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Phosphate, an essential nutrient, is available in organic and inorganic forms. The balance of phosphate is central for cellular homeostasis through the genomic roles of DNA and RNA synthesis and cell signaling processes. Therefore, an imbalance of this nutrient, manifested, either as a deficiency or excess in phosphate levels, can result in pathology, ranging from cytotoxicity to musculoskeletal defects. Inorganic phosphate (Pi) overdosing can result in a wide spectrum of cytotoxicity processes, as noted in both animal models and human studies. These include rewired cell signaling pathways, impaired bone mineralization, infertility, premature aging, vascular calcification, and renal dysfunction. This article briefly reviews the regulation of phosphate homeostasis and elaborates on cytotoxic effects of excessive Pi, as documented in cell‐based models. [ABSTRACT FROM AUTHOR]

Background: Bicuspid aortic valve is the most common congenital valvular heart defect in the general population. BAV is associated with significant morbidity due to valve failure, formation of thoracic aortic aneurysm, and increased risk of infective endocarditis and aortic dissection. Loss of function mutations in NOTCH1 (OMIM 190198) has previously been associated with congenital heart disease involving the aortic valve, left ventricle outflow tract, and mitral valve that segregates in affected pedigrees as an autosomal dominant trait with variable expressivity. Methods: We performed whole‐exome sequencing in four members of a three‐generational family (three affected and one unaffected subject) with clinical phenotypes including aortic valve stenosis, thoracic aortic aneurysm, and ventricular septal defect. Results: We identified 16 potentially damaging genetic variants (one stop variant, one splice variant, and 14 missense variants) cosegregating with the phenotype. Of these variants, the nonsense mutation (p.Tyr291*) in NOTCH1 was the most deleterious variant identified and the most likely variant causing the disease. Conclusion: Inactivating NOTCH1 mutations are a rare cause of familial heart disease involving predominantly left ventricular outflow tract lesions and characterized by the heterogeneity of clinical phenotype. [ABSTRACT FROM AUTHOR]

The synthesis of the protected form of 2‐methylthio‐N6‐threonylcarbamoyl adenosine (ms2t6A) was developed starting from adenosine or guanosine by using the optimized carbamate method and, for the first time, an isocyanate route. The hypermodified nucleoside was subsequently transformed into the protected ms2t6A‐phosphoramidite monomer and used in a large‐scale synthesis of the precursor 17nt ms2t6A‐oligonucleotide (the anticodon stem and loop fragment of tRNALys from T. brucei). Finally, stereochemically secure ms2t6A→ms2ct6A cyclization at the oligonucleotide level efficiently afforded a tRNA fragment bearing the ms2ct6A unit. The applied post‐synthetic approach provides two sequentially homologous ms2t6A‐ and ms2ct6A‐oligonucleotides that are suitable for further comparative structure–activity relationship studies. [ABSTRACT FROM AUTHOR]

The study aimed to find whether journal editorial office administrators were as effective as editors at assigning rigorous reviewers. We analysed four journals using blended systems of editor‐selected reviewers (ESR) and Journal Administrator‐selected reviewers (JASR) from four disciplines: medicine, sociology, education, and business/applied psychology. In blended journals, both editors and Journal Administrators select authors to review using web‐based expert‐finding tools. All reviewers selected were both authors and reviewers. We primarily wanted to assess the quality of reviews from both ESR and JASR reviewer selection methodologies. Reviewer rigour was defined as differences between editor decisions and reviewer recommendations. Timeliness data were also recorded and analysed separately as an indicator of efficiency. Reviewer rigour, the quality of reviewers' evaluations, was estimated from the level of agreement between editors and reviewers. Timeliness was not considered a direct measure of rigour. For two journals, no statistically significant differences were observed; for two, in a small proportion of cases, ESR reviews were more negative. One journal showed some statistically significant major differences but only in 2% of reviews. Timeliness data indicated some statistically significant trends that JASR return reviews more promptly. Therefore, where editors rely on at least two reviewers' recommendations, JASR is equally rigorous as ESR. [ABSTRACT FROM AUTHOR]

A case study of a 17-year-old girl with complains of increasing hemiparesis on the right side and an epileptic insult, is presented. it mentions the patient was diagnosed with primary myxoid mesenchymal tumour with intracranial location. it also mentions the use of immunohistochemistry and molecular analysis to separate the rare entity from its mimics.

Plexiform fibromyxomas are rare neoplasms, being officially recognized as a distinct entity among benign mesenchymal gastric tumours in the 2010 WHO Classification of Tumours of the Digestive System. Characteristically, these tumours have a multinodular/plexiform growth pattern, and histologically contain variably cellular areas of bland myofibroblastic-type spindle cells embedded in an abundant myxoid matrix, rich in capillary-type vessels. As yet, the molecular and/or genetic features of these tumours are unknown. Here we describe a recurrent translocation, t(11;12)(q11;q13), involving the long non-coding gene metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1) and the gene glioma-associated oncogene homologue 1 ( GLI1) in a subgroup of these tumours. The presence of the fusion transcript in our index case was confirmed using polymerase chain reaction ( PCR) on genomic DNA, followed by Sanger sequencing. We showed that the truncated GLI1 protein is overexpressed and retains its capacity to transcriptionally activate its target genes. A specific FISH assay was developed to detect the novel MALAT1-GLI1 translocation in formalin-fixed, paraffin-embedded ( FFPE) material. This resulted in the identification of two additional cases with this fusion and two cases with polysomy of the GLI1 gene. Finally, immunohistochemistry revealed that the GLI1 protein is exclusively overexpressed in those cases that harbour GLI1/12q13 genomic alterations. In conclusion, overexpression of GLI1 through a recurrent MALAT1-GLI1 translocation or GLI1 up-regulation delineates a pathogenically distinct subgroup of plexiform fibromyxomas with activation of the Sonic Hedgehog signalling pathway. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Zusammenfassung Hintergrund Das angiomatöse fibröse Histiozytom (AFH) ist eine seltene, geringgradig maligne, subkutane Neoplasie bei Kindern oder jungen Erwachsenen. Methodik AFH in verschiedenen Krankheitsstadien wurden histologisch, teilweise auch immunhistologisch, sowie mittels Fluoreszenz-in-situ-Hybridisierung untersucht. Ergebnisse Abhängig vom Grad der Fibrosklerose wurden neun AFH in folgende Kategorien eingeteilt: klassischer Typ (n = 3): umschriebene subkutane Läsion, bestehend aus multinodulären Spindel- bis epitheloiden (histiozytoiden) Zellen, die einen pseudoangiomatösen, mit Blut gefüllten Raum umgeben. Peripher befinden sich eine fibröse Pseudokapsel sowie ein entzündliches Infiltrat. Früher sklerotischer Typ (n = 4): die fibröse Kapsel dehnt sich mehr zum inneren Bereich der Läsion aus und ersetzt fokal den zellulären, neoplastischen Bestandteil und die pseudoangiomatösen Räume. Später sklerotischer Typ (n = 2): die Architektur des AFH mit seiner zonenartigen Anordnung eines äußeren fibrösen und inneren zellulären Bestandteils wird größtenteils durch die Fibrose ersetzt, die den pseudovaskulären Raum im Zentrum der Läsion verschließt. Eine Immunhistochemie war in 5 von 9 Fällen möglich, mit einer Positivität für EMA (5/5), Desmin (3/5), Caldesmon (1/2) und CD99 (2/5). Einer der beiden getesteten Fälle zeigte eine EWSR1-Umlagerung. Schlussfolgerung Ein AFH im Spätstadium kann mit deutlicher Fibrose einhergehen, die die wahre Natur der Läsion verschleiert und so als harmloses fibrotisches Geschehen fehlinterpretiert werden. [ABSTRACT FROM AUTHOR]

Background Angiomatoid fibrous histiocytoma (AFH) is a rare, low-grade malignant, subcutaneous neoplasm in children or young adults. Methods AFHs in different disease stages were studied histologically, in part, also immunohistologically, and by fluorescence in situ hybridization. Results Depending on the degree of fibrosclerosis, nine AFH were divided into the following categories: classic type (n = 3): well-defined subcutaneous lesions composed of multinodular spindle to epithelioid (histiocytoid) cells surrounding a pseudoangiomatous space filled with blood. Peripherally, there is a fibrous pseudocapsule and an inflammatory infiltrate. Early sclerotic type (n = 4): the fibrous capsule extends more to the inner circle of the lesion, focally replacing the cellular neoplastic component and pseudoangiomatous spaces. Late sclerotic type (n = 2): the architecture of AFH with its zonal arrangement of an outer fibrous and inner cellular component is largely replaced by fibrosis occluding the pseudovascular space in the center of the lesion. Immunohistochemistry was available in 5/9 cases with positivity for EMA (5/5), desmin (3/5), caldesmon (1/2), and CD99 (2/5). One of two cases tested displayed EWSR1 rearrangement. Conclusion Late-stage AFH may present with marked fibrosis obscuring the real nature of the lesion and may easily be misinterpreted by the unwary as a harmless fibrotic condition. [ABSTRACT FROM AUTHOR]

Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are commonly driven by recurrent gene rearrangements. In conventional low-grade ESS, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1, and recently described ZC3H7- BCOR chimeric fusions have been reported in > 50% of cases. Conversely, oncogenic t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and banding cytogenetics, we identified MBTD1 (malignant brain tumor domain-containing 1) and CXorf67 (chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using reverse-transcription polymerase chain reaction followed by Sanger sequencing. A specific FISH assay was developed to detect the novel t(X;17) translocation in formalin-fixed paraffin-embedded material, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 25 uterine stromal tumors [14 ESS and 11 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of seven ESS (including three with YWHAE and two with JAZF1 rearrangements) and four UES without specific chromosomal aberrations indicated clustering of tumors with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESS. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes. [ABSTRACT FROM AUTHOR]

We report the unusual occurrence of a cellular angiofibroma in prostatic tissue. In this case, a 84-year-old man presented in the emergency room with urinary retention. Ultrasound revealed an enlarged prostate, which was suggestive for benign prostatic hyperplasia. The patient was treated with a Millin retropubic prostatectomy. Macroscopically the prostate contained multiple circumscribed nodules. Microscopic examination of the tumor showed the appearance of cellular angiofibroma, consisting of bland spindle cells and prominent, hyalinized vessels. The diagnosis was supported by FISH, which revealed monoallelic loss of RB1/13q14 region, as seen in spindle cell lipoma, (extra-) mammary myofibroblastoma, and cellular angiofibroma. Cellular angiofibromas are rare, benign soft tissue tumours and were never reported in the prostatic gland. [ABSTRACT FROM AUTHOR]

The cholecystokinin 2 receptor (CCK2R/CCKBR) is expressed in gastrointestinal stromal tumours (GISTs). We sought to investigate the role of CCK2R in GIST pathogenesis. Molecular characterization of CCK2R was performed on a heterogeneous cohort of 50 GISTs. In addition, CCK2R expression was evaluated by immunohistochemistry (IHC), using tissue microarray (TMA) containing 292 GISTs, two cases of hyperplasia of interstitial Cajal's cells (ICC) and six gastric microscopic GISTs. Mono-allelic loss of the CCK2R/11p15 allele was identified in 13.7% of GISTs, having no impact on the level of CCK2R transcript expression. No CCK2R mutations were found. The CCK2Ri4sv, CCK2R splice variant with retention of intron 4 was detected in six of 20 tumours analysed. Wild-type CCK2R transcripts were commonly expressed (57.1% of cases) and this expression was highly correlated with gastric primary site of GISTs ( p < 0.001). At the protein level, expression of CCK2R in incidental ICC hyperplasia and early stages of gastric GIST development was documented, and its gastric association was confirmed on GIST-TMA by IHC. To explore the in vivo effect of CCK2R activation on tumour growth, gastrin versus placebo was administered intraperitoneally in nude mice carrying human GIST xenografts. The tumour volume was followed for 10 weeks. The effect of this stimulation on tumour cell proliferation/apoptosis was assessed by IHC and KIT/PKC-θ signalling was evaluated by western blotting (WB). In vivo experiments showed a two-fold increase in the volume of tumours which were exposed to gastrin in comparison with non-exposed controls ( p = 0.03), with a significant increase in mitotic activity ( p = 0.04) and Ki-67 proliferation index ( p = 0.008). By WB, gastrin stimulation resulted in hyper-activation of KIT and PKC -θ kinases, and in evident PI3K-AKT pathway over-activation. Our results indicate a promoting role of CCK2R on GIST tumourigenesis, particularly in tumours of gastric origin. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Synovial sarcoma (SS), an aggressive type of soft tissue tumor, occurs mostly in adolescents and young adults. The origin and molecular mechanism of the development of SS remain only partially known. Over 90% of SS cases are characterized by the t(X;18)(p11.2;q11.2) translocation, which results mainly in the formation of SS18-SSX1 or SS18-SSX2 fusion genes. In recent years, several reports describing direct and indirect interactions of SS18-SSX1/SSX2 oncoproteins have been published. These reports suggest that the fusion proteins particularly affect the cell growth, cell proliferation, TP53 pathway, and chromatin remodeling mechanisms, contributing to SS oncogenesis. Additional research efforts are required to fully explore the protein-protein interactions of SS18-SSX oncoproteins and the pathways that are regulated by these partnerships for the development of effective targeted therapy. [ABSTRACT FROM AUTHOR]

1. Membranous nephropathy is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane. 2. In the rat model described by Heymann in 1959, the target antigen of antibodies is megalin, a multiligand receptor expressed in the rat glomerulus but absent from the human glomerulus. 3. In recent years, two major antigens have been identified in human membranous nephropathy (MN). The first is neutral endopeptidase (NEP), the alloantigen involved in neonatal cases of MN that occur in newborns from NEP-deficient mothers. The second is the M-type phospholipase A receptor (PLAR), the first autoantigen identified in idiopathic MN in the adult. Megalin, NEP and PLAR are all expressed on the podocyte surface, where they can serve as targets for circulating antibodies, leading to in situ immune complex formation, complement activation and proteinuria. 4. In addition to podocyte antigens, we recently showed that some patients with childhood MN had both circulating cationic bovine serum albumin (BSA) and anti-BSA antibodies, with BSA being present in immune deposits. This suggests that food antigens may be involved in MN through charge-dependent binding to the anionic glomerular capillary wall and in situ formation of immune complexes. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic stress disorder (PTSD) is associated with enhanced noradrenergic activity. Animal and human studies demonstrate that noradrenergic stimulation augments consolidation of fear learning. Retrieval of well-established memories by presenting a learned fear cue triggers reconsolidation processes during which memories may be updated, weakened, or strengthened. We previously reported that noradrenergic blockade in the rat amygdala impairs reconsolidation of fear memories. Here we investigated the effects of noradrenergic enhancement on reconsolidation of learned fear.Methods: Using auditory fear conditioning in rats, we tested the effects of postretrieval intraamygdala infusion of the β-adrenergic receptor agonist isoproterenol or the antagonist propranolol on conditioned fear in the amygdala.Results: A single intraamygdala infusion of isoproterenol following a retrieval of a well-consolidated memory enhanced fear memory elicited by the learned fear stimulus and impaired extinction of this memory 48 hr later. Intraamygdala infusion of the β-adrenergic receptor antagonist propranolol following a consecutive retrieval trial blocked the enhancing effects of isoproterenol on fear memory.Conclusions: Postretrieval β-adrenergic stimulation in the amygdala enhances reconsolidation of fear memories, making them resistant to extinction. Noradrenergic augmentation during retrieval of fear memories may thus contribute to persistence and severity of traumatic memories. Reconsolidation may be a useful tool in understanding the pathology of PTSD and may thus help in developing new and in modifying existing treatments of traumatic memories. [ABSTRACT FROM AUTHOR]

Subungual exostosis is a benign bone- and cartilage-forming tumor known to harbor a pathognomonic t(X;6)(q22;q13-14). Using global gene expression analysis and quantitative real-time PCR, we could show that this translocation results in increased expression of the IRS4 gene, presumably due to disruption and/or exchange of regulatory sequences with the translocation partner, the COL12A1 gene. A corresponding deregulation at the protein level could be demonstrated in primary cell cultures using a combination of fluorescence in situ hybridization and immunostaining. As the t(X;6) usually is the sole cytogenetic aberration in subungual exostosis, the deregulated expression of IRS4 is likely to be pathogenetically essential. The exact role of IRS4 is still poorly investigated, but IRS proteins are known to act as mediators of signaling from receptors, such as the insulin and insulin-like growth factor 1 receptors, and thus have an important effect on cell growth and survival. [ABSTRACT FROM AUTHOR]

The hippocampus is a part of the limbic system and is important for the formation of associative memories, such as acquiring information about the context (e.g., the place where an experience occurred) during emotional learning (e.g., fear conditioning). Here, we assess whether the hippocampus is responsible for pups' newly emerging context learning. In all experiments, postnatal day (PN) 21 and PN24 rat pups received 10 pairings of odor-0.5 mA shock or control unpaired odor-shock, odor only, or shock only. Some pups were used for context, cue or odor avoidance tests, while the remaining pups were used for c-Fos immunohistochemistry to assess hippocampal activity during acquisition. Our results show that cue and odor avoidance learning were similar at both ages, while contextual fear learning and learning-associated hippocampal (CA1, CA3, and dentate gyrus) activity (c-Fos) only occurred in PN24 paired pups. To assess a causal relationship between the hippocampus and context conditioning, we infused muscimol into the hippocampus, which blocked acquisition of context fear learning in the PN24 pups. Muscimol or vehicle infusions did not affect cue learning or aversion to the odor at PN21 or PN24. The results suggest that the newly emerging contextual learning exhibited by PN24 pups is supported by the hippocampus. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background Mammary myofibroblastoma is a benign mesenchymal tumor of the breast. Extramammary location is very rare and usually occurs along the embryonic milk-line. Methods and Results In this article, we present a case of a woman with an infra-auricular swelling. A diagnosis could not be made on CT scans, so the mass was surgically removed. Histological examination showed spindle cells in clusters, with CD34, desmin, and actin expression. The diagnosis of extramammary myofibroblastoma was made. Conclusion We describe this case because of the unusual location of this rare tumor. Furthermore, we want to highlight the possible relationship between (extra)mammary myofibroblastoma and spindle cell lipoma (SCL). SCL has a predilection site in the posterior neck. Both tumors show the same clinical behavior, a close histological resemblance, and their cells are both immunoreactive for CD34 and CD10. The loss of RB/13q14 and FKHR/13q14 loci, which is typically found in SCL cells, was also shown in this case. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

Somatic, activating mutations of KIT or PDGFRA are early oncogenic events in the majority of sporadic gastrointestinal stromal tumors (GISTs). Also a number of families with GISTs have been described in recent years. The familial GIST syndrome is a rare autosomal dominant disorder with high penetrance and diverse manifestations associated mostly with germline KIT mutations. In this report, we show a novel germline mutation in the juxtamembrane domain of KIT, identified in 2 brothers, both presenting with recurrent, high risk/malignant rectal GISTs. The KIT p.Q575_P577delinsH mutation was found in tumor samples as well as in peripheral blood leukocytes from both patients, proving that the mutation was indeed inherited. Besides rectal GISTs, no other features characteristic for the familial GIST syndrome was observed in either brother or any of their first-degree relatives. The patients were treated with imatinib, achieving either long-term partial response or stable disease. This observation confirms that imatinib can be successfully used in familial GISTs, as it is used in the sporadic advanced tumors, and that tumors bearing a KIT p.Q575_P577delinsH mutation are responsive to imatinib treatment. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aims: Lipoblastoma is a rare benign adipocytic neoplasm that occurs primarily in infancy and early childhood. Histologically, there is some morphological overlap with atypical lipomatous tumour and myxoid liposarcoma and the age at presentation is often regarded as a major diagnostic criterion. However, we recently encountered several cases of lipoblastoma occurring in adolescents and young adults. The aim was to document the occurrence of lipoblastoma in older patients, with cytogenetic confirmation. Methods and results: Six cases of lipoblastoma in patients >12 years old were identified. The tumours occurred in four male and two female patients ranging from 14 to 24 years old. Our cases showed the classical histological features of lipoblastoma. Three tumours were composed predominantly of mature adipocytes and the three other cases showed an immature appearance, with a prominent myxoid matrix. Fluorescence in situ hybridization (FISH) demonstrated rearrangements of the PLAG1 region in two cases and polysomy for chromosome 8 in three other cases. None of the tumours had amplification of MDM2 or CDK4. Conclusions: Lipoblastoma occurs rarely in young adults and should enter into the differential diagnosis of ‘atypical’ fatty tumours in adults. Our report underscores the diagnostic value of FISH analysis. [ABSTRACT FROM AUTHOR]

eto aternal llo mmunization with antenatal lomerulopathies (FMAIG) is a recently described alloimmune disorder, which results from maternal antibodies that cross the placenta, bind to fetal glomerular podocytes, and mediate renal disease. The pathogenic antibodies are directed against neutral endopeptidase (NEP). The infant's mother is NEP-deficient and thus she becomes immunized during pregnancy against NEP expressed by placental cells. Because future pregnancies in NEP-immunized mothers are at high risk for the fetus, detection of anti-NEP antibodies in pregnant mothers and antigen-driven therapies including induction of mucosal tolerance, are urgently needed. This ideally requires identification of the pathogenic epitopes born by the antigen. We have recently characterized two linear B cell epitopes on the NEP that are specifically recognized by the mother's antibodies. The identification of these B cell epitopes is useful for diagnostic tests and may lead to future development of new therapeutic approaches based on peptide-specific immune intervention. [ABSTRACT FROM AUTHOR]

Pauwels P, Debiec-Rychter M, Stul M, De Wever I, Van Oosterom A T & Sciot R (2005) Histopathology 47, 41–47 Changing phenotype of gastrointestinal stromal tumours under imatinib mesylate treatment: a potential diagnostic pitfall : The diagnosis of gastrointesinal stromal tumours (GISTs) is widely based on morphological features and KIT (CD117) immunoreactivity. Most patients with advanced GISTs show a major clinical response after treatment with imatinib mesylate. The histopathological features of GISTs in patients on prolonged imatinib treatment have, thus far, not been addressed in detail. In this report, we present three patients with metastatic GISTs, who received more than 1 year of therapy with imatinib, and whose tumours changed their morphological and immunohistochemical characteristics during continued treatment with the drug. : All three primary GISTs from these patients were classical spindle-type tumours, showing diffuse, strong CD117, CD34, and focal α-smooth muscle actin expression. During treatment, two clinically progressive and one clinically stable GIST revealed a diffuse epithelioid, or pseudopapillary epithelioid growth pattern, characterized by rounded cells with eosinophilic cytoplasm and uniform round-to-ovoid nuclei. In addition, GIST specimens from patients on therapy showed complete loss of CD117 immunoreactivity. Remarkably, two of these tumours also became CD34 immunonegative and in one case the progression was accompanied by desmin expression. KIT mutational analysis revealed the presence of distinct exon 11 mutant isoforms in all cases examined, while the same genotype was sustained in the base line and on-therapy tumour specimens, proving the common origin of analysed specimens. : GISTs subject to imatinib treatment can undergo striking (immuno)phenotypic changes, which are not necessarily corroborated by new genotypic modifications. Because these may mimic other tumour types, this feature creates a differential diagnostic challenge, of which the pathologist should be aware. [ABSTRACT FROM AUTHOR]

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Within the human testis, three entities of germ cell tumours are distinguished: the teratomas and yolk sac tumors of newborn and infants, the seminomas and nonseminomas of adolescents and young adults, referred to as testicular germ cell tumours (TGCT), and the spermatocytic seminomas. Characteristic chromosomal anomalies have been reported for each group, supporting their distinct pathogenesis. TGCT are the most common cancer in young adult men. The initiating pathogenetic event of these tumours occurs during embryonal development, affecting a primordial germ cell or gonocyte. Despite this intra-uterine initiation, the tumour will only be clinically manifest after puberty, with carcinoma in situ (IS) as the precursor. All invasive TGCT, both seminomas and nonseminomas, as well as CIS cells are aneuploid. The only consistent (structural) chromosomal abnormalities in invasive TGCT are gains of the short arm of chromosome 12, mostly due to isochromosome (i(12p)) formation. This suggests that an increase in copy number of a gene(s) on 12p is associated with the development of a clinically manifest TGCT. Despite the numerous (positional) candidate gene approaches that have been undertaken thus far, identification of a causative gene(s) has been hampered by the fact that most 12p gains involve rather large genomic intervals, containing unmanageable numbers of candidate genes. Several years ago, we initiated a search for 12p candidate genes using TGCT with a restricted 12p-amplification, cytogenetically identified as 12p11.2–p12.1. This approach is mainly based on identification of candidate genes mapped within the shortest region of overlap of amplification (SROA). In this review, data will be presented, which support the model that gain of 12p-sequences is associated with suppression of apoptosis and Sertoli cell-independence of CIS cells. So far, DAD-R is one of the most likely candidate genes involved in this process, possibly via N-glycosylation.... [ABSTRACT FROM AUTHOR]

Aim: Clear cell sarcoma is a high-grade sarcoma with morphological features resembling malignant melanoma. This tumour is reported to display a characteristic distribution pattern nearly always involving the extremities. We report the first case of clear cell sarcoma of the stomach. Methods and results: A 30-year-old male developed a huge tumour of the stomach, which at first glance could be considered as a poorly differentiated carcinoma. Immunohistochemical and ultrastructural examinations were consistent with a diagnosis of metastatic melanoma. However, cytogenetic examination revealed a t(12;22) translocation, specific for clear cell sarcoma. This was confirmed by fluorescence in-situ hybridization. Conclusion: Making a reliable diagnosis of clear cell sarcoma of the stomach requires cytogenetic or molecular diagnostic investigations, particularly to rule out metastatic melanoma. This diagnosis avoids an unnecessary search for a primary melanoma. [ABSTRACT FROM AUTHOR]

We report the case of a 66-year-old man presenting with a high-grade pleomorphic sarcoma at the left elbow 16 years after the extravasation of adriamycin given for a malignant fibrous histiocytoma of the tibia. We suggest that this sarcoma originated in a multistep way over many years, out of the chronic inflammatory tissue that developed due to a non-specific cellular damage at the nuclear level, interfering with normal cell replication necessary for normal healing tissue healing. As a result, the non-healed chronic inflammatory tissue transformed over several years into a preneoplastic mesenchymal tumour and later into a high-grade pleomorphic sarcoma. [ABSTRACT FROM AUTHOR]

A case of an epidural spinal peripheral primitive neuroectodermal tumor (pPNET) in a 13-year-old girl is presented. The tumor was disseminated at the moment of diagnosis, thus only diagnostic oligobiopsy of the epidural mass was performed. Histologically the tumor was composed of small round blue cells. The neoplastic cells expressed MIC2 and features of neural differentiation on immunohistochemical staining (neuron-specific enolase, synaptophysin and NCAM positivity). Fluorescent in situ hybridization (FISH) analysis was performed for the final diagnosis and the translocation t(11;22)(q24;q12) was detected. The present case emphasizes the usefulness of FISH in differential diagnosis of tumors, especially when only routinely fixed material is available. [ABSTRACT FROM AUTHOR]