Imbalance of regulatory T cells to Th17 cells in IgA nephropathy.

BACKGROUND: Dysregulation of CD4 (+) T cell subsets participates in the pathogenesis of IgA nephropathy (IgAN). FoxP3 (+) regulatory T cells (Treg) and Th17 cells are two novel subsets of CD4 (+) T cells. This study aims to investigate Treg/Th17 balance in IgAN patients. METHODS: Peripheral frequencies of Th17 and Treg functional subsets - CD45RA (+) FoxP3(low) resting Treg (rTreg) and CD45RA(-)FoxP3(high) activated Treg (aTreg) were assessed in 63 adult IgAN patients. Expression of transcription factors (FoxP3 and RORγt) and related cytokines of Treg and Th17 were analysed. Renal expression of FoxP3 and IL-17A were detected by immunohistochemistry. RESULTS: Compared with normal controls, IgAN patients had decreased frequency of CD45RA(-)FoxP3(high) aTreg subset (p < 0.05), increased frequency of Th17 (p < 0.05) and decreased ratio of Treg/Th17 (p < 0.05). Frequency of aTreg subset correlated with SBP(r = - 0.57, p < 0.05), DBP (r = - 0.50, p < 0.05), eGFR (r = 0.68, p < 0.05) and 24 h proteinuria (r = - 0.58, p < 0.05). RORγtmRNA/FoxP3mRNA ratio increased in IgAN (p < 0.05). Serum IL-17A, IL-21, IL-23, IL-1ß and IL-6 elevated while IL-10 decreased in IgAN (p < 0.05), and serum IL-17A correlated with 24 h proteinuria (r = 0.35, p < 0.05). Serum TGF-ß1 wasn't different between the two groups. Renal interstitial infiltration of FoxP3 (+) mononuclear cells were observed in IgAN patients, particularly prominent in those with > 25% tubular atrophy/interstitial fibrosis. Tubular IL-17A expression was found in 34 out of 63 IgAN patients. Compared with 29 patients without IL-17A expression, these patients had lower renal function, greater proteinuria, and more severe tubulointerstitial damage. CONCLUSIONS: Imbalance of Treg/Th17 found in IgAN may play a role in disease pathogenesis and progression.

[Atypical teratoid/rhabdoid tumors of central nervous system in childhood: a clinical and histopathologic study of 6 cases].

OBJECTIVE: To study the clinicopathologic features, immunohistochemical findings, diagnosis and differential diagnosis of atypical teratoid/rhabdoid tumors (AT/RT) of central nervous system in childhood. METHODS: The clinicopathologic data, morphologic features and immunophenotypes were reviewed in 6 cases of AT/RT. EnVision method was applied. Antibodies include cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, smooth muscle actin (SMA), muscle specific actin (MSA), glial fibrinary acid protein (GFAP), desmin, placental alkaline phosphatase (PLAP) and INI1. RESULTS: Five of the six cases of AT/RT occurred in infancy and early childhood. Histologically, the predominant component was rhabdoid cells. Cytoplasmic inclusions were present in all cases. Primitive neuroectodermal tumor (PNET) component was also identified in 5 of the 6 cases studied. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen and vimentin. The staining for INI1, desmin and PLAP was negative. Smooth muscle actin was expressed in 2 cases and glial fibrillary acidic protein in 5 cases. The proliferative index as demonstrated by Ki-67 staining was high. CONCLUSIONS: AT/RT is not a particularly uncommon malignancy in childhood. The histologic hallmark is the presence of rhabdoid cells with cytoplasmic inclusions. The tumor cells are positive for cytokeratin, epithelial membrane antigen and vimentin, and negative for INI1. Differential diagnosis includes PNET, medulloblastoma and medullomyoblastoma.

Characterization of tubo-ovarian abscess mimicking adnexal masses: Comparison between contrast-enhanced CT, 18F-FDG PET/CT and MRI.

0BJECTIVE: We compared the diagnostic accuracy of contrast-enhanced computed tomography (CT), fluorine 18-labeled-fludeoxyglucose (18F-FDG) positron emission tomography (PET)/CT and conventional magnetic resonance imaging (MRI) without and with diffusion-weighted imaging (DWI) for characterization of tubo-ovarian abscesses (TOAs) that mimic adnexal tumors. MATERIALS AND METHODS: We evaluated (retrospectively) 43 patients who underwent contrast-enhanced CT, PET/CT, conventional MRI without and with DWI, and who were found to have TOAs and complex adnexal tumors. All images were evaluated independently by four radiologists using a two-point grading system. Results of contrast-enhanced CT, PET/CT, MRI without DWI, and MRI with DWI were compared for each patient using receiver operating characteristic curves. Sensitivity, specificity, and positive predictive value (PPV) were calculated and compared using the chi-square test. RESULTS: Sensitivity of MRI with DWI (95%) was significantly higher than that of contrast-enhanced CT (78.6%), PET/CT (86.7%) and MRI without DWI (87.5%). Specificities of these modalities were not significantly different. The PPV of MRI with DWI (100%) was significantly higher than that of the other three modalities (CT, 72.4%; PET/CT 78.5%; MRI without DWI, 81.5%). Overall accuracy of MRI with DWI was significantly higher than that of the other three modalities (CT, 74.4%; PET/CT, 81.4%; MRI without DWI, 83.7%). CONCLUSION: MRI with DWI shows high accuracy for characterization of complex ovarian lesions, and is the most useful method for differentiation of TOAs from ovarian tumors.

[Unusual expression and molecular mechanisms of E-cadherin, beta-catenin in correlation with clinicopathologic parameters in neuroblastoma].

OBJECTIVE: To study the expression of E-cadherin and beta-catenin in neuroblastomas of various degrees of differentiation, and to investigate their molecular mechanisms in correlation with clinicopathologic parameters. METHODS: Immunohistochemistry EnVision method was used to detect E-cadherin and beta-catenin expression in 90 paraffin-embedded tissue samples of neuroblastomas. The methylation status of CpG islands of E-cadherin promoter was investigated by MSP in 7 fresh tissue and 24 paraffin-embedded tissue samples. The mutation status of exon 3 of beta-catenin gene was studied by PCR in 7 fresh tissue samples. Statistical analysis of the data was performed by SPSS software. RESULTS: E-cadherin and beta-catenin were abnormally expressed in neuroblastomas in general. The expression of beta-catenin in well-differentiated neuroblastoms was markedly higher (47/70, 67.1%) than that of the poorly differentiated tumors (8/20, 40.0%). There was a markedly decreased expression of both genes in tumors with lymph node metastasis than those without. Demethylation was seen in some regions of the promoter of E-cadherin in 31 cases of nuroblatomas. PCR of the exon 3 of beta-catenin followed by DNA sequencing demonstrated rearrangements and mutations in 7 cases, including 2 cases harboring identical point mutation at gene position 27184, leading to a T-->A alteration. CONCLUSIONS: The abnormal over-expression of E-cadherin in neuroblastomas is independent of the methylation status of their promoter sequences. The abnormal expression of beta-catenin may be related to mutational changes at exon 3 of the gene.

[The effect of breast cancer specific gene 1 in the prognosis of breast cancer].

OBJECTIVE: To detect breast cancer specific gene 1 (BCSG1) expression in different breast tissue, analysis its correlation with clinical parameters and evaluate the prognosis of breast cancer. METHODS: The expression of BCSG1 was detected by reverse transcription-polymerase chain reaction (RT-PCR) in surgical specimens from 84 cases of breast disease patients selected randomly at XinHua Hospital affiliated with Shanghai Second Medical University from September 1999 to December 2002. Of 84 cases, 72 case were breast cancer. Statistic analysis BCSG1 gene expression correlation with clinical parameters of breast cancer. 72 breast cancers were followed up (4 - 43 months) to set up independent prognosis factor by survival analysis. RESULTS: BCSG1 was undetectable in all benign breast lesions, while was detectable in 36.1% of all breast cancer samples (26/72), in which 79.2% of stage III/IV cases were positive (19/24). The expression of BCSG1 was tightly correlated with the stage (P = 0.000) and the size of tumor (P = 0.007). Both ER (P = 0.027) and BCSG1 (P = 0.001) were the independent prognosis factor of breast cancer. CONCLUSION: BCSG1 is one of independent tumor marker of breast cancer, the expression of BCSG1 is closely correlated to the stage of breast cancer and the tumor size. Maybe, BCSG1 is a new prognosis factor of breast cancer.

Calcified cerebral cryptococcal granuloma.

The authors report a 12-mo-old girl with calcified cerebral cryptococcal granuloma. She was admitted with a 6-mo history of seizures. Laboratory examinations showed no abnormal findings. Electroencephalography revealed bilateral slow wave activity, greater in the right occipital region. CT showed an irregular calcified focus with small surrounding low density in the right parieto-occipital region. MRI demonstrated mixed signals without edema and visible flow-voids. The clinical symptoms mimicked intracranial vascular malformations. The diagnosis of cerebral cryptococcal granuloma was made by histopathology. Partial resection of the lesion with post-operatively antifungal and anticonvulsant therapy offered the satisfactory result. Cerebral cryptococcal granuloma is extremely rare, especially in infants. Calcification is indeed unusual. Cerebral cryptococcal granuloma should be included in the differential diagnosis of intracranial mass with calcification in infants.

Lymph node metastasis in gastric cardiac adenocarcinoma in male patients.

AIM: To reveal the clinicopathological features and risk factors for lymph node metastases in gastric cardiac adenocarcinoma of male patients. METHODS: We retrospective reviewed a total of 146 male and female patients with gastric cardiac adenocarcinoma who had undergone curative gastrectomy with lymphadenectomy in the Department of Surgery, Xin Hua Hospital and Rui Jin Hospital of Shanghai Jiaotong University Medical School between November 2001 and May 2012. Both the surgical procedure and extent of lymph node dissection were based on the recommendations of Japanese gastric cancer treatment guidelines. Univariate and multivariate analyses of lymph node metastases and the clinicopathological features were undertaken. RESULTS: The rate of lymph node metastases in male patients with gastric cardiac adenocarcinoma was 72.1%. Univariate analysis showed an obvious correlation between lymph node metastases and tumor size, gross appearance, differentiation, pathological tumor depth, and lymphatic invasion in male patients. Multivariate logistic regression analysis revealed that tumor differentiation and pathological tumor depth were the independent risk factors for lymph node metastases in male patients. There was an obvious relationship between lymph node metastases and tumor size, gross appearance, differentiation, pathological tumor depth, lymphatic invasion at pN1 and pN2, and nerve invasion at pN3 in male patients. There were no significant differences in clinicopathological features or lymph node metastases between female and male patients. CONCLUSION: Tumor differentiation and tumor depth were risk factors for lymph node metastases in male patients with gastric cardiac adenocarcinoma and should be considered when choosing surgery.

Multiple calcified primary central nervous system lymphoma with immunodeficiency in a child.

BACKGROUND: Multiple calcified primary central nervous system lymphoma (PCNSL) is extremely rare in childhood. METHODS: We report a 4-year-old boy suffering from multiple calcified B-cell lymphoma in the brain with immunodeficiency. RESULTS: The boy had a history of walking weakness and seizure for 4 months. The serum levels of immunoglobulin G, A and M were decreased. Brain MRI showed multiple lesions which had ring enhancement. CT showed calcification in all of the lesions. The boy was firstly misdiagnosed with multiple chronic brain abscesses. Pathological analysis of biopsy confirmed the diagnosis of anaplastic diffuse large B-cell lymphoma. CONCLUSION: PCNSL should be included in the differential diagnosis of intracranial mass with calcification.

Intracranial solitary juvenile xanthogranuloma in an infant.

BACKGROUND: Juvenile xanthogranuloma (JXG) is a disorder of histiocyte proliferation. Most cases present with a solitary cutaneous lesion. JXG with systemic involvement is rare with significant morbidity. Intracranial solitary JXG may be misdiagnosed before operation. METHODS: A 5-month-old boy showed an elevated anterior fontanel but no other abnormalities on admission. Brain MRI showed a large mass in the right parietal region. RESULTS: The tumor was removed with the encroached meninges. A JXG in the right parietal region was diagnosed pathologically. CONCLUSION: Total excision of the tumor may be curative with a prerequisite of ensuring normal vital signs and nervous function.

[Expression of KAI1/CD82 in neuroblastoma and its correlation to prognosis].

BACKGROUND & OBJECTIVE: KAI1/CD82 was recently detected as a tumor metastasis suppressor gene. Its silencing contributes to progression and infiltration of some tumors. Our study was designed to investigate the expression of KAI1/CD82 in neuroblastoma, and explore its correlation to clinicopathologic characteristics and prognosis of patients with neuroblastoma. METHODS: The EnVision immunohistochemistry was used to detect the expression of KAI1/CD82 in 90 specimens of neuroblastoma (28 specimens of ganglioneuroblastoma and 62 specimens of neuroblastoma). Clinical data and follow-up data of the 90 patients were analyzed. RESULTS: Positive rate of KAI1/CD82 was significantly higher in ganglioneuroblastoma than in neuroblastoma (39.3% vs. 14.5%, P=0.014). Its expression was negatively correlated to clinical stage of neuroblastoma (P=0.003). CONCLUSIONS: The change of KAI1/CD82 expression is an early event in tumorigenesis of neuroblastoma. Its down-regulation may be considered as a potential indicator to judge the differentiation and metastasis of neuroblastoma, which can serve as one of the combined indexes to clinical assessment of prognosis.