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Glenn mccluggage

Preetha Ramalingam, Sabrina Croce, W Glenn McCluggage
AIM: Abnormalities of SMARCB1 (INI1) gene, a member of the SWI/SNF pathway, are found in neoplasms with rhabdoid morphology such as malignant rhabdoid tumor of the kidney and atypical teratoid/rhabdoid tumor of the central nervous system. SMARCA4 (BRG1), another member of the SWI/SNF pathway, which is mutated in virtually all small cell carcinomas of the ovary, hypercalcemic type, has been investigated in endometrial carcinomas and mutations with resultant loss of immunohistochemical staining has been demonstrated in some endometrial undifferentiated carcinomas /dedifferentiated carcinomas...
September 22, 2016: Histopathology
Leora Witkowski, W Glenn McCluggage, William D Foulkes
The introduction of new sequencing technologies has resulted in the discovery of commonly mutated genes in uncommon cancers, including non-epithelial ovarian neoplasms and other rare gynaecological tumours, such as cervical embryonal rhabdomyosarcoma. In some of these neoplasms, mutations in certain genes are both frequent and specific enough for the genomic mutations and sometimes their associated protein loss or overexpression to be used as an aid to diagnosis. In this review, we contrast previous gene identification methods with newer ones, and discuss how the new sequencing technologies (collectively referred to as 'next-generation sequencing') have permitted the identification of specific molecular events that characterize several rare gynaecological neoplasms...
August 9, 2016: Histopathology
Ian Said, Steffen Böhm, Joanne Beasley, Peter Ellery, Asma Z Faruqi, Raji Ganesan, Lynn Hirshowitz, Sharanpal Jeetle, Sarah Lam Shang Leen, W Glenn McCluggage, Jacqueline McDermott, Reena Merard, Thomas O Millner, Giorgia Trevisan, Jo Vella, C Blake Gilks, Naveena Singh
A 3-tier histopathologic scoring system, the chemotherapy response score (CRS), was previously devised for reporting the histologic response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIc/IV tuboovarian high-grade serous carcinoma. This has been shown to predict the outcome and offer additional information to other methods of assessing the treatment response. In the present study, the reproducibility of this scoring system was assessed by determining the interobserver agreement among reporting pathologists...
June 29, 2016: International Journal of Gynecological Pathology
Jaine K Blayney, Timothy Davison, Nuala McCabe, Steven Walker, Karen Keating, Thomas Delaney, Caroline Greenan, Alistair R Williams, W Glenn McCluggage, Amanda Capes-Davis, D Paul Harkin, Charlie Gourley, Richard D Kennedy
Here, we describe gene expression compositional assignment (GECA), a powerful, yet simple method based on compositional statistics that can validate the transfer of prior knowledge, such as gene lists, into independent data sets, platforms and technologies. Transcriptional profiling has been used to derive gene lists that stratify patients into prognostic molecular subgroups and assess biomarker performance in the pre-clinical setting. Archived public data sets are an invaluable resource for subsequent in silico validation, though their use can lead to data integration issues...
September 30, 2016: Nucleic Acids Research
Tamara McNamee, Stephen Damato, W Glenn McCluggage
AIMS: To report 18 yolk sac tumours (YSTs) of the female genital tract (17 ovary, 1 uterus) in patients aged 40 or over, most arising from a somatic epithelial neoplasm. METHODS/ RESULTS: Six patients had pure YST, 2 were associated with immature teratoma (1 with an endometrioid adenocarcinoma) and in 11 there was an epithelial neoplasm comprising high grade serous carcinoma (HGSC) (n=5), clear cell carcinoma (n=1), borderline clear cell adenofibroma (n=1), endometrioid adenocarcinoma (n=2), serous tubal intraepithelial carcinoma (n=1) and large cell neuroendocrine carcinoma (n=1)...
June 23, 2016: Histopathology
Blaise A Clarke, W Glenn McCluggage
No abstract text is available yet for this article.
June 2016: Surgical Pathology Clinics
Leora Witkowski, Catherine Goudie, William D Foulkes, W Glenn McCluggage
Small-cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a highly malignant and aggressive tumor and is the most common undifferentiated ovarian malignancy to occur in women younger than 40. SCCOHT is characterized by deleterious germline or somatic mutations in SMARCA4. Given the striking morphologic and molecular similarities between SCCOHT and atypical teratoid/malignant rhabdoid tumor, we propose this should be reflected in a nomenclature change and that SCCOHT be renamed malignant rhabdoid tumor of the ovary...
June 2016: Surgical Pathology Clinics
Ayoma D Attygalle, Katherine Vroobel, Dorte Wren, Desmond P J Barton, Stephen J Hazell, Paola Dal Cin, Konrad Koelble, W Glenn McCluggage
Endometrial stromal sarcoma (ESS) characterized by YWHAE-NUTM2A/B genetic fusion is a recently recognized entity that is classified as a high-grade (HG) ESS in the 2014 World Health Organization Classification. These are myoinvasive neoplasms and typically contain a monomorphous HG round-cell cyclinD1-positive component with or without an accompanying low-grade (LG) component that is only focally positive/negative for cyclinD1. We report a case of YWHAE-NUTM2A/B ESS in a 46-yr-old woman that showed a number of unusual histologic features, including being entirely confined to the endometrium with no myoinvasion or lymphovascular space invasion...
May 11, 2016: International Journal of Gynecological Pathology
Seema Angra, W Glenn McCluggage
Endocervical polyps are common benign lesions which rarely result in diagnostic problems, although a variety of alterations occasionally complicate histologic interpretation. We report an unusual, and not previously described, finding of florid "epidermal" metaplasia with keratinization and extensive formation of skin appendages structures (sebaceous and sweat glands and hair follicles) within an endocervical polyp. The features closely resembled an epidermal inclusion cyst. We speculate on the possible pathogenesis of this rare phenomenon and review unusual findings in endocervical polyps...
September 2016: International Journal of Gynecological Pathology
Emily A Goebel, W Glenn McCluggage, Joanna C Walsh
Sclerosing stromal tumor of the ovary is a rare neoplasm that typically occurs in the second and third decades of life. To date, all reported cases have behaved in a benign manner. In their usual form, these neoplasms exhibit scant, if any, mitotic activity. Herein, we report a case series of 6 sclerosing stromal tumors with increased mitotic activity (between 7 and 12 mitoses per 10 high-power fields in the most mitotically active areas). Follow-up is available in 4 of 6 cases (ranging from 3 wk to 68 mo) and 1 tumor recurred within the pelvis...
May 4, 2016: International Journal of Gynecological Pathology
Blaise A Clarke, Leora Witkowski, Tuyet Nhung Ton Nu, Patricia A Shaw, C Blake Gilks, David Huntsman, Tony Karnezis, Neil Sebire, Janez Lamovec, Lawrence M Roth, Colin Jr Stewart, Martin Hasselblatt, William D Foulkes, W Glenn McCluggage
AIMS: Molecular interrogation of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) has revealed that it is a monogenetic tumor characterized by alteration of SMARCA4 (BRG1), a member of the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. A large majority of cases show loss of expression of the corresponding SMARCA4/BRG1 protein. Furthermore, three cases of SCCOHT with retained SMARCA4 protein expression demonstrated loss of expression of SMARCB1/ INI1...
April 21, 2016: Histopathology
Stavroula Stavrinou, Ashleigh Clark, Julie Irving, Cheng-Han Lee, Esther Oliva, Robert Young, Ruethairat Sriraksa, Nesreen Magdy, Susan Van Noorden, W Glenn McCluggage, Mona El-Bahrawy
AIMS: Sex cord stromal tumours (SCSTs) of the ovary encompass several histological tumour subtypes that are defined by characteristic histological features. Some can show morphological overlap with other subtypes of SCSTs, as well as with non-SCSTs. The E-cadherin/catenin complex constitutes the adherens junction, which is well developed in epithelial tissue, but the constituent molecules are also expressed in several non-epithelial tumours. The aim of this study was to determine whether the expression patterns of E-cadherin and catenins in ovarian SCSTs can be of diagnostic utility...
August 2016: Histopathology
William D Foulkes, Martin Gore, W Glenn McCluggage
Rare non-epithelial ovarian neoplasms have posed management challenges for many years. Their rarity means that most specialist practitioners will see one such case every several years, and most generalists may never see a case. The first step in management is to establish the correct diagnosis and this may necessitate specialist pathology review. Here, we review recent developments in the pathology, genetics and treatment of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and sex cord-stromal tumours...
July 2016: Gynecologic Oncology
Naveena Singh, C Blake Gilks, Lynn Hirshowitz, Nafisa Wilkinson, W Glenn McCluggage
There is currently sufficient evidence that nonuterine high-grade serous carcinoma (HGSC) originates in the fallopian tube in the majority of cases, but this is not uniformly reflected in our diagnostic terminology. This is because there remains wide variation in awareness and acceptance of this evidence, which conflicts with traditional views on origin. Accurate disease classification is fundamental to routine clinical practice and research, particularly at a time when exciting new approaches to therapy, early detection, and prevention are appearing on the horizon...
May 2016: International Journal of Gynecological Pathology
Leora Witkowski, Catherine Goudie, Pilar Ramos, Talia Boshari, Jean-Sebastien Brunet, Anthony N Karnezis, Michel Longy, James A Knost, Emmanouil Saloustros, W Glenn McCluggage, Colin J R Stewart, William P D Hendricks, Heather Cunliffe, David G Huntsman, Patricia Pautier, Douglas A Levine, Jeffrey M Trent, Andrew Berchuck, Martin Hasselblatt, William D Foulkes
OBJECTIVE: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive tumor, with long term survival at ~30% in early stage disease. SCCOHT is caused by germline and somatic SMARCA4 mutations, but the effect of the mutation type on patients remains unknown. Furthermore, the rarity of SCCOHT has resulted in varied treatment, with no standardized protocols. We analyzed 293 cases to determine the effect of treatment modalities and SMARCA4 mutations on patient diagnosis and outcome...
June 2016: Gynecologic Oncology
W Glenn McCluggage
Pure mesenchymal tumors may occur anywhere in the female genital tract, but they are most common in the uterine corpus, leiomyoma being by far the most prevalent. These tumors, and other uncommon mesenchymal lesions within the uterine corpus and elsewhere in the female genital tract, may result in several diagnostic problems. Morphology remains paramount and, in most cases, an unequivocal diagnosis can be made based on examination of the hematoxylin and eosin stained sections, combined with an appreciation of the clinical and gross pathologic features...
December 2009: Surgical Pathology Clinics
W Glenn McCluggage
In this review, ovarian metastatic carcinomas from various sites, as well as other neoplasms secondarily involving the ovary, are discussed. As well as describing the morphology, the value of immunohistochemistry in distinguishing between primary and metastatic neoplasms in the ovary is discussed. While immunohistochemistry has a valuable role to play and is paramount in some cases, the results should be interpreted with caution and with regard to the clinical picture and gross and microscopic pathologic findings...
March 2011: Surgical Pathology Clinics
Naveena Singh, C Blake Gilks, Lynn Hirschowitz, Sean Kehoe, Iain A McNeish, Dianne Miller, Raj Naik, Nafisa Wilkinson, W Glenn McCluggage
No abstract text is available yet for this article.
May 2016: Gynecologic Oncology
Wen Yee Chay, W Glenn McCluggage, Cheng-Han Lee, Martin Köbel, Julie Irving, Joanne Millar, C Blake Gilks, Anna V Tinker
OBJECTIVES: The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications. MATERIALS AND METHODS: Cases of incidental STIC and HGSC were identified from 2008...
March 2016: International Journal of Gynecological Cancer
W Glenn McCluggage
The current 2014 World Health Organization (WHO) Classification of mixed epithelial and mesenchymal tumours of the uterus includes categories of carcinosarcoma, adenosarcoma, adenofibroma, adenomyoma and atypical polypoid adenomyoma, the last two lesions being composed of an admixture of benign epithelial and mesenchymal elements with a prominent smooth muscle component. In this review, each of these categories of uterine neoplasm is covered with an emphasis on practical tips for the surgical pathologist and new developments...
January 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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