Germline mosaicism in Rett syndrome identified by prenatal diagnosis

Rett syndrome is an X-linked neurodevelopmental dominant disorder that affects almost exclusively girls. The vast majority of cases are sporadic and are caused by de novo mutations in the MECP2 gene, located in Xq28. Only few familial cases have been reported: in four cases, the mother was an asymptomatic carrier and in other four cases, the germline mosaicism in the mother was postulated. Owing to the above reported cases of germline mosaicism, we decided to offer prenatal diagnosis to all expectant mothers with a Rett daughter despite the absence of the causative mutation in parents' blood. We describe here the outcome of the first nine cases of prenatal diagnosis followed by our center. In eight cases, the fetus did not carry the mutation. In one case, the female fetus did carry the same mutation of the affected sister. The couple decided to interrupt the pregnancy and to devolve fetal tissues for research purposes. Our results indicate that prenatal diagnosis should be proposed to all couples with a Rett daughter, even when the mutation is apparently de novo. Moreover, one positive prenatal test among the first nine cases indicates that germline mosaicism may be seriously considered for the assessment of recurrence risk during genetic counseling

A review of the trends of lymphomas in the equatorial belt of Africa

Lymphomas represent one of the most frequent cancer types in Africa. In particular, approximately 30000 non-Hodgkin lymphomas occur in the equatorial belt of Africa each year and these tumours are in among the top-ten cancers in this geographical region. Several pathogens and environmental factors have been detected in association with these tumours, suggesting that they may contribute to lymphomagenesis. Unfortunately, there are still striking differences between developed and African countries in terms of early detection, diagnosis and treatment of lymphomas. Of note, the disease burden appears to be increasing in Africa. In addition, a much lower cure rate in the low-income countries suggests that the difference in mortality will even become more pronounced in future. Therefore, improving diagnosis is crucial as without it, neither meaningful research projects nor effective patient management can be instituted. In this review, we will summarize the state-of-the-art of lymphoma epidemiology, pathobiology and therapy, and will highlight the still existing gaps between developed and African countries

AN OVARIAN MUCINOUS ADENOCARCINOMA ARISING FROM MATURE CYSTIC TERATOMA ASSOCIATED WITH RESPIRATORY TYPE TISSUE: A CASE REPORT

Mature cystic teratoma (dermoid cyst) is the most common benign germ cell tumor of the ovary, accounting for approximately 30% of all ovarian tumors. Malignant transformation is rare; the most frequent transformation reported is to squamous-cell carcinoma in 80% of cases, whereas transformation to adenocarcinoma is described in about 7% of cases.We report a case of malignant transformation to mucinous adenocarcinoma arising fro

CD-34 stromal expression pattern in normal and altered human corneas

BJECTIVE: To test CD-34 immunoreactivity in stromal cornea cells in normal and pathologic samples obtained from penetrating keratoplasty. DESIGN: Prospective, consecutive histopathologic human tissue study. PARTICIPANTS AND CONTROLS: One hundred two cornea buttons from patients with different diseases, submitted for cornea transplant, were examined. Controls were expired corneas from healthy donor patients who died (n = 4), and globes enucleated for primitive intraocular neoplasias, that is, retinoblastomas (n = 8), and malignant choroidal melanomas (n = 2). METHODS: The expression of CD-34 in stromal cornea cells was examined by immunohistochemistry analysis. Other immunohistochemical stains included an endothelial cell marker (CD-31), common leukocyte antigen, and alpha-smooth muscle actin. MAIN OUTCOME MEASURES: Different diseases that may cause blindness and require penetrating keratoplasty have been tested for CD-34 immunoreactivity. RESULTS: In control corneas, keratocytes present strong and consistent CD-34 immunoreactivity. Diseases leading to the loss of transparency and penetrating keratoplasty, such as keratoconus, herpes keratitis, trauma, and heredofamilial dystrophies, are associated with focal or diffuse loss of CD-34 expression, whereas pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy show normal CD-34 immunoreactivity in most cases and patchy unstained stromal areas in a few cases. CONCLUSIONS: Scar tissue formation in the cornea, as in herpes keratitis and trauma, is always associated with loss of CD-34 immunoreactivity, which may otherwise be a primary event in keratoconus and heredofamilial dystrophies. Both in the pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy, CD-34 immunoreactivity may be normal or lost, hence these two diseases may be considered as one and part of the same group with regard to CD-34 expression, as revealed by immunohistochemistry analysis

Quantitative in situ evaluation of telomeres in fluorescence in situ hybridization-processed sections of cutaneous melanocytic lesions and correlation with telomerase activity

BACKGROUND: Telomere length is correlated with cellular ageing and immortalization processes. In some human cancers telomere length measurement has proved to be of diagnostic and prognostic value. Results comparable with the traditional terminal restriction fragment length determination by Southern blotting have been obtained in metaphase and interphase cells in some studies by fluorescence in situ hybridization (FISH) analysis; FISH additionally allows for the quantification of telomeres at the cellular level. OBJECTIVES: In this study, 32 melanocytic lesions were analysed by FISH, aiming at investigating possible telomere differences among various benign and malignant lesions and correlation with telomerase activity (TA) level. METHODS: FISH was performed on paraffin sections from six common naevi, eight Spitz naevi, 12 melanomas, six melanoma metastases and nine control samples of normal skin. Telomere mean maximum diameter (Feret max), area and number per nuclear area were calculated by image analysis on fluorescent images elaborated through KS400 and in situ imaging system (ISIS) for FISH analysis programs. Mean TA level was also calculated in all lesions and correlated with telomere parameters. RESULTS: Telomere number per nuclear area was significantly lower in melanomas and metastases than in benign common and Spitz naevi and in control skin (7 small middle dot24 +/- 3.3; 6.11 +/- 3 vs. 14.46 +/- 5.6; 16.92 +/- 7.8; and 12.59 +/- 3.4, respectively; P < 0 .001). No significant differences were found for the other telomere parameters. In common and Spitz naevi, telomere number was positively correlated with Feret max (P = 0.046 and P < 0.0001, respectively). TA was significantly higher in melanomas and metastases than in the other groups (70.18 +/- 25.2; 105.07 +/- 30 vs. 2.16 +/- 2.4; 2 .99 +/- 2.1; 2 +/- 1.2, respectively; P< or = 0. 001) and it was inversely correlated with telomere number per nuclear area in melanomas (P = 0.0041). No other significant correlations were found. CONCLUSIONS: Encouraging results have been obtained from quantitative telomere evaluation in the diagnosis of melanocytic lesions, although an analysis of a larger number of cases would be necessary to provide more reliable data. An extreme shortening of some telomeres probably results in the decrease of telomeric signals and the lower mean number of detectable telomeres in melanomas and metastases. In melanomas, telomere number per nuclear area is also inversely correlated with TA levels. Quantitative FISH of melanocytic lesions could give more specific information at the cellular level in telomere and telomerase fields of investigation

Photopheresis for recurrent acute rejection in cardiac transplantation

[No abstract available

VEGF-D is expressed in activated lymphoid cells and in tumors of hematopoietic and lymphoid tissues.

Vascular Endothelial Growth Factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that activate the Vascular Endothelial Growth Factor Receptor (VEGFR)-2 and VEGFR-3, which are mainly expressed in blood and lymphatic vessels. Here we have analyzed by using monoclonal antibodies, the expression of VEGF-D and its cognate receptor VEGFR-3 in normal and pathologic bone marrow and lymph node biopsies. This analysis revealed that VEGF-D is expressed in B cells of the germinal centers, scattered B and T blasts, myeloid progenitors, acute leukemia, several types of non Hodgkin lymphoma, and classical Hodgkin's lymphoma. In normal tissues VEGFR-3 was only expressed in fenestrated capillaries of bone marrow and in lymphatic vessels of lymph nodes, while in VEGF-D expressing tumors newly formed vessels, but not malignant cells, showed high VEGFR-3 expression. These data suggest that VEGF-D could contribute to leukemia and lymphoma growth via the induction of angiogenesis in bone marrow and lymphoid tissues