Imaging characteristics and postoperative pathological analysis of bronchiolar adenoma / 中国胸心血管外科临床杂志

@#Objective    To analyze the pathological manifestations and imaging characteristics of bronchiolar adenoma (BA). Methods    The clinical data of 11 patients with BA who received surgeries in our hospital from January 2019 to September 2020 were retrospectively analyzed, including 5 males and 6 females aged 40-73 (62.40±10.50) years. The intraoperative rapid freezing pathological diagnosis, postoperative pathological classification, cell growth pattern, nuclear proliferation index Ki-67 and other immunohistochemical staining combined with preoperative chest CT imaging characteristics were analyzed. Results    The average preoperative observation time was 381.10±278.28 d. The maximum diameter of imaging lesions was 5-27 (10.27±6.34) mm. Eight (72.7%) patients presented with irregular morphology of heterogeneous ground-glass lesions, and 3 (27.3%) patients presented with pure ground-glass lesions. There were 10 (90.9%) patients with vascular signs, 8 (72.7%) patients with vacuolar signs, 1 (9.1%) patient with bronchus sign, 3 (27.3%) patients with pleural traction and 9 (81.8%) patients with burr/lobular sign. The surgical methods included sub-lobectomy in 10 patients and lobectomy in 1 patient. Five (45.5%) patients were reported BA by intraoperative frozen pathology. The postoperative pathological classification included 8 patients with distal-type and 3 patients with proximal-type, and the maximum diameter of the lesions was 4-20 (8.18±5.06) mm. Eight (72.7%) patients showed characteristic bilayer cell structure under microscope, and 10 (90.9%) patients showed thyroid transcription factor 1 expression in pathological tissues. The expression of NapsinA in intracavity cells was found in 9 (81.8%) patients. The Ki-67 index of the lesion tissue was 1%-5% (3.22%±1.72%). Conclusion    The pathological features and imaging findings of BA confirm the premise that BA is a neoplastic lesion. However, to identify BA as a benign or inert tumor needs more clinical data and evidence of molecular pathological studies.

Clinicopathological features and myeloid differentiation factor 88 L265P gene mutation in patients with diffuse large B-cell lymphoma of central nervous system / 中华神经科杂志

Objective:To analyze the clinical features and mutation of myeloid differentiation factor 88 (MYD88) L265P in patients with diffuse large B-cell lymphoma (DLBCL) of central nervous system (CNS).Methods:The clinicopathological materials of 45 cases of DLBCL of CNS were retrospectively collected in Xuanwu Hospital, Capital Medical University from September 2014 to February 2017. The clinicopathological data were retrospectively analyzed, combined with immunohistochemistry, EB virus in situ hybridization, imaging and medical history. The mutation of MYD88 L265P gene was detected by pyrosequencing and its clinical significance was analyzed. Results:The age of the patients ranged from 42 to 82 years [(57.6±8.8) years], including 24 males and 21 females. Totally 93.3% (42/45) of the patients had supratentorial tumours, which were single or multiple. The cerebral hemisphere (31/45, 68.9%) was the most common involved site, and 21 cases (21/45, 46.7%) had multiple lesions. Histologically, DLBCL in the CNS showed diffuse infiltration of tumor tissue, some of which grew around blood vessels in a "sleeve" arrangement. CD 20 and CD 79a were diffusely and strongly positive. Thirty-nine cases (39/45, 86.7%) were non-germinal center B cell (non-GCB) subtype and 6 cases (6/45, 13.3%) were germinal center B cell (GCB) subtype. MYD88 L265P mutation was found in 64.4% (29/45) patients. There was statistically significant difference between non-GCB type (71.8%, 28/39) and GCB type DLBCL (1/6, P=0.017). Compared with the operation/biopsy group without chemotherapy, operation+chemotherapy, biopsy+chemotherapy, operation/biopsy+chemotherapy+stem cell transplantation can improve the survival and prognosis ( HR=0.05, 95% CI 0.01-0.33 , P=0.002; HR=0.04, 95% CI 0.01-0.36 , P=0.004; HR=0.01, 95% CI 0.00-0.17 , P=0.001; respectively). Conclusions:DLBCL of the CNS is aggressive tumor with poor prognosis, the clinical manifestations are complex and diverse, and the diagnosis is challenging. MYD88 L265P is a common and specific gene mutation in primary CNS lymphoma(PCNSL), which is of great significance in the diagnosis and treatment of lymphoma. The MYD88 L265P mutation was more frequently detected in non-GCB than GCB subtype. Chemotherapy can improve the survival rate of PCNSL patients. If chemotherapy achieves complete remission and autologous hematopoietic stem cell transplantation is performed, there may be a chance of long-term survival.

Prognostic implication of alterations in epidermal growth factor receptor and MGMT in glioblastoma / 中华病理学杂志

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.

Implication of BRAF V600E and CTNNB1 gene mutations in the pathological classification of craniopharyngioma / 中华病理学杂志

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 β-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 β-catenin was observed in 73.6% (39/53) of ACPs, and it was absent in PCPs (0/14). The nuclear translocation of β-catenin usually presented at whorl-like structures or around ghost cells. Of all the cases, mutations analysis in exon 3 of β-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.

Clinicopathological features of intravascular diffuse large B-cell lymphoma in the central nervous system / 中华神经科杂志

Objective@#To investigate the clinicopathologic features of intravascular diffuse large B-cell lymphoma (IVLBCL) in the central nervous system (CNS).@*Methods@#The clinical and radiological data of three cases of CNS-IVLBCL in Xuanwu Hospital, Capital Medical University from 2014 to 2017 were collected. And pathological and immunohistochemical features of these patients were retrospectively analyzed. The related literatures were also reviewed.@*Results@#All the three patients aged from 62 to 76 years, with duration of 4-8 months. Clinical manifestations of the three patients included dizziness, fatigue, seizures, etc. They showed intracranial multiple lesions in the frontal, temporal, parietal and corona radiata, etc. MRI demonstrated cerebral infarction or space-occupying lesions. Microscopic observation showed small vessel lumina filled with tumor cells in the white matter. Tumor cells had large, round nucleus, and prominent nucleoli. The chromatin of tumor cells was broadly granular, and the mitotic figures were visible. Tumor cells expressed B cell markers, such as CD20, CD79α, paired box protein 5 (PAX-5). CD34 staining demonstrated that tumor cells were located in the lumen of the blood vessels. Two patients died within half a year after diagnosis, and the other one was lost to follow-up.@*Conclusions@#The clinical symptoms and MRI demonstrations of CNS-IVLBCL are variable and the prognosis is extremely poor. Morphological observation and immunohistochemical phenotyping for biopsy specimens are helpful for early diagnosis and actively combining chemotherapy to prolong survival of patients.

Clinicopathological features of intravascular diffuse large B?cell lymphoma in the central nervous system / 中华神经科杂志

Objective To investigate the clinicopathologic features of intravascular diffuse large B?cell lymphoma (IVLBCL) in the central nervous system (CNS). Methods The clinical and radiological data of three cases of CNS?IVLBCL in Xuanwu Hospital, Capital Medical University from 2014 to 2017 were collected. And pathological and immunohistochemical features of these patients were retrospectively analyzed. The related literatures were also reviewed. Results All the three patients aged from 62 to 76 years, with duration of 4-8 months. Clinical manifestations of the three patients included dizziness, fatigue, seizures, etc. They showed intracranial multiple lesions in the frontal, temporal, parietal and corona radiata, etc. MRI demonstrated cerebral infarction or space?occupying lesions. Microscopic observation showed small vessel lumina filled with tumor cells in the white matter. Tumor cells had large, round nucleus, and prominent nucleoli. The chromatin of tumor cells was broadly granular, and the mitotic figures were visible. Tumor cells expressed B cell markers, such as CD20, CD79α, paired box protein 5 (PAX?5). CD34 staining demonstrated that tumor cells were located in the lumen of the blood vessels. Two patients died within half a year after diagnosis, and the other one was lost to follow?up. Conclusions The clinical symptoms and MRI demonstrations of CNS?IVLBCL are variable and the prognosis is extremely poor. Morphological observation and immunohistochemical phenotyping for biopsy specimens are helpful for early diagnosis and actively combining chemotherapy to prolong survival of patients.

Application of ATRX in diagnosis and prognostic evaluation of glioma / 中华病理学杂志

Objective@#To investigate the diagnostic and prognostic implications of ATRX mutation and p53 mutation in patients with glioma.@*Methods@#The clinicopathologic and molecular features of Chinese adult glioma patients, including diffuse and anaplastic astroastrocytoma with IDH mutation, oligodendroglioma and anaplastic oligodendroglioma with IDH mutation and 1p/19q co-deletion and diffuse astroastrocytoma with IDH wild type were reviewed and tested for ATRX loss expression and p53 overexpression.@*Results@#Loss of ATRX expression was seen in 85.19% (23/27) diffuse and anaplastic astroastrocytoma with IDH mutation, higher than that of oligodendroglial tumors (0/53; P<0.01). Loss of ATRX expression was strongly linked to p53 overexpression(69.57%, 16/23). The patients who lost ATRX expression combined with normal p53 expression survived longer(P=0.013).@*Conclusions@#ATRX mutation is a molecular marker for astrocytic tumors. ATRX mutation combined with p53 mutation can predict prognosis of patients with glioma.

Diagnostic and prognostic roles of loss of CIC protein expression in oligodendroglial tumors / 中华病理学杂志

Objective@#To investigate the usefulness of loss of CIC expression as the prescreening detection of 1p/19q co-deletion in the diagnosis of oligodendroglial tumors and its prognostic implication.@*Methods@#The retrospective study included 113 oligodendroglial tumors diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University. Expression of CIC protein was detected by immunohistochemistry, and the 1p/19q co-deletion by fluorescence in situ hybridization in all the tumors; and the correlation of the loss of protein and 1p/19q co-deletion with prognosis was assessed.@*Results@#The rate of negative CIC protein expression was 59.3% (67/113) in 113 oligodendroglial tumors. CIC protein expression was differentially lost in various gliomas, 85.7% (42/49) in pure oligodendrogliomas and 39.1% (25/64) in mixed oligodendroglial tumors (P<0.01). The loss of CIC protein expression showed a sensitivity of 76.1% (54/71), specificity 71.1% (27/38), false positive rate of 16.9% (11/65), and a false negative rate of 38.6% (17/44). In 63 cases integrated diagnosis as oligodendroglial tumors with mutant IDH and 1p/19q co-deletion, the loss of CIC protein expression was 81.0% (51/63); the sensitivity and specificity were increased to 81.0% (51/63) and 76.9% (20/26), and the false positive rate and false negative rate decreased to 10.5% (6/57) and 37.5% (12/32), respectively. By using Kaplan-Meier analysis, the CIC negative group showed a trend towards better outcome than the CIC positive group, but there was no statistical difference (overall survival: P=0.218; progression free survival: P=0.249).@*Conclusions@#Detection of the lost CIC protein expression can predict the chromosome 1p/19q co-deletion. In oligodendroglial tumors with IDH mutant and 1p/19q co-deletion, there is no relation between prognosis and CIC protein expression.

The clinical and pathological features of 85 cases with positive cerebrospinal fluid cytology by thin-layer centrifugal cytological test / 中华内科杂志

Objective To evaluate cytological test of cerebrospinal fluid in the diagnosis of meningeal dissemination of tumor cells.Methods The clinical and imaging features of 85 cases with tumor cells diagnosed by thin-layer centrifugal cytological test of cerebrospinal fluid were retrospectively reviewed.The characteristics of cellular morphology and immunocytochemical staining were analyzed.Results The main presentations of all the patinets was meningeal irritation and neurological dysfunction.The features of the brain MRI were meningeal thicking and enhancement,intracranial abnormal signals and intracranial space occupying lesion in part of the patients.Atypical cells were found in 84 cases (98.8％) with the first sample test and immunocytochemical staining was conducted in 48 cases to identify the tissue origin.Meningeal carcinomatosis was shown to be the majority with lung cancer as the dominated tissue type and adenocarcinoma as the most common histological type.Others were lymphatic hematopoietic system (13 cases),melanomas (5 cases),primitive neuroectodermal tumor (3 cases) and glioma (1 case).In addition,12 cases were only proved to be cancer by cytological test of cerebrospinal fluid.Conclusion The thin-layer centrifugal cytological test of cerebrospinal fluid has a relatively high accuracy for detecting disseminated tumor cells of meninges and could be of great help to identify the source and type of lesion with immunocytochemical staining.

Application of therapeutic drug monitoring of vancomycin / 中国感染与化疗杂志

Objective To analyze the relationship between plasma concentration and efficacy , adverse drug reactions by monitoring vancomycin serum concentrations for appropriately treating the infections caused by methicillin‐resistant Staphylococcus aureus or other gram‐positive cocci .Methods Vancomycin concentration was monitored in the patients with indications for vancomycin therapy .Blood sample was taken after vancomycin was administered for at least 4 doses .The blood sample collected within 30 minutes before dosing was used to determine the trough blood concentration .The samples were taken within 30 minutes to 1 hour after infusion of vancomycin were used to estimate the peak concentration by fluorescence polarization immunoassay .The clinical data were collected at the same time to analyze clinical efficacy and safety .Results Vancomycin trough concentration ranged from 3 .22 mg/L to 50 .79 mg/L in 25 patients ,specifically ,＜ 5 mg/L in 3 cases ,5‐＜10 mg/L in 11 cases ,10‐15 mg/L in 3 cases ,and > 15 mg/L in 8 csaes .Peak concentration ranged from 13 .57 mg/L to 60 .47 mg/L ,specifically ,＜ 25 mg/L in 14 cases ,25‐40 mg/L in 7 cases ,and > 40 mg/L in 4 cases .The infection was cured in 80 .0% (20/25) of the patients .The gram‐positive cocci were eradicated in 87 .5% (21/24) of the patients .The dosage of vancomycin was adjusted in 13 patients according to the results of blood concentration monitoring .Majority of these patients (12/13 ,92 .3% ) were cured .Renal impairment was observed in 4 patients .Conclusions Vancomycin is safe and effective in treatment of methicillin‐resistant Staphylococcus aureus and other gram‐positive bacterial infections . Vacomycin concentration varies from person to person . Serum concentration monitoring is required to achieve best outcomes and the goal of individualized treatment of vancomycin.

The treatment of incidental gallbladder carcinoma discovered during laparoscopic cholecystectomy / 中国普通外科杂志

Objective To explore the treatment of incidental gallbladder carcinoma(UGC)discovered during laparoscopic cholecystectomy(LC). Methods The clinical data of 17 cases of incidental gallbladder (carcinoma) discovered during laparoscopic cholecystectomy were reviewed retrospectively. Results 11cases with Nevin stage I or stage II were treated by LC and 1 case with Nevin stage III and 3 cases with Nevin stage V were treated by LC and radical local lymphadenectomy. 2 cases with Nevin stage IV were treated by (cholecystectomy). UGC was incidently found in 0.6% of the cases. Cases with Nevin Stage I and II were (observed) for 5 years with no recurrence. A case with Nevin Stage III was found to have recurrence within one and a half years postoperatively and had a re-operation. The prognosis of patients with Nevin Stage IV and V was poor and they were dead within a year after operation. Conclusions The incidently found gallbladder carcinoma with Nevin Stage I and II disease can be radically resected with laparoscopic cholecystectomy. The incidently found gallbladder carcinoma with Nevin Stage III and IV disease needs to be radically resected, and if the resection margin is found to be free of tumour, the prognosis is enhanced. The ones with Nevin Stage V need to be treated by local lymphadenectomy and wedge-resection of liver.