OBJECTIVE: To systematically determine the role of FDG PET/CT for the diagnosis of bone marrow involvement in mature T- and natural killer (NK)-cell lymphomas.
METHODS: The 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.
RESULTS: Fifteen 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.
CONCLUSIONS: FDG 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.

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.

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with an advanced stage; it occurs frequently and affects the lymph nodes, spleen, blood and bone marrow. The synchronous occurrence of MCL bone marrow involvement (MCLBMI) and malignant tumors is extremely rare. To the best of our knowledge, synchronous extensive-stage small cell lung cancer (ES-SCLC) and MCLBMI have not been previously reported. In the present study, a rare case of ES-SCLC with synchronous MCLBMI is reported in a 59-year-old man. The patient received cisplatin, etoposide, dexamethasone and rituximab chemotherapy for the treatment of both malignancies. The follow-up computed tomography scan disclosed regression of the left upper lobe mass and the routine blood test indicated that the platelet count was gradually increasing to normal levels. Following therapy, the patient achieved a partial response. The experience in this case report indicated that the treatment of synchronous SCLC and MCLBMI requires consideration of the respective patient clinical features, biological behavior and cumulative toxicity of the treatment regimens administered for both malignant tumors. The present study demonstrated that thrombocytopenia was not a chemotherapy contraindication, thus providing a new treatment option for this type of patient.

UNASSIGNED: The role of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in evaluating bone marrow (BM) involvement (BMI) among patients with extranodal natural killer/T-cell lymphoma (ENKTL) is poorly understood. This study investigated whether PET/CT could replace bone marrow biopsy (BMB) in treatment-naive ENKTL patients.
UNASSIGNED: Newly diagnosed ENKTL patients (n = 356) who received BMB and PET/CT to evaluate BMI at the time of diagnosis were retrospectively reviewed at West China Hospital between August 2008 and January 2020. The BMI diagnosis was confirmed using BM histology. Clinical characteristics, survival outcomes, and prognostic indicators were summarized and analyzed.
UNASSIGNED: The cohort included 356 cases, of whom 261 were diagnosed with early-stage and 95 with advanced-stage ENKTL by PET/CT before initial treatment. No early-stage patients were identified with BMI by either BMB or PET/CT. Among the advanced-stage patients, 26 were BMB positive, and 12 of 22 patients (54.5%) with positive PET/BM results were also BMB positive. The sensitivity and specificity of PET/CT to detect BMI were 46% and 97%, respectively. The progression-free survival (PFS) and overall survival (OS) of PET/BM-negative patients were markedly longer (p = 0.010 and p = 0.001 for PFS and OS, respectively), which was consistent with the results of the BMB (p = 0.000 for both PFS and OS).
UNASSIGNED: Although 18F-FDG PET/CT showed the potential to replace BMB in the initial staging of early-stage ENKTL patients, baseline PET/CT cannot provide an accurate BMI evaluation for advanced-stage patients. A prospective study is required to confirm the diagnostic performance of BMI identification by PET/CT, along with targeted BMB and MRI for advanced-stage patients.

Bone marrow involvement (BMI) of solid tumors is a special type of distant metastasis. It has an occult onset, atypical clinical and laboratory features, and a high mortality. We present a nasopharyngeal carcinoma case with cervical and axillary lymph nodes, bilateral lung, multiple bone, and bone marrow metastases, who was treated chemotherapy plus targeted therapy under the guidance of a patient-derived tumor xenograft (PDTX) model, followed by maintenance chemotherapy plus immunotherapy. The patient\'s symptoms were relieved after four cycles of chemotherapy plus targeted therapy. His bone marrow biopsy turned negative after 7 months of therapy. In addition, his total peripheral T cells as well as the proportion of CD8+ T cells increased during the course of therapy. The combination of chemotherapy, targeted therapy, and immunotherapy provides an effective antitumor regimen for advanced NPC patients with BMI.

BACKGROUND: Flow cytometry (FC) is a popular method to detect bone marrow (BM) involvement in patients with B-cell non-Hodgkin lymphoma (B-NHL). The majority of screen panels of FC still rely on finding monoclonal B-cells, e.g., B-cells with immunoglobin (Ig) light-chain restriction, which has many limitations. Therefore, exploring new markers is warranted.
METHODS: A total of 52 cases of B-NHL with BM involvement were collected. The median age was 60 years. Out of these 52 cases, 34 were male, and 18 were female. A 10-color FC panel was used to detect the expression of CD54 on lymphoma cells. The expression of CD54 was calculated as the mean fluorescence index ratio (MFIR) and was described as the mean ± standard error of the mean (SEM).
RESULTS: Up to 18/52 (34.62%) of BM specimens abnormally expressed an increased level of CD54, including 1/10 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 9/13 cases of mantle cell lymphoma (MCL), 2/14 cases of follicular lymphoma (FL), 5/9 cases of marginal zone lymphoma (MZL), and 1/3 cases of high-grade B-NHL (HG B-NHL). The expression level of CD54 was significantly increased in MCL cases (53.41 ± 11.04) compared with CLL/SLL cases (11.66 ± 2.79) and FL cases (13.49 ± 2.81). The lowest percentage of CD54-positive B-cells attained 0.13%. In 5/9 cases of MZL and 1/3 cases of HG B-NHL, increased expression of CD54 was the only abnormal immunophenotype detected besides Ig light-chain restriction. No aberrant CD54 expression was identified by FC in lymphoplasmacytic lymphoma (LPL) (0/2) and Burkitt lymphoma (BL) (0/1) cases. Aberrant expression of CD54 was not related to plasma cell differentiation.
CONCLUSIONS: Lymphoma cells, especially in MCL and MZL cases, frequently show increased expression of CD54. Such aberrant expression is not related to plasma cell differentiation. We highly recommend adding CD54 to the FC screening panel to detect BM involvement in patients with B-NHL.

BACKGROUND: Flow cytometry plays a key role in detecting bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL). To improve its detection sensitivity, we need to explore novel markers. In this study, we detected the expression CD54 on lymphoma cells in BM specimens from DLBCL patients and clarified its diagnostic significance in BM involvement by DLBCL.
METHODS: We collected BM specimens from 76 patients with DLBCL (germinal center B-cell (GCB) = 25, non-GCB = 51) and 10 control patients without lymphoma. We detected and compared the expression of CD54 on lymphoma cells and normal mature B cells by using 10-color panels.
RESULTS: Normal plasma cells expressed a higher level of CD54 as compared with hematogones (p < 0.05) and normal mature B cells (p < 0.05). Among 76 patients, 23 of them (GCB = 12, non-GCB = 11) had BM involvement. Lymphoma B cells from 12 cases (GBC = 4, non-GCB = 8) expressed a higher level of CD54 compared to normal mature B cells (p < 0.05). Additionally, lymphoma cells of the non-GCB subtype frequently expressed a higher level of CD54 in comparison to the GCB subtype (p < 0.05). And the high expression of CD54 was not related to plasmacytoid differentiation.
CONCLUSIONS: Aberrant expression of CD54 on lymphoma cells is frequently seen in patients\' BM specimens involved by DLBCL, especially in the non-GCB subtype. CD54 could be used as a new marker to gate on lymphoma cells and improve the detection sensitivity of BM involvement in patients with DLBCL.

BACKGROUND: Bone marrow infiltration (BMI) is a devastating stage of paediatric lymphoma. Prompt diagnosis of BMI in newly diagnosed paediatric lymphoma patients is critical but can be very challenging at present.
METHODS: We systematically retrieved studies from PubMed, EMBASE, and the Cochrane Library. Data extraction and quality assessment were performed by two reviewers independently. A total of nine eligible studies were included in the quantitative analysis.
RESULTS: The pooled sensitivity and specificity of FDG-PET/CT for diagnosing BMI in newly diagnosed paediatric lymphoma patients were 0.97 (95% confidence interval [CI], 0.93 to 0.99) and 0.99 (95% CI, 0.98 to 0.99), respectively. The pooled PLR, NLR, and DOR were 79.9 (95% CI, 42.7 to 149.6), 0.03 (95% CI, 0.01 to 0.17), and 2414.6 (95% CI, 989.6 to 5891.4), respectively. The AUC of FDG-PET/CT for BMI was 1.00 (95% CI, 0.99 to 1.00). Compared with FDG-PET/CT, BMB had a lower pooled sensitivity (0.44, 95% CI, 0.34 to 0.55) and comparable pooled specificity (1.00, 95% CI, 0.92 to 1.00).
CONCLUSIONS: Compared with BMB, FDG-PET/CT was a more valuable diagnostic method for evaluating BMI in paediatric Hodgkin and non-Hodgkin lymphoma patients with extremely high diagnostic accuracy.

A 58-year-old male was admitted to our hospital due to lasting fever, progressive lymphadenopathy and bicytopenia, with a previously histological diagnosis of follicular lymphoma grade 3a with Epstein-Barr virus-encoded RNA positive one month ago. A second biopsy of axillary lymph node revealed concurrent diffuse large B-cell lymphoma with Epstein-Barr virus-encoded RNA positive. Another diagnosis of hemophagocytic lymphohistiocytosis secondary to Epstein-Barr virus positive diffuse large B-cell lymphoma was further concluded by clinical manifestation, laboratory test and atypical lymphocytes in peripheral-blood smear. After a pulse of steroid pre-phase treatment, the patient\'s clinical condition deteriorated and died in two weeks. The presence of Epstein-Barr virus infection in patients with follicular lymphoma is associated with more aggressive clinical course and increased risk of high-grade transformation. Hemophagocytic lymphohistiocytosis in response to Epstein-Barr virus infection or lymphoma remains fatal. Early diagnosis and initiation of treatment may improve the outcome.

18F-FDG PET / CT is used clinically for the detection of extramedullary lesions in patients with relapsed acute leukemia (AL). However, the visual analysis of 18F-FDG diffuse bone marrow uptake in detecting bone marrow involvement (BMI) in routine clinical practice is still challenging. This study aims to improve the diagnostic performance of 18F-FDG PET/CT in detecting BMI for patients with suspected relapsed AL. Methods: Forty-one patients (35 in training group and 6 in independent validation group) with suspected relapsed AL were retrospectively included in this study. All patients underwent both bone marrow biopsy (BMB) and 18F-FDG PET/CT within one week. The BMB results were used as the gold standard or real \"truth\" for BMI. The bone marrow 18F-FDG uptake was visually diagnosed as positive and negative by three nuclear medicine physicians. The skeletal volumes of interest were manually drawn on PET/CT images. A total of 781 PET and 1045 CT radiomic features were automatically extracted to provide a more comprehensive understanding of the embedded pattern. To select the most important and predictive features, an unsupervised consensus clustering method was first performed to analyze the feature correlations and then used to guide a random forest supervised machine learning model for feature importance analysis. Cross-validation and independent validation were conducted to justify the performance of our model. Results: The training group involved 16 BMB positive and 19 BMB negative patients. Based on the visual analysis of 18F-FDG PET, 3 patients had focal uptake, 8 patients had normal uptake, and 24 patients had diffuse uptake. The sensitivity, specificity, and accuracy of visual analysis for BMI diagnosis were 62.5%, 73.7%, and 68.6%, respectively. With the cross-validation on the training group, the machine learning model correctly predicted 31 patients in BMI. The sensitivity, specificity, and accuracy of the machine learning model in BMI detection were 87.5%, 89.5%, and 88.6%, respectively, significantly higher than the ones in visual analysis (P < 0.05). The evaluation on the independent validation group showed that the machine learning model could achieve 83.3% accuracy. Conclusions: 18F-FDG PET/CT radiomic analysis with machine learning model provided a quantitative, objective and efficient mechanism for identifying BMI in the patients with suspected relapsed AL. It is suggested in particular for the diagnosis of BMI in the patients with 18F-FDG diffuse uptake patterns.