotype in the BM. Hence, we report NGF approach as a novel diagnostic tool for highly sensitive MRD detection in plasma cell dyscrasias including scleromyxedema.

Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor ß and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.

The Role of Integrated Positron Emission Tomography/Computed Tomography (PET/CT) and Bone Marrow Examination in Staging Large B-Cell Lymphoma.

INTRODUCTION: In the era of routine use of positron emission tomography/computed tomography (PET/CT) for staging, it is not yet clear whether PET/CT can replace bone marrow biopsy for the assessment of bone marrow involvement in large B-cell lymphoma. OBJECTIVES: To compare the clinical utility of bone marrow biopsy and PET/CT scanning in the staging of large B-cell lymphoma. METHODS: This was a retrospective analysis of all patients who presented to single center over a 4-year period with large B-cell lymphoma who had concurrent PET/CT and bone marrow biopsy performed in the assessment and staging of the lymphoma. RESULTS: Out of 89 patients, 24 had bone marrow involvement either by PET/CT, by bone marrow biopsy, or by both. Bone marrow biopsy identified 12 patients (sensitivity 50%, specificity 100%, negative predictive value 84%), whereas PET/CT identified 23 patients (sensitivity 96%, specificity 100%, negative predictive value 98%). No patients were upstaged by the bone marrow biopsy result, and no patients had their treatment plan changed based on the bone marrow biopsy result. CONCLUSION: The results show that PET-CT is more sensitive and has better negative predictive value than bone marrow biopsy. This suggests that PET-CT could replace bone marrow biopsy in detecting bone marrow involvement for staging of large B-cell lymphoma.

High-Grade B-Cell Neoplasm with Surface Light Chain Restriction and Tdt Coexpression Evolved in a MYC-Rearranged Diffuse Large B-Cell Lymphoma: A Dilemma in Classification.

According to World Health Organization (WHO) classification (2008), B-cell neoplasms are classified into precursor B-cell or a mature B-cell phenotype and this classification was also kept in the latest WHO revision (2016). We are reporting a male patient in his fifties, with tonsillar swelling diagnosed as diffuse large B-cell lymphoma (DLBCL), germinal center. He received 6 cycles of RCHOP and showed complete metabolic response. Two months later, he presented with severe CNS symptoms. Flow cytometry on bone marrow (BM) showed infiltration by CD10-positive Kappa-restricted B-cells with loss of CD20 and CD19, and downregulation of CD79b. Moreover, the malignant population showed Tdt expression. BM Cytogenetics revealed t(8;14)(q24;q32) within a complex karyotype. Retrospectively, MYC and Tdt immunostains performed on original diagnostic tissue and came negative for Tdt and positive for MYC. It has been rarely reported that mature B-cell neoplasms present with features of immaturity; however the significance of Tdt acquisition during disease course was not addressed before. What is unique in this case is that the emerging disease has acquired an immaturity marker while retaining some features of the original mature clone. No definitive WHO category would adopt high-grade neoplasms that exhibit significant overlapping features between mature and immature phenotypes.

An Unusual Case of Hepatosplenic αß T-Cell Lymphoma Presenting with Coombs'-Negative Hemolytic Anemia.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive extranodal T-cell lymphoma that comprises <5% of peripheral T-cell lymphomas. The majority of cases harbor the γδ T-cell receptor (TCR), but recently, a few cases have been shown to express the αß TCR. Comparison of these two subtypes (αß and γδ) shows similar clinicopathologic and cytogenetic features; however, due to the paucity of reported cases, it is not clear whether they are prognostically distinct entities. We report a case of αß HSTCL with a rather unusual presentation of Coombs'-negative hemolytic anemia. Diagnosis proved challenging due to an unusual blastoid morphology with the absence of typical intrasinusoidal distribution of tumor cells in the bone marrow. This unique case adds to the growing list of this rare subtype of T-cell lymphomas, which warrant urgent attention due to the lack of effective treatment options and dismal prognosis.

Efficacy and Safety of Rituximab for Refractory and Relapsing Thrombotic Thrombocytopenic Purpura: A Cohort of 10 Cases.

OBJECTIVE: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder mediated by autoantibodies directed against ADAMTS13. This provides a rationale for the use of rituximab in this disorder. We report our experience and the outcome of 10 cases of TTP (9 refractory and 1 relapsing) successfully treated with rituximab in combination with plasma exchange (PE) and other immunosuppressive treatments. METHODS: The diagnosis of TTP was based on clinical criteria and supported by severe deficiency of ADAMTS13 activity and presence of inhibitors in seven cases. Rituximab was started after a median of 18.6 sessions of PE (range: 5-35) at the dose of 375 mg/m(2)/week for 4-8 weeks. RESULTS: Complete remission was achieved in all patients after a median time of 14.4 days of the first dose (range: 6-30). After a median follow-up of 30 months (range: 8-78), eight patients were still in remission and two developed multiple relapses, treated again with the same therapy, and achieved complete responses; they are alive, and in complete remission after a follow-up of 12 and 16 months. CONCLUSION: Rituximab appears to be a safe and effective therapy for refractory and relapsing TTP. However, longer follow-up is recommended to assess relapse and detect possible long-term side effects of this therapy.

Epidemiology of idiopathic cardiomyopathy in Qatar during 1996-2003.

OBJECTIVES: To report the rates of cardiomyopathies in the population below 50 years of age in Qatar. SUBJECTS AND METHODS: We conducted a retrospective review of clinical data on patients with cardiomyopathy who were hospitalized in Hamad General Hospital, Doha. Data were collected from medical records during the 1996-2002 period and prospectively from the patients who were hospitalized during the year 2003. All cardiomyopathy patients below 50 years of age who were citizens or permanent residents in Qatar were included in this study. RESULTS: During the study period, a total of 132 cases were recorded with idiopathic cardiomyopathies. Among these, 67.4% were males and 32.6% females; Qatari 31.8%, non-Qatari 68.2%. The consanguinity rate was high among Qatari patients. In the first 7-year study period, 1996-2002, the incidence rate of all types of cardiomyopathies was 2.5/100,000 population per year (95% CI: 1.4-3.5). It increased to 5.2/100,000 population during the year 2003 (95% CI: 3.6-6.7). Dilated cardiomyopathy was most prevalent (75.8%) in all age groups, and the incidence increased remarkably with age. Lower prevalence of hypertrophic cardiomyopathy (13.6%) and left ventricle noncompaction cardiomyopathy (6.1%) was found. In children below 15 years of age, the incidence rate for all types of cardiomyopathies was 2.7/100,000 population. The overall mortality rate was 5.3%. CONCLUSION: Most cases of cardiomyopathy were identified at an early age: below 15 years and above 35 years of age. Introducing preventive and early diagnosis programs may have an impact on reducing the mortality and morbidity from idiopathic cardiomyopathy.