Purpose To study the clinical and pathological features of angiomatoid fibrous histocytoma(AFH)and to ex-plore its diagnosis,differential diagnosis and prognosis.Meth-ods The clinicopathological and follow-up data were analyzed in 14 cases of AFH,and the literatures were reviewed.Results There were 11 males and 3 females.The age ranged from 11 months to 12 years and 11 months,with average 5.9 years.3 cases were located in limbs,and 5 cases in trunk,5 cases in head and neck region,and 1 of intracranial tumor.Histological-ly,14 cases were composed of fibrous capsules and lymphocyte sheaths,and cell nucleus were vacuolar,forming fascicles with focal whirling and synteny.Intralesional pseudoangiomatous spaces were noted in 9 cases.Calcification was found in 2 ca-ses.2 cases showed high mitotic acticity(11/10 HPF).Scle-rosing and/or myxoid stroma was seen in 3 cases.Tumors were immunopositive for desmin(10/14),EMA(12/14),CD99(12/14),SMA(9/12),ALK(7/8),and the average of Ki67 index was 16％.7 cases harbored EWSR1 rearrangenent(part-ner gene not identified),2 cases had EWSR1-ATF1 fusion and 2 EWSR1-CREB1 fusion.Clinical follow-up information was a-vailable for 14 cases(average 46 months).All the 14 cases were alive without recurrence and metastasis.Conclusion AFH is a borderline or low-grade malignant tumor,often demon-strates indolent behavior in children,but rarely recurs and me-tastasizes.The diagnosis and differential diagnosis require a comprehensive analysis of clinical features,histopathologic changes,immunohistochemical finding and EWSR1 or FUS gene detection results.

Objective:To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma.Methods:Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children′s Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics.Results:Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease.Conclusions:Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

Objective:To investigate the clinical manifestations, pathological features, treatment and prognosis of primary bone lymphoma in children.Methods:The clinical data of children who were initially diagnosed as primary bone lymphoma and treated in Beijing Children's Hospital Affiliated to Capital Medical University from January 2016 to January 2020 were retrospectively analyzed, including gender, onset age, primary involvement site, clinical stage, pathological type, fracture, and clinical outcome. The related literature was reviewed.Results:All 11 children were initially diagnosed as primary bone lymphoma, with a median age of onset of 8.6 years old (2.7-12.3 years old), including 7 males and 4 females. There were 7 cases of diffuse large B-cell lymphoma (DLBCL), 3 cases of B lymphoblastic lymphoma (BLL), and 1 case of anaplastic large cell lymphoma (ALCL). The initial symptoms were bone pain in 8 cases, local swelling in 1 case, limp in 1 case, and fever in 1 case. One case was in stage Ⅰ, 7 cases were in stageⅡ, and 3 cases were in stage Ⅳ, and the most common sites of involvement were femur and tibia. All 11 cases were treated with chemotherapy according to different pathological types, with a median follow-up time of 45 months (7-80 months). Ten cases got complete remission, 1 case of BLL died of bone marrow recurrence after chemotherapy remission.Conclusions:The clinical manifestations of primary bone lymphoma in children are insidious, DLBCL is the most common pathological type, and the prognosis is good after standardized treatment.

To analyze the clinical characteristics, treatment and prognosis of mediastinal germ cell tumors (GCTs) with concurrent hematologic malignancy (HM). The clinical features, treatment and prognosis of 3 cases of HM associated with mediastinal GCTs treated in the Department of Medical Oncology, Beijing Children′s Hospital from November 2014 to September 2018 were retrospectively analyzed.Meanwhile, relevant cases were searched in the PubMed and Wanfang database from their establishment to December 2019.Three male cases of HM associated with mediastinal GCTs aged from 12 to 16 years.The pathogenesis of mediastinal masses suggested teratoma or yolk sac tumor.All of them were treated with surgery and chemotherapy.Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) was diagnosed respectively at 5 months, 9 months and 31 months after initial GCTs in the 3 cases.Two patients died and 1 child survived at the last follow-up.A total of 135 cases of concurrent GCTs and HM (or leukemia) were reviewed in online databases, involving 127 cases (94.1%) with the mediastinal GCTs associated with HM and 8 cases(5.9%) with GCTs related HM from another original sites.One hundred and twenty-six cases (99.2%) were male and the median age of GCTs diagnosis was 22 (10-48) years.Fifty-three cases (41.7%) were teratoma and 94 cases (74.0%) were GCTs containing teratoma with or without yolk sac tumor.Among the types of HM, 72 cases (56.7%) were AML and 31 cases (24.4%) were AML-M7.The median interval between GCTs and HM was 3 (0-122) months.Forty-six cases (36.2%) presented 2 malignancies simultaneously.HM were diagnosed within 12 months of GCTs in 85 cases (66.9%). The survival data were known in 107 cases, involving 94 (87.9%) deaths and 13 (12.1%) survivors.The median survival time after diagnosis of HM was 2 (0-48) months.The tendency of HM must be highly concerned in adolescent male patients with primary mediastinal GCTs, especially those with yolk sac tumor or teratoma.Their prognoses are very poor.Allogeneic hematopoietic stem cell transplantation is an alternative treatment.

Objective:To summarize the clinical features of neuroblastoma (NB) with bone metastasis in infants and the prognostic factors.Methods:A retrospective analysis was performed on 32 patients aged ≤12 months who were enrolled in Beijing Children′s Hospital, Capital Medical University from January 2010 to December 2019 and had imaging findings suggesting signs of distant bone metastasis.The control group was included NB children, aged ≤12 months, who were admitted to Beijing Children′s Hospital, Capital Medical University during the same period, without signs of distant bone destruction.The clinical manifestations and auxiliary examinations of infants with bone metastasis were summarized, and the efficacy evaluation and survival analysis of infants with regular treatment and follow-up were conducted until December 31, 2020. Kaplan- Meier survival analysis was used for prognostic analysis, and Log Rank test was used for univariate prognostic analysis. Results:There were 32 NB infants with bone metastases, involving 12 males (37.5%) and 20 females (62.5%), accounting for 16.0% (32/200 cases) of infants diagnosed with NB du-ring the same period.The median age of onset was 9 (4.5-12.0) months.The main primary site included the retroperitoneal and adrenal region in 24 cases(75.0%) and mediastinum in 3 cases (9.4%). Among the 32 cases, 14 cases (43.8%) had simple bone metastasis, 19 cases (59.4%) had distant lymph nodes, 18 cases (56.3%) had bone marrow, and 3 cases (9.4%) had intracranial and meningeal metastasis.Bone metastasis mainly occurred in the skull, with 11 cases of single bone metastases and the remaining with 2 or more bone metastases.Compared with 168 NB infants without bone metastasis, the prognosis of those with bone metastasis was significantly worse [3-year overall survival(OS) rate 97.6% vs.82.7%, P=0.001]. Univariate analysis showed that the prognosis of NB children with bone marrow metastasis, meningeal and intracranial metastasis, MYCN gene amplification, and high-risk group was poor (all P<0.05). Two patients returned to the local hospital for treatment after diagnosis.A total of 30 children were recruited for efficacy evaluation and prognostic analysis.Twenty-nine children underwent surgery, of which 6 cases received surgery before chemotherapy and 23 cases received surgery after chemotherapy.One case received chemotherapy only.The mean course of chemotherapy was 6.2 (4-13) times.One case was treated with radiotherapy, 1 case was treated with Metaiodobenzylguanidine (MIBG) therapy, and 1 case was treated with stem cell transplantation.A total of 18 cases (62.1%) event-free survived, and 12 cases (40.0%) had a mean event at 7 (1.5-32.0) months.Among them, 7 cases survived and 5 cases died (16.7%). The expected 3-year event-free survival rate and OS rate were 57.1% and 82.7%, respectively. Conclusions:The most common sites of infant NB metastasis are bone and bone marrow, and the most common sites of bone metastasis are skull.Infants with bone metastasis had a worse prognosis than those without bone metastasis, and infants with bone and bone marrow metastasis had a worse prognosis than infants with single bone metastasis.

Objective:To analyze the ultrasonographic images and clinical characteristics of congenital mesoblastic nephroma (CMN), and to investigate the differential performances with Wilm′s tumor (WT).Methods:Twenty-one cases of CMN patients confirmed by pathology from December 2008 to December 2019 in Beijing Children′s Hospital, Capital Medical University were collected as the CMN group, and in the same criterion, 51 cases of WT patients were taken as WT group. Ultrasonographic images and clinical characteristics were collected retrospectively, and then the tumor size, site, echo and age were compared and analyzed between the two groups. ROC curve was used to evaluate the differential performance.Results:The difference analysis showed that except for echo ( P=0.694), there were statistically significant differences in tumor size, site and age between the two groups (all P<0.05). In prenatal, the incidence of CMN was significantly higher than WT (61.9% vs 3.9%, P<0.001), and the specificity was 96.1%. The median age (interquartile range) of CMN after birth was significantly earlier than WT( Z=-4.044, P<0.001). The area under the ROC was 0.949, the best cutoff was 112.5 days, with a sensitivity of 87.5% and a specificity of 93.9%. Conclusions:It is difficult to distinguish CMN and WT by echo, but the diagnosis performance can be improved through combining tumor size with site, especially age.

Objective:To investigate the improved performance of hepatic elastography combined with the serum biomarkers for the diagnosis of biliary atresia.Methods:A total of 193 patients with suspected biliary atresia in Beijing Children′s Hospital from March 2019 to November 2020 were consecutively collected. All patients were randomly divided into the training cohort and validation cohort at a ratio of 7∶3. LASSO regression analysis was used for the selection of the model index based on the data set from the training cohort including the serum biomarkers, demographic features (age and sex) and hepatic elastic measurement, and a diagnostic model for biliary atresia was subsequently developed by weighting on the basis of the dominance ration. The performance of the model was respectively evaluated with respect to the discrimination and calibration in each cohort.Results:Alanine aminotransferase (ALT), glutamyl transferase (GGT) and hepatic elastic measurement were selected to build the model. The area under the ROC curve of the final diagnostic model was 0.943 with a sensitivity of 90.9% and a specificity of 85.7% in the training cohort, and 0.955 in the validation cohort. Hosmer-Lemeshow test ( P=0.292, P=0.951) and calibration curves further validated its satisfactory calibration in both cohorts. As demonstrated by Delong et al.test, employing the model in the training cohort achieved the best diagnostic performance compared with using single model index ( P<0.001, P=0.016, P<0.001). In the validation cohort, the decision curve analysis showed the model had a higher overall net benefit over using hepatic elastography alone in every predicted probability. Conclusions:The diagnostic model for biliary atresia, which incorporates ALT, GGT and hepatic elastic measurement, can improve the performance of hepatic elastography with a higher clinical value.

Objective:To investigate the clinicopathologic characteristics, treatments, outcomes and mechanisms of hemolytic uremic syndrome (HUS) complicated with IgA nephropathy (IgAN).Methods:The clinical manifestations, treatments, prognosis and histopathological features of renal biopsy tissues were analyzed in two cases of HUS complicated with IgAN from Beijing Children′s Hospital, Capital Medical University using light microscopy, immunofluorescence detection and electron microscopy. The related literatures were also reviewed.Results:The clinical manifestations were microvascular hemolytic anemia, thrombocytopenia, acute renal impairment with hematuria, proteinuria, and positive anti-H factor antibody. Histological findings confirmed presence of both HUS and IgAN. Histological features included glomerular mesangial and stromal hyperplasia with endothelial cell proliferation, capillary stenosis, arteriolar thickening, and glomerular ischemia and capillary dilatation. Immunofluorescence detection showed diffuse IgA deposition in the glomerular mesangial matrix. Electron microscopy showed proliferation of mesangial and endothelial cells, thickening of the inner layer of the glomerular basement membrane, deposition of massive electronic densification in the mesangial region, and shrinkage of the segmental basement membrane. The two children were very responsive to plasma exchange and steroid treatments. However, their urine protein and occult blood tests remained continuously positive during the follow-up of 5 years 7 months and 8 months respectively.Conclusions:HUS complicated with IgAN is rare. The diagnosis relies on various pathological examinations, which require the combination of light microscopy, immunofluorescence detection and electron microscopy. Plasma exchange and steroid treatments are effective. However, the long-term prognosis is concerning and may relate to pathological grade and secondary factors. The mechanism of connecting HUS and IgAN is unknown, but may be caused by prodromal or secondary factors.

Extrarenal Wilms′ tumor is extremely rare and has no characteristic clinical manifestations. Diagnosis is difficult before surgery, and is often confirmed by histopathology. Comprehensive treatment by surgery, chemotherapy and radiotherapy is currently adopted for such patients, and the overall survival rate can reach about 90%. Here we report a 2-year-old child with Wilms′ tumor in the left scrotum.

Objective: To investigate the clinicopathological manifestations, molecular genetic, diagnostic histology and differential diagnosis of alveolar soft part sarcoma (ASPS) in children. Methods: A total of 13 cases of ASPS diagnosed at Beijing Children′s Hospital from August 2009 to November 2018 were collected. HE staining, histochemical staining for PAS and D-PAS, immunohistochemical (IHC) staining for TFE3, INI1 and CD68 and florescence in situ hybridization (FISH) for TFE3 gene translocation were performed. Results: There were four males and nine females, age ranged from 1 year and 2 months to 13 years and 8 months (mean 7.8 years); and four patients were under 5 years old. Histologically, the tumors showed a distinctive and characteristic nested or organoid growth pattern (11 cases) or solid, diffuse growth (2 cases). The tumor cells possessed abundant eosinophilic, or glycogen-rich and clear to vacuolated cytoplasm. The chromatin was relatively dispersed, with prominent and pleomorphic nucleoli; mitotic figures were rare. Vascular invasion was frequently seen. IHC staining showed specific nuclear TFE3 staining. The tumor cells were also positive for INI1,CD68 and vimentin; but were negative for MyoD1, Myogenin, CK and S-100 protein. Seven cases showed PAS and D-PAS staining, with fuchsia acicular or rod-shaped crystals in tumor cytoplasm. Nine cases showed TFE3 break-apart signals by FISH. Conclusions ASPS is a rare soft tissue sarcoma in children. Compared with ASPA in adults, it has both similarities and unique clinicopathologic characteristics. The diagnosis needs to be confirmed by combining clinical, pathologic, IHC and genetic testing.