Genetic study of a trisomy 13 fetus with a false-negative karyotype by chorionic villi analysis / 中华医学遗传学杂志

OBJECTIVE@#To explore the mechanism of a false-negative result from karyotyping of chorionic villi cells for a trisomy 13 fetus featuring multiple malformations.@*METHODS@#For a fetus with multiple malformations by ultrasonography and a 46,XY karyotype by chorionic villi analysis, amniocytes were further analyzed with quantitative fluorescence PCR (QF-PCR), G-banded karyotyping and chromosomal microarray analysis (CMA). Meanwhile, non-invasive prenatal testing (NIPT) was conducted on peripheral blood sample from the pregnant woman to determine the chromosomal composition of cytotrophoblast. After induction of labor, common aneuploidies in placenta and fetal tissue were also analyzed by QF-PCR.@*RESULTS@#QF-PCR, chromosomal karyotyping and CMA analysis of the amniocytes all suggested complete trisomy 13 (47,XY,+13) in the fetus. NIPT also suggested existence of fetal trisomy 13. QF-PCR analysis of the placenta and fetal tissues revealed that cells derived from the maternal surface and right side of fetal surface harbored mosaic trisomy 13, while those derived from other sites of fetal surface of the placenta, umbilical cord, amniotic membrane and fetal muscle tissue harbored trisomy 13.@*CONCLUSION@#Karyotyping of long-term cultured chorionic villus sample may give rise to false negative results due to placental mosaicism. To ensure accurate prenatal diagnosis, discordance between karyotyping of chorionic villi cells, fetal ultrasound and NIPT result should be verified by amniocentesis or cordocentesis and application of multiple cytogenetic and molecular techniques.

Progress of relationship between sodium-calcium exchanger 1 and tumors / 肿瘤研究与临床

Sodium-calcium exchanger 1 (NCX1) is a type of two-way translocator with cell membrane structure. It is involved in the transport of Ca2+, regulates a variety of physiological and pathological processes, and is closely related to the growth and metastasis of tumors. This article reviews the progress of the relationship between NCX1 and tumor development.

Progress of relationship between sodium-calcium exchanger 1 and tumors / 肿瘤研究与临床

Sodium-calcium exchanger 1 (NCX1) is a type of two-way translocator with cell membrane structure. It is involved in the transport of Ca2+, regulates a variety of physiological and pathological processes, and is closely related to the growth and metastasis of tumors. This article reviews the progress of the relationship between NCX1 and tumor development.

Long non-conding RNA TUG1 and digestive system cancers / 国际肿瘤学杂志

Taurine-upregulated gene 1 (TUG1) is a recently identified oncogenic long non-coding RNA (lncRNA),that is overexpressed in various digestive system tumor tissues and cell lines,including esophageal cancer,gastric cancer,liver cancer,cholangiocarcinoma and biliary tract cancer,pancreatic cancer and colorectal cancer.Studies have shown that TUG1 participates in tumor cells proliferation,apoptosis,migration and invasion,and high expression of TUG1 is associated with clinicopathological features and prognosis of cancer patients,suggesting that lncRNA TUG1 is likely represents a feasible biomarker or therapeutic target in human digestive system cancers.

Clinicopathologic and molecular features of myoepithelial tumors of salivary glands / 中华病理学杂志

Objective@#To investigate the clinicopathological, and molecular characteristics of myoepithelial tumors (MTs) of salivary glands.@*Methods@#A total of 37 MTs cases including 13 malignant epithelial tumors (MMTs) and 24 benign epithelial tumors (BMTs) of salivary glands were identified from the archives of the Department of Pathology, General Hospital of Eastern Theater Command, dating from 2006 to 2016. Clinical features, histological patterns, immunohistochemical characteristics and status of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) analysis were reviewed in all cases.@*Results@#Clinically, 37 MTs cases mainly occurred in the parotid glands, when most of the patients presented with painless masses. Of the 13 MMTs cases, male to female ratio was 7∶6, and the median age was 62 years old. Of the 24 BMTs cases, male to female ratio was 5∶7, and the median age was 54 years old. Immunohistochemically, 37 MTs cases were positive for CKpan, and at least one myoepithelial marker. Twenty six of 37 MTs cases were analyzable for the EWSR1 gene break by FISH. Based on the previous evaluation criterion, the EWSR1 translocation was detected in 4 cases of 11 MMTs, and 4 cases of 15 BMTs. According to the main histological composition of tumor cells, 4 EWSR1-positive MMTs covered 2 clear-cell cases and 2 epithelioid-cell cases, when 4 EWSR1-positive BMTs covered 2 clear-cell cases, 1 plasmacytoid-cell case, and 1 spindle-cell case.@*Conclusions@#Males and females are affected equally. MTs express immunoreactivity for CKpan, and at least one myoepithelial marker. The EWSR1 rearrangement is present in a subset of MTs, with variable morphological characteristics, and has no statistical significance on clinical behavior.

Lung non-terminal respiratory unit type adenocarcinoma: a clinicopathologic study / 中华病理学杂志

Objective@#To evaluate the clinicopathologic characteristics of lung non-terminal respiratory unit (non-TRU) type adenocarcinoma.@*Methods@#Seventy-two cases of lung non-TRU type adenocarcinoma that underwent complete resection and diagnosed at Departments of Pathology, Affiliated Suzhou Hospital of Nanjing Medical University and Nanjing General Hospital of the PLA from January 2005 to December 2016 were retrospectively studied. The histomorphological changes and precursor lesions were observed under microscope. The expression of lineage-specific markers and tumor stem cell markers was detected by immunohistochemistry (IHC). The major driver mutations of lung adenocarcinoma were tested by ARMS and directive gene sequencing.@*Results@#Non-TRU type adenocarcinomas were more commonly found in male (65.3%, 47/72), former or current smokers (68.1%, 49/72), the elder (mean 61 years old), central adenocarcinoma (75.0%, 54/72), tumors with necrosis (61.1%, 44/72) and higher grade (73.6%, 53/72). Histologically, non-TRU type adenocarcinoma displayed complex histomorphology and was often composed of large irregular gland-like and acinar pattern accumulating extracellular mucin, necrotic tumor cell debris and neutrophils, or invasive adenocarcinoma with mucin production. The tumor cells were composed of bronchial surface epithelial cells, mucinous column cells, polygonal cells and goblet cells. Eighteen (25.0%), 23 (31.9%) and 28 (38.9%) cases exhibited ciliated columnar cell metaplasia (CCCM), mucous columnar cell change (MCCC) and bronchiolar columnar cell dysplasia (BCCD) (precursor lesion of lung adenocarcinoma). IHC showed the expression of CK7 (100.0%, 72/72), TTF1 (12.5%, 9/72), Napsin A (5.6%, 4/72), MUC5AC (81.9%, 59/72), MUC5B (87.5%, 63/72), p53 (66.7%, 48/72), CK5/6 (12.5%, 9/72), p63 (18.1%, 13/72), CK20 (19.4%, 14/72) and CDX2 (16.7%, 12/72) in the tumor cells. The expression of tumor stem cell markers was detected in 43.1% cases (31/72) for CD44, 31.9% (23/72) for CD133, 58.3% (42/72) for β-catenin, 36.1% (26/72) for ALDH1, 12.5% (9/72) for GATA6, 20.8% (15/72) for SOX2 and 29.2% (21/72) for OCT4. The driver mutations were 26.4% (19/72) for KRAS, 2.8% (2/72) for EGFR and 1.4% (1/72) for EML4-ALK, and none for BRAF and ROS1.@*Conclusion@#Non-TRU type adenocarcinoma is an uncommon subtype of lung adenocarcinoma with distinct clinicopathologic characteristics, histologic appearances, immunophenotype and molecular genetic alterations.

Analysis of SLC25A13 gene mutations and prenatal diagnosis for 20 families affected with citrin deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them.</p><p><b>METHODS</b>The 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies.</p><p><b>RESULTS</b>Biallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions (c.851del4, c.1092_1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A (p.Y24X)), one duplication mutation (c.1638_1660dup), one insertion (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c.851del4 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated.</p><p><b>CONCLUSION</b>Analysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.</p>

Genetic study of a fetus with 9p direct duplication deletion syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To use next generation sequencing (NGS) to identify unknown abnormality of chromosome 9 in a fetus and explore its mechanism.</p><p><b>METHODS</b>A pregnant woman with abnormal fetal ultrasound finding underwent amniocentesis for G-banded chromosomal analysis. Karyotyping was also performed on peripheral blood samples derived from its parents. Fetal blood sample was obtained for NGS testing to identify abnormality unrecognized by karyotyping.</p><p><b>RESULTS</b>Analysis of amniocytes has revealed a 46,XX,der(9)(?::p21 to qter) karyotype, while both parents had a normal karyotype. NGS analysis of the fetus revealed a 20.67 Mb duplication (4 454 279-25 126 275) at 9p21.3p24.2, which overlapped with that of the 9p duplication syndrome, and a 4.43 Mb deletion at 9p24.2p24.3 (10 001-4 442 364), which partially overlapped with that of 9p deletion syndrome and 46,XY sex reversal 4 region. Comparison of the sequencing data with reference genome database indicated direct duplication of 9p21.3p24.2, which was also supported by review of the morphology of chromosome 9p. Therefore, the karyotype of the fetus was verified to be 46,XX,der(9) dir dup(9)(p21.3p24.2), del(9)(p24.2p24.3).</p><p><b>CONCLUSION</b>Combined G-banded karyotyping and NGS can identify dir dup del(9p) with accuracy. Delineation of the mechanism of dir dup del(9p) and its genotype-phenotype correlation may facilitate genetic counseling and estimation of recurrence risk.</p>

Genotype and phenotype analysis of a child with partial 18q deletion syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genotype-phenotype correlation of a child with chromosome 18q deletion syndrome.</p><p><b>METHODS</b>G-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on the child with abnormal phenotypes. Genotype-phenotype correlation was explored following accurate mapping of the breakpoints on chromosome 18q. SNP array was also performed on the genome DNA derived from peripheral venous blood samples from both parents.</p><p><b>RESULTS</b>Chromosomal analysis revealed that the child has a karyotype of 46, XY, del(18) (q23). SNP array analysis detected a 9.855 Mb deletion (chr18: 68 158 880-78 014 123) at 18q22.2q23. Mapping of the breakpoints suggested that the deletion has overlapped with that of distal chromosome 18q deletion syndrome and encompassed several critical regions for this syndrome. SNP array performed on parental samples suggested that the 18q22.2q23 deletion was de novo in origin. FISH analysis of peripheral blood sample from the child confirmed the presence of 18qter deletion.</p><p><b>CONCLUSION</b>The phenotype of this child may be attributed to the deletion of distal 18q22.2q23, which has encompassed several critical regions for the 18q deletion syndrome.</p>

Detection of epidermal growth factor receptor gene mutations in different types of non-small cell lung cancer by droplet digital PCR and amplification refractory mutation system / 中华病理学杂志

Objective@#To compare amplification refractory mutation system(ARMS) and droplet digital PCR (ddPCR) in the detection of epidermal growth factor receptor (EGFR) gene mutations in patients with non-small cell lung cancer (NSCLC), and to investigate the clinical value of ddPCR.@*Methods@#A total of 79 specimens of NSCLC, including 22 cases of cell block, 18 cases of surgical specimens, 12 cases of biopsy specimens and 27 cases of plasma samples, were analyzed for the mutation status of EGFR gene by ARMS and droplet digital PCR method.@*Results@#In 18 cases of surgical specimens and 12 cases of biopsy specimens, the detection results by the two methods were identical with positive rates of 9/18 and 5/12, respectively. In 22 cases of effusion cell blocks, ARMS detected 19-del and L858R of EGFR gene in two cases, in which droplet digital PCR detected 19-del+ T790M mutations in one case and L858R+ T790M mutation in another. L858R mutation was detected by droplet digital PCR in one case but ARMS assay was negative. The remaining 19 cases were consistent by the two methods. In blood samples, the positive rate was 33.3%(9/27) by ARMS and 37.0%(10/27) by droplet digital PCR. Two cases showed L858R and 19-del+ T790M mutation by droplet digital PCR but ARMS assay detected only 19-del. The remaining 25 cases were consistent by the two methods.@*Conclusion@#Droplet digital PCR method is more sensitive and accurate than ARMS for the detection of EGFR mutations in pleural fluid and blood samples, can be used in clinical test.

Epidermal growth factor receptor (EGFR) mutation status before and after acquired resistance to EGFR tyrosine kinase inhibitors in patients with lung adenocarcinoma / 中华病理学杂志

Objective@#To investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinomas before and after acquiring resistance to EGFR tyrosine kinase inhibitors (TKIs) using ARMS method followed by further verification using droplet digital PCR technique.@*Methods@#Twenty qualified patients were included, among them 13 were male and 7 were female patients. Before EGFR-TKIs treatment, 5 patients were EGFR wild-type by ARMS, and the other 15 patients had L858R or 19-del point mutations. The time to progression varied from 4 to 18 months. Mutation of exons 18, 19, 20 and 21 were detected by ARMS, and were verified by droplet digital PCR system method.@*Results@#EGFR wild-type status was unchanged before and after acquired resistance to EGFR-TKIs in 5 lung adenocarcinoma patients. Alteration of EGFR mutation status occurred in 10 of the 15 patients with pre-treatment L858R or 19-del mutations. Among them, T790M mutation was found in 8 patients, L858R became G719X plus S768I mutation in one patient, and 19-del converted into wild-type in one other patient.@*Conclusions@#T790M mutation is the primary type of EGFR mutation in lung adenocarcinomas with acquired resistance to EGFR-TKIs therapy. Acquired resistance to EGFR-TKIs dose not lead to the alteration of EGFR status in pre-treatment EGFR wild-type patients, but can alter EGFR mutation status in pre-treatment EGFR mutant patients.

Molecular features of metanephric adenoma and their values in differential diagnosis / 中华病理学杂志

Objective@#To study the molecular features of metanephric adenoma (MA) and discuss their values in differential diagnosis.@*Methods@#BRAF V600E immunohistochemistry (IHC) using the mutation-specific VE1 monoclonal antibody and Sanger sequencing of BRAF mutations were performed on 21 MAs, 16 epithelial-predominant Wilms tumors (e-WT) and 20 the solid variant of papillary renal cell carcinomas (s-PRCC) respectively. p16 protein was detected by IHC also. Fluorescence in situ hybridization (FISH) analyses using centromeric probes for chromosome 7 and 17 were performed on the three renal tumors in parallel.@*Results@#Fourteen (14/21, 66.7%) of 21 MA cases demonstrated diffuse, moderate to strong cytoplasmic BRAF V600E IHC staining and the BRAF V600E protein expression was detected in 2 (2/16) of 16 e-WT cases for the first time, whereas all s-PRCCs were negative (P<0.05). All cases (including 14 MAs and 2 e-WTs) with diffuse, moderate to strong cytoplasmic BRAF V600E IHC staining were confirmed to harbor BRAF V600E missense mutations using Sanger sequencing, and no BRAF mutations were detected in cases with negative BRAF V600E protein expression. One case (1/21, 4.8%) showed trisomy of chromosome 7 alone, and another one (1/21, 4.8%) showed trisomy of chromosome 17 alone in 21 MAs. Two cases (2/16) of 16 e-WTs showed trisomy of chromosome 17 alone. In 20 s-PRCCs, trisomy of chromosomes 7 alone was reported in 2 cases (2/20), trisomy of chromosome 17 alone in 3 cases (3/20) and trisomy of chromosome 7 and 17 in 14 cases (14/20). The total positive rates of trisomy of chromosome 7 and/or 17 in MAs, e-WTs and s-PRCCs were 9.6% (2/21), 2/16 and 95.0% (19/20). p16 protein was positive in 81.0% (17/21) MAs, whereas the positive rates in e-WTs and s-PRCCs were 2/16 and 5.0% (1/20).@*Conclusions@#Most MAs harbor BRAF V600E mutations, and MAs lack the gains of chromosome 7 and 17 that are characteristic of papillary renal cell carcinoma. These molecular features can be used to distinguish MA from its mimics. BRAF V600E IHC using the mutation-specific VE1 monoclonal antibody provides an effective method in BRAF V600E mutations detection of renal tumors. p16 is overexpressed in MA, and the finding suggests that the low proliferative rate of the tumor might be attributed to BRAF V600E-induced senescence mediated by p16.

Clinicopathologic features of mammary analogue secretory carcinoma of salivary glands / 中华病理学杂志

Objective@#To investigate the clinicopathological features of mammary analogue secretory carcinoma (MASC) of salivary glands, and its diagnosis, differential diagnosis, immunohistochemistry and molecular pathology.@*Methods@#Seventeen cases of MASC were enrolled, with 9 cases of salivary acinar cell carcinoma and 18 cases of adenoid cystic carcinoma as control groups from Nanjing General Hospital from 1997 to 2014 were included in this retrospective study, combined with immunohistochemistry and molecular detection of ETV6-NTRK3 gene fusion. All cases were histologically reviewed with immunohistochemical staining (EnVision) for S-100 protein, SOX10, GATA3, CD117 expression in each group. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 gene fusion.@*Results@#The age of MASC patients ranged from 27 to 74 years with mean age of 47 and ratio of male and female was 4∶3. All cases showed infiltrative growth and diverse cytology and histology, including lobular (8 cases), cystic papillary (3 cases), cribriform mixed with papillary and glandular structures (6 cases) at various proportions. Some tumors of MASC also exhibited solid growth areas with occasional microcystic honeycombed pattern composed of small cysts merged into larger cysts resembling thyroid follicles. S-100 protein and SOX10 were strongly positive in all MASC cases (17/17). In addition, there was insignificant positivity for GATA3 (3/17) and CD117 (4/17). ETV6 gene fusion detection was informative in 12 MASC cases by FISH with 10 positive cases and 2 negative cases.@*Conclusions@#Combined immunohistochemical positivity of S-100 protein, CD117 and SOX10 are useful in the diagnosis and differential diagnosis of MASC. FISH detection of ETV6-NTRK3 fusion offers an additional molecular diagnostic marker for the diagnosis.

Improved identification for 5p deletion syndrome and partial trisomy 11q presented in a fetus by SNP array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prenatal application of single nucleotide polymorphism array (SNP array) in the identification of 5p deletion syndrome with partial trisomy 11q.</p><p><b>METHODS</b>G-banded karyotyping and SNP array were performed using amniocytes on a fetus with multiple malformations for the identification of chromosome abnormality. Furthermore, karyotyping was carried out on the parental peripheral blood specimens to ascertain the origin of chromosome abnormalities and then fluorescence in situ hybridization (FISH) was also utilized to confirm the results.</p><p><b>RESULTS</b>Karyotype of amniocyte showed 46, XY, der(5) (?::p15 → qter). SNP array revealed a 13.907 Mb deletion at 5p15.33p15.2 (chr5: 113576-14020561), overlapping the region of 5p deletion syndrome, and a 18.254 Mb duplication at 11q23.3 q25 (chr11: 116684627-134938470), overlapping no known syndrome. Karyotype of the parents showed a normal 46,XX in mother and 46,XY,t(5;11)(p15;q23) in father. Three-color metaphase FISH analysis on paternal peripheral blood specimens also confirmed the paternal karyotyping result.</p><p><b>CONCLUSION</b>SNP array could uncover 5p deletion syndrome with partial trisomy 11q unidentified by G-banded karyotyping and accurately locate the genomic breakpoints, facilitating the mapping of pathogenic critical regions and the identification of candidate genes, also accumulating research data for genotype-phenotype study.</p>

Accurate detection of a case with Angelman syndrome (type 1) using SNP array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a case with Angelman syndrome (AS) using single nucleotide polymorphism array (SNP array) and explore its genotype-phenotype correlation.</p><p><b>METHODS</b>G-banded karyotyping and SNP array were performed on a child featuring congenital malformations, intellectual disability and developmental delay. Mendelian error checking based on the SNP information was used to delineate the parental origin of detected abnormality. Result of the SNP array was validated with fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>The SNP array has detected a 6.053 Mb deletion at 15q11.2q13.1 (22,770,421- 28,823,722) which overlapped with the critical region of AS (type 1). The parents of the child showed no abnormal results for G-banded karyotyping, SNP array and FISH analysis, indicating a de novo origin of the deletion. Mendelian error checking based on the SNP information suggested that the 15q11.2q13.1 deletion was of maternal origin.</p><p><b>CONCLUSION</b>SNP array can accurately define the size, location and parental origin of chromosomal microdeletions, which may facilitate the diagnosis of AS due to 15q11q13 deletion and better understanding of its genotype-phenotype correlation.</p>

Mechanisms of imatinib mesylate induced apoptosis of primary T cells / 中国免疫学杂志

Objective:To investigate mechanism of imatinib mesylate induced apoptosis of primary CD3+T cells.Methods:The CD3+T cells were stimulated by 0-100 nmol/L imatinib for 24 h,cell apoptosis was detected by flow cytometry;Caspase-3,Caspase-8, A20 and NF-κB expression levels were detected by Real-time quantitative PCR and Western blot.Results: IM significantly increased apoptosis of T cell;Caspase-3 and A20 gene expression levels were upregulated and NF-κB expression level was downregulated both in gene and protein levels.Conclusion:IM increased apoptosis of T cell by upregulating A20 expression.

Renal cell carcinoma with t(6;11)(p21.2;q13)/MALAT1-TFEB fusion: a clinical and pathological analysis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion.</p><p><b>METHODS</b>A total of 9 cases of such rare tumor were selected for clinicopathologic, immunohistochemical and molecular analysis, with review of literature.</p><p><b>RESULTS</b>The age of the patients ranged from 21 to 42 years (mean=31.3 years). The patients included four men and five women. Histologically, 4 of the 9 cases studied showed classic morphologic features of TFEB RCC, with hyaline material, pigments and psammoma bodies frequently identified. The remaining 5 cases demonstrated uncommon morphology, mimicking perivascular epithelioid cell neoplasm, clear cell RCC, chromophobe RCC or papillary RCC. Immunohistochemical study showed that TFEB and vimentin were positive in all cases. Most of the tumors studied also expressed Ksp-cadherin, E-cadherin, CD117, HMB45, Melan A and Cathepsin K. CKpan showed immunostaining in only 1 case. The staining for TFE3, CD10 and CK7 were all negative. TFEB gene rearrangement was detected in all the 9 cases studied using fluorescence in-situ hybridization. MALAT1-TFEB fusion gene was identified in 2 cases by polymerase chain reaction and direct sequencing. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none developed tumor recurrence, progression, or metastasis.</p><p><b>CONCLUSIONS</b>TFEB fusion-associated RCC is a rare neoplasm, tends to occur in young age group and carries an indolent behavior. Diagnosis relies on clinicopathologic findings and immunohistochemical analysis. TFEB break-apart FISH assay is a reliable tool in confirming the diagnosis.</p>

Clinicopathologic study of primary renal hemangioblastoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic characteristics of primary renal hemangioblastoma.</p><p><b>METHODS</b>The morphologic features, immunophenotype and molecular findings of 3 cases of primary renal hemangioblastoma were studied, with review of literature.</p><p><b>RESULTS</b>The age of patients ranged from 43 to 57 years. There were 2 women and a man. The patients often presented with renal mass. Histologically, the tumors were surrounded by thick fibrous capsule and composed of epithelioid or spindle cells. Two cases had a prominent stromal component and the other one was rich in capillary network. Lipid vacuoles were observed in all cases. Features of hemorrhage were demonstrated in 2 cases. Capsular invasion and necrosis were seen in 1 case. Immunohistochemical study showed that the stromal cells were positive for alpha-inhibin (3/3), S-100 protein (3/3), EGFR (2/2), PAX-2 (2/2), PAX-8 (2/2) and CA9 (2/2) but negative for CKpan (2/2) and HMB45 (2/2). Focal membranous staining for CD10 (3/3) was noted. No VHL gene mutations or chromosome 3p deletion were detected in the 2 cases studied.</p><p><b>CONCLUSIONS</b>Renal hemangioblastoma shows distinctive morphologic appearance with a wide range of variation. The unexpected positive staining for PAX-2, PAX-8 and CD10 in renal hemangioblastoma needs to be aware. Immunohistochemical study may be helpful in differential diagnosis of these renal tumors.</p>

ALK gene fusion associated non-small cell lung cancer: automated immunostainer detection and clinicopathologic perspectives / 中华病理学杂志

To explore the automated immunostainer screening anaplastic lymphoma kinase (ALK) gene fusion non-small cell lung cancer (NSCLC) and clinicopathological characteristics of the molecular subtype lung cancers. Methods Five hundred and sixty-six cases of NSCLC were collected over a 16 month period. The test for ALK was performed by Ventana automated immunostainer with anti-ALK D5F3. The histological features, treatment and outcome of patients were assessed. Results Thirty-eight cases (6.7%, 38/566) of NSCLC showed ALK gene fusion. The frequency of ALK gene fusion was higher in male (7.1%, 25/350) than that in female (6.0%, 13/216) patients, but not achieving statistical significance (chi2 = 0.270, P = 0.604). ALK + NSCLC was more significantly more frequent in patients < or = 60 years (9.9%, 28/282) than >60 years (3.5% , 10/284) of age. Histologically, the ALK + NSCLCs were mostly adenocarcinoma (81.6%, 31/38) , among which eighteen cases were solid predominant subtype with mucin production; nine cases were acinar predominant subtype; one case was papillary predominant subtype and three cases were invasive mucinous adenocarcinoma. The ALK + non-adenocarcinoma included three cases of squamous cell carcinoma, three cases of adenosquamous carcinoma and one case of pleomorphic carcinoma. Among the ALK + NSCLC patients, the number of non/light cigarette smokers (86. 8% , 33/38) was more than that of heavy smokers. Twenty-nine cases were stages III and IV; twenty-nine cases showed lymph node metastasis; twenty cases showed metastases mostly to brain and bone; and one case showed EGFR gene mutation coexisting with ALK gene fusion. Twelve of fifteen patients received crizotinib therapy and remained stable. Conclusions NSCLC with ALK gene rearrangement shows distinctive clinical and histological features. Ventana-IHC may he a feasible and valid technique for detection of ALK rearrangement in NSCLC.

Clinical and pathological observation on primary pulmonary primitive neuroectodermal tumor / 医学研究生学报

Objective Primitive neuroectodermal tumor (PNET) is a rare malignant small round cell tumor .This paper aimed to study the clinical and pathological features of primary pulmonary primitive neuroectodermal tumor . Methods We collected 2 cases of primary pulmonary PNET to review the clinical and pathological features .Immunohistochemical staining was used to detect immune mark-ers, and fluorescence in situ hybridization (FISH) was applied to detect EWS translocation. Results 2 patients were aged 33 years and 17 years.Microscopically, the tumor cell was composed of single small round cells in diffusion or in distribution of sheets or beams , with scant cytoplasm , oval or spindle-shaped nucleus , high mitotic count .Irregular tumor necrosis scattered in the tumor along with visi-ble rosette structure.Immunohistochemical study showed that the tumor cells were positive for CD 99, FLI-1 and Syn, while CKpan, EMA, Desmin, CgA, TTF1, CD34 were negative.EWS/FLI1 translocations were detected positive in both the cases .2 patients died 7 months and 32 months after operation , respectively . Conclusion Primary pulmonary PNET is rare , so the selection of appropriate im-mune markers (CD99, FLI-1, Syn) and FISH for the detection of EWS translocation helps to improve the accuracy of diagnosis .