Clinical analysis of 6 children with Epstein-Barr virus positive diffuse large B cell lymphoma / 中华实用儿科临床杂志

Objective:To analyze the clinicopathological features, treatment and prognosis of Epstein -Barr virus(EBV) positive diffuse large B cell lymphoma(DLBCL) in children, so as to improve the knowledge of pediatricians on this disease.Methods:The data of 6 cases of EBV positive DLBCL who were initially diagnosed and regularly treated in Beijing Children′s Hospital from January 2016 to December 2019 were collected, including basic information (gender, age, first symptom, and course of disease), pathological results [immunohistochemistry, EBV encoded RNA(EBER), latent membrane protein(LMP), and C- MYC gene], immune function, EBV index, treatment group, treatment plan and prognosis. Results:There were 4 males and 2 females, with the average age of 6.67 years.The uric acid was 266.2 μmol/L, lactic dehydrogenase(LDH) was 346.5 U/L at early stage, and 1 patient had immunodeficiency.The immune function test before chemotherapy indicated that the proportion of auxiliary T cells decreased in 4 cases, and the humoral immune function was normal in all patients.There was no evidence of recent infection in 6 patients, and EBV-DNA increased in 3 patients.There were 2 cases of stage Ⅲ, 4 cases of stage Ⅳ, 1 case of giant tumor, 2 cases of symptom B, 6 cases of extranodal invasion, 4 cases of central invasion and 1 case of bone marrow invasion.Three patients died and three survived.Immunohistochemistry showed that: (1) CD 19, CD 20, and CD 79a were expressed in all patients, and CD 30 was expressed in 5 patients.(2) C- MYC gene was detected by immunofluorescence in situ hybridization method in all patients, and no MYC break, Bcl-2 and Bcl-6 break and amplification were found.(3) EBV: EBER and LMP-1 were expressed in all patients. Conclusions:The pathological changes of EBV positive DLBCL are similar to those adults.The origin of non-germinal center and extranodal and central invasion are more common.The prognosis of the patients with central nervous system invasion is very poor, and the recurrence and progress of the disease often occur in the treatment or in the early stage of drug withdrawal.At present, there is no effective and feasible treatment plan.It is suggested that the patients in the late stage should receive allogeneic hematopoietic stem cell transplantation as soon as possible after intensive treatment, so as to improve the survival rate.

Clinical characteristics of 46 pediatric diffuse large B-cell lymphoma and treatment outcome / 中华儿科杂志

Objective@#To summarize the clinical data of diffuse large B-cell lymphoma (DLBCL) in children and to evaluate the efficacy of Beijing Children′s Hospital B cell lymphoma protocol in the treatment of pediatric DLBCL.@*Methods@#The data (clinical, pathology, lab and image data) of 46 pediatric DLBCL admitted to the treatment group of Beijing Children′s Hospital from January 2005 to June 2017 were collected and analyzed retrospectively. According to the risk factors of staging, existence of poor prognosis genes and giant tumors, stratified treatment was carried out according to the international standard modified LMB89 regimen with high dose and short course. The Kaplan-Meier method was used to calculate the event free survival (EFS) and the overall survival (OS).@*Results@#(1) Among the 46 cases, there were 33 males and 13 females. The median age was 8.0 years. The time from the initial symptom onset to the diagnosis was more than 15 days in 45 children. Fourteen cases had B group symptoms (fever, night sweat, and weight lost), 25 cases had extranodal disease, 39 cases were stage Ⅲ and Ⅳ, 12 cases had bone marrow involvement, 3 cases had jawbone involvement. Thirty cases were group B and 16 cases were group C in the treatment group. (2) Initial symptoms: 6 cases had cervical mass, 20 cases had abdominal mass, 10 had abdominal pain with acute abdomen, 8 cases had fever, 2 cases had snore or upper respiratory tract obstruction. (3) Pathology result: 40 cases were germinal center B cell DLBCL, 6 cases were non germinal center B cell DLBCL, no case had the MYC gene rupture, double hit lymphoma and triple hit lymphoma. (4) Complication and evaluation: the tumor lysis syndrome was seen in 3 cases initially, severe infection and delayed treatment was seen in 1 case, no treatment related death. The first evaluation showed all cases were sensitive to chemotherapy (shrink>25%), the second evaluation showed 1 case had residual disease, the others were complete remission. (5) Treatment and outcome: the 5 year-EFS was the same with 5 year-OS, both were (97.8±2.2) %. Two cases relapsed after treatment off, early relapse was seen in 1 case, and died because of abandoning treatment. Late relapse was seen in 1 case and got a complete remission after Rituximab+group C protocol treatment.@*Conclusions@#Pediatric DLBCL was common in school aged boys, most cases were at middle and late stage at the time of diagnosis. DLBCL had a good prognosis after the treatment with Beijing Children′s Hospital′s B cell lymphoma protocol, but late relapse could be seen.

Clinical analysis of methylmalonic acidemia and hyperhomocysteinemia with diffuse lung disease as an initial or main presentation / 中华儿科杂志

Objective@#To improve the awareness of methylmalonic acidemia and hyperhomocysteinemia with diffuse lung disease as an initial or main presentation.@*Methods@#A retrospective analysis of the clinical manifestations, radiological features, laboratory tests, genetic variations, treatments and prognoses was conducted in six children presented with diffuse lung disease and finally diagnosed with methylmalonic acidemia and hyperhomocysteinemia in Ward 2 of Department of Respiratory Diseases, Beijing Children′s Hospital, from August 2017 to November 2018.@*Results@#Six children were included in this study. Two children were male and four were female. The average age of onset was 28 months. The mean age at diagnosis was 34 months. The average interval from onset to diagnosis was 6 months. Four children who underwent genetic tests were found to have variants of gene MMACHC and diagnosed with CblC type. All children had respiratory symptoms and signs as initial or main presentation, which were tachypnea (5 cases), exercise intolerance (5 cases), cough (4 cases), cyanosis (4 cases), clubbing (4 cases), dyspnea (3 cases) and retractions (3 cases). Pulmonary arterial hypertension was found in all six children. Pericardial effusion (4 cases), kidney involvement (3 cases), nervous system involvement (3 cases), gastrointestinal system involvement (3 cases) and anemia (2 cases) also coexisted. The high resolution computed tomography (HRCT) features included dilated pulmonary artery (6 cases), ground-glass opacities (4 cases), diffuse poorly defined ground-glass centrilobular nodules (3 cases), pleural effusion (3 cases), thickening of interlobular septum (2 cases), etc. All children had an elevated concentration of methylmalonic acid in urine and homocysteine in plasma. Genetic tests were performed in four patients, and MMACHC genetic mutations were found in all of them. Clinical manifestations, HRCT features and pulmonary arterial hypertension turned better in five children after treatment. One patient who was not regularly followed-up died.@*Conclusions@#Pulmonary involvement including diffuse lung disease and pulmonary arterial hypertension could coexist with methylmalonic acidemia and hyperhomocysteinemia, which may have respiratory symptoms and signs as the initial or main presentation. Characteristic HRCT features were found in some patients. Plasma homocysteine test is a quick method for screening the disease in children with diffuse lung disease and (or) pulmonary arterial hypertension. Both diffuse lung disease and pulmonary arterial hypertension may turn better after treatment.

Clinical analysis of a modified LMB89 Group C regimen in the treatment of pediatric high-risk Burkitt lymphoma / 中华血液学杂志

Objective@#To analyze the therapeutic effect of a modified LMB89 Group C regimen in the treatment of pediatric high-risk Burkitt lymphoma.@*Methods@#The clinical data of 172 children with newly diagnosed high-risk Burkitt lymphoma from January 2007 to April 2017 were retrospectively analyzed. All the cases were treated with the modified LMB89 Group C regimen.@*Results@#The median age of the patients was 6 (1-14) years. The sex ratio was 5.1∶1, 144 boys (83.7%) and 28 girls (16.3%) . According to St. Jude staging classification, 2 patients (1.2%) were in stage Ⅱ, 54 (31.4%) in stage Ⅲ and 116 (67.4%) in stage Ⅳ. Of them, 46 patients (26.7%) had mature B cell acute lymphoblastic leukemia (B-ALL) , and 52 patients had central nervous system (CNS) involvement. According to risk group, the patients can be divided into group C1 (CNS1, without testicles/ovaries involvement, n=65) , group C2 (CNS2, testicles/ovaries involvement, n=55) and group C3 (CNS3, n=52) . A total of 145 patients received rituximab combined with chemotherapy during the treatment, 10 patients suffered from progressive disease and died, and 5 patients relapsed. Treatment-related mortality was 2.9%. With a median follow-up of 36.0 (0.5-119.0) months, 3-year overall survival (OS) rate was (88.9±2.4) % and event free survival (EFS) rate was (87.9±2.6) % for all patients. 3-year EFS rates were (96.9±2.1) %, (90.9±3.9) % and (73.4±6.5) % for Group C1, C2 and C3 respectively, and that of Group C3 was significantly lower than that of Group C1 (χ2=12.939, P=0.001) and Group C2 (χ2=6.302, P=0.036) . The 3-year EFS rates were (79.3±6.8) % and (44.4±16.6) % for patients in group C3 treated with chemotherapy combined with rituximab and chemotherapy alone (χ2=5.972, P=0.015) . Multivariable Cox regression analysis showed that Stage Ⅳ (including B-ALL) , residual diseases in mid-term evaluation were independent unfavorable prognostic factors[HR=4.241 (95%CI 1.163-27.332) , P=0.026; HR=32.184 (95%CI 11.441-99.996) , P<0.001].@*Conclusions@#The modified LMB89 Group C regimen has ideal effect for the children with high-risk Burkitt lymphoma.

Clinical and prognostic analysis of 186 children with Burkitt's lymphoma / 中华儿科杂志

Objective@#To analyze the clinical features and prognostic factors of childhood Burkitt's lymphoma and to summarize the therapeutic effect of the mature B-cell lymphoma regimen of Beijing Children's Hospital.@*Methods@#It was a retrospective study. From January 2007 to December 2015, 186 patients below 18 years of age with newly diagnosed, untreated Burkitt's lymphoma were enrolled. Three cases were eliminated because of the abandonment of the treatment and 183 cases were stratified and treated according to the mature B-cell lymphoma regimen of Beijing Children's Hospital, groups were as follows: A, n=1; B, n=59; C, n=123 and 97 patients in group C received combined rituximab therapy during the treatment. The clinical features and therapeutic effects of patients were analyzed, overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method. COX regression was used to identify the prognostic factors.@*Results@#The median age at diagnosis was 5 (1-14) years. There were 159 males (85.5%) and 27 females (14.5%) , the male-to-female ratio was 5.9∶1. A total of 174 cases (93.5%) evolved to stage Ⅲ and Ⅳ. Eight cases did not achieve remission and progressed to death, 9 cases relapsed. Only 5 patients (2.7%) died of treatment-related complications. With a median follow-up time of 48.0 (0.5-128.0) months, the 5-year OS rate and EFS rate were (89.1±2.3) % and (87.8±2.5) %. There was significant difference in the 5-year EFS rate between group B and C ( (94.9±2.9) % vs. (84.0±3.4) %, χ2=4.258, P=0.039). The 5-year EFS rate was (73.1±8.7) % and (86.7±3.7) % for patients in the group C treated with chemotherapy only and those treated with chemotherapy combined rituximab, but no statistical difference was found between them (χ2=3.360, P=0.067) . Central nervous system (CNS) involvement, insensitivity to early phase chemotherapy, residual diseases in mid-term evaluation were independent unfavorable prognostic factors (HR=6.167, 9.102, 3.104, 95%CI: 2.293-16.592, 1.837-45.107, 1.182-8.153) .@*Conclusions@#The large dose, short course treatment of mature B-cell lymphoma regimen of Beijing Children's Hospital is effective for pediatric Burkitt's Lymphoma. Combined treatment with rituximab can improve the efficacy. CNS involvement, insensitivity to early phase chemotherapy, residual diseases in mid-term evaluation are associated with increased risk of poor prognosis.

Clinical features and diagnosis of childhood leukoencephalopathy with cerebral calcifications and cysts in four cases / 中华儿科杂志

Objective@#To investigate the clinical features and diagnostic bases of childhood leukoencephalopathy with cerebral calcifications and cysts (LCC).@*Methods@#The clinical data involving manifestations and laboratory examinations of 4 children with LCC admitted to Beijing Children's Hospital Affiliated to Capital Medical University from 2012 to 2017 were retrospectively summarized. Each patient had a follow-up visit ranging from 4 months to 5 years and 9 months after initial examination.@*Results@#Patients consisted of 2 males and 2 females, whose age of onset was respectively 2 years and 9 months, 6 years and 2 months, 7 years and 10 months, and 5 years and 1 month. The main clinical symptoms of these cases included headache, dizziness, partial seizure and claudication, and two of these cases had insidious onset. Cerebral calcifications and cysts with leukoencephalopathy were detected by neuroimaging in all patients. In addition, multifocal microhemorrhages and calcifications were observed by magnetic susceptibility-weighted imaging (SWI) series in 3 patients. Brain biopsy performed on 1 case disclosed a neuronal reduction in the cerebral cortex, loosening of focal white matter, multifocal lymphocyte infiltration, fresh hemorrhages, and gliosis, as well as angiomatous changes of blood vessels with hyalinized thicken-wall, stenotic or occlusive lumina and calcification deposits. The compound heterozygous mutations of n.*10G>A and n.82A>G in SNORD118 were identified in 1 case by target-capture next-generation sequencing. Sanger sequencing verified that the variant n.*10G>A was a novel mutation and it was of paternal-origin, while the variant n.82A>G was of maternal-origin, which had already been reported to be pathogenic to LCC. Follow-up study had shown continued partial seizure in 1 case and remissive claudication in another, while the remaining 2 cases had a relatively favorable outcome without obvious neurological symptoms at present time.@*Conclusions@#The clinical manifestations of LCC are nonspecific, and the onset of the disease tends to be insidious. The triad neuroimaging findings of cerebral calcifications, cysts and leukoencephalopathy are essential to the diagnosis of the disease, and the signals of microhemorrhages revealed by SWI series provide another eloquent reference for the diagnosis. As biopsy is invasive and usually unavailable in the early stage, gene assessment, instead of pathological data, should be the gold standard in the diagnosis of LCC.

Clinical pathologic characteristics and treatment outcomes of 19 relapsed pediatric B-cell lymphoma / 中华儿科杂志

Objective@#To review the clinical-pathology characteristics of 19 relapsed pediatric mature B cell lymphoma and to find the risk factors for recurrence and the feasible treatment after relapse.@*Method@#Data of 212 pediatric B cell lymphomas cases in Beijing Children′s Hospital from January 2006 to June 2015 were collected retrospectively. All the patients were treated according to the B cell lymphoma regimen of Beijing Children′s Hospital. During the study period, 19 of 212 cases were relapsed; the clinio-pathological characteristics of relapsed patients before treatment and after relapse were analyzed retrospectively, the treatment outcomes after relapse were summarized and the patients were followed-up.@*Result@#Nineteen of 212 cases had relapsed disease, for these relapsed patients: the median age at initial diagnosis was 5.5 years old, the median level of uric acid was 384(range, 121-713)μmol/L, the median level of lactate dehydrogenase(LDH) was 1 323(range, 146-6 370)U/L. Among 19 relapsed patients, 10 had local relapse and 9 had multiple relapses; 17 were Burkitt′s lymphoma and 2 were diffuse large B cell lymphoma. Staging: 2 cases were stageⅡ, 3 cases were stage Ⅲ and 14 cases were stage Ⅳ. Risk group: 6 cases were group B and 13 cases were group C. Nine cases had bone marrow involvement and 10 cases had central nervous system(CNS) involvement. Acute tumor lysis syndrome was seen in 6 cases during the early treatment and 13 cases had delayed treatment. Treatment after relapse: 10 cases received further treatment after relapse (rituximab + 1-4 courses high intensity second-line chemotherapy), 3 cases received autologous stem cell transplantation. There was no chemotherapy or infection related death, 3 cases achieved complete remission (CR). For all the 212 patients, the median follow-up time was 47 (range, 1-131)months and the 5-year event free survival(EFS)rate was (89.4±0.2)%. For the 19 relapse cases, the 5-year overall survival (OS) rate was (21.1±0.1)%, CR rate after relapse was 30%, patients died of the progression of the primary disease, no treatment related death occurred. Univariate analyses showed that bulky disease, stage Ⅳ, maxillofacial and CNS involvement, LDH>1 000 U/L, delay treatment, day 7 evaluation shrink <25%, residual diseases after 3 months treatment are relapse risk factors (all P<0.01).@*Conclusion@#Patients relapse during the treatment or at the early stage after the end of all chemotherapy have poor prognosis. So far there is no effective method for early relapse patients; the late relapse patients had the possibility of CR if they are sensitive to salvage treatment. In conclusion, to improve the outcome, the key point is to reduce the relapse.

Clinical characteristics and prognosis of disseminated cryptococcosis in children / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics and prognosis of disseminated cryptococcosis in children.Methods The data of disseminated cryptococcosis inpatients were reviewed retrospectively at Beijing Children's Hospital,Capital Medical University,from January 2002 to September 2014.The demographic data,clinical manifestations,laboratory findings,imaging,antifungal treatments and outcomes of all the patients were analyzed.Results Overall 25 children with disseminated cryptococcosis were enrolled including 17 boys(68.0％).The average age was 7 years old.Four cases (16.0％) had underlying conditions,among them 1 case had human immunodeficiency virus(HIV)-positive.The median time to diagnosis was 32 (23-47) days,44.0％ of the patients (11 cases) were misdiagnosed,and 8 cases misdiagnosed as tuberculosis.All patients had fever.Other common clinical manifestations included cough (16 cases),headache (10 cases),vomiting (10 cases),altered mental status (6 cases) and stomachache (6 cases).Respiratory system involvement was seen in all cases,central nervous system was involved in 18 cases,other organ involvement included lymph nodes,spleen,liver,kidney,skin,skeleton and costicartilage.Amphotericin B (AmB) + Fluconazole (Flu) ± 5-flucytosine (5-FC) was the most common therapy (15 cases),Flu ± 5-FC for 6 cases,AmB ± 5-FC for 2 cases,Voricanazole (VOR) for 1 case.Sixteen cases (66.7％) got recovery/improved on discharge,8 cases (33.3％) rejected to the advise and discharged with treatment failure,and the HIV-infected patient transferred to a special hospital.Fifteen patients (60.0％) were followed up,and 13 cases (87.0％) showed recovery,but 2 died in the long-term prognosis.Conclusions Disseminated cryptococcosis in children is more common in school-age boys.Most patients are without underlying conditions.Disseminated cryptococcosis can cause multiple organ damage.Patients with prolonged fever,cough,headache,with or without underlying diseases,can be suspected as disseminated cryptococcosis.Blood and cerebrospinal fluid culture for fungus,cryptococcal antigen should be performed for early diagnosis and treatment.

The clinical manifestations of children with endocapillary proliferative glomerulonephritis with isolated C3 deposition / 中华实用儿科临床杂志

Objective To study the patients' clinical characteristics and prognosis when only C3 deposition exists in endocapillary proliferative glomerulonephritis and try to understand deeply the role of C3 in kidney damage deeply. Methods The patients who were diagnosed with endocapillary proliferative glomerulonephritis but only had C3 deposited in immunofluorescence(to avoid false positive,C3≥2 ﹢ was included)were selected from Beijing Children's Hospital Affiliated to Capital Medical University during November 2010 to October 2014. Their clinical manifestations,la-boratory examinations,treatments,prognosis,and pathological changes were analyzed,and literature review was performed. Their clinical characteristics and prognosis were summarized. Results There were 11 patients diagnosed with endocapil-lary proliferative glomerulonephritis which had only C3 deposition(≥2 ﹢ ). Nine of them had onset with acute nephritis syndrome(81. 8% ),and 2 cases presented recurrent paroxysmal gross hematuria(18. 2% ). Seven cases were diagnosed with acute post streptococcal glomerulonephritis(63. 6% ). Eleven cases' clinical manifestations were relatively severe, and the complement C3 was significantly lower than the normal(100. 0% ). Their light microscope showed capillary proli-ferative glomerulonephritis,and the electron microscope showed the immune complexes were deposited in the endothelium,the epithelium or the mesangial area. The patients received corresponding treatment respectively,and all the patients had good prognosis during following up of 7 months up to 39 months. Conclusions Streptococcus infection is a common cause in endocapillary proliferative glomerulonephritis with only C3 deposition. The clinical manifestations of some children are similar to post streptococcal glomerulonephritis but relatively severe. Only deposition of C3 without IgG may be involved in another complement activation mechanism.

Advances in stress response of DNA binding with one finger transcription factor family genes in graminaceous plants / 生物工程学报

Transcription factor is a key trans-acting factor to mediate stress response by regulating gene expression. Plants have developed a series of mechanisms to modulate development, stress response, signaling and disease resistance at transcription level. DNA binding with one finger (DOF), containing one C₂-C₂ zinc finger domain, is a special plant transcription factor. Specifically, the conserved domain at N-terminus of DOF has multiple functions, including interacting with DNA and protein, which could be involved in plant development and stress response. Although many DOF family genes are characterized in plant stress response, it is not clear if DOF genes have functions in cereal plants. In the present paper, the role of DOF family genes on cereal plants were discussed based on a comprehensive phylogenetic relationship analysis, expression profiles in different tissues and various environmental conditions. The results obtained here will provide an important reference for further understanding the mechanism of gramineous crops in stress resistance.

Pulmonary CT imaging characteristics of pediatric perinuclear anti-neutrophil cytoplasmic antibody associated systemic vasculitis / 中华放射学杂志

Objective To investigate the chest HRCT characteristics of pediatric perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) associated systemic vasculitis. Methods Retrospectively analysis of the clinical and HRCT data of 15 pediatric cases diagnosed as p-ANCA related pneumonia according to the classification and diagnostic criteria of Chapel Hill meeting of 1994 in our hospital were retrospectively analyzed. They were 13 girls and 2 boys. The age range was 1—17 years and the median was about 10 years old, In the 15 patients, 12 were diagnosed as primary MPA, 2 were secondary MPA, 1 was CSS. Two radiologists with 10 years of radiological experience read the CT imaging together. Results 1 of 12 primary MPA were found large opacities and ground glass shades in both sides of lung,especially the posterior parts on CT images with bilateral pleural effusion; 1 case had focal opacities in left lower lobe, around with thickened interlobular septa and pleural effusion; Another 1 case only had focal thickened interstitial in right middle lobe; The other 9 cases showed scattered or diffused ground glass opacity, with thickened pulmonary interstitial and (or) pleura. 1 of the 2 secondary MPA who had hemoptysis showed ground glass opacity on CT images with no thickened septal nodules or pleural effusion. The other one who had renal anomalies and no respiratory symptoms showed subpleural nodules with halo sign in right low lobe. The CSS showed diffused patchy ground glass opacity, consolidation of both lingular lobes, nodules of centri-and peri-lobular, thickened septa near the pleura, obviously thickened bronchial wall, slightly widened bronchial lumen and thickened pleura. Conclusion The classic imaging features of p-ANCA pneumonia on HRCT is the non-specific small pulmonary vessel hemorrhage.

Clinical analysis of 2 cases with chylothorax due to primary lymphatic dysplasia and review of literature / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics and diagnosis of 2 cases with chylothorax due to primary lymphatic dysplasia and to elevate pediatrician's recognition level for this disease.</p><p><b>METHOD</b>Clinical manifestations of the children were retrospectively analyzed. Primary lymphatic dysplasia was diagnosed by lymphoscintigraphy.</p><p><b>RESULT</b>The first patient was a male aged 2-year-7-month who presented with a history of tachypnea for 43 days, fever and sore throat for 5 days at the early stage of the illness. He had a history of external injury before his illness. Physical examination showed his left chest bulging and left side diminished breath sound. His pleural effusion showed dark red (It was divided into two layers after standing, the upper layer turned into milky white, and the lower turned into hemorrhagic liquid) . White blood cell (WBC) count was 9 000×10(6)/L, mononuclear cell was 0.9, polykaryocytes was 0.1, triglyceride was 12.37 mmol/L in the pleural effusion. Contrast-enhanced lung CT (revascularization) showed pericardial effusion and a massive left sided pleural effusion. The second patient was a male aged 9 years and 6 months, who presented with a history of cough for 24 days, intermittent fever, vomiting, abdominal pain for 19 days, and edema of lower limbs for 4 days. Physical examination showed edema in both eyelids, lower extremities and scrotum. The level of albumin was 14 g/L and the titer of Mycoplasma pneumoniae IgM was 1: 320 in the serum. His hydrothorax pleural effusion showed milk white. White blood cell (WBC) count was 74×10(6)/L, mononuclear cell was 0.78, polykaryocytes was 0.22, triglyceride was 1.01 mmol/L in the pleural effusion. Chyle test showed positive in his pleural effusion and seroperitoneum. High-resolution CT of the lung revealed bilateral interstitial and parenchymal infiltration and both sided pleural effusion. Abdominal ultrasound showed giant hypertrophy of the gastric mucosa and massive ascites. Gastroscopy showed giant hypertrophy of the gastric mucosa. Lymphoscintigraphy revealed primary lymphatic dysplasia in both children.</p><p><b>CONCLUSION</b>Primary lymphatic dysplasia might occur in children and result in dropsy of serous cavity (chylothorax, chylopericardium, chylous ascites). Dropsy of serous cavity showed bloody or milk white. WBC count might elevate with lymphocyte increasing mostly, triglyceride was often higher than 1.0 mmol/L in dropsy of serous cavity. Primary lymphatic dysplasia can be diagnosed by lymphoscintigraphy.</p>

Abnormality of anaplastic lymphoma kinase gene and its expression in pediatric neuroblastoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To correlate the abnormal expression of anapastic lymphoma kinase (ALK) protein with the genetic and epigenetic changes of ALK, and to analyze its clinical application in pediatric neuroblastoma.</p><p><b>METHODS</b>Three neuroblastoma (NB) cell lines (two ALK positive: SH-SY5Y and SK-N-SH, one ALK negative: SK-N-AS) and 43 paraffin-embedded NB tissues were included in the study. In both cell lines and clinical cases, immunohistochemistry was used to detect ALK protein expression; PCR and Sanger sequencing were used to detect ALK point mutation; fluorescence in situ hybridization (FISH) was used to detect ALK abnormality and bisulfite sequencing PCR (BSP) was used to detect methylation of CpG island in the promoter area of ALK.</p><p><b>RESULTS</b>The cell lines SH-SY5Y and SK-N-SH were positive for ALK expression (cytoplasm), while the SK-N-AS was negative; among the 43 cases of NB, 26 (60.5%, 26/43) were positive for ALK protein (membrane and cytoplasm), and the rest were negative. Survival analysis showed ALK protein expression was related to survival time, with ALK positive cases having shorter survival time than ALK negative cases (P = 0.020). But ALK protein expression had no association with tumor differentiation (P = 0.503), tumor sites (P = 1.000) and age of patients (P = 0.063). FISH showed ALK amplification in two cases (4.6%, 2/43), ALK gain was found in 30 cases (69.7%, 30/43), and the remaining cases had normal ALK copy (25.6%, 11/43). The presence of extra copies (amplification and gain) of ALK was associated with ALK positive protein expression (P = 0.020), but there was no association with tumor differentiation (P = 1.000), tumor sites (P = 0.775) and age of patients (P = 0.328). No point mutation was found in all three cell lines. Of the 43 NB cases, only one case (2.3%, 1/43) showed point mutation in exon 23, and was a synonymous mutation [A1200A (G4552C)]. The case was ALK negative, but the patient died two months after diagnosis. BSP analysis showed that CpG island in ALK promoter region were all unmethylated in three cell lines and 6 NB cases (including 3 ALK positive, 3 ALK negative).</p><p><b>CONCLUSIONS</b>ALK protein is expressed in most NB, and the expression indicates poor outcome. ALK expression is associated with extra copies of ALK, but there is no association with the methylation status of CpG island of ALK; the presence of extra copies of ALK is the most common genetic aberration in NB. Point mutation of ALK is rare, and may predict poor prognosis in pediatric NB.</p>

Childhood pleuropulmonary blastoma: a clinicopathologic study of 16 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathological and immunohistochemical features, histogenesis and prognosis of pleuropulmonary blastoma (PPB) in children.</p><p><b>METHODS</b>PPB specimens from 16 pediatric cases with an age ranging from 1 year and 7 months to 5 years and 3 months (mean age of 3 years) were retrieved and analyzed by routine histological, immunohistochemical and electron methods.</p><p><b>RESULTS</b>Among 16 patients, there were 2 type I, 7 type II and 7 type III PPB cases. Type I PPB as multilocular cystic structure, consisted of thin fibrous wall lining the respiratory epithelium, subepithelial primitive blastema or immature mesenchymal cells, with or without rhabdomyoblastic differentiation or cartilage; Type II PPB as cystic-solid tumor, comparing with type I, consisted of intracystic components with appearance of anaplastic tumor cells. Type III PPB consisted of completely solid mass, the same as the solid region of type II, had mixed pattern including blastema, undifferentiated spindle-cell proliferations and sarcomas. In addition, anaplastic tumor cells and intra-and extra- cytoplasmic eosinophilic globules were also commonly present. Epithelial components in PPB were benign. Immunohistochemical study showed primitive mesenchymal differentiation of tumors. All cases were positive for vimentin, desmin, myogenin and SMA in tumors with skeletal muscle differentiation, S-100 was positive in tumors with cartilage differentiation. All tumors were negative for synaptophysin, CD99, and CD117. Benign epithelial components were positive for AE1/AE3 and EMA. In 12 cases, electron microscopy revealed few organelles in the primitive mesenchymal cells and rich heterochromatin in mesenchymal cells, the latter also demonstrating cytoplasmic myofilament dysplasia. Nine cases had clinical follow-up ranging from 5 to 48 months, of which 4 patients died.</p><p><b>CONCLUSIONS</b>PPB is a rare lung neoplasm of children under the age of 6 years, with distinct pathological morphology. PPB may arise from lung or pleura mesenchymal cells and has a poor clinical outcome.</p>

CT findings of pulmonary cryptococcosis in immunocompetent children / 中华放射学杂志

Objective The aim of our study was to study the CT findings of cryptococcosis in immunocompetent children.Methods CT scan and clinical data of 21 immunocompetent children with proven pulmonary cryptococcosis were retrospectively collected and analyzed.Results The CT scans demonstrated 1 mm subpleural nodule in the lingula of left lung in 1 patient and multiple nodules in 20 patients.Of 20 patients with multiple nodules,peripheral or subpleural distribution was found in 12 patients,and diffuse distribution in 8 patients.Of 20 patients with multiple nodules,Nodules of ＜ 10 mm was found in 18 patients,＜3 mm in 14 patients,and ＞ 10 mm in 2 patients.Round nodular with smooth margin was detected in 15 of 20 patients with multiple nodules.Lymphadenopathy was found in 17 patients including 3 patients with mild contrast enhancement and 2 patients with circular enhancement.Extrapulmonary lesions distributing in liver,spleen,kidney,and the nervous system were found in 14 patients.In follow-up,1 patient died and 20 patients fully recovered.ConclusionsPulmonary multiple nodules with lymphadenopathy is the characteristic CT findings in immunocompetent children with pulmonary crytococcosis which is prone to involve multiple extra-pulmonary organs.

Clinicopathological observation of bone marrow involvement of systemic anaplastic large-cell lymphoma / 白血病·淋巴瘤

Objective To investigate the clinicopathological features, immunophenotyping and clinical biological behavior of bone marrow (BM) involvement of systemic anaplastic large-cell lymphoma (S-ALCL).Methods 34 S-ALCL including 24 ALK(+) and 10 ALK(-) cases available with the formalin-fixed, paraffin embedded (FFPE) tissue blocks of BM biopsy (n=19) or BM smear sections (n=15) were included in this study.BM samples were sent to both morphologic evaluation using H&E (Hematoxylin & Eosin)-stained sections and immunophenotypic detection by immunohistochemistry (IHC). EBV status was determined by visualization of EBERs in tumor cells using in situ hybridization (ISH). Results BM involvement was seen in 17.6 % (6/34)S-ALCL patients which were confirmed by BM biopsy. No significant difference in the incidence of BM involvement was observed between ALK(+)[16.7 % (4/24)] and ALK(-) [20.0 % (2/10) S-ALCL (P =0.3555).Age and gender were not associated with the presence or the absence of BM involvement by S-ALCL (P= 0.8089and 0.3085), tumor cells of patients with BM involvement were interstitial distribution. S-ALCL patients with BM involvement have a poor prognosis as compared to those without BM involvement (P =0.0407). Conclusion BM involvement was not frequently seen in S-ALCL. The occurrence of BM involvement by S-ALCL was not associated with age, gender or the expression of ALK protein. BM involvement is an adverse prognostic factor in S-ALCL, BM biopsy is useful to predict the prognosis of S-ALCL.

Significance of detection of EBV-encoded mRNA on bone marrow biopsy tissues of hemophagocytic syndrome / 白血病·淋巴瘤

ObjectiveTo investigate the diagnostic significance of different pathology techniques (Immunohistochemistry and ISH)to detect EBV on bone marrow biopsy tissues of hemophagocytic syndrome. Methods Histological,immunohistochemicalandinsituhybridizationwereusedtostudythe hemophagocytic features and expression of LMP-1,EBER and other markers.Results25 out of 51 cases (49.0 ％)showed an active proliferation growth pattern while other 12 cases(23.5 ％)demonstrated a deterioration morphological character compared with their same age group. The left 14 cases (27.5 ％) showed a normal myeloproliferative pattern. 91.4 ％ (32/35) expressed CD68/KP-1 and 89.5 ％ (17/19) cases expressed CD68/PG-M1, which showed an abnormal increase of monocytes. 26 out of 51 cases (51.0 ％) were positive for EBER,while EBER and immunohistochemistry on LMP-1 were detected simultaneously in 41 cases.The EBER were positive in 19 cases(46.3 ％)but none for LMP-1(P =0.000).ConclusionHypoplasia or hemophagocytic features could be detected on bone marrow biopsy tissues of hemophagocytic syndrome, which might be slightly difficult to diagnose. So immunohistochemistry would be essential. Meanwhile, the detection of EBER is more helpful than LMP-1 for diagnosis.

Clinicopathologic and molecular genetics features of mature aggressive B-cell lymphomas in pediatrics / 白血病·淋巴瘤

Objective To investigate the immunophenotype and molecular genetics of mature aggressive B-cell lymphomas in Chinese pediatric patients and provide the criteris for the diagnosis of them.Methods We collected 97 paraffin-embeded tissue samples of pediatric cases of mature aggressive B-cell lymphomas including 81 Burkitt lymphoma (BL) cases, 8 diffuse large B cell lymphoma (DLBCL) cases and 8unclassifiable B cell lymphoma with featares intermediate between BL and DLBCL (BL/DLBCL) cases. The immunophenotype and genetic features of them were detected by immunohistochemistry and interphase FISH.Results The expression of bcl-2 [3 %(2/66) in BL, 50 % (4/8) in DLBCL, 50 % (4/8) in BL/DLBCL], MUM1 [17 % (12/71) in BL, 63 % (5/8) in DLBCL, 63 % (5/8) in BL/DLBCL] and mean Ki-67 proliferation index [(93±4.4)% in BL, (83±14.3)% in DLBCL, (80±11.5)% in BL/DLBCL] were significantly different between BL and DLBCL and between BL and BL/DLBCL. The frequency of c-myc rearrangement [98 % (79/81) in BL,38 % (3/8) in DLBCL, 50 % (4/8) in BL/DLBCL] and an extra copy of bcl-6 [0 % in BL, 38 % (3/8) in DLBCL, 25 % (2/8) in BL/DLBCL] were also significantly different between BL and DLBCL and between BL and BL/DLBCL. Conclusion Diagnosis of the mature aggressive B cell lymphomas in pediatrics should be based on the comprehensive review and integration of morphologic, immunohistochemical and molecular genetic features. BL/DLBCL is more likely a subgroup of the DLBCL in pediatric population. The expression of CD10 and bcl-6 but not bcl-2, a high Ki-67 PI (＞90 %) and a c-myc rearrangement but not bcl-2 or bcl-6rearrangement are the features of BL. Regardless of the expression of CD10 and bcl-6, positive staining for bcl2, Ki-67 PI below 90 % and an extra copy of the bcl-6 favor a diagnosis of DLBCL or BL/DLBCL.

CT features of inflammatory myofibroblastic tumor in children / 中华放射学杂志

Objective To investigate the CT features of inflammatory myofibroblastic tumor in children. Methods Eighteen patients with inflammatory myofibroblastic tumor proven by surgery and pathology were examined with plain and contrast medium enhancement CT scan. Results Of 18 cases,16 had isolated lesions located at lung (n =4), mesentery (n =3), kidney (n =2) and trachea (n = 1 ),left main bronchus ( n = 1 ), right thoracic cavity ( n = 1 ), peritoneum cavity ( n = 1 ), pancreas ( n = 1 ),left thigh ( n = 1 ), prostate ( n = 1 ), superclvicle soft t tissue ( n = 1 ) , bladder ( n = 1 ). The other 2 cases were with multiple lesions on omentum and mesentery, and in intraperitoneal and side of split of right hepatic lobe, respectively. The CT findings of 18 cases included 16 solid mass with calcifications in 3 of them, and 2 solid-cystic mass. After contrast enhancement, moderate or marked homogeneous or heterogeneous enhancement were shown in all the solid parts of tumor on dynamic CT. Mass can compress surround great vessel and tube-like structure. On pathological examination, the tumor was mainly composed of spindleshaped fibrous cells and inflammatory cells, and the immunohistochemically staining for SMA was observed positively. Conclusion CT can provide specific information for diagnosis of inflammatory myofibroblastic tumor, yet definite diagnosis relies on pathology.

ALK and c-myc gene of anaplastic large cell lymphoma / 白血病·淋巴瘤

Objective To investigate the molecular genetic changes of anaplastic lymphoma kinase (ALK) gene and c-myc gene in anaplastic large cell lymphoma (ALCL). Methods The structural aberrations and changes of copy numbers in ALK and c-myc genes in 72 paraffin-embedded ALCL specimens were detected by interphase fluorescence in situ hybridization (FISH). Results Among 72 ALCL specimens, ALK protein was expressed in 42, ALK gene translocation was detected in 40 specimens in which extra copies of ALK gene were detected in 17. ALK gene translocation was not found in all 30 ALK negative specimens, but extra copies of ALK gene were detected in 14 cases. The difference of incidence rates of extra copies in ALK gene between ALK positive and ALK negative specimens was not significant (P＞0.05). c-myc gene translocation was not found in any of 72 ALCL specimens, but extra copies were detected in 24 cases.Conclusion Most (75.0%) ALCL have ALK gene aberration, in which ALK gene translocations are most common (55.6%), and the extra copies of ALK gene are relatively common genetic changes (43.1%). The ALK gene aberration is only detected in ALK positive ALCL and the gene translocations are in either ALK positive and negative ALCL. There is no or rare c-myc gene translocation in ALCL, but extra copies of c-myc gene are relatively common (33.3%).