Discussion

The patient's initial presentation—fever, AMS, and bilateral upper‐extremity superficial venous thrombosis—closely mimicked infectious, neurologic, and autoimmune disorders, delaying recognition of the underlying hematologic malignancy. Although generalized lymphadenopathy was identified during admission, the diagnostic workup initially remained focused on acute neurologic and thrombotic manifestations before aggressive B‐cell lymphoma was ultimately established.

Lymphoma is a recognized cause of FUO, particularly in the absence of identifiable infection [16]. In retrospect, persistent fever despite broad‐spectrum antibiotics, negative cultures, and markedly elevated inflammatory markers and lactate dehydrogenase favored an aggressive lymphoproliferative process. Venous thromboembolism is common in lymphoma, including DLBCL, but bilateral superficial venous thrombosis of the upper extremities as a presenting manifestation is unusual [17, 18]. The patient also demonstrated coagulation abnormalities, including prolonged PT/aPTT and elevated D‐dimer. Although rivaroxaban may interfere with coagulation assays, the overall pattern raised concern for malignancy‐associated coagulopathy, possibly reflecting a compensated or low‐grade consumptive process described in aggressive B‐cell lymphomas [19, 20]. Because fibrinogen was unavailable, formal ISTH disseminated intravascular coagulation (DIC) scoring could not be applied, and thrombocytosis argued against overt DIC.

Neuroimaging and cerebrospinal fluid studies showed no structural, infectious, or leptomeningeal explanation for the patient's AMS. The encephalopathy was likely multifactorial, potentially related to infectious or metabolic stress in an elderly patient, with possible contribution from lymphoma‐associated functional CNS effects. Emerging evidence suggests extracranial DLBCL may induce metabolic brain alterations even without structural CNS involvement [21, 22]. Although a paraneoplastic mechanism remained a consideration, it could not be definitively confirmed, as the patient did not undergo a comprehensive assessment according to the revised 2021 Graus diagnostic framework for paraneoplastic neurologic syndromes [23].

Microscopic evaluation revealed marked disruption of normal nodal structure by diffuse proliferation of large atypical lymphoid cells, compatible with an aggressive high‐grade lymphoma. The neoplastic cells showed an immunophenotypic profile of mature B‐cell origin, with strong CD20 expression and negative staining for CD3, CD15, and CD30. However, the diagnostic interpretation should be viewed in light of several limitations. Unexpectedly, PAX5 was weakly and focally expressed in < 20% of the cells, leading to ambiguity in the immunophenotypic interpretation. No formal assessment of proliferative activity was performed on Ki‐67 staining. In addition, MYC, BCL2, and BCL6 molecular studies were not performed, precluding WHO 5th‐edition subclassification between DLBCL‐NOS and high‐grade B‐cell lymphoma with double−/triple‐hit genetics [24, 25]. Consequently, the diagnosis of aggressive B‐cell lymphoma, provisionally most consistent with DLBCL‐NOS, relied on morphology and limited immunohistochemistry. This case illustrates the practical diagnostic challenges of lymphoma classification in resource‐limited settings and reinforces recommendations for referral when advanced molecular testing is unavailable [26, 27].

The patient's sudden cardiac arrest on the 13th day of hospitalization resulted in a fatal outcome. Given the hypercoagulable state associated with malignancy and the patient's prior thrombotic event, pulmonary thromboembolism was considered the most likely cause [28, 29]. However, a definitive diagnosis could not be established because neither confirmatory imaging nor autopsy findings were available. Various probable causes, such as lethal arrhythmia, septic cardiovascular collapse, or metabolic abnormalities, could not be excluded.