Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

Adrenocortical carcinoma (ACC) is a rare, heterogeneous malignancy with a poor prognosis. According to WHO classification 2004, ACC variants include oncocytic ACCs, myxoid ACCs and ACCs with sarcomatous areas. Herein, we provide a comprehensive review of these rare subtypes of adrenocortical malignancy and emphasize their clinicopathological features with the aim of elucidating aspects of diagnostic categorization, differential diagnostics and biological behavior. The issue of current terminology, applied to biphasic tumors with pleomorphic, sarcomatous or sarcomatoid elements arising in adrenal cortex, is also discussed. We additionally present emerging evidence concerning the adrenal cortical tumorigenesis and the putative adenoma–carcinoma sequence as well

Dynamics of the solar chromosphere. V. High-frequency modulation in ultraviolet image sequences from TRACE

We search for signatures of high-frequency oscillations in the upper solar photosphere and low chromosphere in the context of acoustic heating of outer stellar atmospheres. We use ultraviolet image sequences of a quiet center-disk area from the Transition Region and Coronal Explorer (TRACE) mission which were taken with strict cadence regularity. The latter permits more reliable high-frequency diagnosis than in earlier work. Spatial Fourier power maps, spatially averaged coherence and phase-difference spectra, and spatio-temporal k-f decompositions all contain high-frequency features that at first sight seem of considerable intrinsic interest but actually are more likely to represent artifacts of different nature. Spatially averaged phase difference measurement provides the most sensitive diagnostic and indicates the presence of acoustic modulation up to f=20 mHz (periods down to 50 seconds) in internetwork areas.Comment: 9 pages, 8 figure

Asymptomatic lipofibroadenoma in a 17-year-old male:a case report and literature review of a rare entity

Background: The most common thymic tumours, thymomas, are derived from thymic epithelium and are generally low-grade neoplasm. Frankly malignant tumours, thymic carcinomas are rarer still. Exceedingly rare thymic tumours contain a mesenchymal tissue component such as fibrous connective tissue and/or mature fat. Lipofibroadenoma (LFA) is a very rare mixed epithelial-mesenchymal thymic tumour, included in the category of thymic epithelial tumors. LFA in addition to a mature adipocytic component, contains variable epithelial and mesenchymal tissue components. Owing to the presence of an epithelial component in LFA, this entity, in contrast to thymolipoma, is included in the World Health Organization (WHO) category of thymic epithelial neoplasm. Currently only 12 LFA cases have been described. The 12 previously reported cases all behaved in a benign fashion, although four cases were associated with a conventional type of thymoma. We here present a new, 13th, case of LFA. Case Description: The LFA was discovered incidentally in a previously healthy 17-year-old male after investigations for suspected pneumonia. On imaging a mass was discovered in the anterior mediastinum which was subsequently surgically removed. The resected tumour was extensively investigated, including the first instance of full molecular analysis of this rare entity and all available literature on LFA was sourced to provide a comprehensive overview. The histology of this LFA was similar to previously described cases. No gene mutations or rearrangements were identified. The patient made an uneventful recovery and after 13 months of follow-up remained well. Conclusions: An additional, 13th case of LFA is presented. Based on the available literature it appears that LFA may be considered a benign composite thymic tumour, although the combination of an additional conventional thymoma component may warrant closer follow-up.</p

Effect of oxygen on the expression of hypoxia-inducible factors in human fetal lung explants

Background: Fetal lung development requires proper coordination between lung epithelial and vascular morphogenesis. A major determinant in lung vascular development is vascular endothelial growth factor (VEGF), which is regulated by hypoxia-inducible factors (HIFs). VEGF is expressed in the airway epithelium, while its receptors (VEGFRs) are expressed in the pulmonary mesenchyme. The hypoxic environment in utero is beneficial for fetal organogenesis, especially vascular development. However, little is known about the expression of HIFs and VEGFR-2 in the human fetal lung in vitro. Objectives: The purpose of this study was to investigate the effects of hypoxia on fetal lung morphology and mRNA expression of VEGF, VEGFR-2, HIF-2α, and HIF-3α. Methods: An explant culture technique was used to study the effects of normoxic and hypoxic conditions on human fetal lung. Results: The morphology remained largely unchanged in explants cultured under hypoxic or normoxic conditions. Quantitative RT-PCR showed that the mRNA expression of VEGF-A, but not VEGFR-2 is upregulated in explants cultured at 1.5% compared with 21% oxygen. We observed a nonsignificant increase in HIF-2α and HIF-3α mRNA expression in explants cultured at 1.5% oxygen. These data suggest that the mRNA expression of VEGF, and possibly HIF-2α and HIF-3α, is regulated by hypoxia in the developing human lung. Conclusion: This lung explant culture model appears to be a valuable model to unravel the molecular mechanisms of human lung development

Horizontal supergranule-scale motions inferred from TRACE ultraviolet observations of the chromosphere

We study horizontal supergranule-scale motions revealed by TRACE observation of the chromospheric emission, and investigate the coupling between the chromosphere and the underlying photosphere. A highly efficient feature-tracking technique called balltracking has been applied for the first time to the image sequences obtained by TRACE (Transition Region and Coronal Explorer) in the passband of white light and the three ultraviolet passbands centered at 1700 {\AA}, 1600 {\AA}, and 1550 {\AA}. The resulting velocity fields have been spatially smoothed and temporally averaged in order to reveal horizontal supergranule-scale motions that may exist at the emission heights of these passbands. We find indeed a high correlation between the horizontal velocities derived in the white-light and ultraviolet passbands. The horizontal velocities derived from the chromospheric and photospheric emission are comparable in magnitude. The horizontal motions derived in the UV passbands might indicate the existence of a supergranule-scale magnetoconvection in the chromosphere, which may shed new light on the study of mass and energy supply to the corona and solar wind at the height of the chromosphere. However, it is also possible that the apparent motions reflect the chromospheric brightness evolution as produced by acoustic shocks which might be modulated by the photospheric granular motions in their excitation process, or advected partly by the supergranule-scale flow towards the network while propagating upward from the photosphere. To reach a firm conclusion, it is necessary to investigate the role of granular motions in the excitation of shocks through numerical modeling, and future high-cadence chromospheric magnetograms must be scrutinized.Comment: 5 figures, accepted by Astronomy & Astrophysic

Renal Tumors of Childhood—A Histopathologic Pattern-Based Diagnostic Approach

Renal tumors comprise approximately 7% of all malignant pediatric tumors. This is a highly heterogeneous group of tumors, each with its own therapeutic management, outcome, and association with germline predispositions. Histopathology is the key in establishing the correct diagnosis, and therefore pathologists with expertise in pediatric oncology are needed for dealing with these rare tumors. While each tumor shows different histologic features, they do have considerable overlap in cell type and histologic pattern, making the diagnosis difficult to establish, if based on routine histology alone. To this end, ancillary techniques, such as immunohistochemistry and molecular analysis, can be of great importance for the correct diagnosis, resulting in appropriate treatment. To use ancillary techniques cost-effectively, we propose a pattern-based approach and provide recommendations to aid in deciding which panel of antibodies, supplemented by molecular characterization of a subset of genes, are required

Cancer-prone syndrome of mosaic variegated aneuploidy and total premature chromatid separation: Report of five infants

Five infants (two girls and three boys) from four families all had severe pre- and post-natal growth retardation, profound developmental delay, microcephaly, hypoplasia of the brain with Dandy-Walker complex or other posterior fossa malformations, and developed uncontrollable clonic seizures. Four infants developed Wilms tumors, and one showed cystic lesions in bilateral kidneys. All five infants showed variegated mosaic aneuploidy in cultured lymphocytes. In two infants whose chromosomes were prepared by us, 48.5%-83.2% lymphocytes showed total premature chromatid separation (PCS). Their parents had 3.5%-41.7% of their lymphocytes in total PCS. The remaining three infants and their parents, whose chromosomes were prepared at outside laboratories, tended to show lower frequencies of total PCS. Another five infants reported with the disorder were reviewed together with the five infants we described. Together, their clinical and cytogenetic manifestations were similar enough to suggest a syndrome. Seven of the 10 infants developed proven or probable Wilms tumors. The age at diagnosis of the tumors was younger than usual at 2-16 months. The tumors were bilateral in four infants and unilateral in three infants, and cystic changes were present in six infants. Two infants developed botryoid rhabdomyosarcoma. The carriers of the syndrome are thus liable to tumorigenesis. The possible role of mitotic checkpoint defects, proven in two infants with the syndrome (Matsuura et al. [2000: Am J Hum Genet 69:483-486]), was discussed in connection with tumor development and progression