Posterior cortical atrophy: a single case cognitive and radiological follow-up

Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterized by initial predominant visuoperceptual deficits followed by a progressive decline in other cognitive functions. This syndrome has not been as thoroughly described as other dementias, particularly from a neuropsychological evolution perspective with only a few studies describing the evolution of its cognitive progression. In this investigation we review the literature on this rare condition and we perform a 7-year neuropsychological and neuroradiological follow-up of a 64-year-old man with PCA. The subject’s deficits initially appeared in his visuoperceptual skills with later affectation appearing in language and other cognitive functions, this being coherent with the patient’s parieto-temporal atrophy evolution.     

孟鲁斯特联合黄芪颗粒在儿童咳嗽变异性哮喘中的疗效观察

目的:研究孟鲁斯特联合黄芪颗粒在儿童咳嗽变异性哮喘(CVA)治疗中的临床疗效。方法:选择确诊为CVA的100例患儿为观察对象,随机分为对照组与治疗组,每组50例,对照组给予丙卡特罗口服及普米克令舒雾化治疗,治疗组在对照组基础上加用孟鲁斯特及黄芪颗粒治疗,比较两组疗效。结果:治疗组疗效显著高于对照组(P<0.05)。结论:孟鲁斯特联合黄芪颗粒在儿童咳嗽变异性哮喘治疗中的临床疗效显著。     

Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia

For biological and statistical reasons it makes sense to combine information from variants at the level of the gene. One may wish to give more weight to variants which are rare and those that are more likely to affect function. A combined weighting scheme, implemented in the SCOREASSOC program, was applied to whole exome sequence data for 1392 subjects with schizophrenia and 982 with obesity from the UK10K project. Results conformed fairly well with null hypothesis expectations and no individual gene was strongly implicated. However, a number of the higher ranked genes appear plausible candidates as being involved in one or other phenotype and may warrant further investigation. These include MC4R, NLGN2, CRP, DONSON, GTF3A, IL36B, ADCYAP1R1, ARSA, DLG1, SIK2, SLAIN1, UBE2Q2, ZNF507, CRHR1, MUSK, NSF, SNORD115, GDF3 and HIBADH. Some individual variants in these genes have different frequencies between cohorts and could be genotyped in additional subjects. For other genes, there is a general excess of variants at many different sites so attempts at replication would be more difficult. Overall, the weighted burden test provides a convenient method for using sequence data to highlight genes of interest.     

Hb F-Avellino [Gγ41(C7)Phe → Leu; HBG2: c.124 T > C]: A New Hemoglobin Variant Observed In A Healthy Newborn

Here we describe Hb F-Avellino [^Gγ41(C7)Phe?→?Leu; HBG2: c.124?T?>?C], a new hemoglobin (Hb) variant observed in a healthy newborn. The proband’s hemolysate was found to be mildly unstable by the isopropanol test. The occurrence of the variant was assessed by both chromatographic and electrophoretic methods. DNA sequencing analysis of the ^Gγ gene showed a T to C transition at codon 41 (TTC?>?CTC) corresponding to the Phe?→?Leu substitution. Normal functional properties have been hypothesized.     

Generalized multinucleate cell angiohistiocytoma with possible origin from fibroblasts: A clinicopathological study of 15 cases

Multinucleate cell angiohistiocytoma (MCAH) is a vascular and fibrohistiocytic proliferation with unknown pathogenesis. Clinical lesions tend to be localized to an anatomical area. Exceptionally, the generalized variant is rare. This study reports three cases of generalized MCAH, and analyzes the clinicopathological features of 15 cases reviewed in the published work. Compared with the localized variant, generalized MCAH affected both sexes equally, had an earlier age of onset and a predilection for the trunk and extremities. Histopathologically, the most characteristic feature is the giant, bizarre multinucleate cells with angulated cytoplasm. Systemic diseases or abnormal immune conditions were revealed in six patients with generalized MCAH. For the first time, we found that the present cases showed increased elastic fibers in the affected areas, suggesting that the synthetic function of fibroblasts was active. This study suggested that MCAH originates from fibroblasts and is a distinct entity with potential correlation with abnormal immune states.     

A familial amyotrophic lateral sclerosis pedigree discordant for a novel p.Glu46Asp heterozygous OPTN variant and the p.Ala5Val heterozygous SOD1 missense mutation

About 10% of Amyotrophic Lateral Sclerosis (ALS) cases are familial (FALS), mainly related to mutations in C9ORF72, SOD1, TARDBP, and FUS genes. Recent data revealed the presence of multiple variants in ALS-associated genes in FALS in excess of what is to be expected by chance. FALS patients not carrying a pathogenic genetic mutation detected in their kindred have been reported. We report a FALS case, who did not carry the p.Ala5Val heterozygous SOD1 mutation that had been detected in other affected subjects of his kindred. He underwent Next-Generation Sequencing, revealing a novel p.Glu46Asp heterozygous OPTN variant of uncertain significance (VUS). Discordant genetic test results in FALS cases within the same family and the detection of variants of uncertain significance increase the complexities of genetic counselling.     

Variants and new entities of bladder cancer

Pathological evaluation of bladder cancer typically reveals great tumour heterogeneity, and therefore the common observation of urothelial carcinoma exhibiting a wide variety of histopathological patterns is not surprising. Some of these patterns are so distinctive that they have been recognised as specific variants of urothelial carcinoma. Classifications have recently been revised in the 2016 World Health Organisation (WHO) classification of tumours of the urinary system and male genital organs. The current WHO classifications clarify terminological issues and provide better definition criteria, but also incorporate some new entities. Many of these variants have important prognostic or therapeutic implications worth knowing by the urologist and oncologist, but also represent diagnostic challenges in daily pathology practice. This review will discuss the features of variants of urothelial carcinoma in the context of our current clinical practice. Histological variations and new entities of bladder cancer not included in the current WHO classification of urothelial tumours will be briefly discussed.     

Next generation immunohistochemistry: Emerging substitutes to genetic testing?

The identification of at-risk kindreds facilitates screening and risk reduction strategies for patients with hereditary cancer predisposition syndromes. Recently, immunohistochemistry (IHC) has emerged as a cost-effective strategy for detecting or inferring the presence of mutations in both tumors and the germline of patients presenting with tumors associated with hereditary cancer predisposition syndromes. In this review we discuss the use of novel IHC markers, including PRKAR1A, β-catenin, SDHB, fumarate hydratase and 2SC, HRASQ61R, BAP1, parafibromin and glucagon, which have either established applications or show promise for surgical pathologists to complement morphological or clinical suspicion of hereditary cancer predisposition syndromes. Specifically, we focus on Carney complex, familial adenomatous polyposis (FAP)-associated cribriform-morular variant of papillary thyroid carcinoma, familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, hereditary leiomyomatosis and renal cell cancer (HLRCC), medullary thyroid cancer and Multiple Endocrine Neoplasia 2 (MEN2), BAP1 hereditary cancer predisposition syndrome, Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), and Pancreatic Neuroendocrine Tumor Syndrome (Mahvash disease).