| Summary: | Abstract Background Fever of unknown origin (FUO) still represents a serious challenge for clinicians, since it can be related to a wide spectrum of disorders, ranging from infections to malignancies. In this scenario, nuclear medicine can be of value to achieve a correct diagnosis both through positron emission computed tomography (PET/CT) and 99mTc labeled hexamethylpropylene amine oxime (HMPAO) white blood cell (WBC) scintigraphy. Case presentation We are presenting the case of 65-year-old male, who was referred to our hospital due to prolonged unexplained fever. He was submitted to abdomen ultrasonography (US) that did not disclose relevant pathological findings. Subsequently, he underwent PET/CT scan with 18F-fluorodeoxyglucose (18F-FDG) that revealed an area of increased tracer uptake in splenic inferior pole. In order to solve differential diagnosis between tumor and infection, he was submitted to 99mTc-HMPAO WBC scintigraphy that resulted negative for sites of pathologic radiolabeled cells’ accumulation but revealed a photopenic area in the splenic inferior pole. The pattern of mismatched uptake between 18F-FDG PET/CT and 99mTc-HMPAO WBC scintigraphy was considered highly suspicious for spleen tumor localization. The patient was scheduled for splenectomy and histology resulted positive for non-Hodgkin lymphoma (NHL) of diffuse large B cell type. After splenectomy, a further 18F-FDG PET/CT revealed the appearance of hypermetabolic hepatic lesions. The patient underwent chemotherapy with complete remission. Conclusion Nuclear medicine provides valuable tools for differential diagnosis in FUO. In case of patients presenting solitary lesion of the spleen, the combined use of 18F-FDG PET/CT and 99mTc-HMPAO WBC scintigraphy can provide relevant information to aid clinicians to a correct diagnosis.
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