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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/29192652/zc3h7b-bcor-high-grade-endometrial-stromal-sarcomas-a-report-of-17-cases-of-a-newly-defined-entity
#1
Natasha Lewis, Robert A Soslow, Deborah F Delair, Kay J Park, Rajmohan Murali, Travis J Hollmann, Ben Davidson, Francesca Micci, Ioannis Panagopoulos, Lien N Hoang, Javier A Arias-Stella, Esther Oliva, Robert H Young, Martee L Hensley, Mario M Leitao, Meera Hameed, Ryma Benayed, Marc Ladanyi, Denise Frosina, Achim A Jungbluth, Cristina R Antonescu, Sarah Chiang
High-grade endometrial stromal sarcoma likely encompasses underrecognized tumors harboring genetic abnormalities besides YWHAE-NUTM2 fusion. Triggered by three initial endometrial stromal sarcomas with ZC3H7B-BCOR fusion characterized by high-grade morphology and aggressive clinical behavior, we herein investigate the clinicopathologic features of this genetic subset by expanding the analysis to 17 such tumors. All of them occurred in adult women with a median age of 54 (range, 28-71) years. They were predominantly based in the endomyometrium and demonstrated tongue-like and/or pushing myometrial invasion...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29192651/myeloid-neoplasms-with-features-intermediate-between-primary-myelofibrosis-and-chronic-myelomonocytic-leukemia
#2
Jennifer Chapman, Julia T Geyer, Mahsa Khanlari, Adrienne Moul, Carmen Casas, Scot T Connor, Yao-Shan Fan, Justin M Watts, Ronan T Swords, Francisco Vega, Attilio Orazi
Monocytosis can develop during disease course in primary myelofibrosis simulating that seen in chronic myelomonocytic leukemia, and should not lead to disease reclassification. In contrast, at presentation, rare cases have clinical, morphologic, and molecular genetic features truly intermediate between primary myelofibrosis and chronic myelomonocytic leukemia. The taxonomy and natural history of these diseases are unclear. We identified cases which either: (1) fulfilled the 2008 World Health Organization criteria for primary myelofibrosis but had absolute monocytosis and, when available, chronic myelomonocytic leukemia-related mutations (ASXL1, SRSF2, TET2) or (2) fulfilled criteria of chronic myelomonocytic leukemia but had megakaryocytic proliferation and atypia, marrow fibrosis, and myeloproliferative-type driver mutations (JAK2, MPL, CALR)...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29192650/intramucosal-lipomas-of-the-colon-implicate-cowden-syndrome
#3
Aybuke Caliskan, Wendy K Kohlmann, Kajsa E Affolter, Erinn Downs-Kelly, Priyanka Kanth, Mary P Bronner
Intramucosal lipomas are rare and easily overlooked by pathologists, despite their diagnostic significance for Cowden syndrome (PTEN hamartoma tumor syndrome), an inherited multiorgan cancer syndrome. Only 25-35% of patients harbor identifiable PTEN mutations, thus clinical features, like intramucosal lipomas, remain the mainstay of diagnosis. The significance and diagnostic approach to intramucosal lipomas have not been thoroughly addressed in the literature. Intramucosal lipomas are mimicked by pseudolipomatosis coli, an artifactual mucosal gas infiltration from endoscopic insufflation...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29192649/the-histopathology-of-erdheim-chester-disease-a-comprehensive-review-of-a-molecularly-characterized-cohort
#4
Neval Ozkaya, Marc K Rosenblum, Benjamin H Durham, Janine D Pichardo, Omar Abdel-Wahab, Meera R Hameed, Klaus J Busam, William D Travis, Eli L Diamond, Ahmet Dogan
Erdheim-Chester disease is a rare, non-Langerhans cell histiocytosis histologically characterized by multi-systemic proliferation of mature histiocytes in a background of inflammatory stroma. The disease can involve virtually any organ system; most commonly the bones, skin, retroperitoneum, heart, orbit, lung, and brain are affected. Although a histiocytic proliferation is the histological hallmark of the disease, a wide range of morphological appearances have been described as part of case studies or small series...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29192648/identification-of-clinically-relevant-cytomegalovirus-infections-in-patients-with-inflammatory-bowel-disease
#5
Nils Wethkamp, Eva-Maria Nordlohne, Volker Meister, Ulf Helwig, Michael Respondek
Several lines of evidence indicate that cytomegalovirus infection can be substantially associated with onset of inflammatory bowel disease, especially in patients refractory to immunosuppressive treatment. As cytomegalovirus is widely spread in the population, here we present a quantitative detection system suitable to differentiate clinically relevant cytomegalovirus infection from common latent cytomegalovirus. Using a quantitative real-time PCR approach, cytomegalovirus viral load was evaluated in 917 formalin-fixed and paraffin-embedded colon biopsy samples of 136 patients diagnosed with inflammatory bowel disease...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29192647/implications-of-the-tumor-immune-microenvironment-for-staging-and-therapeutics
#6
REVIEW
Janis M Taube, Jérôme Galon, Lynette M Sholl, Scott J Rodig, Tricia R Cottrell, Nicolas A Giraldo, Alexander S Baras, Sanjay S Patel, Robert A Anders, David L Rimm, Ashley Cimino-Mathews
Characterizing the tumor immune microenvironment enables the identification of new prognostic and predictive biomarkers, the development of novel therapeutic targets and strategies, and the possibility to guide first-line treatment algorithms. Although the driving elements within the tumor microenvironment of individual primary organ sites differ, many of the salient features remain the same. The presence of a robust antitumor milieu characterized by an abundance of CD8+ cytotoxic T-cells, Th1 helper cells, and associated cytokines often indicates a degree of tumor containment by the immune system and can even lead to tumor elimination...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29192646/development-of-a-novel-histologic-diagnostic-algorithm-for-hepatic-graft-versus-host-disease
#7
Ashley E Stueck, Thomas D Schiano, M Isabel Fiel
The histopathologic diagnosis of hepatic graft-versus-host disease post bone marrow and stem cell transplantation can be challenging, but timely and unambiguous diagnosis is essential for appropriate patient management. To address this diagnostic dilemma, we identified histologic features specific for hepatic graft-versus-host disease and developed a diagnostic algorithm. Two hepatopathologists blindly evaluated 40 liver biopsies from patients with clinically and biologically confirmed graft-versus-host disease, as well as 44 controls, for percent bile duct loss, bile duct damage, intraepithelial lymphocytes, ductular reaction, acidophilic bodies/10 high power fields (HPF), cholestasis, portal and lobular inflammation, and endotheliitis...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148540/single-cell-heterogeneity-in-ductal-carcinoma-in-situ-of-breast
#8
Michael J Gerdes, Yesim Gökmen-Polar, Yunxia Sui, Alberto Santamaria Pang, Nicole LaPlante, Adrian L Harris, Puay-Hoon Tan, Fiona Ginty, Sunil S Badve
Heterogeneous patterns of mutations and RNA expression have been well documented in invasive cancers. However, technological challenges have limited the ability to study heterogeneity of protein expression. This is particularly true for pre-invasive lesions such as ductal carcinoma in situ of the breast. Cell-level heterogeneity in ductal carcinoma in situ was analyzed in a single 5 μm tissue section using a multiplexed immunofluorescence analysis of 11 disease-related markers (EGFR, HER2, HER4, S6, pmTOR, CD44v6, SLC7A5 and CD10, CD4, CD8 and CD20, plus pan-cytokeratin, pan-cadherin, DAPI, and Na+K+ATPase for cell segmentation)...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148539/extrauterine-high-grade-serous-carcinomas-with-bilateral-adnexal-involvement-as-the-only-two-disease-sites-are-clonal-based-on-tp53-sequencing-results-implications-for-biology-classification-and-staging
#9
Naveena Singh, Asma Faruqi, Friedrich Kommoss, W Glenn McCluggage, Giorgia Trevisan, Janine Senz, Amy Lum, C Blake Gilks, Michael Anglesio
A previous multicenter study of 67 cases of Stage I/II tubo-ovarian high-grade serous carcinoma with complete tubal sampling identified 7 cases in which there were only two disease sites, comprising tumor involving opposite adnexa with no extra-adnexal involvement. This study aimed to determine whether such low-stage extrauterine high-grade serous carcinomas with only two sites of involvement, located on opposite adnexa, have identical or different TP53 mutations in order to investigate their clonal relationship...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148538/molecular-testing-for-braf-mutations-to-inform-melanoma-treatment-decisions-a-move-toward-precision-medicine
#10
Liang Cheng, Antonio Lopez-Beltran, Francesco Massari, Gregory T MacLennan, Rodolfo Montironi
Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms 'BRAF,' 'mutation,' and 'cancer/tumor...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148537/adenomatoid-tumors-of-the-male-and-female-genital-tract-are-defined-by-traf7-mutations-that-drive-aberrant-nf-kb-pathway-activation
#11
Benjamin Goode, Nancy M Joseph, Meredith Stevers, Jessica Van Ziffle, Courtney Onodera, Eric Talevich, James P Grenert, Iwei Yeh, Boris C Bastian, Joanna J Phillips, Karuna Garg, Joseph T Rabban, Charles Zaloudek, David A Solomon
Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs)...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148536/characterization-of-foreign-materials-in-paraffin-embedded-pathological-specimens-using-in-situ-multi-elemental-imaging-with-laser-spectroscopy
#12
Benoit Busser, Samuel Moncayo, Florian Trichard, Vincent Bonneterre, Nicole Pinel, Frédéric Pelascini, Philippe Dugourd, Jean-Luc Coll, Michel D'Incan, Julie Charles, Vincent Motto-Ros, Lucie Sancey
Pathologists typically encounter many disparate exogenous materials in clinical specimens during their routine histopathological examinations, especially within the skin, lymph nodes, and lungs. These foreign substances may be free extracellular deposits or induce several clinical abnormalities or histopathological patterns. However, pathologists almost never investigate or report the chemical nature of exogenous metals in clinical specimens due to a lack of convenient and available technologies. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) technology is evaluated for in situ multi-elemental tissue imaging...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148535/the-role-of-apc-in-wnt-pathway-activation-in-serrated-neoplasia
#13
Jennifer Borowsky, Troy Dumenil, Mark Bettington, Sally-Ann Pearson, Catherine Bond, Lochlan Fennell, Cheng Liu, Diane McKeone, Christophe Rosty, Ian Brown, Neal Walker, Barbara Leggett, Vicki Whitehall
Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148534/genetic-testing-of-complement-and-coagulation-pathways-in-patients-with-severe-hypertension-and-renal-microangiopathy
#14
Christopher P Larsen, Jon D Wilson, Alejandro Best-Rocha, Marjorie L Beggs, Randolph A Hennigar
A diagnosis of thrombotic microangiopathy on kidney biopsy in a patient presenting with hypertensive emergency has historically elicited the diagnosis of malignant hypertension-associated thrombotic microangiopathy. Recent studies, however, have raised awareness that a number of these patients may actually represent atypical hemolytic uremic syndrome. To further investigate this premise, we performed next-generation sequencing to interrogate the coding regions of 29 complement and coagulation cascade genes associated with atypical hemolytic uremic syndrome in 100 non-elderly patients presenting with severe hypertension, renal failure and a kidney biopsy showing microangiopathic changes limited to the classic accelerated hypertension-associated lesion of arterial intimal edema ('mucoid intimal hyperplasia') in isolation and without accompanying glomerular microthrombi...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29099504/atypical-fibroxanthoma-and-pleomorphic-dermal-sarcoma-harbor-frequent-notch1-2-and-fat1-mutations-and-similar-dna-copy-number-alteration-profiles
#15
Klaus G Griewank, Thomas Wiesner, Rajmohan Murali, Carina Pischler, Hansgeorg Müller, Christian Koelsche, Inga Möller, Cindy Franklin, Ioana Cosgarea, Antje Sucker, Dirk Schadendorf, Jörg Schaller, Susanne Horn, Thomas Brenn, Thomas Mentzel
Atypical fibroxanthomas and pleomorphic dermal sarcomas are tumors arising in sun-damaged skin of elderly patients. They have differing prognoses and are currently distinguished using histological criteria, such as invasion of deeper tissue structures, necrosis and lymphovascular or perineural invasion. To investigate the as-yet poorly understood genetics of these tumors, 41 atypical fibroxanthomas and 40 pleomorphic dermal sarcomas were subjected to targeted next-generation sequencing approaches as well as DNA copy number analysis by comparative genomic hybridization...
November 3, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29099503/recurrent-eml4-ntrk3-fusions-in-infantile-fibrosarcoma-and-congenital-mesoblastic-nephroma-suggest-a-revised-testing-strategy
#16
Alanna J Church, Monica L Calicchio, Valentina Nardi, Alena Skalova, Andre Pinto, Deborah A Dillon, Carmen R Gomez-Fernandez, Namitha Manoj, Josh D Haimes, Joshua A Stahl, Filemon S Dela Cruz, Sarah Tannenbaum-Dvir, Julia L Glade-Bender, Andrew L Kung, Steven G DuBois, Harry P Kozakewich, Katherine A Janeway, Antonio R Perez-Atayde, Marian H Harris
Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing...
November 3, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29099502/active-surveillance-of-women-diagnosed-with-atypical-ductal-hyperplasia-on-core-needle-biopsy-may-spare-many-women-potentially-unnecessary-surgery-but-at-the-risk-of-undertreatment-for-a-minority-10-year-surgical-outcomes-of-114-consecutive-cases-from-a-single
#17
Gelareh Farshid, Suzanne Edwards, James Kollias, Peter Grantley Gill
A needle core biopsy diagnosis of atypical ductal hyperplasia is an indication for open biopsy. The launch of randomized clinical trials of active surveillance for low-risk ductal carcinoma in situ leads to the paradoxical situation of women with low-grade ductal carcinoma in situ being observed, whereas those with atypical ductal hyperplasia have surgery. If the malignancies diagnosed after surgery for atypical ductal hyperplasia are dominated by low-risk ductal carcinoma in situ, women with atypical ductal hyperplasia may also be considered for surveillance...
November 3, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29076496/androgen-receptor-splice-variant-7-positive-prostate-cancer-a-novel-molecular-subtype-with-markedly-worse-androgen-deprivation-therapy-outcomes-in-newly-diagnosed-patients
#18
Heng Li, Zhize Wang, Wei Xiao, Libin Yan, Wei Guan, Zhiquan Hu, Lily Wu, Qihong Huang, Ji Wang, Hua Xu, Xu Zhang, Zhangqun Ye
Androgen-deprivation therapy has been the standard treatment for metastatic and locally advanced prostate cancer, but the majority of patients will progress to castration-resistant prostate cancer within 2-3 years. Unlike the case in breast cancer, no clinically validated biomarker has been used to predict the outcomes of androgen-deprivation therapy. To evaluate androgen-receptor splice variant-7 (AR-V7) detection in newly diagnosed advanced prostate cancer and describe the distinctive prognosis of this novel molecular subtype, this study retrospectively enrolled 168 newly diagnosed prostate cancer patients from 2003 to 2015 who received androgen-deprivation therapy...
October 27, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29052601/intratubular-amyloid-in-light-chain-cast-nephropathy-is-a-risk-factor-for-systemic-light-chain-amyloidosis
#19
Jean-Baptiste Gibier, Viviane Gnemmi, François Glowacki, Eileen M Boyle, Benjamin Lopez, Evelyne MacNamara, Maxime Hoffmann, Raymond Azar, Thomas Guincestre, Franck Bourdon, Marie-Christine Copin, David Buob
Light chain cast nephropathy is the most common form of kidney disease in patients with multiple myeloma. Light chain casts may occasionally show amyloid staining properties, that is, green birefringence after Congo red staining. The frequency and clinical significance of this intratubular amyloid are poorly understood. Here, we retrospectively assessed the clinicopathological features of 60 patients with histologically proven light chain cast nephropathy with a specific emphasis on intratubular amyloid, especially, its association with extrarenal systemic light chain amyloidosis...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29052600/ultrasensitive-automated-rna-in-situ-hybridization-for-kappa-and-lambda-light-chain-mrna-detects-b-cell-clonality-in-tissue-biopsies-with-performance-comparable-or-superior-to-flow-cytometry
#20
Ling Guo, Zhen Wang, Courtney M Anderson, Emerald Doolittle, Siobhan Kernag, Claudiu V Cotta, Sarah L Ondrejka, Xiao-Jun Ma, James R Cook
The assessment of B-cell clonality is a critical component of the evaluation of suspected lymphoproliferative disorders, but analysis from formalin-fixed, paraffin-embedded tissues can be challenging if fresh tissue is not available for flow cytometry. Immunohistochemical and conventional bright field in situ hybridization stains for kappa and lambda are effective for evaluation of plasma cells but are often insufficiently sensitive to detect the much lower abundance of light chains present in B-cells. We describe an ultrasensitive RNA in situ hybridization assay that has been adapted for use on an automated immunohistochemistry platform and compare results with flow cytometry in 203 consecutive tissues and 104 consecutive bone marrows...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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