Alveolar soft part sarcoma in children: a clinicopathological study of 13 cases / 中华病理学杂志

To investigate the clinicopathological manifestations, molecular genetic, diagnostic histology and differential diagnosis of alveolar soft part sarcoma (ASPS) in children. A total of 13 cases of ASPS diagnosed at Beijing Children's Hospital from August 2009 to November 2018 were collected. HE staining, histochemical staining for PAS and D-PAS, immunohistochemical (IHC) staining for TFE3, INI1 and CD68 and florescence in situ hybridization (FISH) for TFE3 gene translocation were performed. There were four males and nine females, age ranged from 1 year and 2 months to 13 years and 8 months (mean 7.8 years); and four patients were under 5 years old. Histologically, the tumors showed a distinctive and characteristic nested or organoid growth pattern (11 cases) or solid, diffuse growth (2 cases). The tumor cells possessed abundant eosinophilic, or glycogen-rich and clear to vacuolated cytoplasm. The chromatin was relatively dispersed, with prominent and pleomorphic nucleoli; mitotic figures were rare. Vascular invasion was frequently seen. IHC staining showed specific nuclear TFE3 staining. The tumor cells were also positive for INI1,CD68 and vimentin; but were negative for MyoD1, Myogenin, CK and S-100 protein. Seven cases showed PAS and D-PAS staining, with fuchsia acicular or rod-shaped crystals in tumor cytoplasm. Nine cases showed TFE3 break-apart signals by FISH. ASPS is a rare soft tissue sarcoma in children. Compared with ASPA in adults, it has both similarities and unique clinicopathologic characteristics. The diagnosis needs to be confirmed by combining clinical, pathologic, IHC and genetic testing.

Clinicopathologic features of peripheral neuroblastic tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics of peripheral neuroblastic tumors and to evaluate the prognostic significance of these features.</p><p><b>METHODS</b>The clinical and pathologic findings were retrospectively reviewed in 121 cases of peripheral neuroblastic tumor. The clinical outcomes of patients were evaluated. The three-year event-free survival rate was analyzed, with respect to age of patients, Evan's staging, International Neuroblastoma Pathology Classification and mitosis-karyorrhexis index.</p><p><b>RESULTS</b>The median age at diagnosis was 2.7 years; and 96 cases (79.3%) occurred in patients younger than 5 years old. The number of cases in Evan's staging I, II, III, IV and IVs was 24, 39, 24, 29 and 5, respectively. There were 82 cases of neuroblastoma (NB) (including 2 cases of undifferentiated NB, 52 cases of poorly differentiated NB and 28 cases of differentiating NB), 9 cases of ganglioneuroblastoma, intermixed type (GNBi), 19 cases of ganglioneuroma, maturing type (GN) and 11 cases of ganglioneuroblastoma, nodular type (GNBn). Forty-nine cases were in the favorable histology subgroup and 72 cases in the unfavorable histology subgroup. The overall three-year event-free survival rate of the 121 cases was 73.0% ± 4.3%. The three-year event-free survival rates were associated with age (P = 0.002), Evan's staging (P = 0.000), histologic category (P = 0.000), mitosis-karyorrhexis index (P = 0.043), prognostic subgroup (P = 0.000).</p><p><b>CONCLUSIONS</b>Most of the peripheral neuroblastic tumors occur in the children younger than 5 years old. It is composed of NB, GNBi, GN and GNBn. The three-year event-free survival rate is approximately 70%. Significant prognostic parameters include age of patients, Evan's staging, International Neuroblastoma Pathology Classification and mitosis-karyorrhexis index.</p>

Pathological changes in rat model of urinary calculus induced by melamine / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate melamine-induced pathological changes in the kidney.</p><p><b>METHOD</b>Wistar rats were fed with a diet containing 0, 1% and 2% melamine for 15 weeks. After melamine feeding was stopped, various outcome measures were observed for 4 weeks.</p><p><b>RESULT</b>Rats fed with melamine showed reduced caloric intake, slower weight gain and impaired renal function. The blood urea nitrogen of group A and B [(13.23 ± 5.10) mmol/L and (18.30 ± 5.90) mmol/L, respectively] and serum creatinine levels of group B [(19.90 ± 2.90) mmol/L] were higher than that of group C [(8.23 ± 2.30) mmol/L and (10.04 ± 1.73) mmol/L](P < 0.01, respectively). Additionally, the kidney coefficients of group A and B were higher than that of group C (P < 0.01, respectively). Crystals, tubular ectasia and interstitial inflammation and fibrosis were found in the kidneys of melamine fed rats. Four weeks after discontinuation of feeding with melamine-contained diet, the caloric intake and weight of the rats increased, the coefficients of the kidney decreased, and the blood urea nitrogen of group A and B [(17.96 ± 2.04) mmol/L and (19.20 ± 3.36) mmol/L, respectively] and serum creatinine levels of group B [(24.20 ± 5.28) mmol/L], which became worse than 4 weeks before (P < 0.01;P < 0.05, respectively), and were still higher than that of group C [(8.30 ± 1.79) mmol/L and (9.87 ± 2.71) mmol/L, P < 0.01, respectively]. Crystals remained inside the kidney, changes in the renal interstitium did not improve.</p><p><b>CONCLUSION</b>(1) Melamine-induced urinary calculus rat model can be established by feeding 3-week old male Wistar rats with a diet containing 2% melamine for 15 weeks. The main constituent of the urinary calculus was melamine (> 90%), with a little uric acid and traces of cyanuric acid. (2) Melamine damaged the renal function, formed renal crystals, and led to the pathological changes of kidneys. All the influences seemed to be dose-depended and was related with the obstruction of the crystals or calculus in the kidney. (3) The renal function and the pathological changes did not improve 4 weeks after discontinuation of feeding with melamine-contained diet.</p>

Ultrasonographic diagnosis of urinary calculus caused by melamine in children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intake of melamine can cause renal and ureteral lithiasis in infants and children. The present study aimed to understand the value of ultrasonography in the diagnosis of renal and ureteral lithiasis in infants and young children caused by melamine, and the characteristics of ultrasonograms of melamine-associated calculi.</p><p><b>METHODS</b>Ultrasonographic examination on the urinary system was performed for 28 332 children who ingested milk powder that was possibly tainted with melamine; 395 of the children were diagnosed by ultrasonography as having urinary calculus, and 231 cases had lump-like calculi and 164 cases had sand gravel-like calculi. The features of the calculi, the sites of obstruction and the status of hydronephrosis and hydroureterosis were analyzed. Ultrasonographic reexamination was performed for 116 patients and the findings were compared with those of the first ultrasonography, and the short-term expulsion of the calculi was evaluated.</p><p><b>RESULTS</b>Most of the 395 patients with urinary lithiasis, except for those who developed renal failure, had no symptoms. The whole profile of the calculi could be seen in most of the cases, because the echogenicity of the calculi with no sharp or absent acoustical shadowing, was weaker as compared with those from calcium-containing calculi. Comet tail sign could be seen behind the echogenicity of single gravel calculus. The rate of diagnostic consistency of ureteral lithiasis between the ultrasound and the results of clinical observation (including stones expelled spontaneously or after cystoscopic intervention) in 51 cases for 76 ureters was 100%. Percutaneous renal biopsy was performed for one case, and histopathological examination showed flocculent, fine strip-like, ellipse and circular deeply stained sand gravel-like material in the renal tubules, and the circular calculi were found to be attached to the walls of the tubules. Chemical analysis of the calculi expelled from 12 cases showed that the main contents of the calculi were uric acid and melamine. Short-term ultrasound reexamination in 116 patients showed that gravel-like calculi disappeared in 80.4% of the cases; in 26 non-hospitalized cases who had lump-like calculi without hydronephrosis or hydroureterosis, none of the lump-like calculi were expelled.</p><p><b>CONCLUSIONS</b>The ultrasonographic findings of urinary calculi in children caused by ingestion of melamine-tainted milk powder have a certain features as compared to the calculi containing calcium. Careful ultrasound examination can avoid missed diagnoses of ureteral calculi. Most of the gravel-like calculi can be expelled within a short period of term, while lump-like calculi can hardly be expelled. Ultrasonography is an accurate and reliable method of diagnosis of urinary calculus caused by melamine intake in children and it can be used as diagnostic method of choice although abdominal X-ray plain film can also visualize some of larger calculi.</p>

Clinicopathologic features of systemic EBV-positive T-cell lymphoproliferative disease of childhood / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, diagnosis and differential diagnosis of systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood (CSEBV(+)T-LPD).</p><p><b>METHODS</b>Thirty cases of CSEBV(+)T-LPD were retrospectively studied by light microscopy, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The clinical information and follow-up data were analyzed.</p><p><b>RESULTS</b>Nineteen of the 30 patients were males and 11 females. The median age of disease onset was 9 years (range = 1.5 to 32 years). The average duration between disease onset and diagnosis was 14 months. The major clinical manifestations were fever (96.7%), lymphadenopathy (83.3%) and hepatosplenomegaly (66.7%). Cutaneous manifestations were not uncommon, which included hypersensitivity to mosquito bite (13.3%) and skin rash (20.0%). Six of the 20 patients died on follow up. Histologically, the lymph nodes showed expansion of T zone, with diminished or effaced lymphoid follicles. The lymphoid cells were of small to medium size. Scattered large lymphoid cells were also identified in the expanded T zone. Furthermore, the liver and spleen showed mild to marked sinusoidal infiltration. In some cases, various degrees of sinus histiocytosis with erythrophagocytosis were present. Skin biopsies showed mild to marked degree of lymphocytes infiltration in dermis. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T lineage and CD3 positive. They also expressed cytotoxic molecules granzyme B and TIA-1. Seven of the 8 cases examined were CD8 positive, while the remaining case was mainly CD4 positive. Thirteen of 15 cases were shown to be CD56 negative. The number of EBER-positive cells ranged from 5 to more than 500 per high-power field. These cells included small to large lymphoid cells located mostly in the expanded T zone and sometimes in the germinal centers. Nine of the 30 cases, which consisted mainly of medium to large-sized lymphoid cells, were also EBER positive.</p><p><b>CONCLUSIONS</b>Systemic EBV-positive T-cell lymphoproliferative disease of childhood occurs most often in children and young adults, with a median age of 9 years. It has a subacute or chronic clinical course. Most of the patients have evidence of systemic disease, often with lymph node, liver, spleen and skin involvement. It carries a poor clinical outcome and can be life-threatening. The disease is characterized by a clonal proliferation of EBV-infected T cells with cytotoxic immunophenotype. Definitive diagnosis requires correlation between clinical, pathologic and ancillary investigation findings.</p>

Detection of group B streptococcus in the cases died of neonatal pneumonia / 中华儿科杂志

<p><b>OBJECTIVE</b>From the 1970s, group B streptococci (GBS) have been widely recognized as an important pathogen in neonatal infectious disease, and it emerged as the leading cause of neonatal morbidity and mortality in the Western world. However, there are few data on the prevalence of neonatal GBS infections in China. The aim of this retrospective study was to estimate whether GBS is an important pathogen in severe neonatal pneumonia, and to develop a method for detection of GBS infections in fatal neonatal pneumonia.</p><p><b>METHODS</b>A total of 234 neonatal cases (0 - 28 days) died in Beijing Children's Hospital from 1953 to 2004 were enrolled in this study. They were divided into two groups. Two hundred cases diagnosed as neonatal pneumonia were assigned to study group and the remaining 34 cases died of neonatal hemolysis or surgical operation without any confirmed infectious diseases were designated as control group. Formalin-fixed, paraffin-embedded lung tissues were used as source for total genomic DNA extraction. PCR and Southern blot analyses were applied to detect GBS specific cfb gene target sequence. And the clinical data of these cases were reviewed as well.</p><p><b>RESULTS</b>In the study group, 52 cases were detected positive for GBS DNA by PCR (26%), 130 cases were positive by Southern blot (65%). In the control group, 1 case was detected positive GBS DNA by PCR (3%), and 6 cases were positive by Southern blot (18%). The positive rate was significantly lower in the control group than that in the study group (PCR, chi(2) = 8.82, P < 0.01; Southern blot, chi(2) = 26.77, P < 0.01). The positive rate in the neonates younger than 7 days (early-onset) was significantly higher than that in neonates older than 7 days (late-onset) (PCR: 37% vs. 13%, chi(2) = 15.537, P < 0.01; Southern blot: 72% vs. 52%, chi(2) = 4.37, P < 0.05). In the positive early-onset cases, 39% of whom were born prematurely (29/74). Out of the 200 cases, 75 had complete clinical data. Neither blood nor lung culture for GBS was performed in any of these cases. But risk factors were identified for 35 cases, such as premature delivery, low birth weight, premature rupture of the membrane and abnormal amniotic fluid. GBS was positive in all these cases. Severe apnea appeared to be a common symptom and was present in most of the early-onset GBS-positive cases, while cough and wheezing were found in most of the late-onset GBS-positive cases. In the control group, one PCR positive case was suffered from malignant teratoma. The other 5 positive cases confirmed by Southern blot were diagnosed as kernicterus, hepatoma, aproctia complicating with cysti-urethral fistula, neonatal physio logical bleeding and aproctia complicated with archo-perineal fistula.</p><p><b>CONCLUSION</b>Group B Streptococcus is an important pathogen in fatal neonatal pneumonia, especially in early-onset cases. southern blot may be a sensitive method to detect GBS infection in archival tissues. In the clinical work, more attention should be paid to the neonates with GBS risk factors. And GBS detection and prevention in neonates should be put into clinical practice.</p>

Study on Haemophilus influenzae type b: data from autopsy of community acquired pneumonia among children / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the status of Haemophilus influenza type b(Hib) on death cases of children from community-acquired pneumonia (CAP) and to estimate the value of direct in-situ polymerase chain reaction (ISPCR) on diagnosis of children CAP, pathogenically.</p><p><b>METHODS</b>Ordinary PCR, Southern blot and direct ISPCR were applied and compared in detecting Hib in 100 paraffin-embedded lung tissues of autopsy children died of CAP.</p><p><b>RESULTS</b>No major difference on the detection rate of Hib between 50-60s and 80s-2002 was found. The detection rate of Hib by direct ISPCR was higher than the other two methods. By Southern blot, Hib was identified from 8 out of 100 samples (8%), including 4 out of 56 in 1950-60s (7.1%) and 4 out of 44 (9.1%) (chi2 = 0.084, P>0.05) in 1980s-2002. By ISPCR, Hib was identified from 17 out of 100 samples (17%), including 8 out of 56 in 1950-60s (14.3%) and 9 out of 44 (20.5%) with chi2 = 0.665, P > 0.05, in 1980s-2002. Positive cases diagnosed by both Southern blot and ISPCR were 7%.</p><p><b>CONCLUSION</b>Hib was one of the main bacterial pathogens causing CAP and deaths among children. Direct ISPCR was prefertable to be used in pathogenic diagnosis on children pneumonia, in terms of its sensitivity, specificity and localization.</p>

Clinicopathological study of 145 childhood rhabdomyosarcoma cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathological, immunohistochemical and electron microscopic characteristics of pediatric rhabdomyosarcomas (RMS).</p><p><b>METHODS</b>One hundred and forty-five cases of pediatric rhabdomyosarcomas were studied by routine histological, immunohistochemical and electron microscopic studies.</p><p><b>RESULTS</b>There were 97 male and 48 female patients with ages ranging from 4 months to 13 years and a mean of 4.2 years. The follow-up period of 100 patients was from 1 year to 20 years with a mean of 5 years after diagnosis. All cases were subtyped into the following histological categories: embryonal RMS, botryoid RMS, spindle cell RMS, alveolar RMS and solid RMS. Histopathological subtypes, tumor site and tumor stage correlated significantly with the patients' 5 years survival. The best prognosis was observed in spindle cell and botryoid RMS. Embryonal RMS carried an intermediate prognosis. Patients with alveolar RMS and solid RMS had the worst prognosis. Tumors involving bladder, head and neck carried a favorable clinical outcome. Patients with tumors involving trunk extremities retroperitoneum and pelvis did poorly. Immunohistochemically, all cases were positive for Vimentin. The positive staining rates for desmin, SMA and myoglobin were 78%, 75% and 37%, respectively. All tumors were negative for NSE, CD99 and LCA. Electron microscopy study showed features of myofilament and sarcomere in 10 of 15 cases.</p><p><b>CONCLUSIONS</b>RMS is the most common soft tissue sarcoma of childhood. Immunohistochemistry and electron microscopy are helpful in diagnosis and classification of RMS.</p>

Study on MYCN gene amplification and CD44 expression in neuroblastoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To assess the relationship between MYCN amplification in neuroblastoma (NB), tumor stage and prognosis; and to evaluate the usefulness of CD44 in predicting prognosis of NB.</p><p><b>METHODS</b>Differential polymerase chain reaction (D-PCR) with serial dilution assay was used to quantify the MYCN gene copy number in 33 paraffin-embedded tissue samples of NB. All the samples were also studied by immunohistochemistry for CD44. The results were correlated with various prognostic factors of NB, including patient age, tumor stage, pathologic type and MYCN gene amplification.</p><p><b>RESULTS</b>MYCN amplification was identified in 10 of the 33 samples studied (30.3%), which all were in high clinical stage (stage III or IV) and occurred in patients older than 1 year of age. MYCN amplification also significantly correlated with poor clinical outcome (P < 0.01). CD44 was positive in 21 cases and often occurred in patients below 1 year of age, in low clinical stage, with favorable histology and without MYCN gene amplification. The two-year survival rate of CD44-positive group (57.1%) was higher than that of CD44-negative group (8.3%, P < 0.01). Stronger CD44 expression was also associated with better prognosis (P < 0.01).</p><p><b>CONCLUSIONS</b>MYCN gene amplification is significantly associated with advanced tumor stage and poor prognosis in patients with NB. CD44 expression is a reliable marker for better prognosis and is complementary to MYCN amplification assay. D-PCR with serial dilution assay is also suitable for clinical use in quantifying MYCN copy number in NB.</p>