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Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc

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https://www.readbyqxmd.com/read/30065261/htert-promoter-mutations-in-chondrosarcomas-associate-with-progression-and-disease-related-mortality
#1
Yingbo Lin, Nelly Seger, Yi Chen, Asle C Hesla, Johan Wejde, Mehran Ghaderi, Panagiotis Tsagkozis, Olle Larsson, Felix Haglund
Chondrosarcomas are malignant skeletal tumors with chondroid differentiation. Prognosis is largely dependent on histological grading, which suffer from significant interobserver variability. Telomerase activity and abundant telomerase reverse transcriptase (hTERT) expression has previously been associated with chondrosarcoma grade and metastasis. We therefore analyzed the hTERT promoter in clinicopathologically well-characterized chondrosarcomas (grade 1-3) from 87 patients. Using Sanger sequencing we identified an activating -124 C > T mutation in 23 cases (26%)...
July 31, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29985454/pax7-expression-in-sarcomas-bearing-the-ewsr1-nfatc2-translocation
#2
LETTER
Gregory W Charville, Wei-Lien Wang, Davis R Ingram, Angshumoy Roy, Dafydd Thomas, Rajiv M Patel, Jason L Hornick, Matt van de Rijn, Alexander J Lazar
No abstract text is available yet for this article.
July 9, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29976944/role-of-columnar-cell-lesions-in-breast-carcinogenesis-analysis-of-chromosome-16-copy-number-changes-by-multiplex-ligation-dependent-probe-amplification
#3
Mirthe de Boer, Anoek H J Verschuur-Maes, Horst Buerger, Cathy B Moelans, Maryvonne Steenkamer, Suvi Savola, Paul J van Diest
Columnar cell lesions have been proposed as precursor lesions of low-grade breast cancer. The molecular characteristic of low-grade breast neoplasia is whole-arm loss of chromosome 16q. Copy number changes of 6 genes on 16p and 20 genes on 16q were analysed by multiplex ligation-dependent probe amplification in 165 lesions of 103 patients. Twenty-three columnar cell lesions and 19 atypical ducal hyperplasia lesions arising in columnar cell lesions were included, as well as cases of usual ductal hyperplasia, blunt duct adenosis, ductal carcinoma in situ, lobular neoplasia and invasive carcinoma...
July 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29976943/lipoblastoma-like-tumor-of-the-vulva-a-clinicopathologic-immunohistochemical-fluorescence-in-situ-hybridization-and-genomic-copy-number-profiling-study-of-seven-cases
#4
J Kenneth Schoolmeester, Michael Michal, Petr Steiner, Michal Michal, Andrew L Folpe, William R Sukov
Lipoblastoma-like tumor of the vulva was first described as a benign mesenchymal neoplasm of adipocytic differentiation having features of lipoblastoma, myxoid liposarcoma, and spindle cell lipoma. Prior studies of lipoblastoma-like tumor have evaluated PLAG1, HMGA2, and RB1 immunohistochemistry and DDIT3 rearrangement status, with results supporting its distinction from lipoblastoma and myxoid liposarcoma. However, absent RB1 expression was reported in a majority of tested cases, suggesting that lipoblastoma-like tumor may have underlying 13q alterations and be related to RB1-deleted soft tissue tumors...
July 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29973653/expression-of-pd-l1-pd-1-in-lymphoepithelioma-like-carcinoma-of-the-thymus
#5
David Suster, German Pihan, Alexander C Mackinnon, Saul Suster
Poorly differentiated non-keratinizing squamous cell carcinoma of the thymus, also known as lymphoepithelioma-like carcinoma, is a rare primary malignant neoplasm of thymic origin. The mainstay of treatment for these tumors is surgical and they tend to respond poorly to chemotherapy. The checkpoint programmed cell death ligand-1 protein (PD-L1) bound to its receptor (PD-1) has been demonstrated to be an important therapeutic target for many different tumors. Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus may indicate that these tumors are potential targets for inhibitor therapy...
July 4, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29973652/subependymal-giant-cell-astrocytoma-like-astrocytoma-a-neoplasm-with-a-distinct-phenotype-and-frequent-neurofibromatosis-type-1-association
#6
Doreen N Palsgrove, Jacqueline A Brosnan-Cashman, Caterina Giannini, Aditya Raghunathan, Mark Jentoft, Chetan Bettegowda, Murat Gokden, Doris Lin, Ming Yuan, Ming-Tseh Lin, Christopher M Heaphy, Fausto J Rodriguez
Neurofibromatosis type-1 is a familial genetic syndrome associated with a predisposition to develop peripheral and central nervous system neoplasms. We have previously reported on a subset of gliomas developing in these patients with morphologic features resembling subependymal giant cell astrocytoma, but the molecular features of these tumors remain undefined. A total of 14 tumors were studied and all available slides were reviewed. Immunohistochemical stains and telomere-specific FISH were performed on all cases...
July 4, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29968850/correction-tert-promoter-mutation-in-adult-granulosa-cell-tumor-of-the-ovary
#7
Jessica A Pilsworth, Dawn R Cochrane, Zhouchunyang Xia, Geraldine Aubert, Anniina E M Färkkilä, Hugo M Horlings, Satoshi Yanagida, Winnie Yang, Jamie L P Lim, Yi Kan Wang, Ali Bashashati, Jacqueline Keul, Adele Wong, Kevin Norris, Sara Y Brucker, Florin-Andrei Taran, Bernhard Krämer, Annette Staebler, Hannah van Meurs, Esther Oliva, Sohrab P Shah, Stefan Kommoss, Friedrich Kommoss, C Blake Gilks, Duncan M Baird, David G Huntsman
The original version of this Article omitted the author Hannah van Meurs from the Department of Gynecology, Center for Gynecologic Oncology Amsterdam, Academic Medical Center, 1100 DD Amsterdam, The Netherlands. This has been corrected in both the PDF and HTML versions of the article.
July 3, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29967424/discordant-molecular-subtype-classification-in-the-basal-squamous-subtype-of-bladder-tumors-and-matched-lymph-node-metastases
#8
Gottfrid Sjödahl, Pontus Eriksson, Kristina Lövgren, Nour-Al-Dain Marzouka, Carina Bernardo, Iver Nordentoft, Lars Dyrskjøt, Fredrik Liedberg, Mattias Höglund
Molecular subtypes of muscle-invasive bladder tumors have emerged as a promising research tool with potential to stratify patients for neoadjuvant treatment. Prior to radical cystectomy, the utility of molecular classification and biomarkers depend on concordance between tissue from transurethrally resected specimens and disseminated disease. We assess the concordance of molecular subtypes and a large number of potential biomarkers in 67 pairs of muscle-invasive bladder tumors and synchronous lymph-node metastases...
July 2, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29967423/two-stain-immunohistochemical-screening-for-lynch-syndrome-in-colorectal-cancer-may-fail-to-detect-mismatch-repair-deficiency
#9
Rachel Pearlman, Michael Markow, Deborah Knight, Wei Chen, Christina A Arnold, Colin C Pritchard, Heather Hampel, Wendy L Frankel
Universal screening for Lynch syndrome in colorectal cancer is recommended, and immunohistochemistry for the mismatch repair proteins is commonly used. To reduce cost, some screen using only MSH6 and PMS2, with reflex to the partner stain if either are absent (two-stain method). An expression pattern revealing absent MSH2 and intact MSH6 is not expected, but could result in failed Lynch syndrome detection. We analyzed tumors with absent MSH2 but any degree of MSH6 expression to determine if the two-stain method could miss MSH2 mutations...
July 2, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955149/saccharomyces-cerevisiae-like-1-sec14l1-is-a-prognostic-factor-in-breast-cancer-associated-with-lymphovascular-invasion
#10
Sultan N Sonbul, Mohammed A Aleskandarany, Sasagu Kurozumi, Chitra Joseph, Michael S Toss, Maria Diez-Rodriguez, Christopher C Nolan, Abhik Mukherjee, Stewart Martin, Carlos Caldas, Ian O Ellis, Andrew R Green, Emad A Rakha
Lymphovascular invasion is strongly related to breast cancer metastasis. However, the underlying mechanisms of lymphovascular invasion and its driver molecules in breast cancer remain to be defined. In this study, we explore differential expression of genes in large molecularly characterized and clinically annotated datasets of invasive breast cancer patients (n = 8056) coupled with histological review and strict definition for lymphovascular invasion status. The METABRIC series was used to identify genes associated with lymphovascular invasion, as defined using hematoxylin and eosin staining supplemented by immunohistochemistry, at the genomic/transcriptomic levels...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955148/assessing-colorectal-cancer-mismatch-repair-status-in-the-modern-era-a-survey-of-current-practices-and-re-evaluation-of-the-role-of-microsatellite-instability-testing
#11
Erika Hissong, Elizabeth P Crowe, Rhonda K Yantiss, Yao-Tseng Chen
Results of DNA mismatch repair testing are used to detect Lynch syndrome and have prognostic and therapeutic implications among patients with sporadic colorectal carcinomas. Immunohistochemistry for mismatch repair proteins (MLH1, PMS2, MSH2, MSH6) and PCR for microsatellite instability are two established methods for assessing mismatch repair function. Older literature suggested a discordance rate of approximately 5% between these assays, leading some institutions to perform dual testing on all cases. Although universal mismatch repair testing is now recommended by multiple professional organizations, none provide guidelines regarding preferred assays...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955147/alternative-pdgfd-rearrangements-in-dermatofibrosarcomas-protuberans-without-pdgfb-fusions
#12
Bérengère Dadone-Montaudié, Laurent Alberti, Adeline Duc, Lucile Delespaul, Tom Lesluyes, Gaëlle Pérot, Agnès Lançon, Sandrine Paindavoine, Ilaria Di Mauro, Jean-Yves Blay, Arnaud de la Fouchardière, Frédéric Chibon, Marie Karanian, Gaëtan MacGrogan, Valérie Kubiniek, Frédérique Keslair, Nathalie Cardot-Leccia, Audrey Michot, Virginie Perrin, Yanis Zekri, Jean-Michel Coindre, Franck Tirode, Florence Pedeutour, Dominique Ranchère-Vince, François Le Loarer, Daniel Pissaloux
Dermatofibrosarcoma protuberans is underlined by recurrent collagen type I alpha 1 chain-platelet-derived growth factor B chain (COL1A1-PDGFB) fusions but ~ 4% of typical dermatofibrosarcoma protuberans remain negative for this translocation in routine molecular screening. We investigated a series of 21 cases not associated with the pathognomonic COL1A1-PDGFB fusion on routine fluorescence in situ hybridization (FISH) testing. All cases displayed morphological and clinical features consistent with the diagnosis of dermatofibrosarcoma protuberans...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955146/clinicopathologic-and-molecular-features-in-hairy-cell-leukemia-variant-single-institutional-experience
#13
Evgeniya A Angelova, L Jeffrey Medeiros, Wei Wang, Tariq Muzzafar, Xinyan Lu, Joseph D Khoury, Farhad Ravandi, Keyur P Patel, Zhihong Hu, Rashmi Kanagal-Shamanna
Hairy cell leukemia-variant is rare. Only a small number of cases have been reported in the literature with little cytogenetic or molecular data available. In this study, we describe the clinicopathologic and genetic features of 23 patients with hairy cell leukemia-variant (16 men and 7 women) with a median age of 70 years. Most patients had splenomegaly (90%), leukocytosis (77%), and lymphocytosis (82%); no patients had monocytopenia. Histologically, the bone marrow biopsy specimens showed a mixed pattern of predominantly interstitial and lesser intrasinusoidal infiltration by leukemic cells...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955145/detection-of-a-microrna-molecular-signature-of-ultraviolet-radiation-in-the-superficial-regions-of-melanocytic-nevi-on-sun-exposed-skin
#14
Achim Bell, Diana Bell, Nitin Chakravarti, Junsheng Ma, Nicholas Henton, Victor G Prieto
How melanocytes transform into melanoma cells remains largely unknown. However, prolonged ultraviolet radiation exposure is linked with melanoma, and the DNA of melanomas arising in chronically sun-exposed skin is characterized by an elevated number of pyrimidine transitions, mainly C>T (predominantly caused by ultraviolet B), and transversions of GC>TA or AT>CG (caused by ultraviolet A over indirect mechanisms). Since ultraviolet penetrates mostly only the superficial dermis, we sought to determine the extent to which superficial and deep melanocytes of nevi in sun-exposed skin differ in their miRNA expression and consider the changes as likely secondary to ultraviolet radiation-induced damage...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955144/validation-of-a-targeted-next-generation-sequencing-approach-to-detect-mismatch-repair-deficiency-in-colorectal-adenocarcinoma
#15
David J Papke, Jonathan A Nowak, Matthew B Yurgelun, Alexander Frieden, Amitabh Srivastava, Neal I Lindeman, Lynette M Sholl, Laura E MacConaill, Fei Dong
Mismatch repair protein deficiency is a hallmark of cancers associated with Lynch syndrome and is a biomarker for response to immunotherapy. With the increasing adoption of cancer next-generation sequencing, there has been a movement to develop screening approaches that take advantage of the unique mutational signatures of mismatch repair-deficient tumors. Here, we develop a sequencing-based metric that distinguishes mismatch repair-deficient from mismatch repair-proficient colorectal adenocarcinomas with comparison to immunohistochemical staining...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955143/refinement-of-high-risk-endometrial-cancer-classification-using-dna-damage-response-biomarkers-a-transportec-initiative
#16
Aurélie Auguste, Catherine Genestie, Marco De Bruyn, Julien Adam, Audrey Le Formal, Françoise Drusch, Patricia Pautier, Emma J Crosbie, Helen MacKay, Henry C Kitchener, Melanie Powell, Pamela M Pollock, Linda Mileshkin, Richard J Edmondson, Remi Nout, Hans W Nijman, Carien L Creutzberg, Tjalling Bosse, Alexandra Leary
The TransPORTEC consortium previouslclassified high-risk endometrial cancer including poor-risk histologies such as clear cells, into four molecular subtypes "POLE mutated," "microsatellite unstable," "TP53 mutated," and "no specific molecular profile." We evaluated whether DNA damage response biomarkers could further refine this high-risk tumors classification, in particular the heterogeneous "no specific molecular profile" and "TP53 mutated" subsets recently qualified as poor prognosis in high-risk endometrial cancer...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955142/thioredoxin-interacting-protein-is-an-independent-risk-stratifier-for-breast-ductal-carcinoma-in-situ
#17
Islam M Miligy, Kylie L Gorringe, Michael S Toss, Abdulbaqi A Al-Kawaz, Peter Simpson, Maria Diez-Rodriguez, Christopher C Nolan, Ian O Ellis, Andrew R Green, Emad A Rakha
Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behavior, but they are insufficient to define high-risk patients for disease progression precisely. Thioredoxin-interacting protein (TXNIP) is a key player of oxidative stress. This study aims to evaluate the role of TXNIP as a predictor of ductal carcinoma in situ progression. Tissue microarrays from 776 pure ductal carcinoma in situ and 239 mixed ductal carcinoma in situ and invasive tumors were constructed. All patients were treated at a single institution with a long-term follow-up and TXNIP expression was assessed using immunohistochemistry...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29955141/comparison-of-melanoma-gene-expression-score-with-histopathology-fluorescence-in-situ-hybridization-and-snp-array-for-the-classification-of-melanocytic-neoplasms
#18
Julie D R Reimann, Sadia Salim, Elsa F Velazquez, Lu Wang, Kelly Morrissey Williams, Wendy L Flejter, Linda Brooke, Sujatha Sunder, Klaus J Busam
While most melanomas can be distinguished from nevi by histopathology, the histology is ambiguous for some melanocytic tumors, contributing to diagnostic uncertainty. Therefore molecular assays, including FISH or SNP array, and more recently a gene expression test (myPath, Myriad Genetics) have been proposed to aid in the work-up of ambiguous tumors. Two hundred and sixty-eight prospectively submitted cases were gathered, with the goal of comparing the myPath assay to morphologic diagnosis in (1) morphologically unequivocal cases (198), and to morphologic diagnosis and FISH in (2) morphologically ambiguous cases (70)...
June 28, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29946185/optimization-and-validation-of-pd-l1-immunohistochemistry-staining-protocols-using-the-antibody-clone-28-8-on-different-staining-platforms
#19
Christina Koppel, Helena Schwellenbach, Dirk Zielinski, Sina Eckstein, Mercedes Martin-Ortega, Corrado D'Arrigo, Hans-Ulrich Schildhaus, Josef Rüschoff, Bharat Jasani
Several immunohistochemistry (IHC) assays have been developed to assess tumor programmed death-ligand 1 (PD-L1) expression levels in patients who are candidates for programmed death-1 (PD-1)/PD-L1 inhibitor therapy. The PD-L1 IHC 28-8 pharmDx kit is FDA-approved as a complementary diagnostic and CE-marked as an in vitro diagnostic device for nivolumab therapy in melanoma and specific lung cancer subtypes (and for squamous cell carcinoma of the head and neck/urothelial carcinoma in Europe only). Kit availability is limited outside the United States, and its use requires the Dako Autostainer Link 48 platform, which is unavailable in many laboratories...
June 26, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29946184/inferior-survival-for-patients-with-malignant-peripheral-nerve-sheath-tumors-defined-by-aberrant-tp53
#20
Maren Høland, Matthias Kolberg, Stine Aske Danielsen, Bodil Bjerkehagen, Ina A Eilertsen, Merete Hektoen, Nils Mandahl, Eva van den Berg, Sigbjørn Smeland, Fredrik Mertens, Kirsten Sundby Hall, Piero Picci, Anita Sveen, Ragnhild A Lothe
Malignant peripheral nerve sheath tumor is a rare and aggressive disease with poor treatment response, mainly affecting adolescents and young adults. Few molecular biomarkers are used in the management of this cancer type, and although TP53 is one of few recurrently mutated genes in malignant peripheral nerve sheath tumor, the mutation prevalence and the corresponding clinical value of the TP53 network remains unsettled. We present a multi-level molecular study focused on aberrations in the TP53 network in relation to patient outcome in a series of malignant peripheral nerve sheath tumors from 100 patients and 38 neurofibromas, including TP53 sequencing, high-resolution copy number analyses of TP53 and MDM2, and gene expression profiling...
June 26, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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