OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied.
METHODS: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children\'s Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations.
RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006).
CONCLUSIONS: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4) is a rare lymphoid neoplasm, usually occurring in the pediatric/young-adult age. Despite this, subsets of cases occur in elderly patients and express CD5, possibly entering the differential diagnosis with adult aggressive lymphomas, such as blastoid/pleomorphic mantle cell lymphoma (MCL-B/P). To better characterize the clinical-pathological features and differential diagnosis of LBCL-IRF4, we conducted a multi-centric study on 12 cases, focusing on CD5, Cyclin D1, and SOX11 expression. While most cases had typical presentation, adult-to-elderly age at diagnosis and unusual anatomic locations were reported in 3/12 (25.0%) and 2/12 (16.7%) patients, respectively. Histologically, CD5 was positive in 4/12 (33.3%) cases, Cyclin D1 was invariably negative, and SOX11 was weakly/partially expressed in 1/12 (8.3%) case. In conclusion, LBCL-IRF4 can have unconventional clinical presentations that may challenge its recognition. Although CD5 is frequently expressed, negativity for Cyclin D1 and SOX11 contributes to the differential diagnosis with MCL-B/P.

BACKGROUND: Although primary cutaneous B-cell lymphomas (PCBCL) comprise 25% of all cutaneous lymphomas, their incidence in the pediatric population is unknown, and the information on pediatric PCBCL has mostly been gathered from individual case reports or series from single centers.
METHODS: This was a population-based, retrospective cohort study of patients in 18 cancer registries in the United States diagnosed between 2000 to 2016 through the Surveillance, Epidemiology, and End Results (SEER) program. Age-adjusted incidence rates were calculated for PCBCL in pediatric (<20 years) and adult (≥20 years) populations. Demographic, clinical, and pathological characteristics of PCBCL were compared between the two groups.
RESULTS: A total of 48 pediatric and 5128 adult PCBCL cases were included. Median age at diagnosis was 16.5 years and 65 years in the two groups, respectively. The major histologic subtypes of pediatric cases were marginal zone lymphoma (77.1%), followed by diffuse large B-cell lymphoma (12.5%) and follicle center lymphoma (10.4%), which were equally distributed in adults. The age-adjusted pediatric PCBCL incidence rate (per 1,000,000 person-years) was 0.12 (95% CI 0.09-0.16). The incidence in the adult population was approximately 40-fold higher than the one observed in the pediatric group (IRR 41.4, 95% CI 31.2-56.2). All 48 pediatric cases were alive during a median follow-up time of 48 months.
CONCLUSIONS: Pediatric PCBCL is a very rare disease affecting mostly adolescents of both sexes. The major histologic subtype is marginal zone lymphoma, and the prognosis is favorable.

OBJECTIVE: The objective of our study was to compare the diagnostic performance of sequential (18)F-FDG PET/MRI (PET/MRI) and (18)F-FDG PET/CT (PET/CT) in a pediatric cohort with lymphoma for lesion detection, lesion classification, and disease staging; quantification of FDG uptake; and radiation dose.
METHODS: For this prospective study of 25 pediatric patients with lymphoma, 40 PET/CT and PET/MRI examinations were performed after a single-injection dual-time-point imaging protocol. Lesions detected, lesion classification, Ann Arbor stage, and radiation dose were tabulated for each examination, and statistical evaluations were performed to compare the modalities. Quantification of standardized uptake values (SUVs) was performed for all lesions. All available examinations and clinical history were used as the reference standard.
RESULTS: No statistically significant differences between PET/MRI and PET/CT were observed in lesion detection rates, lesion classification, or Ann Arbor staging. Fifty-four regions of focal uptake were observed on PET/MRI compared with 55 on PET/CT. Both modalities accurately classified 82% of the lesions relative to the reference standard. Disease staging based on PET/MRI was correct for 35 of the 40 studies, and disease staging based on PET/CT was correct for 35 of the 40 studies; there was substantial agreement between the modalities for disease staging (κ = 0.684; p < 0.001). PET SUVs were strongly correlated between PET/CT and PET/MRI (ρ > 0.72), although PET/MRI showed systematically lower SUV measurements. PET/MRI offered an average 45% reduction in radiation dose relative to PET/CT.
CONCLUSIONS: In a pediatric cohort with lymphoma, sequential PET/MRI showed lesion detection, lesion classification, and Ann Arbor staging comparable to PET/CT. PET/MRI quantification of FDG uptake strongly correlated with PET/CT, but the SUVs were not interchangeable. PET/MRI significantly reduced radiation exposure and is a promising new alternative in the care of pediatric lymphoma patients.