Multicolor flow cytometry (MFC) is crucial in detecting occult or minimal bone marrow (BM) involvement by non-Hodgkin lymphomas (NHL), which may not be detected using trephine biopsy or imaging studies. Detection of low-level BM involvement can be challenging without definite immunophenotypic aberrancies. We studied the utility of CD305 in MFC detection of minimal BM involvement by B-NHL, especially in the absence of aberrancies by commonly used markers. The study included 1084 consecutive BM samples submitted for the staging of B-NHLs (excluding CLL) over two years. Samples were studied for morphological, immunophenotypic, and histopathological assessment. MFC studies were performed using 10-13 color MFC, including CD305-antibody (clone, DX26). Minimal BM involvement was defined with a cutoff of ≤10% lymphoma cells in viable cells on MFC assessment. Of 1084, 148 samples revealed overt morphological involvement by B-NHL and were excluded from analysis. BM samples of 172/936 patients were morphologically negative but revealed involvement using MFC independently. Corresponding trephine biopsy involvement was detected in only 79/172 (45.9%) patients. On MFC, 23/172 samples showed BM involvement with >10% lymphoma cells, and 149/172 (86.6%) samples revealed minimal involvement. In 54/149 (36.24%) samples, lymphoma cells were detected only with aberrant loss of CD305 expression. In 78 of the remaining 95 samples (82.1%), it provided an immunophenotypic aberrancy addition to other markers and supported the results. CD305 is a highly useful marker in the flow cytometric assessment of minimal BM involvement by B-NHL. MFC is a superior modality to trephine biopsy in detecting low-level BM involvement.

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.

BACKGROUND: Assessment of bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) is crucial for determining patient prognosis and treatment strategy. We assessed the prognostic value of next-generation sequencing (NGS)-based immunoglobulin (Ig) gene clonality analysis as an ancillary test for BMI evaluation in NHL.
METHODS: A retrospective cohort of 124 patients newly diagnosed with B-cell NHL between 2019 and 2022 was included. NGS-based Ig clonality analysis was conducted using LymphoTrak IGH FR1 Assay and IGK Assay (Invivoscribe Technologies, San Diego, CA, USA) on BM aspirate samples, and the results were compared with those of histopathological BMI (hBMI).
RESULTS: Among the 124 patients, hBMI was detected in 16.9% (n = 21). The overall agreement of BMI between Ig clonality analyses and histopathological analysis for IGH, IGK, and either IGH or IGK was 86.3%, 92.7%, and 90.3%. The highest positive percent agreement was observed with clonal rearrangements of either IGH or IGK gene (90.5%), while the highest negative percent agreement was observed with clonal rearrangement of IGK gene (96.1%). For the prediction of hBMI, positive prediction value ranged between 59.1% and 80.0% and the negative prediction value ranged between 91.3% and 97.9%.
CONCLUSIONS: NGS-based clonality analysis is an analytic platform with a substantial overall agreement with histopathological analysis. Assessment of both IGH and IGK genes for the clonal rearrangement analysis could be considered for the optimal diagnostic performance of BMI detection in B-cell NHL.

UNASSIGNED: Bone marrow (BM) involvement is an indicator of a poor prognosis in diffuse large B-cell lymphoma (DLBCL); however, few studies have evaluated the role of immunoglobulin gene rearrangement (IgR) in detecting BM involvement.
UNASSIGNED: We evaluated the clinical characteristics and treatment outcomes of patients with DLBCL based on histological BM involvement or positive BM IgR using polymerase chain reaction or next-generation sequencing. We also investigated the role of consolidative upfront autologous hematopoietic stem cell transplantation (ASCT) in patients with DLBCL and BM involvement.
UNASSIGNED: Among 624 patients, 123 (19.7%) with histological BM involvement and 88 (17.5%) with positive IgR in histologically negative BM had more advanced disease characteristics. Overall (OS) and progression-free (PFS) survival was better for patients with negative BM histology and negative IgR than that in patients with histological BM involvement (P = 0.050 and P < 0.001, respectively) and positive IgR with negative BM histology (P = 0.001 and P = 0.005, respectively). Survival rates did not differ among 82 (13.1%) patients who were treated with upfront ASCT and had histological BM involvement or positive IgR with negative BM histology. The survival outcomes were worse for patients who were not treated with upfront ASCT and for those with histological BM involvement or positive IgR, than for those with negative BM histology and negative IgR.
UNASSIGNED: Patients diagnosed with DLBCL and BM involvement based on histology or IgR had aggressive clinical features and poor survival. Upfront ASCT mitigated poor prognosis due to BM involvement.

Juvenile xanthogranuloma is a benign self-limiting lesion commonly described in infants and young children. It most commonly involves the skin presenting as single or multiple yellowish-brown papules. Clinical scenario with the classic histomorphology showing histiocytic aggregates in the dermis with xanthomatous cytoplasm, toutan type giant cells, immunohistochemistry with positive CD68, CD163, factor XIIIa and negative CD1a and S-100 help in diagnosis. However, diagnosis becomes challenging with predominant systemic bone marrow involvement in post-B-lymphoblastic leukemia settings.

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.

UNASSIGNED: Disseminated carcinomatosis of the bone marrow in prostate cancer is rare and has a poor prognosis. Although strong evidence suggests that novel hormonal agents improve the prognosis of metastatic prostate cancer, their effectiveness in cases of disseminated carcinomatosis of the bone marrow remains unclear.
UNASSIGNED: We encountered two cases of prostate cancer with disseminated carcinomatosis of the bone marrow at the time of initial diagnosis. One patient was treated with enzalutamide, abiraterone, docetaxel, cabazitaxel, denosumab, and radium-223 and died 38 months after the initial diagnosis. The other patient was treated with apalutamide and denosumab, and had progression-free survival for 17 months after the initial diagnosis.
UNASSIGNED: These results suggest that novel hormonal agents may improve the prognosis of prostate cancer even in patients with disseminated carcinomatosis of the bone marrow.

Histoplasma capsulatum is a dimorphic fungus found in certain parts of North, Central, and South America. Transmission is primarily through airborne inoculation from inhaled fungal microconidia. Histoplasmosis is typically a self-limited mycosis; however, in patients with immunodeficiency, disseminated disease can occur and may lead to high disease burden. This report studies a case of disseminated histoplasmosis in a patient newly diagnosed with human immunodeficiency virus. His presentation on admission was consistent with infectious pulmonary granulomatous disease, and further imaging and laboratory results showed evidence of multi-organ involvement. It is likely his presentation in Central California was a reactivation infection after inoculation in Central America many years ago.

Sarcoidosis is a systemic granulomatous disease characterized by the hyperactivation of CD4 T cells, CD8 T cells, and macrophages. Clinical presentations of sarcoidosis are highly variable. Sarcoidosis is unknown in its etiology, but it suggests it may result from exposure to specific environmental agents in genetically susceptible people. Sarcoidosis commonly involves the lungs and lymphoid system. Bone marrow involvement in sarcoidosis is uncommon. Sarcoidosis rarely results in intracerebral hemorrhage due to severe thrombocytopenia secondary to bone marrow involvement. We present the case of a 72-year-old woman who has been in remission from sarcoidosis for 15 years and developed intracerebral hemorrhage secondary to severe thrombocytopenia due to sarcoidosis recurrence in the bone marrow. The patient presented to the emergency department with a generalized, non-blanching petechiae rash and nose and gum bleeding. Her labs showed a platelet count of less than 10.000/mcL, and computed tomography (CT) showed intracerebral hemorrhage. A bone marrow biopsy revealed a small, non-caseating granuloma indicative of a sarcoidosis relapse in the bone marrow.

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.