Metastatic potential of an aneurysmal bone cyst

Aneurysmal bone cysts (ABCs) are benign bone tumors consisting of blood-filled cavities lined by connective tissue septa. Recently, the hypothesis that ABCs are lesions reactive to local hemodynamics has been challenged after the discovery of specific recurrent chromosomal abnormalities. Multiple cases of malignant transformation of ABC into (osteo)sarcoma have been described, as well as a number of cases of telangiectatic osteosarcoma which had been misdiagnosed as ABC. We herewith document a case of a pelvic ABC metastatic to the lung, liver, and kidneys. Diagnosis was confirmed by the presence of a break in the USP6 gene, which is pathognomonic for ABC, in a pulmonary metastasis of our patient. Sarcomatous transformation as an explanation for this behavior was ruled out by demonstrating diploid DNA content in both the pulmonary lesion and the primary tumor

Toll-like receptors in the immature human brain

Toll-like receptors (TLR), found on glial and neuronal cells, are major components of the innate immune system. They act as sensors that recognise pathogen-associated or damage-associate molecular patterns. There is limited information on these receptors in the immature brain. Generally TLR-2 is triggered via gram-positive bacterial infections, however, recent research in animal models have found that TLR2 plays an important role in brain injury following hypoxic-ischaemia (HI)1 and TLR3 activation further enhances HI-induced brain injury2, whilst LPS-induced (gram negative) oligodendrocyte injury was shown to be mediated by TLR4 activation.3 We used immunohistochemistry and in situ hybridisation to investigate TLR2, 3 and 4 expression in the immature human brain. Post-mortem neonatal cases (22-39wk GA) were recruited with parental consent and ethics approval. The preterm study cohort consisted of cases without overt brain pathology on post-mortem MRI and conventional autopsy (control), cases with evidence of germinal matrix/intraventricular haemorrhage (GMH/IVH), periventricular leukomalacia (PVL), suspected ascending amniotic fluid infection and term hypoxic-ischaemic encephalopathy (HIE). Immunohistochemistry results showed that control brains had mainly TLR4 expression, whilst the most prominent expression of TLR2, 3 and 4 was seen in PVL cases. Of interest is the activation of all three TLRs in the infection cases, even in the absence of overt injury to the brain on MRI. GMH/IVH and HIE cases showed predominantly TLR3 expression. The validity of the protein expression was confirmed using in situ hybridisation. We have demonstrated, for the first time, the expression of TLRs in the immature human brain with and without pathology

A Fetus With De Novo 2q33.2q35 Deletion Including MAP2 With Brain Anomalies, Esophageal Atresia, and Laryngeal Stenosis

Deletions of the long arm of chromosome 2 are rare. Few cases of interstitial deletions of the 2q33q35 region have been reported. Individuals with deletions in this region have growth retardation, psychomotor retardation, micrognathia, microcephaly, and apparently low-set ears. We describe a female fetus with a de novo deletion of 2q33.2 to q35 with delayed gyral formation with widespread neuronal heterotopia of the white matter, small cerebellum, esophageal atresia, laryngeal stenosis, micrognathia, and intrauterine growth retardation. With the use of karyotyping and high-resolution array comparative genomic hybridization the boundaries and gene content of the deletion were identified. Our aim was to determine whether a candidate gene for the brain phenotype was present in the deletion. By this means and based on literature we pinpointed the microtubule associated gene MAP2 as a candidate for the brain anomalies. (c) 2013 Wiley Periodicals, In

A placental phenotype for intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease associated with significant risk of fetal complications. It is hypothesised that the risk of adverse fetal outcomes relates to the toxic effects of bile acids, the levels of which are increased in both maternal and fetal serum. Human and rodent studies have shown that transplacental transfer of bile acids is impaired in ICP. Furthermore, the morphology of placentas from the rodent model of ICP is markedly abnormal, and is associated with increased expression of apoptotic markers and oxidative stress. Using placental tissue from ICP cases and normal pregnancies and cultured placental explant fragments we investigated the histological and molecular effects of cholestasis. We also examined the influence of ursodeoxycholic acid (UDCA) administration on these parameters. Here we report that ICP is associated with several morphological abnormalities of the placenta, including an increase in the number of syncytial knots, and that these can be reproduced in an in vitro (explant) model exposed to the bile acids taurocholic acid and taurochenodoexycholic acid. Furthermore, we demonstrate that ursodeoxycholic acid, a drug commonly used in the management of ICP, has a protective effect on placental tissue both in vivo and in vitro

Toll-Like Receptor 3 Expression in Glia and Neurons Alters in Response to White Matter Injury in Preterm Infants

Toll-like receptors (TLRs) are members of the pattern recognition receptor family that detect components of foreign pathogens or endogenous molecules released in response to injury. Recent studies demonstrate that TLRs also have a functional role in regulating neuronal proliferation in the developing brain. This study investigated cellular expression of TLR3 using immunohistochemistry on human brain tissue. The tissue sections analysed contained anterior and lateral periventricular white matter from the frontal and parietal lobes in post-mortem neonatal cases with a postmenstrual age range of 23.6-31.4 weeks. In addition to preterm brains without overt pathology (control), preterm pathology cases with evidence of white matter injuries (WMI) were also examined. In order to identify TLR-positive cells, we utilized standard double-labelling immunofluorescence co-labelling techniques and confocal microscopy to compare co-expression of TLR3 with a neuronal marker (NeuN) or with glial markers (GFAP for astrocytes, Iba-1 for microglia and Olig2 for oligodendrocytes). We observed an increase in the neuronal (28 vs. 17%) and astroglial (38 vs. 21%) populations in the WMI group compared to controls in the anterior regions of the periventricular white matter in the frontal lobe. The increase in neurons and astrocytes in the WMI cases was associated with an increase in TLR3 immunoreactivity. This expression was significantly increased in the astroglia. The morphology of the TLR3 signal in the control cases was globular and restricted to the perinuclear region of the neurons and astrocytes, whilst in the cases of WMI, both neuronal, axonal and astroglial TLR3 expression was more diffuse (i.e., a different intracellular distribution) and could be detected along the extensions of the processes. This study demonstrates for the first time that neurons and glial cells in human neonatal periventricular white matter express TLR3 during development. The patterns of TLR3 expression were altered in the presence of WMI, which might influence normal developmental processes within the immature brain. Identifying changes in TLR3 expression during fetal development may be key to understanding the reduced volumes of grey matter and impaired cortical development seen in preterm infants

Postinfectious Gastroparesis Related to Autonomic Failure: A Case Report

Background and aim: Severe dysautonomia may be secondary to viral infections, resulting in impaired autoimmune, cardiovascular, urinary, and digestive dysfunction. Herein, we present a case of a 31-year-old white female patient who had severe gastroparesis related to autonomic failure following an episode of acute gastroenteritis. This seems to be the first report providing thorough assessment of the enteric and autonomic nervous system by analysis of full-thickness small intestinal biopsies, cardiovagal testing, and autopsy. Hospital course: This patient affected by a severe gastroparesis was treated with antiemetics, prokinetics, analgesics, and gastric electrical stimulation to control symptoms. Nutritional support was made using jejunal feeding tube and, in the final stage of disease, with total parenteral nutrition. Autonomic studies revealed minimal heart rate variability and a disordered Valsalva maneuver although the enteric nervous system and the smooth muscle layer showed a normal appearance. Hospital courses were complicated by episodes of bacteremia and fungemia. Serum antiphospholipid antibodies were noted but despite anticoagulation, she developed a pulmonary embolism and shortly thereafter the patient died. Autopsy revealed acute hemorrhagic Candida pneumonia with left main pulmonary artery thrombus. Sympathetic chain analysis revealed decreased myelinated axons with vacuolar degeneration and patchy inflammation consistent with Guillain-Barre syndrome. The evaluation of the enteric nervous system in the stomach and small bowel revealed no evidence of enteric neuropathy or myopathy. Conclusion: A Guillain-Barre-like disease with gastroparesis following acute gastroenteritis is supported by physiologic and autonomic studies with histologic findings.Background and aim: Severe dysautonomia may be secondary to viral infections, resulting in impaired autoimmune, cardiovascular, urinary and digestive dysfunction. Herein, we present a case of a 31-year-old white female patient who had severe gastroparesis related to autonomic failure following an episode of acute gastroenteritis. This seems to be the first report providing thorough assessment of the enteric and autonomic nervous system by analysis of full-thickness small intestinal biopsies, cardiovagal testing and autopsy. Hospital course: This patient affected by a severe gastroparesis was treated with antiemetics, prokinetics, analgesics and gastric electrical stimulation to control symptoms. Nutritional support was made using jejunal feeding tube and, in the final stage of disease, with total parenteral nutrition. Autonomic studies revealed minimal heart rate variability and a disordered Valsalva manoeuvre although the enteric nervous system and the smooth muscle layer showed a normal appearance. Hospital courses were complicated by episodes of bacteraemia and fungemia. Serum antiphospholipid antibodies were noted but despite anticoagulation, she developed a pulmonary embolism and shortly thereafter the patient died. Autopsy revealed acute haemorrhagic Candida pneumonia with left main pulmonary artery thrombus. Sympathetic chain analysis revealed decreased myelinated axons with vacuolar degeneration and patchy inflammation consistent with Guillain-Barre syndrome. The evaluation of the enteric nervous system in the stomach and small bowel revealed no evidence of enteric neuropathy or myopathy. Conclusion: A Guillain-Barre-like disease with gastroparesis following acute gastroenteritis is supported by physiological and autonomic studies with histological findings. © 2006 The Authors