Bone Marrow Infiltration Research Articles

Machine Learning Models Based on [18F]FDG PET Radiomics for Bone Marrow Assessment in Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma is a heterogeneous group of cancers that triggers bone marrow infiltration in 20–40% of cases. Bone marrow biopsy in combination with a visual assessment of [18F]FDG PET/CT images is used to assess the marrow status. Despite the potential of both techniques, they still have limitations due to the subjectivity of visual assessment. The present study aims to develop models based on bone marrow uptake in [18F]FDG PET/CT images at the time of diagnosis to differentiate bone marrow status. For this purpose, a model trained for skeleton segmentation and based on the U-Net architecture is retrained for bone marrow segmentation from CT images. The mask obtained from this segmentation together with the [18F]FDG PET image is used to extract radiomics features with which 11 machine learning models for marrow status differentiation are trained. The segmentation model yields very satisfactory results with Jaccard and Dice index values of 0.933 and 0.964, respectively. As for the classification models, a maximum F1_score_weighted and F1_score_macro of 0.962 and 0.747, respectively, are achieved. This highlights the potential of these features for bone marrow assessment, laying the foundation for a new clinical decision support system.

Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry.

Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow-up of 5.7 years, 156 patients progressed, most of them to symptomatic WM (SWM). The cumulative incidence of progression was 13% and 20% at 5 and 10 years, respectively. The serum IgM ≥10 g/L, bone marrow (BM) infiltration ≥20%, β2-microglobulin ≥3 mg/L, and albumin <4 g/dL were the most potent predictors of disease progression in a multivariate Cox regression model, allowing the identification of three risk categories. The probability of progression to symptomatic disease at 5 years was 4.5%, 15.7%, and 42.8% for low-, intermediate-, and high-risk groups, respectively. In patients without a BM evaluation, the presence of none or 1 risk factor and 2 or 3 risk factors conferred a progression risk of 6% and 27% at 5 years, respectively. The model was independent of the presence of MYD88 L265P, which conferred a negative impact only in AWM patients. The relative survival (RS) ratio at 5 years of asymptomatic patients was similar to the Spanish population, which contrasted with the 0.76 5-year RS of SWM patients. Overall, the Spanish Multicenter Model comprehensively describes the risk of progression of asymptomatic patients and shows that the excess mortality is increased only in the symptomatic stage of the disease.

Prevalence of Asymptomatic Changes in the Groin Region Among Adult Professional Soccer Players and Their Association With Limb Dominance.

To investigate the prevalence of asymptomatic radiologic groin region findings in adult professional soccer players using magnetic resonance imaging (MRI) and examine the influence of age and limb dominance on their occurrences. Cross-sectional trial. Soccer club medical service, private practice. Forty-seven male professional soccer players. Players underwent a groin presigning MRI scan with a magnetic field induction of 1.5 Tesla. Image analysis of their pubic bones was performed according to The Copenhagen Standardized MRI protocol to assess the pubic symphysis and adductor regions of players. The prevalence of various changes in the symphysis, pubic bone, and adjacent areas. Fifty images of pubic bones and adjacent regions (53.2%) highlighted 1 to 4 changes, while another 44 images (46.8%) demonstrated 5 or more changes. The most frequent changes observed in the pubic bone were joint surface irregularities (100%), symphyseal sclerosis (93.6%), pubic bone swelling (56.3%), parasymphyseal high-intensity line (55.3%), fatty infiltration in bone marrow (38.3%), and adductor tendinopathy (34%). When comparing the prevalence of different changes in the dominant and nondominant limbs, no statistically significant differences were found. In adult professional soccer players with no prior groin pain complaints in recent history (12 months), asymptomatic changes are extremely common in the pubic joint and adjacent areas, including those that are very likely to be considered the main cause of pain when investigated in soccer players with groin pain. None of these changes were associated with limb dominance.

Prominent Bone Marrow Infiltration in the Appendicular Skeleton in a B-cell Acute Lymphoblastic Leukemia Patient Demonstrated by FDG PET-MRI.

Leukemia spread in the bone marrow typically is greater in the axial skeleton than in the appendicular skeleton. We report an unusual pattern of FDG-avid bone marrow infiltration that is more prominent in the appendicular skeleton than the axial skeleton in a pediatric patient with B-cell acute lymphoblastic leukemia.

Waldenstrom's Macroglobulinemia: A Case Report

Waldenström's macroglobulinemia (WM) is a rare, slow-growing hematologic malignancy marked by elevated levels of monoclonal immunoglobulin M (IgM) and bone marrow infiltration by lymphoplasmacytic cells. This case details a 72-year-old man who, during a pre-anesthetic consultation for lumbar spinal stenosis surgery, presented with neurological symptoms, fatigue, and headaches. Examination revealed pallor, and laboratory tests indicated anemia and an elevated erythrocyte sedimentation rate. Serum protein electrophoresis identified a monoclonal IgM spike, and bone marrow aspiration showed significant infiltration by small lymphoid cells, lymphoplasmacytoid cells, and plasma cells. WM was confirmed, and the patient was treated with dexamethasone, rituximab, and cyclophosphamide, with positive follow-up progress. This case underscores the importance of considering WM in the differential diagnosis for patients with unexplained anemia and elevated IgM levels, highlighting the need for timely diagnosis and treatment to manage potential complications.

Visual assessment and quantitative analysis of dual-energy CT virtual non-calcium in imaging diagnosis of multiple myeloma.

To evaluate the reliability and diagnostic performance of dual-energy CT virtual non-calcium imaging in diagnosing bone marrow infiltration in multiple myeloma. Seventy-two patients with multiple myeloma and ten controls were recruited. Patients received dual-energy CT and MRI while controls underwent dual-energy CT only, covering the cervical, thoracic, and lumbar spine and the pelvis. Virtual non-calcium images were compared with magnetic resonance images for confirmation and pattern classification. Fleiss Kappa analysis assessed consistency between virtual non-calcium and MRI classifications. Inter-observer agreement for virtual non-calcium and CT attenuation values was evaluated using Bland-Altman analysis. Diagnostic performances across various sites were evaluated using analysis of variance and receiver operating characteristic curve analysis. Dual-energy CT achieved higher consistency in classifying bone marrow infiltration in multiple myeloma than did MRI (kappa = 0.944). In the overall analysis, the mean virtual non-calcium attenuation values in the bone marrow infiltration group (- 28.3 HU; 95% confidence interval (CI), - 32.1, - 24.6) were higher than those in the non-bone marrow infiltration (- 97.5 HU; 95% CI, - 104.7, - 90.3) and control (- 89.1 HU; 95% CI, - 95.1, - 83.1; F = 172.027, P < 0.001) groups. The optimal cutoff values for virtual non-calcium attenuation varied across the overall (- 42.2 HU), cervical spine (- 21.9 HU), thoracic spine (- 42.8 HU), lumbar spine (- 56.9 HU), and pelvis (- 66.3 HU). Dual-energy CT virtual non-calcium imaging and MRI exhibited good consistency in categorising bone marrow infiltration patterns in multiple myeloma. Different virtual non-calcium attenuation value cutoffs should be used to diagnose bone marrow infiltration in various body regions.

Linfoma não Hodgkin da Zona Marginal Extranodal Tipo MALT com Acometimento da Coluna Torácica: revisão Sistemática da Literatura e Relato de Caso em um Hospital Universitário no Brasil

Background: Primary bone lymphomas are rare, accounting for less than 1% of non-Hodgkin's lymphomas (NHL). Extranodal marginal zone non-Hodgkin lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the vertebral spine is extremely rare, with only seven cases reported. Methodology: A systematic literature review was conducted on cases from 2012 to 2022 of extranodal marginal zone MALT lymphoma involving the vertebral spine and associated with spinal cord compression. Additionally, a case report from a university hospital in Rio de Janeiro is described. The study was approved by the Research Ethics Committee (approval number: 5.818.416). Searches were performed in SciELO, PubMed, and LILACS databases, using the Health Sciences Descriptors: ("Vertebral Body" OR Spine) AND ("Lymphoma B-Cell Marginal Zone" OR "MALT Lymphoma" OR "Lymphoma of Mucosa Associated Lymphoid Tissue" OR "Mucosa Associated Lymphoid Tissue Lymphoma"). Articles with full texts available in English or Portuguese were selected. Case Description: A 56-year-old female presented with right-sided back pain, progressing to right flank irradiation, lower limb weakness (LLLL), and constitutional symptoms. MRI revealed a solid extradural mass occupying two-thirds of the vertebral canal's diameter, displacing and compressing the dorsal cord to the left. A bone marrow biopsy confirmed infiltration. Laminectomy was performed, and histopathology identified stage IVB extranodal marginal zone MALT lymphoma. Adjuvant chemotherapy led to complete remission. Results and Discussion: The literature review uncovered two relevant case reports. The thoracic spine was the most commonly affected region, and LLLL weakness was the most frequent symptom, with normal laboratory results. Treatment typically involved surgical tumor removal combined with radiotherapy or chemotherapy. Recurrence occurred in both cases, but follow-up showed no evidence of disease. The clinical presentation and exam findings of the current patient were similar to those in the literature, though with bone marrow infiltration. Treatment was consistent with cases in the review, with no recurrence to date. Conclusion: This case represents an uncommon manifestation of primary extranodal marginal zone MALT lymphoma with spinal cord compression, distinguished by bone marrow infiltration—a feature not previously reported in the two cases found in the literature. The case may be considered within the same group of cases reviewed.

8194 Extramedullary Hematopoiesis Involving Bilateral Adrenal Glands In A Patient With Sickle Cell Anemia

Abstract Disclosure: V.T. Pham: None. L.N. Sendos: None. Title: Extramedullary hematopoiesis involving bilateral adrenal glands in a patient with sickle cell anemia Background: Extramedullary hematopoiesis refers to blood cell production occurring outside the bone marrow. It is a reactive process caused by inadequate production or excessive destruction of blood cells typically seen in patients with hereditary anemias or infiltrative bone marrow disorders. Extramedullary hematopoiesis usually occurs in the spleen, liver and lymph nodes, but it can also very rarely arise from the adrenal glands. Case Presentation:We present a case of a 42-year-old male with a history of sickle cell anemia who presented with chest pain and shortness of breath and had a chest CT angiography which incidentally showed a 5.6 x 3.8 cm left adrenal mass and a 2.9 x 2.1 cm right adrenal mass. Further evaluation with an MRI abdomen with and without contrast revealed a 5.5 cm lobulated left adrenal mass with patchy areas of microscopic fat and faint delayed heterogeneous enhancement as well as a 2.2 cm right adrenal nodule. The nodules were described as markedly T2 hypointense with heterogeneous T1 hyperintense/isointense signal on MRI with a broad differential diagnosis including extramedullary hematopoiesis in bilateral adrenal glands, lipid poor adenoma or neoplasm. Regarding his sickle cell disease history, the patient was diagnosed as an infant and had very rare episodes of sickle cell pain crisis as a child. However, once he entered adulthood, he began to have multiple episodes of sickle cell pain crisis requiring hospitalizations and transfusions. On further review of patient’s prior imaging scans during these previous hospitalizations, he was first noted to have bilateral sub centimeter adrenal nodules on a CT Abdomen without contrast done almost a decade prior to his current presentation. We ordered biochemical evaluation which did not show any evidence of adrenal hormonal hypersecretion. His case was discussed at our multidisciplinary conference with the radiology and surgery team and it was concluded that the imaging characteristics were most consistent with extramedullary hematopoiesis in the setting of bilateral adrenal gland involvement and patient’s history of sickle cell anemia. Therefore, no immediate surgical resection was recommended. Given the size of the left adrenal mass being greater than 4 cm in size, we advised follow-up imaging for surveillance. Discussion:There has been a rise in detection of adrenal incidentalomas due to the increased use of advanced diagnostic imaging in healthcare settings. When patients with hematologic diseases are found to have adrenal incidentalomas, it is important to consider extramedullary hematopoiesis in the differential diagnosis to avoid unnecessary invasive procedures and surgeries. Presentation: 6/2/2024

Efficacy and safety of CAR-T therapy targeting CLL1 in patients with extramedullary diseases of acute myeloid leukemia

BackgroundsThe incidence of extramedullary diseases (EMDs) in patients diagnosed with acute myeloid leukemia (AML) is approximately 10–20%. These patients exhibit a significantly distinct etiology, therapeutic response, and prognosis compared to patients without EMDs. CLL1 CAR-T therapy has been demonstrated satisfactory efficacy and safety in the treatment of refractory and relapsed AML patients. However, concerns have been raised regarding the potential impact of extramedullary niduses on the effectiveness of CLL1 CAR-T therapy.MethodsA total of 47 patients were enrolled in this study, including 27 patients with isolated AML tumor bone marrow infiltration and 20 patients with both extramedullary and bone marrow infiltration of AML. CLL1 CAR-T cells were manufactured and subjected to rigorous quality control in the hematology laboratory of Tianjin First Central Hospital. The efficacy and adverse reactions were assessed following CAR-T cell infusion, while expansion of CAR-T cells, levels of cytokines releasing, and other indicators were closely monitored.ResultsAmong the 20 patients with EMDs and the 27 individuals without EMDs, complete remission in bone marrow was achieved by 65.00% and 81.48% of patients, respectively. Meanwhile, among the patients with EMDs, 55.00% achieved complete remission while 10.00% achieved partial remission when assessing the efficacy of CLL1 CAR-T cells against extramedullary niduses. Although the overall survival, progression-free survival, and duration of remission period appeared to be shorter for patients with EMDs compared to those without EMDs, this difference did not reach statistical significance. The incidence rates of complications were comparable between both groups. Meanwhile, there were no significant differences observed in the levels of CAR-T cell expansion and accompanying cytokines release between patients with and without EMDs.ConclusionsOur study findings have demonstrated the efficacy of CLL1 CAR-T therapy in the treatment of AML patients with EMDs, while also indicating manageable occurrence rates of complications within a tolerable range. The CLL1 CAR-T therapy, serving as an ideal strategy for AML patients irrespective of the presence of EMDs, effectively ameliorates the conditions of AML patients and provides them with an opportunity to undergo curative hematopoietic stem cell transplantation while significantly enhancing their prognosis.

Prognostic impact of concordant and discordant bone marrow involvement on diffuse large B-cell lymphoma.

In diffuse large B-cell lymphoma (DLBCL), bone marrow (BM) involvement includes two types that are concordant involvement and discordant involvement. It has been reported that concordant BM involvement has a worse prognosis than discordant involvement in previous studies. However, the prognostic effects of concordant or discordant BM involvement on DLBCL still need further research. In this work, DLBCL cases with BM involvement were collected and analyzed to better reflect the prognostic implications of concordant and discordant BM involvement. We reviewed the cases with newly diagnosed DLBCL and BM involvement from April 2018 to April 2022 in Northern Jiangsu People's Hospital. Overall survival (OS) and progression-free survival (PFS) were accessed by the Kaplan-Meier method and compared between groups by the log-rank test. A multivariate regression analysis based on Cox proportional hazard model was used to test the independent effect of each variable on survival. In total, 32 patients were included and 15 (46.9%) patients had concordant BM involvement and 17 (53.1%) patients had discordant BM involvement. Compared with the discordant group, the concordant group tended to be older and had elevated lactate dehydrogenase level. The outcome of patients with concordant BM involvement was worse than the discordant subset, including OS (P=0.04) and PFS (P=0.03). Furthermore, the discordant BM involvement was excluded to acquire a BM-adjusted International Prognostic Index (IPI) score. The significance of BM-adjusted IPI scores to predict OS was improved greatly compared with the previous IPI scores (P=0.053 vs. P=0.16). Multivariate analysis showed that the BM-adjusted IPI was an independent predictor for OS [hazard ratio =3.406; 95% confidence interval (CI): 1.145-10.127; P=0.03]. These results highlight the requirement for identifying BM infiltration type accurately and then adjusting the IPI score by excluding discordant BM involvement since concordant involvement can partly predict a poor prognosis of DLBCL with BM involvement other than discordant involvement.

Outcome of radiotherapy for metastatic neuroblastoma

Background. Neuroblastoma (NB) is a prevalent solid extracranial tumor that primarily affects children. It is the third most common type of cancer in children, following leukemia and brain tumors. Aim. The study aimed to discuss the clinical outcomes after adjuvant radiotherapy to the primary site in case of metastatic NB after good response to chemotherapy. Methods. A retrospective clinical-dosimetric study of 25 patients metastatic NB treated with radiotherapy at Baghdad Radiotherapy and Nuclear Medicine Center, at Baghdad Medical City Complex, Baghdad, Iraq. Data collection begin from December 2023 and March 2024. Data were collected retrospectively with review of records. The following variables were studied: sex, age, date of diagnosis, site of primary tumor, site of metastasis, chemotherapy, surgery, RT, RT sites, doses of RT, fractions of RT, recurrence sites, date of relapse and survival outcome for each patient. Follow-up period include look up to metastasis, site of metastasis, recurrence, site of recurrence and survival rates. Results. In relation to sex, males (14, 56%) were more than females (11, 44%). The mean age of NB cases was 45.64±17.6 months. In NB, suprarenal masses were the most common site of primary in 21 (84%) of patients. The most common site of metastasis of NB was bone marrow in 12 (48). The multi sites of recurrence was the commonest presentation in 48%. The relapse-free survival (RFS) was 22.38 months. 5 out of 25 patients were alive whereas 20 (80%) of cases were dead. The median follow-up time was 6 years, and the OS of NB in this study after optimal treatment was 2.46 years (95%CI= 1.705-3.21) for survivors. The MS was 4.84 years. The OS was 6 yrs for those diagnosed at 2017, 2 yrs for those diagnosed at 2018, 1.5 yrs for those diagnosed at 2019, 1.75 yrs for those diagnosed at 2020, 3 yrs for those diagnosed at 2021 and 1.5 yrs for those diagnosed at 2022. There was a significant difference among doses (Log Rank (Mantel-Cox)= 11.425, p=0.044). Conclusions. This study is the first study in Iraq that examines the clinical results of radiotherapy on the primary site in cases of metastatic neuroblastoma following induction chemotherapy. The suprarenal masses of neuroblastoma are the most often occurring main site. The primary sites of metastases for neuroblastoma (NB) are the bone marrow and bones. Timely detection and proactive treatment of NB can improve overall results. Reoccurrence of skeletal issues and the infiltration of bone marrow are frequently observed. There were no significant differences observed in terms of relapse-free survival and overall survival based on factors such as sex, age, location of the main tumor, chemotherapy, radiation treatment, surgery, and radiation therapy dosages.

Metachronous Bilateral Adrenal Neuroblastoma: A Case Report and Literature Review.

A baby presented with a large right adrenal mass, multiple hepatic lesions and diffuse bone marrow infiltration when she was just over 1 month old. After needle biopsy and a histologic definition of neuroblastoma, she underwent chemotherapy and a subsequent complete resection. Three years after diagnosis, a large left adrenal localized mass was detected. The patient underwent complete surgical excision, and a diagnosis of poorly differentiated neuroblastoma with multiple lymph nodes involvement was defined. Adjuvant chemotherapy was initiated. To our knowledge, it is the first case report of metachronous bilateral adrenal neuroblastomas harboring completely different genetic expression profiles.

A new digital droplet PCR method for looking at epigenetics in diffuse large B-cell lymphomas: The role of BMI1, EZH2, and USP22 genes.

Epigenetics has been shown to be relevant in oncology: BMI1 overexpression has been reported in leukemias, EZH2 mutations have been found in follicular lymphoma, and USP22 seems to stabilize BMI1 protein. In this study, we measured the expression of BMI1, EZH2, and USP22 in lymph nodes from 56 diffuse large B-cell lymphoma (DLBCL) patients. A new multiplex digital droplet PCR (ddPCR) has been set up to measure the expression of 4 genes (BMI1, EZH2, USP22, and GAPDH) in the same reaction on RNA extracted from paraffin-embedded tissues. The specificity of ddPCR was confirmed by a 100% alignment on the BLAST platform and its repeatability demonstrated by duplicates. A strict correlation between expression of BMI1 and EZH2 and BMI1 and USP22 has been found, and high expression of these genes was correlated with extra-nodal lymphomas. Progression-free survival (PFS) and overall survival (OS) were conditioned by IPI, bone marrow infiltration, and the complete response achievement. High levels of BMI1 and USP22 did not condition the response to therapy, but impaired the PFS, especially for patients defined at "high risk" based on the cell of origin (no germinal center [GCB]), high BCL2 expression, and IPI 3-5. In this subgroup, the probability of relapse/progression was twice higher than that of patients carrying low BMI1 and USP22 levels. High expression of BMI1 and of USP22 might be a poor prognostic factor in DLBCL, and might represent the target for novel inhibitors.

Епідеміологічні дані, етіологія, патогенез, фактори ризику, клінічні прояви, сучасні методи діагностики і лікування, прогнозування перебігу Неходжкінських лімфом (огляд літератури)

Non-Hodgkin lymphoma (NHL) is a group of malignant diseases characterized by clonal proliferation of lymphoid cells corresponding to different stages of differentiation of normal B- and T- lymphocytes or natural killer (NK) cells. NHL is histopathologically and clinically diverse and divided into two groups: B-cell lymphomas and T-cell lymphomas, and subtypes: indolent (slow) and aggressive, classic and extranodal. The etiology of NHL is environmental, infectious, immunological, iatrogenic and genetic factors. The pathogenesis of NHL consists in: 1) translocations of oncogenes; 2) cytogenetic aberrations and mutations of tumor suppressor genes. Clinical manifestations of NHL: 1) lymphadenopathy; 2) symptoms of the presence of an extranodal tumor (abdominal pain; jaundice; shortness of breath and/or pleural effusion; bleeding, symptoms of gastrointestinal obstruction; symptoms associated with infiltration by lymphoma cells of the skin, thyroid gland, salivary glands, etc.; neurological symptoms of central and/or peripheral origin); 3) symptoms of bone marrow infiltration; 4) general symptoms (fever, night sweats, weight loss, fatigue, loss of appetite). Diagnosis of NHL involves: 1) auxiliary research (histological, immunohistochemical, cytogenetic and molecular, use of more specific monoclonal antibodies, immunophenotypic diagnosis, gene sequencing); 2) diagnostic tactics (estimation of stage and determination of prognostic factors according to IPI); 3) differential diagnosis (covers other causes of symptoms). The choice of treatment program for NHL depends on the type of lymphoma and the patient's condition. The main methods of treatment: wait and watch; monotherapy with alkylating drugs; RT; combined РCT; combined РCT with the use of purine analogs; therapy with monoclonal antibodies; PCT+monoclonal antibodies; HDCT+THSC. Survival prognosis for NHL depends on the origin of the tumor and its stage.

Direct comparison of bone marrow biopsy and PET/CT for the detection of bone marrow infiltration in patients with non-Hodgkin lymphoma: a meta-analysis.

The diagnostic utility of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) compared to bone marrow biopsy (BMB) in patients with non-Hodgkin lymphoma (NHL) remained to be confirmed. This study aimed to compare BMB and PET/CT for bone marrow infiltration (BMI) in patients with NHL. PubMed, Embase, and the Cochrane library were searched for papers published up to October 2021. The outcomes were the true positive and negative and false positive and negative rates for BMB and PET/CT. The summarized sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratios (DOR) were calculated. Thirteen studies with a total of 2396 patients were included. Significant differences are observed between BMB and PET/CT for sensitivity (relative ratio: 0.749; 95% CI: 0.586-0.956; P=0.020) and NLR (relative ratio: 1.839; 95% CI: 1.106-3.058; P=0.019), but not for specificity (P=0.819), PLR (P=0.802), and DOR (P=0.150). The summary area under the receiver operating characteristic curves for BMB is 0.692 (SE: 0.170) and 0.977 (SE: 0.021) for PET/CT. PET/CT presents a better sensitivity and NLR for the detection of BMI in patients with NHL, whereas no differences are found regarding specificity, PLR, and DOR compared with BMB.

Prognostic significance of diffuse increased fluorine-18-fluorodeoxyglucose (18F-FDG) uptake within the reticuloendothelial system in lymphoma patients.

As constituents of the reticuloendothelial system, the spleen and bone marrow (BM) have been recognized as integral components of the systemic inflammatory response in cancer contexts, thereby serving as predictive indicators for assessing cancer prognosis. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has attained widespread utilization for staging, assessing treatment response, and prognostication in lymphoma patients. Several investigations have proposed that focal increased 18F-FDG uptake in the BM or spleen may correlate with malignant involvement in lymphoma. However, scant data exist regarding the implications of diffuse BM and splenic uptake. This study aimed to explore the relationships between metabolic parameters of the spleen and BM on 18F-FDG PET/CT and inflammatory markers, and to assess their prognostic value in patients with lymphoma. A retrospective analysis was conducted on 118 patients newly diagnosed with malignant lymphoma, who underwent 18F-FDG PET/CT and exhibited diffuse increased splenic or BM uptake in 18F-FDG PET/CT imaging. The mean standardized uptake value (SUV) of the spleen, BM, and liver was calculated. The association between metabolic variables and systemic inflammatory markers was investigated, and the prognostic significance of clinicopathological and PET parameters was assessed using overall survival (OS) and progression-free survival (PFS). A statistically significant correlation was found between the spleen-to-liver SUV ratio (SLR) and inflammatory markers such as C-reactive protein (r=0.264, P=0.007) and platelet-to-lymphocyte ratio (r=0.227, P=0.021). No significant correlation was observed between BM-to-liver SUV ratio (BLR) and hematologic parameters, while concordance analysis revealed a fair agreement between BLR and bone marrow biopsy (BMB) (Cohen's Kappa-κ =0.271, P=0.002). In patients with aggressive non-Hodgkin lymphoma, both SLR [P=0.017, HR 2.715, 95% confidence interval (CI): 0.875-8.428] and BLR (P=0.044, HR 0.795, 95% CI: 0.348-1.813) were significantly linked to OS, while SLR (P=0.019, HR 2.223, 95% CI: 1.139-4.342) emerged as a significant prognostic factor for PFS. This study highlighted that diffuse increased splenic 18F-FDG uptake in lymphoma patients was closely associated with inflammation, whereas diffuse BM uptake was likely attributable to BM infiltration rather than inflammatory changes. Furthermore, both parameters held promise as prognostic indicators for patients with aggressive lymphoma.

Double-hit primary central nervous system lymphoma with histogenetically proven bone marrow infiltration: a case report and a review of the literature.

Double-hit lymphoma (DHL) formerly referred to high-grade B-cell lymphoma with concurrent MYC and BCL2 or BCL6 rearrangements, however, the updated 2022 World Health Organization Classification (5th edition online) excludes those with MYC and BCL 6 rearrangements from the high-grade category. DHL confined to the central nervous system (CNS), known as double-hit primary CNS lymphoma (DH-PCNSL), is rare with poorly understood clinical features. Here, we report a case of a 64-year-old man with multiple brain tumors diagnosed with DH-PCNSL who showed bone marrow (BM) infiltration early in the clinical course. The histological diagnosis was high-grade B-cell lymphoma with MYC and BCL6 rearrangements. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal accumulation except in the CNS. The patient received whole-brain radiotherapy following the failure of high-dose methotrexate. After completion of radiotherapy, the patient developed thrombocytopenia, and BM biopsy showed infiltration of DHL cells, which were not detected by repeated FDG-PET. This is the first report of DH-PCNSL where identical gene rearrangements were confirmed in both the resected CNS tumor and BM tissue. Patients with DH-PCNSL require careful follow-up because they may be at a potential risk of BM infiltration, which may be undetectable by FDG-PET, particularly early in the disease course.

Tuning the B-CLL microenvironment: evidence for BAG3 protein- mediated regulation of stromal fibroblasts activity

The Bcl2-associated athanogene-3 (BAG3) protein, a critical regulator of cellular survival, has been identified as a potential therapeutic target in various malignancies. This study investigates the role of BAG3 within stromal fibroblasts and its interaction with B-cell chronic lymphocytic leukemia (B-CLL) cells. Previous research demonstrated that BAG3 maintains the active state of pancreatic stellate cells (PSCs) and aids pancreatic ductal adenocarcinoma (PDAC) spread via cytokine release. To explore BAG3’s role in bone marrow-derived stromal fibroblasts, BAG3 was silenced in HS-5 cells using siRNA. In co-culture experiments with PBMCs from B-CLL patients, BAG3 silencing in HS-5 cells increased apoptosis and decreased phosphorylation of BTK, AKT, and ERK in B-CLL cells, thus disrupting their pro-survival key signaling pathways. The observation of fibroblast-activated protein (FAP) positive cells in infiltrated bone marrow specimens co-expressing BAG3 further support the involvement of the protein in fibroblast-mediated tumor survival. Additionally, BAG3 appears to support B-CLL survival by modulating cytokine networks, including IL-10 and CXCL12, which are essential for leukemic cell survival and proliferation. A robust correlation between BAG3 expression and the levels of CXCL12 and IL-10 was observed in both co-cultures and patient specimens. These findings point out the need for a more in-depth comprehension of the intricate network of interactions within the tumor microenvironment and provide valuable insights for the selection of new potential therapeutic targets in the medical treatment of CLL.

A 22-Year-Old Man With Headache, Facial Numbness, Diplopia and Left Leg Numbness

We present a 22-year-old male with a subacute course of chin numbness, ophthalmoplegia, headache and left leg numbness in the setting of fever, chills and night sweats. Initial imaging investigations revealed cauda equina enhancement plus an infiltrative process at the basis of the skull associated with extensive bone marrow infiltration and lymphadenopathy elsewhere. We discuss the localization, differential diagnosis, and appropriate investigations for this unique clinical scenario. Important laboratory findings and treatment considerations are reviewed for this unusual final diagnosis.

Simultaneous merkel cell carcinoma and acute myeloid leukaemia: A diagnostic challenge.

Merkel cell carcinoma is a very aggressive primary skin tumour with a high risk of local recurrences and lymphatic and distant metastases. The frequent association between this carcinoma and other skin tumour and lymphoid malignancies, its similar cellular morphology with leukocytes, and limited infiltration in bone marrow constituted a challenging diagnosis. We report an unusual case of an 82-year-old male who simultaneously presented Merkel cell carcinoma and acute myeloid lymphoma. The diagnosis was established through flow cytometry, immunohistochemical studies and next generation sequencing (NGS) analysis. Flow cytometry allowed for the differentiation of the two cell populations in bone marrow aspirate, which was crucial to the diagnosis of Merkel cell carcinoma and acute myeloid leukaemia (AML), after confirmed by immunohistochemistry. AML could be classified based on NGS results. Following diagnosis, the patient received palliative care and died 50days later. immunophenotypic analysis by flow cytometry and Immunohistochemical study was crucial to establish the diagnosis of simultaneous affection of Merkel cell carcinoma and hematologic disorder.