0.05).TNF-? mRNA in the intervenient group was significantly decreased to that of the control group(P

Objective: To analyze the clinicopathologic characteristics of poorly-differentiated chordoma with INI1 loss in children and to discuss the differential diagnosis. Methods: The clinical, radiological, histopathological profiles and molecular pathologic characteristics of two pediatric poorly differentiated chordoma cases with INI1 loss were reviewed. Results: The patients were a girl and a boy. Both lesions involved the slope. Both patients were presented with progressive muscle weakness or neck pain. Radiological examination showed clivus bone destruction and compression of the brain stem and cervical spinal cord. Histologically, the tumor cells lacked typical organization and were associated with inflammatory cells infiltration. On high power field, the tumor cells were ovoid or fusiform with prominent atypia, vacuolated nuclei and prominent nucleoli. By immunohistochemistry, the tumor cells expressed cytokeratin, epithelial membrane antigen, brachyury and were negative for INI1. In both cases, INI1 gene deletion was detected by FISH. Conclusions Poorly-differentiated chordoma with INI1 loss mainly occurs in children. The morphology is different from classical chordoma.INI1 gene deletion is detectable by FISH. It can be distinguished from atypical teratoid/rhabdoid tumors and other neoplasms by the identification of nuclear brachyury expression. The loss of INI1 expression in poorly-differentiated chordoma might be associated with a poorly-differentiated morphology and an adverse prognosis.

Objective: To evaluate the diagnostic value of a histologic scoring system in congenital biliary atresia and its prognostic relevance. Methods: From January 2017 to June 2018 at Children′s Hospital of Fudan University, 172 wedge liver biopsy specimens were obtained from infants with neonatal cholestasis [119 patients with congenital biliary atresia (CBA) and 53 patients with non-obstructive cholestasis as control]. A pathologist, single-blinded to the final diagnosis, made the histological diagnosis individually based on an 8-feature (portal ductal proliferation, bile duct reaction, bile plugs in portal ductules, liver fibrosis, edema in portal region, cholestasis, inflammatory cells infiltration in portal region, and ductal plate malformation), 21-point scoring system. Results: The main pathologic changes of biliary atresia were hepatocyte cholestasis, hyperplasia of bile ducts, fibrosis and infiltration of inflammatory cells in the portal area. There were significant difference in the degree of portal edema, bile duct hyperplasia and fibrosis between two groups (P<0.01). In addition, there were characteristic bile duct thrombosis in 97.5%(116/119) of the cases and abnormal development of bile duct plate in 9.2%(11/119) of the cases. Compared with non-CBA infant cholestasis group, the difference was statistically significant (P<0.05). The scoring system has high sensitivity, specificity (both 94.1%) and accuracy (94.3%) in the diagnosis of CBA. A score equal to or more than 11 points supported a diagnosis of CBA; whereas a score less than 11 points might suggest cholestasis. The degree of hepatic fibrosis and ductal plate malformation were related to prognosis. Conclusions The liver pathology scoring system (8-feature, 21-point) is more accurate in diagnosing CBA than previous methods, which may guide the clinicopathological diagnosis. This histological scoring system also helps to assess the prognosis of CBA.

Objective: To investigate the clinicopathological features, diagnosis, differential diagnosis, treatment and prognosis of pediatric alveolar rhabdomyosarcoma (ARMS). Methods: The clinical and pathological data of 25 pediatric ARMS from 2008 to 2018 in Children′s Hospital of Fudan University were collected. This histomorphology was assessed, and FOXO1 gene rearrangement was detected with FISH. The treatment details and outcome were analyzed. Results: There were 13 males and 12 females, with ages range from 19 days to 14 years (median 6 years, mean 6.2 years). The ARMS were located in the limbs (13 cases), head and neck (4 cases), trunk (3 cases), abdominal cavity (3 cases), scrotum (1 case) and perianal region (1 case). The ARMS were classified histologically as classic group (18 cases), solid group (5 cases) and embryonic-alveolar mixed group (2 cases). The typical pathological characteristics were small dark round cells arranged in solid, glandular and papillary patterns. The tumor cells expressed ALK (D5F3) (21/25, 84.0%), muscle origin DES (23/25, 92.0%), myogenin (22/25, 88.0%), MYOD1 (19/25, 76.0%), and in some cases they also expressed neurogenic marker Syn (6/25, 24.0%). FOXO1 gene rearrangement was detected by FISH in 24/25 cases (96.0%). Conclusion Pediatric ARMS is rare and has unique clinicopathological characteristics, and needs to be differentiated from other common small round cell malignancies in children. ALK, DES, myogenin, MYOD1 immunohistochemistry and FOXO1 gene rearrangement are valuable aid in the diagnosis of ARMS.

Objective: To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Methods: Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. Results: A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ²=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ²=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ²=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ²=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ²=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. Conclusion The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.