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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/27910947/renal-cell-carcinoma-with-tfe3-translocation-and-succinate-dehydrogenase-b-mutation
#1
Anna Calió, David J Grignon, Bradley A Stohr, Sean R Williamson, John N Eble, Liang Cheng
Translocation renal cell carcinoma and succinate dehydrogenase (SDH)-deficient renal cell carcinoma are now recognized as specific renal tumor types in the World Health Organization (WHO) classification. Both have limited immunohistochemical positivity for epithelial markers, and the spectrum of morphology continues to widen for both of these entities. We identified four renal cell carcinomas with positive TFE3 immunohistochemical staining and negative SDHB staining. The patients (2F, 2M) ranged in age from 19 to 65 years...
December 2, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27910946/ki-67-in-endometrial-cancer-scoring-optimization-and-prognostic-relevance-for-window-studies
#2
Sarah Kitson, Vanitha N Sivalingam, James Bolton, Rhona McVey, Mashid Nickkho-Amiry, Melanie E Powell, Alexandra Leary, Hans W Nijman, Remi A Nout, Tjalling Bosse, Andrew G Renehan, Henry C Kitchener, Richard J Edmondson, Emma J Crosbie
Ki-67, a marker of cellular proliferation, is increasingly being used in pre-surgical window studies in endometrial cancer as a primary outcome measure. Unlike in breast cancer, however, there are no guidelines standardizing its measurement and its clinical relevance as a response biomarker is undetermined. It is, therefore, imperative that Ki-67 scoring protocols are optimized and its association with patient survival rigorously evaluated, in order to be able to clinically interpret the results of these studies...
December 2, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27910945/thyroid-transcription-factor-1-distinguishes-subependymal-giant-cell-astrocytoma-from-its-mimics-and-supports-its-cell-origin-from-the-progenitor-cells-in-the-medial-ganglionic-eminence
#3
Jen-Fan Hang, Chih-Yi Hsu, Shih-Chieh Lin, Chih-Chun Wu, Han-Jui Lee, Donald Ming-Tak Ho
Subependymal giant cell astrocytoma is a benign brain tumor mostly associated with tuberous sclerosis complex. However, it may be misinterpreted as other high-grade brain tumors due to the presence of large tumor cells with conspicuous pleomorphism and occasional atypical features, such as tumor necrosis and endothelial proliferation. In this study, we first investigated thyroid transcription factor-1 (TTF-1) expression in a large series of subependymal giant cell astrocytomas and other histologic and locational mimics to validate the diagnostic utility of this marker...
December 2, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27910944/thyroid-sclerosing-mucoepidermoid-carcinoma-with-eosinophilia-a-clinicopathologic-and-molecular-analysis-of-a-distinct-entity
#4
Akeesha A Shah, Kristin La Fortune, Caitlyn Miller, Stacey E Mills, Zubair Baloch, Virginia LiVolsi, Sanja Dacic, Alyssa L Mahaffey, Marina Nikiforova, Yuri E Nikiforov, Raja R Seethala
Sclerosing mucoepidermoid carcinoma with eosinophilia is a rare thyroid neoplasm of uncertain pathogenesis that resembles salivary gland mucoepidermoid carcinoma. This multi-institutional study characterizes the clinicopathologic and molecular features of this tumor by utilizing next-generation sequencing to assess common mutations and gene fusions involved in thyroid carcinogenesis as well as fluorescence in-situ hybridization for MAML2 translocations typical of salivary gland mucoepidermoid carcinoma. Nine cases (6 females and 3 males, mean age: 59 years, range 30-77 years) were identified...
December 2, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27834350/quantitative-and-pathologist-read-comparison-of-the-heterogeneity-of-programmed-death-ligand-1-pd-l1-expression-in-non-small-cell-lung-cancer
#5
Jamaal A Rehman, Gang Han, Daniel E Carvajal-Hausdorf, Brad E Wasserman, Vasiliki Pelekanou, Nikita L Mani, Joseph McLaughlin, Kurt A Schalper, David L Rimm
PD-L1 is expressed in a percentage of lung cancer patients and those patients show increased likelihood of response to PD-1 axis therapies. However, the methods and assays for the assessment of PD-L1 using immunohistochemistry are variable and PD-L1 expression appears to be highly heterogeneous. Here, we examine assay heterogeneity parameters toward the goal of determining variability of sampling and the variability due to pathologist-based reading of the immunohistochemistry slide. SP142, a rabbit monoclonal antibody, was used to detect PD-L1 by both chromogenic immunohistochemistry and quantitative immunofluorescence using a laboratory-derived test...
November 11, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27834349/differentiated-exophytic-vulvar-intraepithelial-lesions-are-genetically-distinct-from-keratinizing-squamous-cell-carcinomas-and-contain-mutations-in-pik3ca
#6
Jaclyn C Watkins, Brooke E Howitt, Neil S Horowitz, Lauren L Ritterhouse, Fei Dong, Laura E MacConaill, Elizabeth Garcia, Neal I Lindeman, Larissa J Lee, Ross S Berkowitz, Marisa R Nucci, Christopher P Crum
Human papillomavirus-negative keratinizing vulvar cancers typically harbor TP53 mutations as do their precursors, differentiated vulvar intraepithelial neoplasia. However, atypical verruciform proliferations are also associated with these malignancies and their pathogenesis is poorly understood. This study compared 11 atypical verruciform lesions, including atypical verruciform hyperplasia, vulvar acanthosis with altered differentiation, and verruciform lichen simplex chronicus, with 14 human papillomavirus-negative keratinizing squamous cell carcinomas...
November 11, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27813512/genomic-profiling-of-malignant-peritoneal-mesothelioma-reveals-recurrent-alterations-in-epigenetic-regulatory-genes-bap1-setd2-and-ddx3x
#7
Nancy M Joseph, Yunn-Yi Chen, Anthony Nasr, Iwei Yeh, Eric Talevich, Courtney Onodera, Boris C Bastian, Joseph T Rabban, Karuna Garg, Charles Zaloudek, David A Solomon
Malignant mesothelioma is a rare cancer that arises from the mesothelial cells that line the pleural cavity and less commonly from the peritoneal lining of the abdomen and pelvis. Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear, suggesting that the genetic alterations that drive malignant peritoneal mesothelioma may be unique from those in pleural mesothelioma...
November 4, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27813511/clinicopathologic-profile-immunophenotype-and-genotype-of-cd274-pd-l1-positive-colorectal-carcinomas
#8
Shingo Inaguma, Jerzy Lasota, Zengfeng Wang, Anna Felisiak-Golabek, Hiroshi Ikeda, Markku Miettinen
The CD274 (PD-L1)/PDCD1 (PD-1) pathway is crucial for the modulation of immune responses and self-tolerance. Aberrantly expressed CD274 allows tumor cells to evade host immune system and is considered to be a mechanism of adaptive immune resistance. Inhibition of the CD274/PDCD1 immune checkpoint offers a promising new therapeutic strategy. Although CD274-expressing tumor cells have been identified in different types of tumors including colorectal cancer, clinicopathologic profile of these CD274-positive tumors has not been extensively studied...
November 4, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27767100/ccne1-copy-number-gain-and-overexpression-identify-ovarian-clear-cell-carcinoma-with-a-poor-prognosis
#9
Ayse Ayhan, Elisabetta Kuhn, Ren-Chin Wu, Hiroshi Ogawa, Asli Bahadirli-Talbott, Tsui-Lien Mao, Haruhiko Sugimura, Ie-Ming Shih, Tian-Li Wang
Ovarian clear cell carcinoma is a unique type of ovarian cancer, often derived from endometriosis, and advanced-stage disease has a dismal prognosis primarily due to the resistance to conventional chemotherapy. Previous studies have shown frequent somatic mutations in ARID1A, PIK3CA, hTERT promoter, and amplification of ZNF217; however, the molecular alterations that are associated with its aggressiveness remain largely unknown. This study examined and compared cyclin E1 expression in endometriosis-related ovarian tumors, with the aim of determining the relationship between hTERT mutations and ARID1A expression and evaluating the effects of these molecular alterations on patient survival...
October 21, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27767099/assessing-her2-testing-quality-in-breast-cancer-variables-that-influence-her2-positivity-rate-from-a-large-multicenter-observational-study-in-germany
#10
Josef Rüschoff, Annette Lebeau, Hans Kreipe, Peter Sinn, Claus Dieter Gerharz, Winfried Koch, Stefanie Morris, Johannes Ammann, Michael Untch
Despite >10 years of routine human epidermal growth factor receptor 2 (HER2) testing in breast cancer, testing quality is still an issue. Guidelines recommend assessing HER2 positivity rates as a quality indicator; however, the extent to which patient- or tumor-related factors influence HER2 positivity is still unknown. The present study analyzed these influences to identify pathology centers with HER2 positivity rates unexplained by patient- or tumor-related factors. This observational, prospective study monitored routine HER2 testing at 57 institutes of pathology in Germany (January 2013-August 2014)...
October 21, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27767098/a-novel-quantitative-immunohistochemistry-method-for-precise-protein-measurements-directly-in-formalin-fixed-paraffin-embedded-specimens-analytical-performance-measuring-her2
#11
Kristian Jensen, Rikke Krusenstjerna-Hafstrøm, Jesper Lohse, Kenneth H Petersen, Helene Derand
In clinical routine pathology today, detection of protein in intact formalin-fixed, paraffin-embedded tissue is limited to immunohistochemistry, which is semi-quantitative. This study presents a new and reliable quantitative immunohistochemistry method, qIHC, based on a novel amplification system that enables quantification of protein directly in formalin-fixed, paraffin-embedded tissue by counting of dots. The qIHC technology can be combined with standard immunohistochemistry, and assessed using standard bright-field microscopy or image analysis...
October 21, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27739441/non-ampullary-duodenal-carcinomas-clinicopathologic-analysis-of-47-cases-and-comparison-with-ampullary-and-pancreatic-adenocarcinomas
#12
Yue Xue, Alessandro Vanoli, Serdar Balci, Michelle M Reid, Burcu Saka, Pelin Bagci, Bahar Memis, Hyejeong Choi, Nobuyike Ohike, Takuma Tajiri, Takashi Muraki, Brian Quigley, Bassel F El-Rayes, Walid Shaib, David Kooby, Juan Sarmiento, Shishir K Maithel, Jessica H Knight, Michael Goodman, Alyssa M Krasinskas, Volkan Adsay
Literature on non-ampullary-duodenal carcinomas is limited. We analyzed 47 resected non-ampullary-duodenal carcinomas. Histologically, 78% were tubular-type adenocarcinomas mostly gastro-pancreatobiliary type and only 19% pure intestinal. Immunohistochemistry (n=38) revealed commonness of 'gastro-pancreatobiliary markers' (CK7 55, MUC1 50, MUC5AC 50, and MUC6 34%), whereas 'intestinal markers' were relatively less common (MUC2 36, CK20 42, and CDX2 44%). Squamous and mucinous differentiation were rare (in five each); previously, unrecognized adenocarcinoma patterns were noted (three microcystic/vacuolated, two cribriform, one of comedo-like, oncocytic papillary, and goblet-cell-carcinoid-like)...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27739440/-non-classical-her2-fish-results-in-breast-cancer-a-multi-institutional-study
#13
Morgan Ballard, Florencia Jalikis, Gregor Krings, Rodney A Schmidt, Yunn-Yi Chen, Mara H Rendi, Suzanne M Dintzis, Kristin C Jensen, Robert B West, Richard K Sibley, Megan L Troxell, Kimberly H Allison
The 2013 CAP/ASCO HER2 Testing Guidelines Update modified HER2 FISH categories such that some cases with 'monosomy', 'co-amplification/polysomy', low-level increased HER2 signals or clustered heterogeneity now are considered amplified or equivocal. This study examines the frequency and clinico-pathologic characteristics of breast cancers with equivocal or 'non-classical' HER2 FISH results. Breast cancers (2001-2014) with HER2 FISH results, HER2 immunohistochemistry, ER, grade, and age from three institutions (Stanford, UCSF, UWMC) were collected...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27739439/usefulness-of-p16-ink4a-staining-for-managing-histological-high-grade-squamous-intraepithelial-cervical-lesions
#14
Ester Miralpeix, Jordi Genovés, Josep Maria Solé-Sedeño, Gemma Mancebo, Belen Lloveras, Beatriz Bellosillo, Francesc Alameda, Ramon Carreras
p16(INK4a) (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions. However, there is a paucity of data regarding p16 status as a surrogate marker of HSIL/CIN2 evolution. The aim of this study was to evaluate the outcome of HSIL/CIN2 patients followed up without treatment for 12 months according to p16 immunohistochemical staining...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27739438/microrna-profiling-of-low-grade-glial-and-glioneuronal-tumors-shows-an-independent-role-for-cluster-14q32-31-member-mir-487b
#15
Heather Marion Ames, Ming Yuan, Maria Adelita Vizcaíno, Wayne Yu, Fausto J Rodriguez
Low-grade (WHO I-II) gliomas and glioneuronal tumors represent the most frequent primary tumors of the central nervous system in children. They often have a good prognosis following total resection, however they can create many neurological complications due to mass effect, and may be difficult to resect depending on anatomic location. MicroRNAs have been identified as molecular regulators of protein expression/translation that can repress multiple mRNAs concurrently through base pairing, and have an important role in cancer, including brain tumors...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27739437/the-myeloproliferative-neoplasms-unclassifiable-clinical-and-pathological-considerations
#16
Umberto Gianelli, Daniele Cattaneo, Anna Bossi, Ivan Cortinovis, Leonardo Boiocchi, Yen-Chun Liu, Claudia Augello, Arturo Bonometti, Stefano Fiori, Nicola Orofino, Francesca Guidotti, Attilio Orazi, Alessandra Iurlo
In this study, we investigate in detail the morphological, clinical and molecular features of 71 consecutive patients with a diagnosis of myeloproliferative neoplasms, unclassifiable. We performed a meticulous morphological analysis and found that most of the cases displayed a hypercellular bone marrow (70%) with normal erythropoiesis without left-shifting (59%), increased granulopoiesis with left-shifting (73%) and increased megakaryocytes with loose clustering (96%). Megakaryocytes displayed frequent giant forms with hyperlobulated or bulbous nuclei and/or other maturation defects...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27739436/p53-expression-correlates-with-poorer-survival-and-augments-the-negative-prognostic-effect-of-myc-rearrangement-expression-or-concurrent-myc-bcl2-expression-in-diffuse-large-b-cell-lymphoma
#17
Xuan J Wang, L Jeffrey Medeiros, Carlos E Bueso-Ramos, Guilin Tang, Sa Wang, Yasuhiro Oki, Parth Desai, Joseph D Khoury, Roberto N Miranda, Zhenya Tang, Nishitha Reddy, Shaoying Li
In patients with diffuse large B-cell lymphoma, MYC rearrangement (MYC-R), MYC expression, or concurrent expression of MYC and BCL2 is associated with a poorer prognosis. P53 expression also has been shown to confer inferior survival in diffuse large B-cell lymphoma patients, but less is known about the role of P53 expression in those with MYC-R, MYC expression (MYC+), or MYC&BCL2 co-expression (MYC+/BCL2+). We studied P53 expression in 201 patients with untreated de novo diffuse large B-cell lymphoma. Sixty-seven (33%) cases were P53 positive, 56 (28%) had MYC-R (including 17 MYC/BCL2 double hit lymphoma), 86 (45%) were MYC+/BCL2+, and 47 (24%) were positive for both MYC and P53...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27739435/identification-of-recurrent-mutational-events-in-anorectal-melanoma
#18
Hui Min Yang, Susan J Hsiao, David F Schaeffer, Chi Lai, Helen E Remotti, David Horst, Mahesh M Mansukhani, Basil A Horst
Anorectal melanoma is a rare disease that carries a poor prognosis. To date, limited genetic analyses confirmed KIT mutations as a recurrent genetic event similar to other mucosal melanomas, occurring in up to 30% of anorectal melanomas. Importantly, a subset of tumors harboring activating KIT mutations have been found to respond to c-Kit inhibitor-based therapy, with improved patient survival at advanced tumor stages. We performed comprehensive targeted exon sequencing analysis of 467 cancer-related genes in a larger series of 15 anorectal melanomas, focusing on potentially actionable variants based on gain- and loss-of-function mutations...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27713424/5-hydroxymethylcytosine-is-an-independent-predictor-of-survival-in-malignant-melanoma
#19
Gerald Saldanha, Kushal Joshi, Kathryn Lawes, Mark Bamford, Farhaan Moosa, Kah Wee Teo, J Howard Pringle
Outcomes for melanoma patients vary within cancer stage. Prognostic biomarkers are potential adjuncts to provide more precise prognostic information. Simple, low-cost biomarker assays, such as those based on immunohistochemistry, have strong translational potential. 5-hydroxymethylcytosine (5 hmC) shows prognostic potential in melanoma but prior studies were small. We, therefore, analysed 5 hmC in a retrospective cohort to provide external validation of its prognostic value. Two hundred primary melanomas were evaluated for 5 hmC expression using immunohistochemistry...
October 7, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27713423/downregulation-of-acetyl-coa-synthetase-2-is-a-metabolic-hallmark-of-tumor-progression-and-aggressiveness-in-colorectal-carcinoma
#20
Jeong Mo Bae, Jung Ho Kim, Hyeon Jeong Oh, Hye Eun Park, Tae Hun Lee, Nam-Yun Cho, Gyeong Hoon Kang
Acetyl-CoA synthetase-2 is an emerging key enzyme for cancer metabolism, which supplies acetyl-CoA for tumor cells by capturing acetate as a carbon source under stressed conditions. However, implications of acetyl-CoA synthetase-2 in colorectal carcinoma may differ from other malignancies, because normal colonocytes use short-chain fatty acids as an energy source, which are supplied by fermentation of the intestinal flora. Here we analyzed acetyl-CoA synthetase-2 mRNA expression by reverse-transcription quantitative PCR in paired normal mucosa and tumor tissues of 12 colorectal carcinomas, and subsequently evaluated acetyl-CoA synthetase-2 protein expression by immunohistochemistry in 157 premalignant colorectal lesions, including 60 conventional adenomas and 97 serrated polyps, 1,106 surgically resected primary colorectal carcinomas, and 23 metastatic colorectal carcinomas in the liver...
October 7, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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