Application Value and Cognitive Challenges of PET/CT in the Diagnosis and Treatment of Visceral Leishmaniasis: A Retrospective Single-Center Case Series and Literature Review

Background and Clinical Significance: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in visceral leishmaniasis (VL) remains undefined. We sought to characterize the PET/CT features of VL and assess its diagnostic and therapeutic value. Case Presentation: Four VL patients undergoing PET/CT at our hospital (2022–2025) were retrospectively analyzed as a single-center case series, combined with a literature review of published VL PET/CT cases up to December 2025. Three of the four cases exhibited increased 18F-fluorodeoxyglucose (18F-FDG) uptake in the spleen, bone marrow, and lymph nodes, with additional tonsillar uptake in one case and hepatic uptake in another; one case presented with isolated lymph node uptake. In three cases, initial bone marrow smears were negative for amastigotes, and PET/CT was performed for fever of unknown origin (FUO). One case was diagnosed within one week via metagenomic next-generation sequencing (mNGS) prompted by PET/CT and epidemiological history. In the other two, VL was not suspected; they received chemotherapy/corticosteroids for presumed hemophagocytic syndrome (HPS) or connective tissue disease, and the time from symptom onset to VL diagnosis ranged from 2.5 to 4.5 months. The fourth case, confirmed by bone marrow smear, underwent PET/CT for suboptimal treatment response to exclude other diseases. Among 99 published VL cases undergoing PET/CT, indications were documented in 35, with FUO representing 83%. Initial bone marrow smears were negative in 69% of 64 evaluable cases. Of the 88 cases with evaluable PET/CT findings, 5 showed no abnormal FDG uptake. The predominant pattern was increased 18F-FDG uptake in the reticuloendothelial system (RES), most frequently involving the spleen (73/88, 83%), bone marrow (44/88, 50%), lymph nodes (29/88, 33%), and liver (15/88, 17%); other sites (lungs/pleura, colon, tonsils) were rarely involved. Accompanying enlargement of the spleen or liver was seen in approximately 50% of cases. The most common involvement patterns were combined splenic and bone marrow (23/88, 26%) and isolated splenic (20/88, 23%). Conclusions: PET/CT can provide diagnostic clues for VL, screen for comorbidities, and guide biopsy. Typical PET/CT findings—increased RES uptake without significant other organ involvement—reflect the parasite’s RES tropism. However, these findings mimic lymphoma, HPS, hematological disorders, and connective tissue diseases, risking misdiagnosis. Thus, VL should be promptly excluded in such patients using epidemiological history and etiological testing before considering alternative diagnoses.