Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

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 relationship between 1p/16q loss of heterozygosity (LOH) and 1p gain in Wilms tumor and their clinicopathologic characteristics and prognosis.Methods:A total of 175 Wilms tumor samples received from the Department of Pathology, Beijing Children′s Hospital from September 2019 to August 2022 were retrospectively analyzed. The histopathologic type and presence of lymph node involvement were evaluated by two pathologists. The clinical data including patients′gender, age, tumor location, preoperative chemotherapy, and tumor stage were summarized. Fluorescence in situ hybridization (FISH) was done to detect 1p/16q LOH and 1p gain and their correlation with the clinicopathological features and prognosis were analyzed.Results:Among the 175 samples, 86 cases (49.1%) were male and 89 (50.9%) were female. The mean age was (3.5±2.9) years, and the median age was 2.6 years. There were 26 (14.9%) cases with 1p LOH, 28 (16.0%) cases with 16q LOH, 10 (5.7%) cases of LOH at both 1p and 16q, and 53 (30.3%) cases with 1q gain. 1q gain was significantly associated with 1p LOH ( P<0.01) and 16q LOH ( P<0.01). There were significant differences ( P<0.01) between 1q gain, 1p LOH and 16q LOH among different age groups. The rate of 16q LOH in the high-risk histopathological subtype (50.0%) was significantly higher than that in the intermediate-risk subtype (13.6%, P<0.05). The frequency of 1q gain, 1p LOH, and 16q LOH in children with advanced clinical stages (Ⅲ and Ⅳ) was significantly higher than that in children with early clinical stages (Ⅰ and Ⅱ). 1q gain, 1p LOH, and 16q LOH showed no significant correlation with gender, unilateral or bilateral disease, chemotherapy, or lymph node metastasis. The progression-free survival (PFS) time for patients with 1q gain and 1p LOH was significantly shorter than those without these aberrations ( P<0.05). Additionally, the PFS time of patients with 16q LOH was slightly shorter than those with normal 16q, although the difference was not statistically significant. Patients with stage Ⅲ to Ⅳ disease exhibiting 1q gain or 1p LOH had a significantly higher relative risk of recurrence, metastasis, and mortality. Conclusions:1p/16q LOH and 1q gain are associated with age, high-risk histological type, and clinical stage in Wilms tumor. 1q gain and 1p LOH are significantly correlated with the prognosis of Wilms tumor.

Objective:To analyze the clinical characteristics and prognosis of infants with rhabdomyosarcoma (RMS), thus enhancing the understanding of this disease.Methods:Clinical data of all RMS patients younger than 12 months treated in the Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from May 2006 to June 2019 were retrospectively analyzed, including the age, gender, histological type, tumor primary site, tumor size, and the prognosis.Patients were followed up until December 31, 2019.The 3-year event free survival (EFS) rate of children was performed by plotting the Kaplan-Meier survival curves.Results:A total of 15 RMS children younger than 12 months were enrolled, accounting for 4.9% of all RMS cases in the same period, including 6 males and 9 females.The median age at diagnosis was 7.0 months (3.0-11.5 months). Classified by the primary site, 40.0% (6 cases) located in the head and neck, followed by 26.7% (4 cases) located in the limbs, 26.7% (4 cases) located in other parts, and 6.7% (1 case) located in the urogenital system.Embryonal RMS, alveolar RMS and spindle cell RMS accounted for 46.6% (7 cases), 26.7% (4 cases), and 26.7% (4 cases), respectively.Ten cases (66.7%) were stage Intergroup Rhabdomyosarcoma Study (IRS)-Ⅲ and 1 case (6.7%) was in stage Ⅳ.There were 10 cases (66.6%) in the middle-risk group, 4 cases (26.7%) in the low-risk group, and 1 case (6.7%) in the high-risk group.Two cases had a larger than 5 cm primary tumor; lymph node involvement was confirmed in 3 cases, and pulmonary metastasis occurred in 1 case at the time of diagnosis.All children were treated with chemotherapy, and 13 cases received postoperative chemotherapy and 1 case received preoperative chemotherapy.One case were not operated.Only 3 children underwent radiotherapy, including 1 case underwent particle implantation and 2 cases received external radiotherapy.Among the 15 children with RMS, 5 cases had relapse and disease progression with the 3-year EFS rate of (59.1±14.5)%, and 2 died with the 3-year overall survival rate of (80.8±12.6)%.Conclusions:The median age of diagnosis of RMS in single-center infants is 7 months.Head and neck are the most common primary sites of RMS.Nearly 50% of the children have the primary site of RMS with poor prognosis.More than a quarter of the pathological subtypes are the spindle cell type.Local treatment significantly influences the local progression or recurrence of RMS.

Objective:To study the clinicopathologic features, and the diagnosis and differential diagnosis of mycobacterial spindle cell pseudotumor in children.Methods:The clinical data, histopathological features, immunophenotype and special staining of 2 mycobacterial spindle cell pseudotumors were analyzed. The related literatures were reviewed.Results:The age of the two boys was 11 months and 22 months respectively, but their clinical symptoms became apparent at the age of about 4 months. The lesions involved lymph nodes and skin. The first patient also had fever for more than 4 months. Both patients received anti-inflammatory treatment in the outside hospital, but had no obvious improvements of the symptoms. A tumor resection was performed at the outside hospital. Histologically, mycobacterial spindle cell pseudotumor consisted of bland spindle cells, which formed fascicles, without any obvious atypia and mitoses. The cell nuclei were vesicular, with small nucleoli and abundant cytoplasm in some of the cases. The spindle cells expressed histiocyte-associated markers, such as CD68. The Ki-67 proliferation index was low. The mycobacteria were usually readily highlighted by acid-fast staining, which located in the cytoplasm of proliferative spindle cells. In the first case, there was obstructive jaundice because of the progressive enlargement of live portal lymph nodes and systemic disseminated lesions. The second patient had disease recurrence after only operation, and gradually developed other skin nodules and superficial lymph node enlargement. The high-throughput molecular analysis of the skin biopsy confirmed the diagnosis of mycobacterium tuberculosis. After 11 days of anti-tuberculosis treatment, the patient′s condition improved significantly.Conclusions:Mycobacterial spindle cell pseudotumor in children is a very rare benign lesion. It is characterized by spindle-histiocyte proliferation caused by mycobacterium infection. An acid-fast stain appears necessary for confirming the diagnosis.

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.

Objective:To improve the awareness of neuroblastoma (NB) with cervical lymph node metastasis in children patients by summarizing the clinical features of such patients and analyzing their survival situation.Methods:The research analyzed the medical records of 225 patients with cervical lymph node metastasis of NB from April 1, 2007 to May 31, 2017 in Beijing Children′s Hospital, Capital Medical University.The treatment were divided into 2 phases according to treatment time (one from April 1, 2007 to December 31, 2011 and the other from January 1, 2012 to May 31, 2017). The survival situation and treatment effect in each phase were analyzed.The following up time ended at Jan 1, 2018.Results:(1)Clinical features: total 225 cases admitted in the research with about 37.3% of all the NB patients.One hundred girls(44.4%) and 125 boys(55.6%). The age from 2 months to 147 months, the me-dian age of patients was 37 months.The age under 18 months were 27 cases(12.1%). The majority primary site of tumor was located in retroperitoneal(174 cases, 77.3%) and mediastinum(48 cases, 21.3%). There were 33 cases which metastasic site confined to cervical lymph node(4N stage, 14.7%); 139 cases (62.1%) with bone marrow metastasis, 159 cases (71.0%) with bone metastasis.The number of patients in high-risk group was 208 cases(91.2%), while the low-risk and the medium-risk group was 17 cases(7.5%). (2)Treatment effect and survival analysis: a total of 200 cases received systemic treatment and followed-up in our hospital.The follow up time from 2 months to 123 months, the median follow up time was 23 months.The 3 year overall survival (OS) rate of all the patients was 56.4%, the 3 year event free survival (EFS) rate was 52.0%.While the 5-year OS was 46.5%, and the 5-year EFS was 39.7%.According to the first phase of treatment(April 1, 2007 to December 31, 2011), the 3-year EFS was 49.6%, and the 3-year OS was 54.4%, the 5-year EFS was 39.5%, and the 5-year OS was 44.7%.According to the second phase of treatment(January 1, 2012 to May 31, 2017), the 3-year EFS was 58.1%, and the 3-year OS was 57.3%.The 5-year EFS was 48.7%, and the 5-year OS was 46.8%.About the 4N patients, the 3-year EFS was 71.2%, and the 3-year OS was 82.2%.The 5-year EFS was 61.5%, and the 5-year OS was 76.7%.Conclusions:Cervical lymph node is one of the most common distant metastasis of NB.More than half of the patient with bone or bone marrow metastasis.The prognosis of patients′ metastatic disease limited to cervical lymph nodes(4N stage), but still worse than the foreigner haver reported.The probable reason is the proportion of high-risk patients in the center is higher than the foreign research.

Objective:To summarize the clinical features, therapeutic effects and prognostic factors of children with extracranial malignant germ cell tumor (MGCT), and further to improve the recognition of this disease.Methods:The clinical information and therapeutic effects of children patients diagnosed with MGCT and treated in Hematology-Oncology Center in Beijing Children′s Hospital, Capital Medical University from January 2008 to December 2018 were analyzed retrospectively, and the risk factors affecting the prognosis were discussed.Results:A total of 35 patients were collected in this study, including 19 girls and 16 boys, with a median age of 71 months.Forty-two point four percent (14/33 cases) of them were <3 year-old, and 39.3% (13/33 cases) of them were >6 year-old.The primary tumors were located at the gonad in 9 cases (6 cases in the ovary and 3 cases in the testis), and extragonadal sites in 26 cases (8 cases in the pelvic cavity, 8 cases in the mediastinum, and 10 cases in the sacrococcygeal region). Five cases were in stage Ⅱ, 16 cases in stage Ⅲ, and 14 cases in stage Ⅳ.Eleven cases were at intermediate risk, and 24 cases were at high risk.All children were followed up for (25.43±4.82) months, and given standard treatment of surgery plus chemotherapy.The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 87.4% and 67.1%, respectively.The 2-year OS rate and EFS rate in patients at stage Ⅱ and Ⅲ (93.8% and 80.4%, respectively) were significantly higher than those at stage Ⅳ (66.7% and 45.1%, respectively) ( χ2=0.649, 0.739; P=0.021, 0.037). The 2-year EFS rate in patients with and without distant metastasis at the early stage of the disease was 43.8% and 86.9%, respectively, and the differences were significant ( χ2=0.694, P=0.028). The complete remission (CR) rates of intermediate-risk and high-risk children with tumor completely resected at the early stage of the disease were 100.0% (8/8 cases) and 71.4% (5/7 cases), respectively.The CR rate of patients who received 2-4 cycles of chemotherapy and had complete tumor resection after diagnosis by puncture was 72.7% (8/11 cases), and 40.0% (2/5 cases) of the children with incomplete resection got tumor progression.For eight patients with events, their alpha-fetoprotein (AFP) levels decreased slowly at the early stage of the disease and increased significantly as the disease progressed. Conclusions:The onset-age of MGCT is mainly <3 year-old and >6 year-old.The stan-dard treatment that combines surgery and chemotherapy can achieve a good overall prognosis.Incomplete surgical resection and a slow decline of AFP during treatment contribute to adverse prognosis.The outcomes of patients with tumor progression can be improved by increasing chemotherapy courses, secondary surgery and autologous stem cell transplantation.

Objective:To analyze the clinical features and prognosis of pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), and further understand these tumors.Methods:Twenty-nine NRSTS children were admitted to the Hematological Oncology Ward of Beijing Children′s Hospital from June 2011 to May 2018.The clinical and pathological data of these children were collected, and the relationships of the prognosis with clinical characteristics Intergroup Rhabdomyosarcoma Study(IRS) stage, Children′s Oncology Group(COG) risk grouping were analyzed.All the patients were followed up until October 31, 2018.The survival analysis was performed by Kaplan-Meier method.Results:There were 14 boys and 15 girls in the enrolled 29 children, aging from 7 to 169 months, with a median age of 59.5 months.There were 10 pathological types, including synovial sarcoma, infantile fibrosarcoma and malignant rhabdomyoid tumors in 5 cases, and other pathological types in 14 cases.Tumors originated from the head and neck in 10 cases, limbs or trunk in 6 cases, visceral sites in 13 cases.Ten cases showed distant metastasis.There were 12 cases at IRS stage Ⅰand Ⅱ, and 17 cases of stage Ⅲ and Ⅳ.All the children were treated with surgery and chemotherapy with or without radiotherapy.Nine cases received preoperative chemotherapy, 17 cases received postoperative chemotherapy, 3 cases could not be resected surgically.The follow-up period ranged from 4 to 89 months, with a median follow-up of 16 months.Six of 29 children died, including 3 cases of malignant rhabdomyoid sarcoma.The 2-year overall survival(OS) rate of all the children was 77.4% and the 2-year event-free survival (EFS) rate of all the children was 53.2%.By analyzing the clinical factors, it was found that the IRS stage, COG risk group, primary sites were related to prognosis.The 2-year EFS rate of children with IRS Ⅰ-Ⅱ and Ⅲ-Ⅳ were 75.0% and 35.9%, respectively ( χ2=7.303, P=0.007), the 2-year OS rate was 100% and 61.8%, respectively( χ2=4.81, P=0.028); The 2-year EFS of children in COG low-risk group and median/high-risk group were 66.7% and 44.7%, respectively( χ2=4.155, P=0.042), the 2-year OS rate of children in COG low and median/high-risk was 100% and 66.3%, respectively( χ2=3.383, P=0.066); the 2-year OS rate of children in visceral and non-visceral sites were 59.3% and 92.9%, respectively ( χ2=4.202, P=0.04). Conclusions:NRSTS in children is heterogeneous, and surgery is the main treatment. Children with primary tumors located in visceral sites and at IRS Ⅲ-Ⅳ had poor outcomes.

Objective:To summarize the clinical features, treatment and outcomes of cervical neuroblastoma (NB) subjected to multi-disciplinary treatment.Methods:The clinical features of cervical NB patients who were admitted to Beijing Children′s Hospital, Capital Medical University from February 2015 to October 2018, were retrospectively analyzed.The tumor makers [lactate dehydrogenase(LDH), neuron-specific enolase(NSE), urine homovanillic acid/creatinine(HVA/Crn), and urine vanillyl-mandelic acid/creatinine(VMA/Crn)], index of tumor burden(KTB), bone marrow examination, histopathologic types, N- MYC, gene amplification and 11q23 depletion type, staging and grouping, treatment and outcomes were analyzed.Follow-up was ended on March 31 st, 2019. Results:The 13 cervical NB patients aged from 1 month to 47 months (median age: 10 months), and 8 patients (61.5%) were younger than 18 months old.The course of disease ranged from 0.5 to 24.0 months (median course: more than 1 month). Seven patients (53.8%) presented with cervical masses.According to International Neuroblastoma Staging System (INSS), 8 patients (61.5%) were identified as stage Ⅱ, 3 patients (23.1%) as stage Ⅲ, and 2 patients (15.4%) as stage Ⅳ.There were 8 patients (61.1%) at low risk, 4 patients (30.8%) at intermediate risk, 1 patient (7.7%) at high risk.As for the laboratory examinations, LDH was increased in 7 patients (53.8%), and normal in 5 patients (38.5%). NSE was increased in 9 patients (69.2%), and normal in 4 patients (30.8%). Urine VMA/Crn was increased in 5 patients (38.5%), and normal in 8 patients (61.5%). HVA/Crn was increased in 8 patients (61.5%), and normal in 5 patients (38.5%). KTB was increased in 5 patients (38.5%), and normal in 5 patients (38.5%). No NB cell was detected in bone marrow of 13 patients.The pathologic type was NB in 9 patients (69.2%), and ganglioneuroma in 4 patients (30.8%). N-MYC gene amplification and 11q depletion were not detected.All the 13 patients accepted regular chemotherapy, radiotherapy and primary tumor resection in accordance with the staging and clinical risk grouping.The range of follow-up time was 5 to 48 months (median: 24 months). All of the patients fi-nished their treatment and were followed up regularly.Nine patients (69.2%) achieved complete remission, 4 patients (30.8%) achieved partial remission, and none of the patients had progression of disease.Conclusions:Cervical NB subjected to multi-disciplinary treatment has a smaller age at admission, mostly presented with cervical masses and rarely accompanied with distant metastasis.They are mostly at low risk or intermediate risk, and can achieve good outcomes after regular treatment.