Synchronous Bilateral Adrenal and Central Nervous System Involvement of Extranodal Non-Hodgkin Lymphoma Detected on 18F-FDG PET/CT

To the Editor, Extranodal involvement occurs in approximately one-third of non-Hodgkin lymphoma (NHL) cases [1,2].Highgrade B-cell lymphoma (HGBCL) is an aggressive subtype, often associated with MYC, BCL2, and BCL6 rearrangements, carrying a poor prognosis and complex treatment challenges [3].Synchronous involvement of multiple extranodal sites in immunocompetent individuals is exceedingly rare.We present a unique case of extranodal HGBCL with synchronous bilateral adrenal and central nervous system (CNS) involvement mapped primarily by 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT).A 60-year-old male with no significant medical history presented with impaired consciousness.Brain magnetic resonance imaging (MRI) revealed a left temporal mass with vasogenic edema [Figure 1D].To investigate potential malignancy, an 18 F-FDG PET/CT was performed (Figure 1A), demonstrating a hypermetabolic lesion (SUVmax: 21.9) in the left temporal lobe [Figure 1B, 1C].Additionally, intensely hypermetabolic nodular lesions (SUVmax: 15.2) were incidentally detected in both adrenal glands: a 15 mm lesion on the right [Figure 1E, 1F] and two lesions measuring 10 mm and 11 mm on the left [Figure 1H, 1I].Except for increased uptake in a thyroid nodule, no other pathological FDG accumulation or lymphadenopathy was observed.Following the excision of the temporal mass, histopathology revealed HGBCL with CD20, BCL2, BCL6, and MUM1 positivity, alongside a high Ki-67 proliferation index (90-95%).Subsequent dynamic abdominal MRI showed enlargement of the adrenal lesions with mild heterogeneity and minimal contrast enhancement [Figure 1G, 1J].A tru-cut biopsy of the right adrenal gland confirmed HGBCL involvement, concordant with the temporal lesion.Subsequent fluorescence in situ hybridization (FISH) analysis was performed to evaluate for gene rearrangements.The FISH results demonstrated a BCL6 gene rearrangement, while C-MYC and BCL2 were negative.These findings confirmed the diagnosis of a triple-expressor diffuse large B-cell lymphoma without double-hit or triple-hit genetics.Lumbar puncture demonstrated a cytologically normal cerebrospinal fluid with no atypical or malignant cells, aiding in the evaluation of CNS involvement.Bone marrow biopsy was also negative for lymphoma.Although both temporal and adrenal lesions were histopathologically confirmed as HGBCL, the primary site of disease could not be definitively established.The absence of nodal involvement and the synchronous presentation of two extranodal sites raise the possibility of either primary CNS lymphoma with secondary adrenal involvement, primary adrenal lymphoma with secondary CNS dissemination, or disseminated extranodal lymphoma at presentation.The patient was treated with six cycles of the R-IRDAM regimen, achieving a complete clinical and radiological response with full regression of both the systemic and CNS lesions.To consolidate this remission, autologous stem cell transplantation was successfully performed using a CNS-penetrating conditioning regimen.At the latest outpatient follow-up, the patient remained in stable clinical remission with no signs of disease recurrence.Regarding the PET/CT findings, the incidental 8-mm thyroid u n c o r r e c t e d p r o o f nodule (SUVmax 5.0) remained stable across all consecutive scans, and further diagnostic evaluation was deferred for observational monitoring due to the clinical priority of managing the hematological malignancy.Primary CNS lymphoma represents 4-6% of extranodal lymphomas, whereas primary adrenal lymphoma accounts for <1% [4,5].Bilateral adrenal involvement occurs in about 70% of primary adrenal lymphomas [6].While synchronous extranodal NHL in different organs is documented [7,8], simultaneous CNS and bilateral adrenal involvement is extraordinarily rare, with only one previously reported case [9].18 F-FDG PET/CT is crucial for the comprehensive staging of NHL, effectively detecting metabolically active, unexpected extranodal sites that conventional imaging might miss [10].Although the initial neurological presentation strongly raised the suspicion of primary CNS lymphoma, staging is critical as some cases represent secondary CNS involvement from an undiagnosed systemic lymphoma.Therefore, systemic screening including bone marrow evaluation is essential in this differential diagnosis.This case highlights the indispensable role of whole-body functional imaging in identifying the exact extent of highly aggressive extranodal lymphomas, thereby guiding precise biopsy and management strategies.