[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.

[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.

[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.

[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.

[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.

[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.

[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.

[Clinicopathological analysis of 12 cases of children synovial sarcoma].

Objective: To investigate histopathological characteristics, and differential diagnoses of childhood synovial sarcoma. Methods: HE staining, immunohistochemical staining and fusion gene detection by FISH were performed in 12 cases of synovial sarcoma in childhood at Beijing Children's Hospital from 2016 to 2018. Results: There were 6 cases of biphasic type, 1 case of monophasic epithelial type, 3 cases of monophasic spindle cell type and 2 cases of poorly differentiated synovial sarcomas. EMA, CKpan, bcl-2, CD99, TLE1 and CD34 immunostain positivities were observed in 10/12, 9/12, 12/12, 10/12, 10/12 and 0/12 cases respectively. Unique INI1 immunohistochemical staining was observed in 9/12 cases. SS18-SSX gene fusion was detected in 8 of 11 cases by FISH. Conclusions: Synovial sarcoma is rare in children. Histological morphology combined with immunohistochemistry and FISH SS18-SSX fusion gene detection are important for the diagnosis and differential diagnosis of synovial sarcoma in children.

[Langerhans cell histiocytosis in children: clinicopathological and ultrastructural analyses of 345 cases].

Objective: To investigate the clinicopathological and ultrastructural characteristics of Langerhans cell histiocytosis (LCH) in children. Methods: A total of 345 cases of LCH from the Department of Pathology, Beijing Children Hospital from January 2012 to March 2016 were investigated by hematoxylin-eosin stain, EnVision immunohistochemistry and transmission electron microscopy. Results: The rate of primary clinical diagnosis of LCH in children was 46.0%(210/457). Among 345 patients of LCH, 213 were male and 132 were female, the male to female ratio was 1.6∶1.0, and the median age was 21 months (range from 2 days after birth to 13.3 years). There were total 597 lesions, including bony lesions (258, 43.2%), skin lesions (206, 34.5%) , followed by lymph node (16, 2.7%), lung (28, 4.7%), liver (25, 4.2%) and head-neck (50, 8.4%). Single organ system LCH (SS-LCH) was seen in 295 cases (85.5%) and 50 cases (14.5%) presented with multiple organ system involvement LCH (MS-LCH). There was no significant difference in age and gender between SS-LCH and MS-LCH groups. Regarding sites, more lesions were seen in bone and skin in SS-LCH group, in contrast lymph node, lung, liver and head-neck involvements were often seen in MS-LCH group. Immunohistochemically, the expression of CD1a and Langerin was seen in 99.7% (341/342) and 98.8% (338/342) of the cases respectively. The diagnostic rates by light and transmission electron microscopy were 98.8% (341/345) and 97.4% (112/115) respectively (P>0.05). Conclusions: LCH of children occurs predominantly in SS-LCH pattern, frequently involving bone, skin, lymph node, lung and liver and other sites with unique histopathological, immunophenotypical and ultrastructural features. Accurate diagnosis relies on the morphology, immunophenotype and ultrastructural features. Further refinement of specimen processing may improve the accuracy of pathological diagnosis.

[Prevalence and risk factors of diabetes and prediabetes in adults in Jingyuan Ningxia].

Objective: To investigate the prevalence and risk factors of diabetes and prediabetes in Jingyuan County in Ningxia. Methods: A cross-sectional survey including 10 639 participants (18-88 years of age) with a multistage sampling was conducted in Jingyuan County between January, 2014 and April, 2015. Questionnaires, physical examinations, and laboratory tests were included in the survey. Results: Among all the subjects, 10 491 participants (men: 4 826, women: 5 665) with complete data were included in the analysis. The standardized prevalence of diabetes and prediabetes was 4.2% (men: 3.9%, women: 4.5%) and 8.8% (men: 7.6%, women 10.3%), respectively, in which the standardized prevalence of diabetes was higher in Hui (4.5%) than that in Han (3.5%) (P< 0.05). Logistic regression analyses showed that age, family history of diabetes, overweight/obesity, hypertriglyceridemia and hypertension were positively associated with prediabetes and diabetes with the odds ratios being 1.60 and 2.14 (age, P< 0.001), 1.40 and 3.32 (family history, P< 0.05), 1.47 and 1.57 (overweight/obesity, P< 0.001), 1.88 and 2.55 (hypertriglyceridemia, P< 0.001), 1.44 and 1.89 (hypertension, P< 0.001), respectively. Conclusions: The prevalence of diabetes was relatively low in the rural area in Ningxia. However, it is still essential to take active interventions in people at high risk of diabetes in order to prevent the incident diabetes.

[Chest wall hamartoma of infancy: a clinicopathologic observation of five cases].

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of chest wall hamartoma of infancy. Methods: The clinical data, histopathologic features and immunophenotype of five chest wall hamartomas were analyzed, and the relevant literature was reviewed. Results: The patients' age ranged from seven months and eight days to 20 months at time of resection, although the lesions were detected in the neonatal period. The male-to-female ratio was 4∶1. Three cases were unilateral, two presented with multiple lesions; and four were located on the right side. CT-scan of the chest showed expansile soft tissue masses with heterogeneous density containing calcifications or ossifications in one or more ribs showing partial bone destruction. Patients were all treated by complete resection. Grossly, the lesions comprised solid and cystic areas, the latter showing hemorrhage. Microscopic examination revealed the solid areas were composed of islands of multilobulated hyaline cartilage interspersed within spindle or oval mesenchymal cells, waved bone and collagen fibers. Around the chondroid tissue, there were focal endochondral ossification and mucus-like background. In addition, there were areas of aneurysmal bone cyst-like changes formed by hemorrhagic dilated cystic spaces. Immunohistochemistry was generally not necessary to establish the diagnosis. Conclusions: Chest wall hamartoma is a rare but benign lesion of infancy, showing characteristic clinicopathologic features. The prognosis are excellent after complete surgical excision.

[The prevalence of metabolic syndrome among adults in rural areas of Ningxia Hui autonomous region].

Objective: To investigate the prevalence of metabolic syndrome (MS) among adults in rural areas of Ningxia Hui autonomous region. Methods: A cross-sectional study was conducted in 10 639 adults enrolled with a multistage method from Jingyuan County. The MS was identified according to Chinese type 2 diabetes prevention guide (2013). Results: Among all the subjects, 17.4% of them met the MS definition with the standardized prevalence of 14.7% after adjustment of sex and age. The prevalence and standardized rate of MS in men were 19.9% and 17.3%, and in women were 15.3% and 13.5%.The prevalence of MS in men was higher than that in women(P<0.001) and increased with aging in both genders. The prevalence and standardized rate of abdominal obesity, hyperglycemia, hypertension, high triglycerides, and low HDL-C were 19.5% and 16.7%, 15.0% and 12.9%, 42.0% and 37.1%, 25.8% and 23.1%, 28.5% and 27.7%, respectively. The rate of abdominal obesity was higher in women than in men (20.5% vs 18.2%, P=0.004), whereas the rate of hypertension, high triglycerides, and low HDL-C were higher in men than in women (all P<0.01). The prevalence of having one parameter of the MS was 68.4%. Conclusion: The prevalence of MS is higher in rural areas of Ningxia Hui autonomous region, suggesting that a series of comprehensive prevention measures should be carried out to prevent and control the MS so as to improve the public health conditions in rural areas.

[Diagnostic utility of tyrosine hydroxylase in peripheral neuroblastic tumors].

Objective: To investigation the diagnostic utility of tyrosine hydroxylase (TH) immunohistochemically as a marker of peripheral neuroblastic tumors(pNT). Methods: The study included 1 024 cases, 643 primary and metastatic pNT cases, 381 non-pNT cases, including small round cell tumors such as primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, lymphoma, nephroblastoma, as well as other more common tumors (medulloblastoma, hepatoblastoma, pleuropulmonary blastoma, renal clear cell sarcoma, Langerhans cell histiocytosis, lipoblatoma etc). Tissue slides of these 1 024 cases were stained with TH and other common antibodies to evaluate whether TH was useful to identify pNT. Results: TH showed cytoplasmic staining in 100.0% (643/643) of pNT and 3.9% (15/381) of non-pNT. TH expression was seen in some poorly differentiated and undifferentiated tumors with focal or scattered patterns. In some cases, more scattering was seen in neuroblastoma with poor differentiation. The sensitivity, specificity, positive predictive value and negative predictive value of TH was 100.0% (643/643), 96.1%(366/381), 97.7%(643/658) and 100.0% (366/366), respectively. There was no TH expression in the 248 cases of other small round cell tumors (PNET, rhabdomyosarcoma, lymphoma, etc), thus suggesting TH was useful to differentiate between PNET and neuroblastoma. As CD99 was positive in 95% PNET, some PNET would be CD99 negative. In those cases, particularly with diffuse rosettes forming, TH immunostaining would be useful. Conclusion: TH is sensitive and specific for pNT in the differential diagnosis from other tumors of childhood and shows high diagnostic utility.