Primary bone marrow lymphoma: A hematological emergency in adults with fever of unknown origin

Abstract

Primary bone marrow lymphoma (PBML) represents non‐Hodgkin lymphoma (NHL) that primarily arises in the bone marrow (BM) without lymphadenopathy. This condition has various definitions and can be masked by prolonged fever, leading to delayed diagnosis. We aimed to identify clinical features and risk indicators of PBML. We enrolled 269 adults with fever of unknown origin (FUO) who underwent a BM study for potential PBML. Thirty patients were diagnosed with PBML (26 and 4 patients in the training and validation cohort, respectively), and 20 patients (67%) showed initial manifestation of hemophagocytic lymphohistiocytosis (HLH). Among PBML patients in the training cohort, their median overall survival is short (8 days), with pneumonia being the most common direct cause of early mortality, followed by life‐threatening HLH. Despite extremely poor prognoses, some B‐cell PBML patients who survived 30 days after BM studies achieved long‐term survival with rituximab‐based treatment. To assist general practitioners in early PBML diagnosis when approaching adults with naïve FUO, we identified several risk indicators, including elevated serum alkaline‐phosphate levels, lowered serum immunoglobulin‐G levels, cytopenia in ≥2 lineages, and peripheral blood leukoerythroblastosis. Our recently published scoring system, which can predict hematological BM disease in FUO adults, showed excellent ability in recognizing PBML early, with high sensitivity and specificity. We conclude that PBML is a specific “clinical” phenotype of NHL; moreover, we have identified diagnostic clues for early identification of FUO adults with underlying PBML, which should be considered a hematological emergency once suspected in any adult with FUO.

Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma

“…BLS-type DLBCL, including cases of primary bone marrow DLBCL [28][29][30][31] , is a distinct type of DLBCL with very aggressive behavior. In this study, we found that expression of the stem cell markers HOXA9 and NANOG in DLBCL correlates with poorer prognosis.…”

Clinical Features and Long-term Outcomes of Lymphoma Patients Initially Presenting as Fever With Unknown Origin

“…In addition to the similar increase of liver enzymes in the previous studies, the total bilirubin and direct bilirubin of our patients also increased signi cantly. 18 In ammation-related indicators like CRP were also signi cantly increased. In addition, patients in the FUO group are more likely to suffer from hypoalbuminemia, which may be related to longterm fever, physical consumption and liver function damage.…”

Primary bone lymphoma presenting as fever of unknown origin

“…The prognosis of PBL is correlated to the stage of disease, and the 5‐year overall survival of PBL ranges from 38% to 82%. 2 It is a very rare disease that accounts for less than 2% of all adult lymphomas 2 ; however, up to 11% of patients who had previously undergone bone marrow examination with fever of unknown origin were later diagnosed with PBL, 3 which suggests that there may be many cases of misdiagnosis. “B” symptoms, which were our patient's presenting complaint, are not always observed; the most common symptom in PBL is local bone pain.…”