[Pay attention to molecular pathological diagnosis of pediatric glioma].

Glioma is one of the most common central nervous system tumors in children.Increasing studies show that compared with adults, some gliomas in children have unique molecular genetic characteristics and completely different biological behaviors, although they are similar to adults in morphology and nomenclature. Therefore, pediatric glioma is by no means a "miniature version" of adults. In the 5th edition of WHO classification of central nervous system tumors published in the end of 2021, one of the most important revisions is the division of the classification into adult-type and pediatric-type diffuse gliomas, and the latter is further divided into pediatric-type diffuse low-grade gliomas and pediatric-type diffuse high-grade gliomas. In addition to histological morphology and clinical features, the basis of classification includes more molecular features. Therefore, in clinical practice, we need to pay more attention to the significance of molecular pathological diagnosis in the diagnosis and treatment of gliomas in children.

[Research progress of pyruvate kinase type M2 in hepatocellular carcinoma].

Primary hepatocellular carcinoma is one of the most common high-grade malignant tumors in the world. Its incidence ranks fifth among malignant tumors in China, and various therapeutic measures have poor curative effect. Pyruvate kinase type M2 is a key enzyme in the glycolytic pathway, and its abnormal expression in liver cancer is closely related to the proliferation, metastasis, diagnosis, treatment, prognosis, as well as drug and radiation resistance. Therefore, multi-pathway targeted regulation of pyruvate kinase type M2 use is expected to become a new direction for the treatment of primary liver cancer.

[Extraskeletal mesenchymal chondrosarcoma in central nerve system: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system (CNS). Methods: The clinicopathological findings, immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up. Results: The ages of patients ranged from 20-35 years. Three patients had intracranial lesions and one had intradural tumor. The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage. There was hemangiopericytoma-like pattern with calcification and ossification. The tumor cells were positive for VIM and SOX9; and the small cells were positive for CD99, NSE and NKX3.1. The cells in chondroid matrix were positive for S-100. All tumor cells were negative for markers including CKpan, EMA and desmin. At molecular analysis, HEY1-NCOA2 fusion transcripts were identified in three patients. The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2. Follow-up information was obtained in two patients, and both were free from recurrence or metastasis at 8 and 20 months. Conclusions: Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis. In addition to SOX9, NKX3.1 can be another useful antibody for the differential diagnosis. The combination of pathological characteristics, immunophenotype and genetic profile of tumor is essential for diagnosis.

[Chordoid glioma: a clinicopathological study].

Objective: To analyze the clinicopathological features of chordoid glioma. Methods: A total of 12 cases of chordoid gliomas from 2009 to 2020 in Xuanwu Hospital of Capital Medical University and General Hospital of Chinese People's Liberation Army were retrospectively analyzed. The clinical and imaging characteristics, pathologic and molecular characteristics were analyzed, and the relevant literature was reviewed. Results: All 12 patients (4 males and 8 females) aged from 25 to 67 years (mean 39 years) and mainly had a history of headache or/and vision loss. MRI showed that the lesions located in the third ventricle, and they showed abnormal enhancement. Pathologically, these 12 cases displayed the morphologic characteristics of chordoid gliomas, including papillary structures in two cases. Immunohistochemically, GFAP and vimentin were expressed in all 12 cases (12/12). TTF1 was also expressed in all cases (10/10). CD34 and CKpan were seen in 11 cases (11/12). EMA with dot-and/or-ring like positivity was seen in 9 cases (9/10). Tissues were available in nine chordoid gliomas for Sanger sequencing to detect PRKCA and IDH gene mutation, and eight cases (8/9) showed PRKCA gene D463H mutation. None of these cases showed IDH1 R132 and IDH2 R172 mutation. All 12 patients underwent surgery, and four were lost to follow up. The remaining eight patients were progression or recurrence free at last follow-up in January 2021. Conclusions: Chordoid gliomas have relatively distinguishing clinical and histopathological features. PRKCA gene mutation in chordoid gliomas can be considered as a biomarker for the diagnosis and differential diagnosis of chordoid gliomas, and may provide a direction for future targeted therapy.

[Clinicopathological features of diffuse leptomeningeal glioneuronal tumor].

Objective: To investigate the clinicopathological features, diagnosis and prognosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). Methods: Five cases of DLGNT diagnosed from January 2016 to January 2020 were collected from Xuanwu Hospital, Capital Medical University. The clinical features, histopathologic characteristics, immunohistochemical and molecular genetic findings and prognosis were analyzed and the relevant literature was reviewed. Results: The five patients (two males and three females) were aged 2 to 52 years (median 11 years), and had history of increased intracranial pressure (headache and vomiting) or limb weakness. Three of them were younger than 16 years of age. The imaging studies showed diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement, with or without parenchymal involvement. At times there were associated small cyst-like lesions. Imaging interpretations were inflammatory lesions in three cases and space occupying lesions in two. Microscopically, in three cases the tumors showed low to moderate cellularity, consisting of relatively monomorphous oligodendrocyte-like cells arranged in small nests or diffusely distribution. No mitosis and necrosis were observed. In two cases there were increased cellularity with a diffuse honeycomb pattern. The tumor showed mild to moderate polymorphism with hyperchromatic nuclei. Mitosis, endothelial vascular proliferation and glomeruloid vessels were seen. Necrosis was absent. The tumor cells in all five cases were positive for synaptophysin,Olig2 and negative for IDH1 and H3 K27M. GFAP was focally positive in four cases and only one case expressed NeuN partly. The Ki-67 labeling index was 1%-35%. BRAF fusion was detected in four cases. Genetic analysis showed solitary 1p deletion in two cases (2/5), while all cases were negative for 1p/19q co-deletion (0/5). The five patients were followed up for 13 to 28 months (median 15 month). One patient died after 27 months. There was no evidence of tumor progression in the remaining four patients. Conclusions: DLGNT is rare and easily confused with other central nervous system tumors and inflammatory lesions. Therefore, the diagnosis of DLGNT should be made based on comprehensive information including imaging, morphologic and corresponding immunohistochemical examinations and molecular genetics to avoid misdiagnosis and delay in management.

[Clinicopathological and molecular genetic characteristics of adult IDH wild-type diffuse gliomas].

Objective: To analyze the clinicopathological and molecular features and prognostic implications of adult isocitrate dehydrogenase wild type (IDH-wt) diffuse gliomas. Methods: A total of 87 cases of adult IDH-wt diffuse gliomas from 2016 to 2020 in Xuanwu Hospital of Capital Medical University were retrospectively collected. The clinicopathological characteristics and prognosis were analyzed. Molecular characteristics were also analyzed using Sanger sequencing and next generation sequencing. Results: There were 53 males and 34 females, aged from 19 to 78 years (mean 53 years). Histopathologically, there were 63 (72.4%) glioblastomas, 16 (18.4%) anaplastic astrocytomas, six (6.9%) diffuse astrocytomas, and one (1.1%) each of anaplastic oligodendrocytoma, and anaplastic oligodendroglioma. Common molecular genetic changes in IDH-wt gliomas included TERT promoter mutation which was found in 60 cases (69.0%); MGMT promoter methylation in 43 cases (49.4%); EGFR mutation in 38 cases (43.7%); PTEN mutation in 35 cases (40.2%) and TP53 mutation in 32 cases (36.8%). In addition, PDGFRA mutation was detected in 17 cases (19.5%), CDK4 amplification in 15 cases (17.2%) and MDM2 amplification in 11 cases (12.6%). In IDH-wt diffuse gliomas, there was no significant difference in the overall survival between TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4, MDM2 mutations and the wild-type, since these gene mutations could co-occur in any case (P>0.05). Also there was no significant difference in the overall survival between the WHO grade Ⅱ/Ⅲ gliomas and glioblastoma patients with these gene mutations (P>0.05). Conclusions: TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4 and MDM2 gene mutations are common molecular genetic changes in adult IDH-wt gliomas, and are associated with poor prognosis. It is suggested that these genes are potentially useful for predicting the prognosis and should be tested in adult IDH-wt gliomas.

[Sporadic meningioangiomatosis: a clinicopathological analysis].

Objective: To analyze the clinicopathological characteristics, diagnosis and prognosis of meningioangiomatosis (MA), and to investige the possible origion of spindle cells. Methods: Seventeen cases of MA were collected at Xuanwu Hospital of Capital Medical University and the First Affiliated Hospital of Fujian Medical University, from June 2012 to March 2020. The clinical manifestations, radiologic, histopathologic, immunohistochemical features and patients' outcome were analyzed. The presumed origin of spindle cells was evaluated by immunohistochemical staining. Results: Of the 17 patients, 9 were males and 8 were females. The age ranged from 3 to 56 years old. Thirteen patients presented with seizure as the initial symptom. The lesions were solitary and located in the cerebral cortex. Histopathologically, there were proliferation of small blood vessels and perivascular spindle cells in the cerebral cortex. The spindle cells had no obvious atypia, mitoses and necrosis. Four cases were combined with transitional meningioma. Immunohistochemically, the proliferative perivascular spindle cells were positive for vimentin in all cases, and focally positive for EMA and SSTR2. Ki-67 proliferation index was low. Neurofibrillary tangles were demonstrated by AT8. All 17 patients received surgical treatment and were followed up for one to 93 months. None had seizure attacks or tumor recurrence. Conclusions: MA is a rare slow-growing intracranial lesion, and the perivascular spindle cells could be derived from meningothelial cells, and MA is often associated with degeneration of the cerebral cortex and meningioma. The patients have good prognosis after surgical treatment.

[Analysis of the short-and medium-term curative effect of TIPS approach combined with AngioJet thrombus aspiration technology treatment in acute portal vein thrombosis].

Objective: To evaluate the short- and medium-term clinical efficacy of TIPS approach combined with AngioJet thrombus aspiration technology treatment in acute portal vein thrombosis. Methods: 63 cases with acute portal vein thrombosis treated in our center from May 2017 to July 2019 were studied retrospectively, including 49 males and 14 females, aged 35-61 (46 ± 5) years. TIPS approach (with/without) combined with Angiojet thrombus aspiration and gastroesophageal varices embolization was performed simultaneously according to the patient's condition. Regular follow-up for 3-33 (22 ± 3) months after surgery was used to observe the curative effect. Results: The technical success rate was 100%. Portal vein and superior mesenteric vein blood flow were returned to normal after the operation. Two cases of biliary tract injury were untreated. Simultaneously, two cases of intrahepatic arteriovenous fistula were treated with superselective arterial embolization. During the follow-up period, 47 cases (74.61%) had complete portal vein recanalization, 13 cases (20.63%) had partial recanalization, 3 cases (4.76%) had complete portal cavernoma, 7 cases (11.11%) had symptomatic hepatic encephalopathy, 1 case had received artificial liver treatment (1.59%), 1 case had peptic ulcer (11.11%), 6 cases (9.52%) had lost to follow-up, and there was no portal hypertension-related bleeding or death. Conclusion: TIPS approach combined with AngioJet thrombus aspiration technology is safe, effective and feasible in the treatment of acute portal vein thrombosis, and the short- and medium-term clinical effects are satisfactory.

Interfacial mode coupling as the origin of the enhancement of T(c) in FeSe films on SrTiO3.

Films of iron selenide (FeSe) one unit cell thick grown on strontium titanate (SrTiO3 or STO) substrates have recently shown superconducting energy gaps opening at temperatures close to the boiling point of liquid nitrogen (77 kelvin), which is a record for the iron-based superconductors. The gap opening temperature usually sets the superconducting transition temperature Tc, as the gap signals the formation of Cooper pairs, the bound electron states responsible for superconductivity. To understand why Cooper pairs form at such high temperatures, we examine the role of the SrTiO3 substrate. Here we report high-resolution angle-resolved photoemission spectroscopy results that reveal an unexpected characteristic of the single-unit-cell FeSe/SrTiO3 system: shake-off bands suggesting the presence of bosonic modes, most probably oxygen optical phonons in SrTiO3 (refs 5, 6, 7), which couple to the FeSe electrons with only a small momentum transfer. Such interfacial coupling assists superconductivity in most channels, including those mediated by spin fluctuations. Our calculations suggest that this coupling is responsible for raising the superconducting gap opening temperature in single-unit-cell FeSe/SrTiO3.

[High-grade gliomas with H3 G34R mutation: a clinicopathological study].

Objective: To analyze the clinicopathological features and probable mechanisms of high-grade gliomas with H3 G34R mutation. Methods: Five cases of high-grade gliomas with H3 G34R mutation were collected at Xuanwu Hospital, Capital Medical University, Beijing, China, from 2016 to 2019. The clinical and pathological data for each case was retrospectively reviewed. Results: The 5 patients (2 males and 3 females) aged from 15 to 45 years (mean 23 years), and had a history of headache or motor weakness. Four of them were younger than 20 years of age. Magnetic resonance imaging showed that the lesions of 3 cases were seen separately in frontal lobe, parietal lobe or temporal lobe, 1 case involved both frontal lobe and parietal lobe, and otherwise multiple lobes were involved in 1 case. Contrast enhancement could be observed in 2 cases. Pathological examination showed that glioblastoma was the most common entity, with or without primitive neuronal component. All 5 cases showed that H3 G34R was diffusely positive in tumor nuclei with ATRX loss. Moreover, p53 was overexpressed in 4 cases. None of them showed Olig2 expression. Two patients showed disease progression after surgery at 18 months and 24 months, respectively. The latter of the two deceased 3 months after tumor progression. Conclusions: The clinicopathological and molecular genetics features of high-grade gliomas with H3 G34R mutation have relatively similar clinicopathological and genetic features, and more commonly seen in young adults (vs. older adults). Thus, these tumors may be discussed further as a distinct tumor entity.

Spectroscopic Evidence for Electron-Boson Coupling in Electron-Doped Sr_{2}IrO_{4}.

The pseudogap, d-wave superconductivity and electron-boson coupling are three intertwined key ingredients in the phase diagram of the cuprates. Sr_{2}IrO_{4} is a 5d-electron counterpart of the cuprates in which both the pseudogap and a d-wave instability have been observed. Here, we report spectroscopic evidence for the presence of the third key player in electron-doped Sr_{2}IrO_{4}: electron-boson coupling. A kink in nodal dispersion is observed with an energy scale of ∼50 meV. The strength of the kink changes with doping, but the energy scale remains the same. These results provide the first noncuprate platform for exploring the relationship between the pseudogap, d-wave instability, and electron-boson coupling in doped Mott insulators.

[Implication of BRAF V600E and CTNNB1 gene mutations in the pathological classification of craniopharyngioma].

Objective: To investigate the clinicopathological significance of BRAF V600E and CTNNB1 gene mutations in adamantinomatous craniopharyngiomas (ACP) and papillary craniopharyngiomas (PCP). Methods: The retrospective study included a total of 67 craniopharyngiomas diagnosed from October 2009 to August 2018 at Xuanwu Hospital, Capital Medical University. The immunohistochemical staining for ß-catenin and BRAF V600E expression, Sanger sequencing of exon 3 of CTNNB1, BRAF mutation analysis by scorpions amplification refractory mutation system (ARMS) fluorescence quantitative PCR were performed. Univariate survival analysis was used to correlate with tumor recurrence. Results: Of the 67 patients, 53 were ACPs and 14 were PCPs. Four patients underwent multiple operations and one of them presented with malignant transformation into squamous cell carcinoma. Histologically, ACPs were characterized by whorl-like cell clusters, peripheral palisaded layer, stellate reticulum, finger-shaped protrusions, ghost cells and wet keratinous substances. While PCPs usually consisted of mature squamous epithelium associated with fibrovascular stroma resulting in papillary appearance. The nuclear immunopositivity for ß-catenin was observed in 73.6% (39/53) of ACPs, and it was absent in PCPs (0/14). The nuclear translocation of ß-catenin usually presented at whorl-like structures or around ghost cells. Of all the cases, mutations analysis in exon 3 of ß-catenin gene CTNNB1 were successful in 46 cases and 42.1% (16/38) of ACP showed CTNNB1 gene mutation, while none of the PCPs harbored CTNNB1 gene mutation (0/8). The cytoplasmic immunopositivity for BRAF V600E mutant protein was found in all PCPs (14/14) and negative in all ACPs (0/53). ARMS-PCR results showed that BRAF V600E mutations were observed in 13/14 of PCPs but not seen in ACPs (0/53). Follow-up data were available in 35 patients with duration of 2 to 120 months. Ten patients experienced recurrences after the first surgery. Upon univariate survival analysis, only subtotal excision was found to be associated with increased recurrence (P=0.032), while pathological type, postoperative radiotherapy and CTNNB1 gene mutation were not (P>0.05). Conclusions: There is significant difference in the expression of BRAF V600E and CTNNB1 genes between ACP and PCP, and their immunohistochemical and molecular detection therefore can be used in the diagnosis and differential diagnoses of craniopharyngiomas.

[Prognostic implication of alterations in epidermal growth factor receptor and MGMT in glioblastoma].

Objective: To investigate the prognostic impact of alterations of epidermal growth factor receptor(EGFR) and MGMT in glioblastoma. Methods: The retrospective study included 161 supratentorial glioblastomas diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University from 2009 to 2015. EGFR and EGFRvⅢ protein expression was detected by immunohistochemistry; EGFR amplification was detected by fluorescence in situ hybridization; MGMT promoter methylation was detected by pyrosequencing. The change of molecular genetics EGFR and MGMT and outcome were assessed statistically. Results: There were 161 patients, including 85 (52.8%) males and 76 (47.2%) females. The mean age was 53 years, and the median overall survival was 13 months. The integrated classification of glioblastoma included 16 IDH-mutant, 134 wild type, and 11 NOS. The rate of overexpression of EGFR protein was 32.9%(53/161), and that of EGFR amplification was 37.5%(18/48). There was high concordance between immunohistochemistry and FISH(85.4%, Kappa=0.475, P<0.01) and between the level of EGFR protein and EGFR amplification (P<0.01). Twelve cases showed EGFRvⅢ expression, and all also showed EGFR protein overexpression; 149 cases were EGFRv Ⅲ wild type, and EGFR protein overexpression was seen in 27.5%(41/149) of cases. There was no correlation between EGFR and EGFRv Ⅲ expression. Of all cases, 70.2%(106/151) showed MGMT promoter methylation by pyrosequencing. The changes of molecular genetics of EGFR and MGMT were not related. EGFR amplification and protein overexpression had no significant relationship with prognosis. Patients with EGFRv Ⅲ-mutant had shorter survival time than the EGFRv Ⅲ-wild type(P=0.014); patients with MGMT promoter methylation had better prognosis than without (PFS:P=0.002,OS:P=0.006),and MGMT promoter methylation was an independent predictor for overall survival (HR=0.269, 95%CI 0.124-0.583, P=0.001). Conclusions: EGFR protein expression by immunohistochemistry correlates with the status of EGFR amplification. Patients with EGFRv Ⅲ-mutant tumors have poorer prognosis than that with EGFRv Ⅲ-wild type tumors. MGMT promoter methylation is closely associated with prognosis and an independent predictor for overall survival.

Spectral Evidence for Emergent Order in Ba_{1-x}Na_{x}Fe_{2}As_{2}.

We report an angle-resolved photoemission spectroscopy study of the iron-based superconductor family, Ba_{1-x}Na_{x}Fe_{2}As_{2}. This system harbors the recently discovered double-Q magnetic order appearing in a reentrant C_{4} phase deep within the underdoped regime of the phase diagram that is otherwise dominated by the coupled nematic phase and collinear antiferromagnetic order. From a detailed temperature-dependence study, we identify the electronic response to the nematic phase in an orbital-dependent band shift that strictly follows the rotational symmetry of the lattice and disappears when the system restores C_{4} symmetry in the low temperature phase. In addition, we report the observation of a distinct electronic reconstruction that cannot be explained by the known electronic orders in the system.

[Neuropathologic study of massive subcortical heterotopia].

Objective: To investigate the clinicpathologic features and probable mechanisms of massive subcortical heterotopia. Methods: Clinical data, histologic features and neuropathologic data were analyzed in five cases of massive subcortical heterotopia collected from Xuanwu Hospital, Capital Medical University from January 2014 to October 2017. Results: All five patients (three males and two females) had a history of refractory epilepsy with a mean period of 15.4 years (range 7 to 21 years). The median age at surgery was 28.6 years(range 20 to 39 years). Magnetic resonance imaging showed that the lesions were located in the temporal lobe (two cases), parietal lobe (one case), both temporal and occipital lobes (one case) and both temporal and parietal lobes (one case). Pathologic examination disclosed that massive gray matter in subcortical and deep white matter with various shape and size. Moreover, one case also showed subpial and periventricular heterotopias and polymicrogyria. Polymicrogyria or hippocampal sclerosis were seen in the remaining three cases. None of the five patients experienced seizure attacks during the follow-up period. Conclusions: Heterotopia is malformations due to abnormal neuronal migration. Massive subcortical heterotopia due to widespread abnormal neuronal migration is relatively rare. The mechanism of heterotopia together with polymicrogyria needs further discussion.

Coexistence of Replica Bands and Superconductivity in FeSe Monolayer Films.

To elucidate the mechanisms behind the enhanced T_{c} in monolayer (1 ML) FeSe on SrTiO_{3} (STO), we grew highly strained 1 ML FeSe on the rectangular (100) face of rutile TiO_{2}, and observed the coexistence of replica bands and superconductivity with a T_{c} of 63 K. From the similar T_{c} between this system and 1ML FeSe on STO (001), we conclude that strain and dielectric constant are likely unimportant to the enhanced T_{c} in these systems. A systematic comparison of 1 ML FeSe on TiO_{2} with other systems in the FeSe family shows that while charge transfer alone can enhance T_{c}, it is only with the addition of interfacial electron-phonon coupling that T_{c} can be increased to the level seen in 1 ML FeSe on STO.