Detection Of Bone Marrow Involvement Research Articles

Diagnosis of bone marrow involvement in angioimmunoblastic T-cell lymphoma should be based on both [18F]FDG-PET/CT and bone marrow biopsy findings

Objective During the initial staging of certain lymphoma subtypes, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) has become an alternative to bone marrow biopsy (BMB) for detecting bone marrow (BM) involvement. However, whether [18F]FDG-PET/CT can accurately detect BM involvement in angioimmunoblastic T-cell lymphoma (AITL) remains unknown. Our study aimed to assess the diagnostic and prognostic capability of [18F]FDG-PET/CT for detecting BM involvement in AITL. Methods: This retrospective study included 84 individuals newly diagnosed with AITL who underwent baseline BMB and [18F]FDG-PET/CT. “BM involvement” was defined as one or both of the following: 1) angioimmunoblastic T-cells detected in the BM; or 2) initially heightened focal uptake having disappeared on follow-up [18F]FDG-PET/CT. The ability of [18F]FDG-PET/CT to detect BM cancerous lesions was respectively analyzed by BM involvement confirmed by BMB or the aforementioned definition as the reference standard. The patients’ clinical characteristics and survival and prognostic outcomes were respectively analyzed. Results Of the 84 participants, five (6.0%) displayed positive BMB and PET/BM results, 17 (20.2%) had BMB-positive but PET/BM-negative results, eight (9.5%) showed BMB-negative but PET/BM-positive outcomes, and 54 (64.3%) displayed negative BMB and PET/BM outcomes. Using pre-defined BM involvement as the reference standard, [18F]FDG-PET/CT exhibited a specificity of 100%, sensitivity of 40%, negative predictive value (NPV) of 75%, and positive predictive value (PPV) of 100%. In contrast, using BMB-detected BM involvement as reference, [18F]FDG-PET/CT exhibited a sensitivity, specificity, PPV, and NPV of 38.5%, 76.1%, 22.7%, and 87.1%, respectively. Among patients with PET/BM-positive and BMB-negative outcomes, 62.5% (5/8) underwent upstaging from III to IV. In 58.8% (10/17) of patients who were initially diagnosed with stage II/III disease based on the [18F]FDG-PET/CT results, repeat BMB resulted in upstaging to IV. PET/BM-negative patients had a higher 3-year progression-free survival rate (38.3% vs. 22.8%, p = 0.018) and 3-year overall survival rate (64.4% vs. 34.6%, p = 0.011) than PET/BM-positive patients. Conclusion In AITL patients, PET/BM-positive results may obviate the necessity for repeat BMB to ascertain confirm BM involvement. PET/BM-negative results do not definitively exclude BM involvement. The combined use of [18F]FDG-PET/CT and BMB can increase the diagnostic accuracy of BM involvement for AITL patients.

A comprehensive review of the role of bone marrow biopsy and PET-CT in the evaluation of bone marrow involvement in adults newly diagnosed with DLBCL.

Diffuse large B cell lymphoma (DLBCL) is one of the most prevalent subtypes of non-Hodgkin lymphoma (NHL) and is known for commonly infiltrating extra-nodal sites. The involvement of the bone marrow by lymphoma cells significantly impacts the staging, treatment, and prognosis among the extra-nodal sites in DLBCL. Bone marrow biopsy has been considered the standard diagnostic procedure for detecting bone marrow involvement. However, advancements in imaging techniques, such as positron emission tomography-computed tomography (PET-CT), have shown an improved ability to detect bone marrow involvement, making the need for bone marrow biopsy debatable. This review aims to emphasize the importance of bone marrow evaluation in adult patients newly diagnosed with DLBCL and suggest an optimal diagnostic approach to identify bone marrow involvement in these patients.

Detection performance and prognostic value of initial bone marrow involvement in diffuse large B-cell lymphoma: a single centre 18F-FDG PET/CT and bone marrow biopsy evaluation study.

Detection of bone marrow involvement (BMI) in diffuse large B-cell lymphoma (DLBCL) typically relies on invasive bone marrow biopsy (BMB) that faces procedure limitations, while 18F-FDG PET/CT imaging offers a noninvasive alternative. The present study assesses the performance of 18F-FDG PET/CT in DLBCL BMI detection, its agreement with BMB, and the impact of BMI on survival outcomes. This retrospective study analyzes baseline 18F-FDG PET/CT and BMB findings in145 stage II-IV DLBCL patients, evaluating both performance of the two diagnostic procedures and the impact of BMI on survival. DLBCL BMI was detected in 38 patients (26.2%) using PET/CT and in 18 patients (12.4%) using BMB. Concordant results were seen in 79.3% of patients, with 20.7% showing discordant results. Combining PET/CT and BMB data, we identified 29.7% of patients with BMI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for detecting DLBCL BMI were 88.4%, 100%, 100%, 95.3%, and 96.5%, respectively, while BMB showed lower sensitivity (41.9%) and NPV (46.8%). The median overall survival (OS) was not reached in any gender subgroup, with 5-year OS rates of 82% (total), 84% (female), and 80% (male) (p = 0.461), while different International Prognostic Index (IPI) groups exhibited varied 5-year OS rates: 94% for low risk (LR), 91% for low-intermediate risk (LIR), 84% for high-intermediate risk (HIR), and 65% for high risk (HR) (p = 0.0027). Bone marrow involvement did not impact OS significantly (p = 0.979). 18F-FDG PET/CT demonstrated superior diagnostic accuracy compared to BMB. While other studies reported poorer overall and BMI 5-year OS in DLBCL, our findings demonstrated favourable survival data.

FDG PET/CT may replace bone marrow biopsy for the evaluation of bone marrow involvement in selected mature T- and natural killer-cell lymphomas: A meta-analysis

PurposeTo systematically determine the role of FDG PET/CT for the diagnosis of bone marrow involvement in mature T- and natural killer (NK)-cell lymphomas. MethodsThe PubMed, Embase and Cochrane Library databases were searched to identify eligible studies. Data extraction and quality assessment were independently conducted. Then, pooled diagnostic performance with the 95 % confidence interval (CI) was calculated and further analyzed based on different interpretation criteria, tumor type and stage. ResultsFifteen studies were eventually included for quantitative analysis. Overall, the methodological quality of included studies was acceptable. For detecting bone marrow involvement, FDG PET/CT achieved a poor sensitivity of 0.62 (95 % CI, 0.48–0.71) and a reasonable specificity of 0.92 (95 % CI, 0.87–0.96). Similar performance was observed for the specific type of extranodal NK/T‐cell lymphoma (ENKTCL). In early-stage patients revealed by PET/CT, extremely small proportion (2/777) showed positive bone marrow biopsy, especially for the specific type of ENKTCL, whereas in advanced-stage patients, the specificity of FDG PET/CT dropped to 0.77 (95 % CI, 0.72–0.82). Regarding the interpretation, both diffuse and focal increased uptake patterns as positivity may result in increased sensitivity but decreased specificity compared with focal pattern alone as positivity. ConclusionsFDG PET/CT demonstrated excellent negative predictive value for detecting marrow involvement in early-stage patients with mature T- and NK-cell lymphomas, especially the ENKTCL. Conversely, FDG PET/CT showed poor performance for the diagnosis of bone marrow involvement in advanced-stage patients.

The Role of FDG- PET/CT in Detecting Bone Marrow Involvement in Childhood Solid Tumors.

To compare the results of 18F-Fluorodeoxy positron emission tomography/computed tomography (18 F-FDG-PET/CT) and bone marrow biopsy (BMB) procedures in the initial evaluation of bone marrow involvement (BMI) in pediatric solid tumors. We conducted a retrospective analysis of newly diagnosed pediatric cases with lymphoma, neuroblastoma, Ewing sarcoma, rhabdomyosarcoma. Each case underwent both PET-CT imaging and BMB. Presence of tumor infiltration in BMB specimens and/or positive FDG-PET/CT findings indicate as BMI were regarded as true positive results. Sixty-four patients were included in the study. BMI was detected in 23/64 (36%) patients, FDG-PET/CT imaging and BMB results were concordant in 54/64 patients. In 9/64 patients the finding was FDG-PET/CT (+), BMB (-) indicating a false negative BMB result. In only 1/64 patients FDG- PET/CT (-), BMB (+), indicating a false negative FDG-PET/CT result. In the whole patient group, the sensitivity, specificity, positive predictive value and negative predictive value of PET/CT and BMB in detecting bone marrow involvement were 95.6%, 100%, 100% and 97.6% and 60.8 %, 100%, 100% and 82%, respectively. PET/CT has a high sensitivity and specificity for the assessing marrow involvement in pediatric solid tumors. We believe that PET/CT imaging should be performed as the first step in diagnostic staging, and BMB may not be necessary in every patient, only in patients with suspicious PET/CT results for bone marrow involvement. Additionally, for a more precise determination of bone marrow involvement, it is reasonable to perform BMB from FDG-retaining areas, using PET/CT as a guide tool.

Assessment of Bone Marrow Involvement in Extranodal NK/T-Cell Lymphoma: Positron Emission Tomography versus Bone Marrow Biopsy, and the Significance of Minimal Involvement by EBV+ Cells (KROG 18-09).

This study aims to investigate the diagnostic significance of positron emission tomography/computed tomography (PET/CT) in assessing bone marrow (BM) involvement through a comparison of PET/CT findings with BM biopsy in extranodal natural killer/T-cell lymphoma. The medical records of 193 patients were retrospectively reviewed. Patients were categorized as having early-stage (PET-ES) or advanced-stage (PET-AS) disease based on PET/CT results. The BM involvement was classified into three groups according to BM biopsy: gross BM involvement, minimal BM involvement (defined as the presence of a limited number of Epstein-Barr virus-positive cells in BM), and no involvement. Calculations of the accuracy of PET/CT in detecting BM involvement and analysis of the clinical outcomes (progression-free survival [PFS] and overall survival [OS]) according to the BM biopsy status were performed. PET/CT exhibited a sensitivity of 64.7% and a specificity of 96.0% in detecting gross BM involvement. For detecting any (both gross and minimal) BM involvement, the sensitivity was 30.4%, while the specificity was 99.0%. Only one patient (0.7%) demonstrated gross BM involvement among the PET-ES group. Survival outcomes of the PET-ES group with minimal BM involvement (3-year PFS, 55.6%; OS, 77.0%) were closer to those of the PET-ES group with no BM involvement (3-year PFS, 62.2%; OS, 80.6%) than to those of the PET-AS group (3-year PFS, 20.1%; OS, 29.9%). PET/CT exhibits high specificity, but moderate and low sensitivity in detecting gross and minimal BM involvement, respectively. The clinical significance of minimal BM involvement for patients in the PET-ES group may be limited.

Positron emission tomography to detect bone marrow involvement for patients with follicular lymphoma: a systematic review and meta-analysis.

Detection of bone marrow involvement (BMI) for patients with follicular lymphoma (FL) is of great significance for staging and treatment. The clinical value of positron emission tomography/computed tomography (PET/CT) in assessing BMI is still under debate and investigation. PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify studies evaluating PET/CT in detecting BMI in FL patients. Data extraction and quality evaluation were independently conducted by two reviewers, and nine eligible studies were selected as final quantitative analysis. Nine studies comprising 1119 FL patients were included. The pooled sensitivity was 0.67 (95% CI, 0.38-0.87), and the pooled specificity was 0.82 (95% CI, 0.75-0.87). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 3.7 (95% CI, 2.1-6.3), 0.4 (95% CI, 0.18-0.91), and 9 (95% CI, 2-33), respectively. The area under the curve of PET/CT to detect BMI in FL patients was 0.83 (95% CI, 0.8-0.86). Current evidence suggests that PET/CT cannot replace bone marrow biopsy to detect BMI, but it is still of partial clinical significance for the prognosis of patients with follicular lymphoma.

Diagnostic performance of integrated whole-body 18F-FDG PET/MRI for detecting bone marrow involvement in indolent lymphoma: Comparison with 18F-FDG PET or MRI alone.

To investigate the diagnostic performance of integrated whole-body 18F-FDG PET/MRI for detecting bone marrow involvement (BMI) in indolent lymphoma compared with 18F-FDG PET or MRI alone. Patients with treatment-naive indolent lymphoma who underwent integrated whole-body 18F-FDG PET/MRI and bone marrow biopsy (BMB) were prospectively enrolled. Agreement between PET, MRI, PET/MRI, BMB, and the reference standard was assessed using kappa statistics. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of each method were calculated. A receiver operating characteristic (ROC) curve was used to determine the area under the curve (AUC). AUCs of PET, MRI, PET/MRI, and BMB were compared using the DeLong test. Fifty-five patients (24 males and 31 females; mean age: 51.1 ± 10.1 years) were included in this study. Of these 55 patients, 19 (34.5%) had BMI. Two patients were upstaged as extra bone marrow lesions were detected via PET/MRI. 97.1% (33/34) of participants were confirmed as BMB-negative in the PET-/MRI-group. PET/MRI (parallel test) and BMB showed excellent agreement with the reference standard (k = 0.843, 0.918), whereas PET and MRI showed moderate agreement (k = 0.554, 0.577). The sensitivity, specificity, accuracy, PPV, and NPV for identifying BMI in indolent lymphoma were 52.6%, 97.2%, 81.8%, 90.9%, and 79.5%, respectively, for PET; 63.2%, 91.7%, 81.8%, 80.0%, and 82.5%, respectively, for MRI; 89.5%, 100%, 96.4%, 100%, and 94.7%, respectively, for BMB; and 94.7%, 91.7%, 92.7%, 85.7%, and 97.1%, respectively, for PET/MRI (parallel test). According to ROC analysis, the AUCs of PET, MRI, BMB, and PET/MRI (parallel test) for detecting BMI in indolent lymphomas were 0.749, 0.774, 0.947, and 0.932, respectively. The DeLong test showed significant differences between the AUCs of PET/MRI (parallel test) and those of PET (P = 0.003) and MRI (P = 0.004). Regarding histologic subtypes, the diagnostic performance of PET/MRI for detecting BMI in small lymphocytic lymphoma was lower than that in follicular lymphoma, which was in turn lower than that in marginal zone lymphoma. Integrated whole-body 18F-FDG PET/MRI showed excellent sensitivity and accuracy for detecting BMI in indolent lymphoma compared with 18F-FDG PET or MRI alone, demonstrating that 18F-FDG PET/MRI is an optimal method and a reliable alternative to BMB. ClinicalTrials.gov (NCT05004961 and NCT05390632).

The evaluation of minimal disseminated disease in the bone marrow of children with Burkitt lymphoma using next generation sequencing

The effectiveness of treatment for children with B-cell non-Hodgkin lymphomas (B-NHL) has reached 85–90% after the introduction of modern risk-adapted treatment regimens that involve risk group stratification based on tumor stage. Bone marrow involvement is traditionally evaluated using quantitative morphological analysis of tumor cells which has, however, a lower sensitivity compared to molecular genetic methods. In our study, we used next generation sequencing (NGS) to identify tumor-specific V-(D)/J-rearrangements of immunoglobulin genes which can be used as a marker for the evaluation of minimal disseminated disease (MDD) in children with B-NHL. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Here we demonstrated that NGS allows detection of bone marrow involvement at a sensitivity of 10–6 in patients with Burkitt lymphoma, in whom standard morphological analysis failed to reveal the presence of tumor cells. The detection of molecular MDD can improve tumor staging and risk stratification in children with B-cell non-Hodgkin lymphomas.

The Diagnostic Accuracy of Bone Marrow Biopsy Versus PET/CT Scan in Identifying Bone Marrow Involvement in Diffuse Large B Cell Lymphoma Patients at a Cancer Hospital.

Background It is of great importance to assess bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL)for staging, prognostic, and therapeutic purposes.The gold standard method used for the identification of bone marrow involvement isbone marrow biopsy (BMB), but it has certain drawbacks. In recent years, positron emission tomography/computed tomography (PET/CT) has become ahighly effective method in the diagnosis and staging of lymphoma. Objective The objective of this study is to estimate the diagnostic accuracy of PET/CT in identifying bone marrow involvement in DLBCL patients in a cancer care hospital in Lahore, using BMB as a reference standard. Methods This descriptive cross-sectional study was conducted at the Department ofPathology of Shaukat KhanumMemorial Cancer Hospital and Research Centre (SKMCH&RC) from January 1, 2013, to December 31, 2018. A retrospective dataof 146 patients fulfilling the inclusion and exclusion criteria was retrieved from the hospital information system (HIS). The inclusion criteria includepatients aged 18-80 years, of either gender, and with a confirmed diagnosis of DLBCL on tissue biopsy. The exclusion criteria includepatients who had startedchemotherapy or radiotherapyfor DLBCL or were using granulocyte colony-stimulatingfactor (G-CSF) prior to their PET/CT scan. All patients underwent PET/CT and BMB, and the diagnostic accuracy of PET/CT was calculated, with BMB taken as the reference standard. Results The mean age of cases was 52.73 ± 16.27 years.There were 95 (65.1%) maleand 51 (34.9%) female cases, with a high male-to-female ratio. In the present study, 32.19% of cases had bone marrow involvement on BMB, and 34.2% of cases had bone marrow involvement on PET/CT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy ofPET/CT were found to be 93.61%, 93.93%, 88%, 96.88%, and 93.84%, respectively. Conclusion It is concluded that PET/CT scan has good sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. So, it is suggested to choose this non-invasive technique because the presence of a disease in extra-medullary space can also be detected and the evaluation of bone marrow in the whole body can be performed. PET/CT scan is an effective imaging modality in the detection of bone marrow involvement in DLBCL patients, and its relative advantages over bone marrow biopsy might conclude this to be a preferred technique.

Predictive value of staging PET/CT to detect bone marrow involvement and early outcomes in marginal zone lymphoma

Predictive value of staging PET/CT to detect bone marrow involvement and early outcomes in marginal zone lymphoma

FDG-PET/CT Provides Clues on Bone Marrow Involvement in Follicular Lymphoma and Carries Important Prognostic Information.

Objectives: To compare the diagnostic efficacy of PET-CT and bone marrow biopsy (BMB) in the detection of bone marrow involvement (BMI) in newly diagnosed patients with follicular lymphoma (FL), as well as their prognostic implications in such patients. Methods: Retrospective analysis was conducted on clinical data from 165 newly diagnosed FL patients. The benefits and drawbacks of PET-CT and BMB in assessing BMI in FL patients were compared and evaluated. Moreover, the prognostic outcomes and factors affecting the survival of FL patients were examined. Results: Among 165 patients, bone marrow involvement (BMI) was diagnosed by PET-CT (PET+) in 54 cases (32.7%), by bone marrow biopsy (BMB+) in 50 cases (30.3%), and by either PET+ or BMB+ in 80 cases (48.5%). PET-CT scans upgraded 32 patients (19.4%) to stage IV, including 1 stage I and 4 stage II cases. Four patients were elevated to stage IV by BMB, all of whom had a previous stage III diagnosis. No patients with previous stages I or II were elevated to stage IV by BMB. The median follow-up time was 6.6 years (range,0-11.0 years). The 5-year OS was 86.7%, and the 5-year PFS was 44.8%. Multivariate analysis revealed that BMI by PET-CT was the only independent predictor of PFS reduction. Regarding OS, grade 3a and BMI by PET-CT were independent predictors of decreased survival. Conclusion: PET-CT enables a thorough evaluation of bone marrow involvement in patients with FL, and BMI identified by PET-CT can have substantially implications for patient prognosis. PET-CT obtains vital data for the diagnosis, treatment, and prognosis of FL patients. By contrast, BMB seldom augments crucial data.

Predictive Value of Staging PET/CT to Detect Bone Marrow Involvement in Marginal Zone Lymphoma (MZL): An Analysis from LEO MZL Working Group

Introduction: Bone marrow (BM) involvement impacts stage and prognosis in lymphoma, remaining an important factor in risk-stratification scores, including the MALT-IPI. PET/CT is routinely implemented in the staging and response assessment of patients with lymphoma. However, FDG avidity to detect marginal zone lymphoma (MZL) remains debatable. In this study we aimed to assess the predictive value of PET/CT to detect BM involvement and survival implications in MZL using prospectively collected data from the Lymphoma Epidemiology of Outcomes (LEO) cohort. Methods: The LEO cohort is a prospective cohort from 8 academic cancer centers in which patients are enrolled within 6 months of lymphoma diagnosis and followed. We extracted baseline data of MZL patients enrolled in the LEO cohort between 5/2015 and 2/2020. BM biopsy was used as a gold standard for BM involvement. In addition, radiology reports were reviewed for PET/CT-suggested BM involvement. Event-free survival (EFS) defined as time from diagnosis to relapse/progression, retreatment, or death due to any cause and overall survival (OS) defined as time from diagnosis to death due to any cause were estimated by Kaplan-Meier. Results: Of 706 MZL patients enrolled in LEO, 311 (44%) with data on BM status by both biopsy and PET/CT were included in the analysis. Patients’ characteristics were median age 64 (range 24-89) years with most <70 years (n=217, 69.8%), non-Hispanic (n=264, 84.9%) white (n=276, 88.7%), without B symptoms (n=246, 79.1%), and normal LDH (n=185, 59.5%). The most common MZL subtype was extranodal (EMZL, n=208, 66.9%) followed by nodal (NMZL, n=61, 19.6%) and splenic (SMZL, n=42, 13.5%). Stage distribution was as follows: early-stage (I-II; n=134, 43.1%), advanced-stage (III-IV; n=159, 51.1%), and unknown (n=18, 5.8%). BM biopsy was positive in 99 (31.8%) and negative in 212 (68.2%) patients. Across all MZL subtypes, biopsy-proven and PET/CT-suggested BM involvement was present in 11.6% (n=36/311), and positive BM biopsy with negative PET/CT was observed in 20.3% (n=63/311) (EMZL=9.6%, n=20/208; NMZL=31.1%, n=19/61; and SMZL=57.1%, n=24/42). For EMZL, 15.9% (n=33) demonstrated pathologically confirmed BM involvement, and among those patients PET/CT was positive in 39.4% (n=13) and negative in 60.6% (n=20). For NMZL, 50.8% (n=31) demonstrated pathologically confirmed BM involvement, and among those patients PET/CT was positive in 38.7% (n=12) and negative in 61.3% (n=19). Most patients (83.3%, n=35) with SMZL demonstrated pathologically confirmed BM involvement, with positive PET/CT in 31.4% (n=11) and negative in 68.6% (n=24). Considering BM result from biopsy as the standard, PET/CT-based sensitivity and specificity in EMZL, NMZL, and SMZL were 39.4% & 98.9%, 38.7% & 100%, and 31.4% & 100%, respectively. PET/CT-based positive and negative predictive values in EMZL, NMZL, and SMZL were 86.7% & 89.6%; 100% & 61.2%; and 100% & 22.6%, respectively. With a median follow up of 35.4 months there were 70 EFS events and 18 OS events across all MZL subtypes. The 2-year EFS and OS were 81.7% (95%CI 76.8-85.7%) and 96.8% (95%CI 93.9-98.3%), respectively. The 2-year EFS and OS by histology were EMZL= 84.7% (95%CI 78.7-89.1%) & 97.2% (95%CI 93.5-98.8%); NMZL= 69.6% (95%CI 56.1-79.6%) & 96.5% (95%CI 86.9-99.1%); and SMZL= 85.6% (95%CI 70.7-93.3%) & 95.2% (95%CI 82.3-98.8%), respectively. Acknowledging the low number of events and unspecific criteria for treatment selection, those patients exhibiting pathological BM involvement (n= 99) did not show significantly different EFS (p=0.097) (EMZL p=0.48; NMZL p=0.68; and SMZL p=0.75, respectively) or OS (p=0.978) (EMZL p=0.46; NMZL=0.53; and SMZL=0.21, respectively) compared to those without BM disease. Conclusions: While PET/CT may be positive in nodal and some extranodal locations, assessment of BM involvement by PET/CT is characterized by a low sensitivity across all MZL subtypes and low negative predictive value in SMZL, underscoring the limitations of current Lugano criteria in staging MZL. With currently relatively limited follow-up, we did not observe significantly different survival based on BM status.

Flow cytometry to detect bone marrow involvement by follicular lymphoma.

High-quality data on bone marrow involvement (BMI) assessed by flow cytometry (FC) in follicular lymphoma (FL) is lacking. We set up a prospective protocol with a 10-color tube and acquisition of 500.000 leukocytes on a Nav flow cytometer for evaluation of BMI in FL by FC. FC was compared with a combination of histopathology and IGH gene rearrangement, which were considered the gold standard. We also compared BMI by FC with PET. Fifty-two patients were included (median 67 years, 54% female). BMI by FC was seen in 35 (67%), with a median involvement of 1.2% (interquartile range: 0.3%-7%) of leukocytes. Comparison with the gold standard revealed two false negatives and two false positives (potentially true involvement undetected by the gold standard). BMI by PET was seen in 14/46 (30%). Immunophenotype of FL in the bone marrow was highly heterogeneous. The most common phenotypic abnormality was dim expression of CD19 (>0.5 log loss in 30% of patients). CD10 was negative in 13 (37%) and incompletely positive (overlap with the negative population) in a further 8 (28%) while entirely positive only in 14 (48%). Other abnormalities (loss of CD20, gain or loss of CD79b, expression of CD43, and substantial loss of CD45) were rare. Computational analysis by means of FlowSOM confirmed the heterogeneous phenotype, with FL from different patients clustering in unrelated metaclusters. BMI by FL was frequent and immunophenotype was heterogeneous. However, this protocol enabled detection of FL in bone marrow in the vast majority of patients with bone marrow involvement by the gold standard.

Diagnostic Accuracy of Positron Emission Tomography-Computed Tomography (PET-CT Scan) In Detecting Bone Marrow Involvement in Patients with Diffuse Large B cell Lymphoma

Objective: To evaluate the diagnostic accuracy of positron emission tomography combined with CT scan (PET-CT Scan) in detecting bone marrow involvement in patients with diffuse large B-cell lymphoma, keeping bone marrow biopsy as gold standard. Methodology: From November 2017 to May 2018, a cross sectional validation study was carried out at the Aga Khan University in Karachi Department of Oncology's Section of Clinical Hematology. The study comprised a total of 112 patients who were identified as having diffuse large B cell lymphoma after a lymph node was implicated was histopathologically examined. All patients had a PET-CT scan and bone marrow biopsy technique as part of the staging workup. With bone marrow biopsy acting as the gold standard, the diagnostic efficacy of a PET-CT scan for identifying bone marrow involvement was evaluated. Results: Of 112 patients, there were 71(63.39%) males and 41(36.61%) females. The mean age was 45.09±17.36 years. The mean duration of diagnosis was 17.19±6.02 days. Through biopsy, bone marrow involvement was identified in 40 (35.7%) cases. Through a PET-CT scan, bone marrow involvement was identified in 47 (41.9%) cases. The PET- CT scan in comparison with bone marrow biopsy for detecting bone marrow involvement in patients with DLBCL had a sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of 95%, 87.7%, 80.85%, 96.92% and 90.18% respectively. Conclusion: PET-CT scan can accurately detect bone marrow involvement in patients with DLBCL so it can be used in most patients instead of invasive bone marrow biopsy procedure for staging of DLBCL patients.

Factors associated with bone marrow involvement in lymphoma staging bone marrow examination: A South African single-centre retrospective study

Background: Accurate detection of bone marrow involvement (BMI) in lymphoma is important as it signifies stage 4 disease. Staging bone marrow examination (BME), therefore, influences treatment decisions and prognostication. The prevalence of BMI depends on multiple factors at presentation including lymphoma subtype, age, sex, human immunodeficiency virus (HIV) status and haematological parameters.Aim: To determine risk factors for BMI in lymphoma staging.Setting: The study was conducted in the department of haematological pathology, Tygerberg Hospital, Cape Town, South Africa.Methods: Retrospective cross-sectional descriptive study in adult patients, reviewing BMI and associated parameters, during their initial lymphoma staging procedure between 2016 and 2019.Results: Of a total of 387 lymphoma staging cases that were evaluated, 30.0% of them showed BMI. Diffuse large B-cell lymphoma, Hodgkin lymphoma and high-grade B-cell lymphoma were the most frequent subtypes diagnosed. The highest prevalence of BMI was in low-grade lymphomas. There was a statistically significant association between BMI and advanced age, pancytopenia and bicytopenia (anaemia with leucopenia, anaemia with thrombocytopenia or leucopenia with thrombocytopenia). Bicytopenia and pancytopenia showed high positive predictive values of BMI, respectively, 61.0% and 69.0%. Human immunodeficiency virus positivity (34.6%) was not predictive of BMI across all lymphoma subtypes. Normal blood counts had a high negative predictive value for BMI.Conclusion: BME remains an important part of lymphoma staging with 30.0% of all lymphomas showing BMI.

Utility and prognostic value of PET/CT, bone marrow biopsy and aspirate for detection of bone marrow involvement in diffuse large B-cell lymphoma

Objective: This study aimed to determine the value of bone marrow biopsy (BMB) , bone marrow aspiration (BMA) , and positron emission tomography combined with computed tomography (PET/CT) in bone marrow (BM) involvement and prognosis evaluation in diffuse large B-cell lymphoma (DLBCL) . Methods: The clinical data of patients with DLBCL who underwent PET/CT, BMB, and BMA of the iliac crest were retrospectively analyzed in Peking Union Medical College Hospital from January 2015 to November 2017. The BM involvement on PET/CT was defined as the ratio of maximal standardized uptake values of iliac crest BM to liver parenchyma intensity ≥1. Results: A total of 76 patients without liver involvement were enrolled, there were 32 males, and the median age was 53 (17-79) . Moreover, 16 patients (21.1%) had BM involvement on PET/CT, 12 (15.8%) had positive BMB, and 13 (17.1%) had positive BMA. Excellent correlation between BMA and BMB (κ=0.943) was found, including good correlation between PET/CT and BMB/BMA (κ=0.763 and 0.776, respectively) . After a median follow-up of 52 (0-82) months, BM involvement by BMB (P=0.037) and BMA (P=0.007) were poor prognostic factors for overall survival, positive PET/CT had no significant effect on prognosis (P>0.05) . Conclusion: PET/CT, BMB, and BMA are effective methods to detect BM involvement with great concordance. However, iliac crest BMB and BMA showed superior performance in prognosis evaluation.

Modern imaging techniques for monitoring patients with multiple myeloma.

Bone disease is a serious problem for many patients, often causing pathological bone fractures. A spinal collapse is a condition that affects the quality of life. It is the most frequent feature of multiple myeloma (MM), used in establishing the diagnosis and the need to start treatment. Because of these complications, imaging plays a vital role in the diagnosis and workup of myeloma patients. For many years, conventional radiography has been considered the gold standard for detecting bone lesions. The main reasons are the wide availability, low cost, the relatively low radiation dose and the ability of this imaging method to cover the entire bone system. Because of its incapacity to evaluate the response to therapy, more sophisticated techniques such as whole-body low-dose computed tomography (WBLDCT), whole-body magnetic resonance imaging, and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) are used. In this review, some of the advantages, indications and applications of the three techniques in managing patients with MM will be discussed. The European Myeloma Network guidelines have recommended WBLDCT as the imaging modality of choice for the initial assessment of MM-related lytic bone lesions. Magnetic resonance imaging is the gold-standard imaging modality for the detection of bone marrow involvement. One of the modern imaging methods and PET/CT can provide valuable prognostic data and is the preferred technique for assessing response to therapy.

Critical Role of Flow Cytometric Immunophenotyping in the Diagnosis, Subtyping, and Staging of T-Cell/NK-Cell Non-Hodgkin's Lymphoma in Real-World Practice: A Study of 232 Cases From a Tertiary Cancer Center in India.

BackgroundT-cell/NK-cell non-Hodgkin’s lymphoma (T/NK-NHL) is an uncommon heterogeneous group of diseases. The current classification of T/NK-NHL is mainly based on histopathology and immunohistochemistry. In practice, however, the lack of unique histopathological patterns, overlapping cytomorphology, immunophenotypic complexity, inadequate panels, and diverse clinical presentations pose a great challenge. Flow cytometric immunophenotyping (FCI) is a gold standard for the diagnosis, subtyping, and monitoring of many hematological neoplasms. However, studies emphasizing the role of FCI in the diagnosis and staging of T/NK-NHL in real-world practice are scarce.MethodsWe included T-cell non-Hodgkin’s lymphoma (T-NHL) patients evaluated for the diagnosis and/or staging of T/NK-NHL using FCI between 2014 and 2020. We studied the utility of FCI in the diagnosis and subtyping of T/NK-NHL and correlated the FCI findings with the results of histopathology/immunohistochemistry. For correlation purposes, patients were categorized under definitive diagnosis and subtyping, inadequate subtyping, inadequate diagnosis, and misdiagnosis based on the findings of each technique.ResultsA total of 232 patients were diagnosed with T/NK-NHL. FCI findings provided definitive diagnoses in 198 patients and subtyping in 187/198 (95.45%) patients. The correlation between FCI and histopathological/immunohistochemistry results (n = 150) demonstrated an agreement on the diagnosis and subtyping in 69/150 (46%) patients. Of the remaining cases, the diagnosis and subtyping were inadequate in 64/150 (42.7%), and 14/150 (9.33%) were misdiagnosed on histopathology/immunohistochemistry results. FCI provided definitive diagnosis and subtyping in 51/64 (79.7%) patients. Among these, 13 patients diagnosed with peripheral T-cell lymphoma not-otherwise-specified were reclassified (angioimmunoblastic T-cell lymphoma (AITL)-11 and prolymphocytic leukemia-2) on FCI. It corrected the diagnosis in 14 patients that were misdiagnosed (6 B-cell NHL (B-NHL), 3 Hodgkin’s lymphoma, 1 acute leukemia, and 1 subcutaneous panniculitis-like T-cell lymphoma) and misclassified (3 T-NHL) on histopathological results. AITL was the commonest T-NHL misclassified on histopathological results. FCI also confirmed the definite involvement in 7/83 (8.4%) and 27/83 (32.5%) bone marrow (BM) samples reported as suspicious and uninvolved, respectively, on histopathological evaluation.ConclusionAITL was the most frequently diagnosed T/NK-NHL in this study. FCI provided a distinct advantage in detecting BM involvement by T/NK-NHL, especially in patients with low-level involvement. Overall, our study concluded that FCI plays a critical role in the diagnosis, subtyping, and staging of T/NK-NHL in real-world practice.

The Diagnostic Value of 18F-FDG PET/CT Bone Marrow Uptake Pattern in Detecting Bone Marrow Involvement in Pediatric Neuroblastoma Patients.

Objectives To explore the diagnostic value of 18F-FDG PET/CT bone marrow uptake pattern (BMUP) in detecting bone marrow involvement (BMI) in pediatric neuroblastoma (NB) patients. Methods Ninety-eight NB patients were enrolled in BMI analysis. Four patterns of bone marrow uptake were categorized based on pretreatment cF-FDG PET/CT images. Some crucial inspection indexes and 18F-FDG PET/CT metabolic parameters were analyzed. The BMUP was divided into BMUP1, BMUP2, BMUP3, and BMUP4. Paired-like homeobox 2b (PHOX2B) of bone marrow and blood, bone marrow biopsy (BMB) result, and 18F-FDG PET/CT were compared to detect BMI. All patients were followed up for at least six months. Results BMUP had excellent consistency among different physicians. Kappa coefficients of two residents and two attending physicians and between the resident and attending physician, were 0.857, 0.891, and 0.845, respectively. The optimal cut-off value of SUVmax-Bone/Liver was 2.08 to diagnose BMI for BMUP3 patients, and the area under curve (AUC) was 0.873. AUC of PHOX2B of bone marrow (PHOX2B of BM), PHOX2B of blood, BMB, and 18F-FDG PET/CT were 0.916, 0.811, 0.806, and 0.904, respectively. There was no significant difference between PHOX2B of BM and PET/CT. Positive predictive value, negative predictive value, sensitivity, and specificity in diagnosis of BMI were 92.9%, 92.9%, 97.0%, and 83.9% for PET/CT and 96.7%, 80.6%, 89.6%, and 93.5% for PHOX2B of BM, respectively. Conclusions BMUP of pretreatment 18F-FDG PET/CT is a simple and practical method, which has a relatively high diagnostic efficiency in detecting BMI and might decrease unnecessary invasive inspections in some pediatric NB patients.