G Anderson

Great Ormond Street Hospital for Children NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (6)12.63 Total impact

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    ABSTRACT: BACKGROUND: Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations, however the lineage of the mutated cells remains uncertain. This study was designed to test the hypothesis that CMN may be derived from cutaneous stem cells. METHODS: Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (Nestin, Fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67), and MTOR/Wnt-signaling pathway activation (pS6, β-catenin). Semi-quantitative scoring compared samples with naevus cell nesting (group 1) to those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples. RESULTS: A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was significantly correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and stronger superficially. Expression of beta-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli. CONCLUSIONS: CMN development frequently co-exists with normal overlying melanocyte development, leading us to hypothesise that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem cell origin, capable of some degree of melanocytic differentiation superficially.
    British Journal of Dermatology 03/2013; · 3.76 Impact Factor
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    ABSTRACT: Some lysosomal storage disorders cause progressive prenatal accumulation of undegradable metabolites that manifest as membrane-bound vacuoles in endothelial cells, fibroblasts, and trophoblast, identifiable by electron microscopic examination of chorionic villus samples (CVS). There were 111 CVS, which had ultrastructural examination for suspected storage disorders at Great Ormond Street Hospital (1988-2005). There were 31 positive diagnoses, including glycogen storage disease type II, gangliosidosis type 1, mucopolysaccharidosis type 1, MPS not specified, Niemann-Pick type A, sialidosis/mucolipidosis type 1, neuronal ceroid lipofuscinoses (including variant forms), Wolman disease, sialic acid storage disease, and storage disease not specified. In most of these cases the indication was a previously affected individual. Seventy-seven cases showed no evidence of storage disease; 3 samples were inadequate for ultrastructural diagnosis. In selected cases, one-third of CVS may demonstrate distinctive ultrastructural features allowing prenatal diagnosis of a range of storage diseases.
    Ultrastructural Pathology 01/2007; 31(1):15-21. · 0.98 Impact Factor
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    V V Smith, G Anderson, M Malone, N J Sebire
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    ABSTRACT: Microscopic examination of scalp hair can provide important diagnostic information in a range of paediatric conditions. It is a non-invasive and cost effective investigation, which is not widely performed. To examine retrospectively the value of hair examination by light microscopy, including polarising microscopy, in a specialist paediatric pathology department during a 15 year period (1989-2004) and to describe the morphological abnormalities indicative of specific paediatric conditions. Three hundred and twenty two hair samples were submitted. Microscopic changes were analysed in the light of clinical information categorised as: (1) erythroderma, (2) neurological impairment, (3) immunological/haematological defect, (4) ectodermal dysplasia, (5) abnormal hair only, and (6) non-specific/absent clinical details. Abnormalities were evident in 49% of the samples. In 25%, the changes were compatible with specific diagnoses including Menkes disease, Netherton's syndrome, trichothiodystrophy, Griscelli and Chediak-Higashi syndromes, monilethrix, uncombable hair, and loose anagen syndromes. In respect of the clinical presentation groups noted above, diagnostic changes were seen in 41%, 32%, 33%, 0%, 29%, and 0%, respectively. Morphological light microscopic examination of scalp hair is an inexpensive, rapid, and non-invasive investigation, which can provide valuable diagnostic information in a range of paediatric conditions.
    Journal of Clinical Pathology 01/2006; 58(12):1294-8. · 2.44 Impact Factor
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    ABSTRACT: The classical ultrastructural features of Gaucher disease include large numbers of intracytoplasmic, membrane-bound lysosomal inclusions containing characteristic tubular structures on an electron-lucent background, representing the periodic acid schiff (PAS)-positive Gaucher cells identifiable on light microscopy. Following enzyme replacement therapy (ERT), many of the manifestations of the condition are ameliorated, but persistent mesenteric lymphadenopathy has been reported, the ultrastructural features of which previously have not been described. Two children, aged 4 and 8 years old, respectively, both presented with persistent abdominal lymphadenopathy whilst receiving ERT for Gaucher disease. Needle core biopsies were carried out, that demonstrated collections of macrophages and only scattered storage-type cells on light microscopy. PAS staining was negative in one case and only focally positive in the other Electron microscopic examination, however, confirmed the cells represented macrophages, the cytoplasm of which contained scattered abnormal inclusions containing occasional twisted tubular structures of the type reported in classic Gaucher disease. ERT in Gaucher disease appears to reduce accumulation of the metabolic products at many sites. But for uncertain reasons, abdominal lymphadenopathy may occur containing macrophages that do not form granulomas or classic Gaucher cells on light microscopy. These probably represent incomplete clearance, incomplete/partial enzyme replacement, or possibly an unusual response to a relatively small amount of storage material.
    Fetal and Pediatric Pathology 01/2006; 25(5):241-8. · 0.58 Impact Factor
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    G Anderson, V V Smith, M Malone, N J Sebire
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    ABSTRACT: A range of metabolic diseases can result in abnormal accumulation of metabolic byproducts, resulting in abnormal lymphocyte cytoplasmic vacuolation, identifiable on routine blood film examination. This study retrospectively examines the usefulness of blood film examination for vacuolated lymphocytes in a specialist paediatric pathology department in relation to patient's age and presentation. It also describes specific diagnostic features in relation to specific classes of metabolic disease. Retrospective review of a histopathology database to identify all blood films examined for the detection of vacuolated lymphocytes during a 15 year period (1989-2004). In total, 2,550 blood films were investigated. The median age at submission was 2 years (range, birth to 88), and>90% of samples were from children<18 years. The most common indications were developmental delay/regression, ataxia, seizures, and cardiomyopathy. Vacuolated lymphocytes were identified in 156 films (6.1%). The frequency of vacuolated lymphocytes varied with clinical presentation, with ophthalmic indications having the highest positive rate (40%). In cases with vacuolated lymphocytes, a wide range of underlying metabolic diagnoses was apparent, the most common being juvenile neuronal ceroid lipofuscinosis and acid maltase deficiency, which accounted for more than half of the diagnoses. The examination of blood films for lymphocyte vacuolation is clinically useful in patients with a history suggestive of metabolic disease. The test is cheap, rapid, minimally invasive, and provides first line screening, with some findings indicating clues to a specific underlying diagnosis.
    Journal of Clinical Pathology 12/2005; 58(12):1305-10. · 2.44 Impact Factor
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    ABSTRACT: Human astrovirus infection often causes outbreaks of self limiting diarrhoea, but may also infect patients who are immunodeficient or immunocompromised. Although there are previous publications relating to various aspects of astroviruses, there is a minimal amount of literature on the histopathological features of gastrointestinal astrovirus infection in humans. We report the histopathological findings, including immunohistochemical and electron microscopic features, of astrovirus infection in a bone marrow transplant recipient aged 4 years with diarrhoea. The appearance of a small intestinal biopsy did not suggest graft versus host disease, but demonstrated villous blunting, irregularity of surface epithelial cells, and an increase in lamina propria inflammatory cell density. Immunohistochemical staining with a murine astrovirus group specific monoclonal antibody demonstrated progressively more extensive staining in the duodenal and jejunal biopsies, predominantly restricted to the luminal surface and cytoplasm of surface epithelial cells, most marked at the villus tips. Electron microscopic examination demonstrated viral particles within the cytoplasm of enterocytes, focally forming paracrystalline arrays.
    Journal of Clinical Pathology 10/2004; 57(9):1001-3. · 2.44 Impact Factor