[Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis].

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.

[Interpretation on genetic tumour syndromes in the 5th WHO classification of paediatric tumours: part â ¡].

WHO firstly published the classification of paediatric tumours, in which genetic tumour syndromes were introduced as a separate chapter, covering the clinicopathological features, molecular genetic alterations, and diagnostic criteria of various tumor susceptibility syndromes common in children. This article briefly introduces and interprets 5 hotspot genetic tumour syndromes (neurofibromatosis type 1, naevoid basal cell carcinoma syndrome, von Hippel-Lindau syndrome, familial adenomatous polyposis and xeroderma pigmentosum) based on relevant literature, in order to bring new perspectives and insights to pathologists and clinicians.

[Correlation of 1p/16q loss of heterozygosity and 1p gain with clinicopathological characteristics and prognosis in Wilms tumor].

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.

Analysis of changes in serum high t-PINP/ß-CTX ratio and risk of re-fracture after vertebral osteoporotic fracture surgery.

OBJECTIVE: This study's aim was to investigate the expression changes of total type I procollagen amino-terminal peptide (t-PINP) and type I collagen C-terminal peptide (ß-CTX) in serum after vertebral osteoporotic fracture surgery and the clinical value of predicting the risk of refracture. PATIENTS AND METHODS: The clinical data of 100 patients with vertebral osteoporotic fractures treated in our hospital from January 2019 to January 2020 were retrospectively analyzed, and the patients were divided into the control group (patients without re-fracture, n = 68) and the observation group (patients with re-fracture, n = 32) according to whether they had re-fracture at 2-year follow-up. The risk factors of postoperative re-fracture were analyzed using Multivariate logistic regression analysis. The serum contents of t-PINP, ß-CTX, osteocalcin (BGP), and calcium (Ca) were measured. Bone mineral density (BMD) was measured by bone densitometer. The correlation between the t-PINP/ß-CTX ratio and the bone metabolic index was analyzed by Pearson correlation. The area under the curve (AUC), sensitivity, and specificity of t-PINP/ß-CTX in predicting the risk of re-fracture were determined by the receiver operating characteristic (ROC) curve. RESULTS: There was a significant difference in age, the number of vertebral bodies with initial fracture, and whether there was leakage of bone cement between the two groups (p < 0.05). Age, the number of vertebral bodies with primary fracture, and the leakage of bone cement were risk factors affecting re-fracture after operation (p < 0.05). Compared with those in the control group, the level of t-PINP and the ratio of t-PINP/ß-CTX were higher, and the ß-CTX level was lower in the observation group (p < 0.05). The BGP level was higher, and the levels of BMD and Ca were lower in the observation group than those in the control group (p < 0.05). Pearson correlation analysis showed that t-PINP had a positive correlation with BGP (r = 0.222, p < 0.05). ß-CTX was positively correlated with BMD and Ca (r = 0.230, 0.269, p < 0.05). The ratio of t-PINP/ ß-CTX was negatively correlated with BMD and Ca (r = -0.621 and -0.660, p < 0.05), but positively correlated with BGP (r = 0.517, p < 0.05). ROC curve analysis showed that the AUC of t-PINP, ß-CTX, and the ratio of t-PINP/ß-CTX in predicting the risk of re-fracture after vertebral osteoporotic fracture surgery was 0.724, 0.736, and 0.838, respectively. CONCLUSIONS: The t-PINP/ß-CTX ratio was significantly correlated with the bone metabolic indexes in patients with vertebral osteoporotic fractures. The detection of the changes in its index can help predict the risk of postoperative re-fracture, providing a new idea for clinical assessment of the risk of postoperative re-fracture.

PDCA cycle management combined with detailed management of postoperative deep vein thrombosis in patients undergoing hip replacement surgery.

OBJECTIVE: This study aimed to analyze and explore the effect of Plan-Do-Check-Act (PDCA) cycle management combined with detailed management on postoperative deep venous thrombosis in patients undergoing hip replacement surgery. PATIENTS AND METHODS: Patients who underwent hip replacement surgery in our hospital between November 2021 and April 2023 were recruited for the study. After screening, patients who met all the inclusion criteria were assessed for eligibility. Finally, 80 adults were enrolled. All patients were assigned into observation and control groups (1:1) according to the sequence of admission, i.e., patients admitted between November 2021 and August 2022 were the control group, and patients admitted between September 2022 and April 2023 were the observation group. RESULTS: The intraoperative blood loss and hospital stay in the observation group were significantly less than those in the control group (p<0.05). After the intervention, the levels of plasma prothrombin time (PT), thrombin time (TT), and thromboplastin time (APTT) in the observation group were higher than those in the control group, and the DD level was lower than that in the control group (p<0.05). There was one patient in the observation group who developed deep venous thrombosis after the operation, and the incidence was 2.50%. The rate was significantly lower than that of the control group (p<0.05). The hip joint function score of the observation group was higher than that of the control group, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale score was lower than that of the control group (p<0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group (p<0.05). CONCLUSIONS: PDCA cycle management plus detailed management in patients with hip replacement surgery yields a favorable clinical outcome, which can effectively prevent postoperative deep vein thrombosis, and improve surgical indicators and postoperative coagulation function. Also, it reduces the incidence of adverse reactions in patients and facilitates recovery. It has a beneficial impact on the prognosis of patients and deserves promotion.

[Retropharyngeal lymph node dissection in head and neck cancers treated with transoral robotic surgery].

Objective: To evaluate the indications, safety, feasibility, and surgical technique for patients with head and neck cancers undergoing transoral robotic retropharyngeal lymph node (RPLN) dissection. Methods: The current study enrolled 12 consecutive head and neck cancer patients (seven males and four females) who underwent transoral robotic RPLN dissection with the da Vinci surgical robotic system at the Sun Yat-sen University Cancer Center from May 2019 to July 2020. Seven patients were diagnosed as nasopharyngeal carcinoma with RPLN metastasis after initial treatments, 4 patients were diagnosed as thyroid carcinoma with RPLN metastasis after initial treatments, and one patient was diagnosed as oropharyngeal carcinoma with RPLN metastasis before initial treatments. The operation procedure and duration time, intraoperative blood loss volume and complications, nasogastric feeding tube dependence, tracheostomy dependence, postoperative complications, and hospitalization time were recorded and analyzed. Results: All patients were successfully treated by transoral robotic dissection of the metastatic RPLNs, none of which was converted to open surgery. RPLNs were completely resected in 10 patients, and partly resected in 2 patients (both were nasopharyngeal carcinoma patients). The mean number of RPLN dissected was 1.7. The operation duration time and intraoperative blood loss volume were (191.3±101.1) min and (150.0±86.6) ml, respectively. There was no severe intraoperative complication such as massive haemorrhage or adjacent organ injury during surgery. Nasogastric tube use was required in all patients with (17.1±10.6) days of dependence, while tracheotomy was performed in 8 patients with (11.6±10.7) days of dependence. The postoperative hospitalization stay was (8.5±5.7) days. Postoperative complications occurred in 4 patients, including 2 of retropharyngeal incision and 2 of dysphagia. During a follow-up of (6.5±5.1) months, disease-free progression was observed in all patients, 10 patients were disease-free survival and other 2 patients were survival with tumor burden. Conclusions: The transoral robotic RPLN dissection is safety and feasible. Compared with the traditional open surgical approach, it is less traumatic and safer, has fewer complications and good clinical application potentiality. The indications for transoral robotic RPLN dissection include thyroid carcinoma, oropharyngeal carcinoma, and some selected nasopharyngeal carcinoma and other head and neck cancers. Metastatic RPLNs from some nasopharyngeal carcinoma with incomplete capsule, unclear border and adhesion to the surrounding vessels are not suitable for transoral robotic RPLN dissection.

Change of zinc mobilization and gene expression of key zinc transport proteins between the yolk sac membrane and liver of duck embryonic developing.

Zinc (Zn) deposition in egg yolk is essential for the rapid growth and complete development of the avian embryo. Thus, it is crucial to obtain maximal Zn mobilization at an appropriate time during development in favor of the survival of avian embryos. The aim of this study was to study the developmental change of Zn mobilization and gene expression related to key Zn transport proteins between the yolk sac membrane and embryonic liver from the incubation d 17 (E17) to d 32 (E32) during duck embryonic developing. The weights of duck embryo, embryo without yolk sac, and embryonic liver increased as well as the yolk sac weight decreased linearly (P < 0.0001) when incubation day increased. The Zn concentration in the yolk sac did not change from E17 to E29 and only declined significantly from E29 to E32 of duck embryos, while hepatic Zn level decreased linearly as with the increased incubation time (P < 0.01). When the incubation day increased, the decreased Zn amount in the yolk sac and the increased Zn amount in the embryonic liver were observed (P < 0.0001). The calculated transfer-out rate of Zn in the yolk sac and transfer-in rate of Zn in livers were both increased from E23-26 to E29-32 (P < 0.01). Among E17, E23 and E29, the solute carrier family 39 member (ZIP) of ZIP10, ZIP13, and ZIP14 genes mRNA expressions were increased in yolk sac membrane but were decreased in the embryonic liver, while metallothionein 1 mRNA expression was increased both in the yolk sac membrane and liver (P < 0.05). In conclusion, yolk sac membrane and embryonic liver tissues displayed the similar developmental patterns of Zn mobilization and metallothionein 1 mRNA expression from E17 to E32 during duck embryonic developing. The appropriate time of the maximal rate of Zn mobilization were observed between E29 and E32 of duck embryo, associated with the significant changes of gene expression related to some key Zn transport proteins on E29 in yolk sac membrane and liver tissues.

[Hemolytic uremic syndrome complicated with IgA nephropathy: a clinicopathological study].

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.

[Mycobacterial spindle cell pseudotumor in children: a clinicopathological study of two cases].

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.

[Clinical characteristics and prognostic analysis of 458 children with high-risk neuroblastoma in a single center].

Objective: To summarize the clinical characteristics of high-risk neuroblastoma (HR-NB) in a single center, analyze the prognostic factors of HR-NB. Methods: The clinical data of children with HR-NB who were treated and followed up at the hematology-oncology center of Beijing Children's Hospital from February 1, 2007 to June 30, 2018 were analyzed retrospectively. The clinical features were summarized. Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. The last follow-up time was June 30, 2019. Results: A total of 458 children with HR-NB were enrolled in this study, including 265 males (57.9%) and 193 females (42.1%), the age at diagnosis was 40.0 months (4.5-148.0 months), the follow-up time was 22.0 months (0.2-138.0 months) and the time of tumor progression or recurrence was 15 months (1-72 months). The 5-year event-free survival (EFS) rate was (31.2±2.6)% and the 5-year overall survival (OS) rate was (43.9±3.2)%. The 5-year EFS rate and 5-year OS rate in 142 hematopoietic stem cell transplantation (HSCT) patients with bone marrow metastases were better than that in 196 non-transplantation cases with bone marrow metastases ((26.5±4.5)% vs. (25.1±3.6)%, χ²=13.773, P=0.001; (38.1±5.5)% vs. (35.7±4.7)%, χ²=9.235, P=0.002); 128 transplantation patients with bone metastases had higher 5-year EFS rate and 5-year OS rate than 188 non-transplantation cases with bone metastases ((28.5±5.0)% vs. (26.7±3.8)%, χ²=10.222, P=0.001; (37.1±6.0)% vs. (36.2±4.8)%, χ²=7.843, P=0.005). The 5-year EFS rate was higher in 37 HSCT patients with MYCN amplification than in 49 non-transplantation cases with MYCN amplification ((26.8±8.0) % vs. (20.5±6.4) %, χ²=5.732, P=0.017). No significant difference was found in 5-years OS rate between transplantation group with MYCN amplification and non-transplantation group with MYCN amplification ((31.4±8.6) % vs. (26.2±7.4) %, χ²=3.230, P=0.072). Univariate survival analysis showed that lactate dehydrogenase (LDH)≥1 500 U/L was associated with poor prognosis of patients with MYCN amplification (χ²=6.960, P=0.008). Multivariate Cox analysis showed bone marrow metastasis and LDH≥1 500 U/L were independent risk factors for poor prognosis of patients with non-MYCN amplification (HR=2.427, 1.618;95%CI：1.427-4.126, 1.275-2.054, P<0.05) for both comparisons. Conclusions: LDH≥1 500 U/L was the poor prognostic factor for patients with MYCN amplification. The bone marrow metastasis and LDH≥1 500 U/L were the poor prognostic factors for HR-NB patients with non-MYCN amplification. HSCT can improve the prognosis of patients with bone or bone marrow metastasis. It can also retard the time of progression or recurrence for patients with MYCN amplification.

[Alveolar soft part sarcoma in children: a clinicopathological study of 13 cases].

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.

[Leydig cell hyperplasia of testis in children: a clinicopathological study].

Objective: To investigate the clinical, pathological features and differential diagnosis of testicular Leydig cell hyperplasia (LCH) . Methods: Clinical data, histological features, immunohistochemical findings, ultrastructural characteristics and follow-up data were analyzed in three cases of LCH. The cases were collected from 2011 to 2014 at Beijing Children's Hospital. A literature review was performed. Results: Two males (1.8 years and 2.9 years of age) showed isosexual pseudoprecocity with elevated serum testosterone. Imaging study showed bilateral testicular enlargement with multiple small nodules in the parenchyma. Another 13 years-old patient showed male pseudohermaphroditism and cryptorchism. Gross examination showed the bilateral markedly enlarged testis without discrete lesion. Histologically, LCH was seen in both nodular and diffuse patterns without destruction of seminiferous tubules. Adjacent spermatogenesis was noted. Immunohistochemically, the Leydig cells were positive for inhibin, calretinin and Melan A and ultrastructural analysis showed enriched cytoplasmic endoplasmic reticulum. Two cases had followed up for 7 years. One patient was symptom-free and one was stable. Conclusion: LCH is a rare benign condition, which is easily misinterpreted as testicular tumor or non-neoplastic diseases. Clinical presentation, imaging study and pathological evaluation are required for the diagnosis.