Douglass Hanly Moir Pathology

Port Macquarie, Australia

Douglass Hanly Moir Pathology

Port Macquarie, Australia
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Amary M.F.,Royal National Orthopaedic Hospital | Damato S.,Royal National Orthopaedic Hospital | Halai D.,Royal National Orthopaedic Hospital | Eskandarpour M.,University College London | And 15 more authors.
Nature Genetics | Year: 2011

Ollier disease and Maffucci syndrome are characterized by multiple central cartilaginous tumors that are accompanied by soft tissue hemangiomas in Maffucci syndrome. We show that in 37 of 40 individuals with these syndromes, at least one tumor has a mutation in isocitrate dehydrogenase 1 (IDH1) or in IDH2, 65% of which result in a R132C substitution in the protein. In 18 of 19 individuals with more than one tumor analyzed, all tumors from a given individual shared the same IDH1 mutation affecting Arg132. In 2 of 12 subjects, a low level of mutated DNA was identified in non-neoplastic tissue. The levels of the metabolite 2HG were measured in a series of central cartilaginous and vascular tumors, including samples from syndromic and nonsyndromic subjects, and these levels correlated strongly with the presence of IDH1 mutations. The findings are compatible with a model in which IDH1 or IDH2 mutations represent early post-zygotic occurrences in individuals with these syndromes. © 2011 Nature America, Inc. All rights reserved.

Machalek D.A.,University of New South Wales | Poynten M.,University of New South Wales | Jin F.,University of New South Wales | Fairley C.K.,Melbourne Sexual Health Center | And 15 more authors.
The Lancet Oncology | Year: 2012

Background: Men who have sex with men (MSM) are at greatly increased risk of human papillomavirus (HPV)-associated anal cancer. Screening for the presumed cancer precursor, high-grade anal intraepithelial neoplasia (AIN), followed by treatment in a manner analogous to cervical screening, has been proposed. We aimed to assess available data for anal HPV disease that can inform pre-cancer screening programmes. Methods: We searched PubMed, OVID Medline, and Embase for all studies published before Nov 1, 2011, that reported prevalence and incidence of anal HPV detection, AIN, and anal cancer in MSM. We calculated summary estimates using random-effects meta-analysis. Findings: 53 studies met the inclusion criteria, including 31 estimates of HPV prevalence, 19 estimates of cytological abnormalities, eight estimates of histological abnormalities, and nine estimates of anal cancer incidence. Data for incident HPV and high-grade AIN were scarce. In HIV-positive men, the pooled prevalence of anal HPV-16 was 35·4% (95% CI 32·9-37·9). In the only published estimate, incidence of anal HPV-16 was 13·0% (9·6-17·6), and clearance occurred in 14·6% (10·2-21·2) of men per year. The pooled prevalence of histological high-grade AIN was 29·1% (22·8-35·4) with incidences of 8·5% (6·9-10·4) and 15·4% (11·8-19·8) per year in two estimates. The pooled anal cancer incidence was 45·9 per 100 000 men (31·2-60·3). In HIV-negative men, the pooled prevalence of anal HPV-16 was 12·5% (9·8-15·4). Incidence of HPV-16 was 11·8% (9·2-14·9) and 5·8% (1·9-13·5) of men per year in two estimates. The pooled prevalence of histological high-grade AIN was 21·5% (13·7-29·3), with incidence of 3·3% (2·2-4·7) and 6·0% (4·2-8·1) per year in two estimates. Anal cancer incidence was 5·1 per 100 000 men (0-11·5; based on two estimates). There were no published estimates of high-grade AIN regression. Interpretation: Anal HPV and anal cancer precursors were very common in MSM. However, on the basis of restricted data, rates of progression to cancer seem to be substantially lower than they are for cervical pre-cancerous lesions. Large, good-quality prospective studies are needed to inform the development of anal cancer screening guidelines for MSM. Funding: Australian Government Department of Health and Ageing. © 2012 Elsevier Ltd.

Roberts J.M.,Douglass Hanly Moir Pathology | Thurloe J.K.,Douglass Hanly Moir Pathology
Sexual Health | Year: 2012

Cervical cytology screening has a long history and has successfully reduced the impact of cervical cancer in many countries. Anal cytology is a relative newcomer and anal screening is currently offered in only a few centres around the world. Many questions need to be answered before anal screening is more widely adopted. While there are many similarities between cervical and anal squamous cell carcinoma, there are also important differences: differences in the prevalence of disease, in the 'at-risk' target populations and possibly in the robustness of the reference standard of biopsy. The performance of cytology as a screening test in the literature varies widely but it is essential to understand that some of this variability is due to differences in the definitions of key parameters in the various studies. For cervical screening, estimates of sensitivity have ranged from 19% to 94% and specificity from 94% to 98%. For anal screening, data are fewer and more limited. Estimates of the sensitivity of anal cytology in men who have sex with men and HIV-positive populations have ranged from 55% to 87% and specificity from 37% to 76%. Ultimately, rather than comparing anal with cervical cytology, it may be more helpful to assess the value of anal cytology independently through well designed trials. Journal compilation CSIRO © 2012.

Wilsher M.J.,Douglass Hanly Moir Pathology
Pathology International | Year: 2011

Within the gastrointestinal tract, osseous metaplasia is an extremely rare phenomenon. It has only recently been described within a traditional serrated adenoma. Serrated colorectal carcinoma is the end point of the serrated neoplasia pathway. Left sided lesions typically arise from traditional serrated adenomas and represent only 8% of colorectal carcinomas. Herein reported is a case of colorectal adenocarcinoma arising from a traditional serrated adenoma with the rare occurrence of osseous metaplasia within the adenoma. The significance of the finding is discussed. © 2011 The Author. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.

Roberts J.M.,Douglass Hanly Moir Pathology | Ekman D.,Douglass Hanly Moir Pathology
Sexual Health | Year: 2012

Our understanding of the human papillomavirus (HPV) related cytomorphology and histopathology of the anal canal is underpinned by our knowledge of HPV infection in the cervix. In this review, we utilise cervical reporting of cytological and histological specimens as a foundation for the development of standardised and evidence-based terminology and criteria for reporting of anal specimens. We advocate use of the Australian Modified Bethesda System 2004 for reporting anal cytology. We propose the use of a two-tiered histological reporting system for noninvasive disease - low-grade and high-grade anal intraepithelial neoplasia. These classification systems reflect current understanding of the biology of HPV and enhance diagnostic reproducibility. Biomarkers such as p16INK4A may prove useful in further improving diagnostic accuracy. Standardisation is important because it will increase the value of the data collected as Australian centres develop programs for screening for anal neoplasia. Journal compilation CSIRO © 2012.

Xu Y.,University of New South Wales | Bonar F.,Douglass Hanly Moir Pathology | Murrell G.A.C.,University of New South Wales
Journal of Shoulder and Elbow Surgery | Year: 2012

Background: Our understanding of the pathogenesis of frozen shoulder and why it is so painful is undetermined. This study investigated the expression of neuronal proteins in the capsular tissue of frozen shoulder. Methods: Shoulder capsular samples were collected from 8 patients with idiopathic adhesive capsulitis and 10 patients with a rotator cuff tear but no stiffness (controls). Samples were analyzed by immunohistochemistry using antibodies against protein gene product 9.5 (PGP9.5), a general nerve marker; growth associated protein 43 (GAP43), a nerve growth marker; nerve growth factor receptor p75; and CD34, an endothelial cell marker. Results: Samples from frozen shoulders showed subsynovial hypercellularity and fibroblastic proliferation, with increased expression of nerve growth factor receptor p75 and CD34 compared with controls. Nerves positive for PGP9.5 and GAP43 were more abundant in samples of frozen shoulder (2.8 ± 0.2 and 2.4 ± 0.4 per field; P < .01) compared with controls (1.6 ± 0.3 and 1.3 ± 0.3 per field; P < .05). Expression of neuronal proteins followed that of CD34. Conclusion: Increased expression of nerve growth factor receptor and new nerve fibers were found in the shoulder capsular tissue of patients with frozen shoulder compared with those without a frozen shoulder. These data suggest that neoinnervation and neoangiogenesis in the shoulder capsule are important events in the pathogenesis of frozen shoulder and may help explain the often-severe pain of patients with frozen shoulder. © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees.

Low grade adenosquamous carcinoma (LGASC) is rare but commonly reported to arise in association with benign proliferative and sclerosing breast lesions which themselves may show associated sclerosing or 'adenosquamous proliferation' (ASP) resembling LGASC, but are often derided as reactive mimics or attributed to earlier biopsy. Among other benign lesions, radial sclerosing lesion (RSL) may be associated with LGASC, yet attention is typically focused on its relationship to more common forms of mammary carcinoma. This study aimed to assess the presence and extent of ASP in the context of RSL in a small cohort of 20 cases and its similarity to LGASC. Twenty consecutive breast excisions that had a principal or incidental diagnosis of RSL were reviewed. RSLs that displayed foci of ASP were further examined with immunohistochemical markers for p63, calponin, cytokeratin 5/6, oestrogen and progesterone receptors. Sixty percent of excisions contained ASP either associated with a RSL or a concurrent papilloma, which morphologically and immunohistochemically were indistinguishable from the neoplastic ducts of LGASC. RSL with and without ASP broadly corresponded to accepted definitions for 'early' and 'late' lesions, respectively. ASP corresponded to the characteristic compact branching ducts of the core or nidus of a RSL. The morphological and immunophenotypic similarity of the ASP found in RSL and papillomata to LGASC warrants serious consideration that they are a potential precursor to LGASC, which may most commonly involute given the rarity of clinically apparent LGASC. Further study including micro-dissection of foci of ASP to compare its molecular genetic profile to that of LGASC is required. Copyright © 2014 Royal College of pathologists of Australasia.

Wilsher M.J.,University of London | Bonar F.,Douglass Hanly Moir Pathology
Histopathology | Year: 2016

Aims: We recently identified the presence of Rosai–Dorfman-type histiocytes (RDH) in sinonasal tissue removed from individuals with eosinophilic chronic rhinosinusitis (ECR). We sought to determine their clinical significance. Methods and results: Sinonasal biopsies from 10 individuals (index cases) with classical features of ECR and the additional finding of RDH were collected during a two-and-a-half-year period. Twenty-one sinonasal biopsies with a diagnosis of ECR accrued during a 6-month period were reviewed at one institution to assess the presence of this phenomenon in archived material. Five of the 10 index cases were recurrent; in four of these in which archival material was available, three had RDH on review. Of the 21 review cases, 52% contained RDH. Six of the review cases represented recurrent disease and in five of these RDH were demonstrable. Archival material was available from five cases that recurred, RDH being demonstrable in three. RDH were seen to persist across multiple recurrences. Conclusions: The presence of RDH within ECR samples is associated highly with recurrence. RDH have properties of antigen-presenting cells and may play a hitherto unrecognized role in the initiation and persistence of ECR. © 2016 John Wiley & Sons Ltd

Australia has a unique and highly successful screening program for cervical cancer which is based on the conventional Pap smear. Since its introduction in 1991 there has been a decline in both the incidence of and mortality from this disease. Part of the success of this program has been the introduction of Pap test registers and strict quality assurance measures for cervical cytology, including compulsory key performance indicators for laboratories. Using these measures, nationwide calculations give cervical cytology in Australia a sensitivity of 78% for high-grade lesions and a positive predictive value (PPV) of 78%. Australia was the first country to introduce a widespread government-funded human papillomavirus (HPV) vaccination program in 2007. Because of the high accuracy of Australian cytology, HPV testing alone, given its low PPV and high cost, is unlikely to be a viable alternative to cytology for primary screening in this country. Australia therefore faces unique issues and choices in integrating its extensive vaccination program with a successful cervical screening program. Copyright © 2011 S. Karger AG, Basel.

Xu Y.,University of New South Wales | Bonar F.,Douglass Hanly Moir Pathology | Murrell G.A.C.,University of New South Wales
Sports Medicine and Arthroscopy Review | Year: 2011

The aim of this study was to determine whether there are more nerves in tendinopathic human tendon, and if so, where are they located. Tendon biopsies were collected from normal, tendinopathic, and torn human rotator cuff tendons and then analyzed using immunohistochemistry and antibodies against a general nerve marker (protein gene product 9.5, PGP9.5), a nerve regeneration marker (growth-associated protein 43, GAP43), and an endothelial cell marker (CD34). Nerve fibers exhibiting PGP9.5 or GAP43 immunoreactivity were often observed intimately in association with tiny blood vessels in the endotendineum of tendinopathic tendons. The expression of PGP9.5 and GAP43 were significantly higher in tendinopathic tendon compared with control tendon and torn tendon. These data support the hypothesis that early tendinopathy is associated with increases of newly grown nerve fibers and blood vessels inside and around tendinopathic tendon, and these may be the source of pain in tendinopathy. © 2011 by Lippincott Williams & Wilkins.

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