Pitfalls on 18‐fluorodeoxyglucose positron emission tomography‐computed tomography: Immunoglobulin G4‐related lymphadenopathy

A 27-year-old man was referred to our hospital with symptoms of jaundice and shortness of breath that had been going on for a week. The laboratory tests showed anemia (hemoglobin of 9.8 g/dL), hyperbilirubinemia (indirect bilirubin of 4.9 mg/dL), and a high level of lactate dehydrogenase (LDH at 515 U/L). A direct Coombs test was positive and we diagnosed him with autoimmune hemolytic anemia (AIHA). Considering the possibility of secondary AIHA, a total body computed tomography (CT) was performed, revealing left axillary lymphadenopathy with a major diameter of 4 cm. 18-Fluorodeoxyglucose (FDG) positron emission tomography with CT (PET-CT) showed a maximum standardized uptake value of 9.3 (Figure 1A). Malignant lymphoma was strongly suspected and an excisional biopsy of the node was performed. Histopathological analysis of the node revealed densely proliferated lymph follicles with preserved nodular structure. Immunostaining for Bcl2 was negative within the germinal centers and for CD21 highlighting follicular dendritic cell meshwork was also localized, suggesting a reactive process. Flow cytometry revealed no specific findings and fluorescent in-situ hybridization for identification of BCL2, BCL6, and MYC split was all negative. The karyotype of lymph node cells was normal. There were no findings suggestive of malignant lymphoma, Castleman disease, and fungal infection, leading to a diagnosis of lymphoid hyperplasia (Figure 1B). Next, we focused on immunoglobulin G4 (IgG4) because it was elevated to 274 mg/dL at the time of the initial visit. Immunostaining of the lymph nodes showed a large number of IgG4-positive cells within the germinal center and an IgG4/IgG ratio was estimated to be more than 40%. From the above, finally, the diagnosis of IgG4-related lymphadenopathy was confirmed and the lesion was histopathologically classified as type II, although accumulation of IgG4-positive cells was evident in germinal centers [1] (Figures 1C,D). Lymphoid hyperplasia results in high metabolic activity and glucose uptake which lead to significant FDG accumulation [2, 3]. Known causes of lymphoid hyperplasia include collagen diseases such as systemic lupus erythematosus, Castleman disease, viral infections, drug allergy, and IgG4-related lymphadenopathy as seen in this case [4, 5]. Therefore, it is crucial to perform both biopsy and imaging tests for accurate diagnosis. TO collected the data and wrote the first draft of the manuscript. Naomi Katsuki, Mitsuo Kishimoto, and Hirokazu Nakamine provided pathological information and comments. Yasuko Miyahara and Mitsuru Itoh coordinated the project and edited the manuscript. All authors read and approved the final manuscript. We thank all the members of the Department of Hematology at Kyoto City Hospital for their indispensable patient care. The authors declare no conflict of interest. The authors have confirmed ethical approval statement is not needed for this submission. Informed consent for the publication of this article was obtained from all enrolled patients. This study did not require institutional ethics committee approval. The authors have confirmed clinical trial registration is not needed for this submission. Data from this study have not been deposited in a publicly accessible database.