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https://www.readbyqxmd.com/read/28644513/benign-vascular-lesions-of-the-breast-diagnosed-by-core-needle-biopsy-do-not-require-excision
#1
Christopher Sebastiano, Lucas Gennaro, Edi Brogi, Elizabeth Morris, Zenica L Bowser, Cristina R Antonescu, Fresia Pareja, Sandra Brennan, Melissa P Murray
AIMS: Surgical excision of all benign vascular lesions of the breast identified by core needle biopsy has been recommended in the past to rule out a more serious lesion. In this study we investigated the clinical, radiologic, and pathologic findings in patients diagnosed with a benign vascular lesion at our institution to assess whether excision may be spared for lesions without atypia. METHODS AND RESULTS: We searched the electronic medical record for patients with a vascular lesion of the breast diagnosed between 2000 and 2015...
June 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28621321/bcor-is-a-robust-diagnostic-immunohistochemical-marker-of-genetically-diverse-high-grade-endometrial-stromal-sarcoma-including-tumors-exhibiting-variant-morphology
#2
Sarah Chiang, Cheng-Han Lee, Colin J R Stewart, Esther Oliva, Lien N Hoang, Rola H Ali, Martee L Hensley, Javier A Arias-Stella, Denise Frosina, Achim A Jungbluth, Ryma Benayed, Marc Ladanyi, Meera Hameed, Lu Wang, Yu-Chien Kao, Cristina R Antonescu, Robert A Soslow
Recognition of high-grade endometrial stromal sarcoma is important because of its aggressive clinical behavior. Morphologic features of YWHAE-NUTM2 high-grade endometrial stromal sarcoma may overlap with other uterine sarcoma types. BCOR immunoexpression was studied in these tumors and their morphologic mimics to assess its diagnostic utility. BCOR immunohistochemical staining was performed on archival tissue from 28 high-grade endometrial stromal sarcomas with classic morphology (20 YWHAE-NUTM2, 5 ZC3H7B-BCOR, 3 BCOR-ZC3H7B), 3 high-grade endometrial stromal sarcomas with unusual morphology and unknown gene rearrangement status, 66 low-grade endometrial stromal sarcomas, 21 endometrial stromal nodules, 38 uterine leiomyosarcomas, and 19 uterine leiomyomas...
June 16, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28611108/wnt-%C3%AE-catenin-signaling-contributes-to-tumor-malignancy-and-is-targetable-in-gastrointestinal-stromal-tumor
#3
Shan Zeng, Adrian M Seifert, Jennifer Q Zhang, Michael J Cavnar, Teresa S Kim, Vinod P Balachandran, Juan A Santamaria-Barria, Noah A Cohen, Michael J Beckman, Benjamin Medina, Ferdinand Rossi, Megan H Crawley, Jennifer K Loo, Joanna H Maltbaek, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. While the Wnt/b-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed b-catenin and contained active, dephosphorylated nuclear b-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28574194/the-big-and-intricate-dreams-of-little-organselles-embracing-complexity-in-the-study-of-membrane-traffic
#4
REVIEW
Allen P Liu, Roberto J Botelho, Costin N Antonescu
Compartmentalization of eukaryotic cells into dynamic organelles that exchange material through regulated membrane traffic governs virtually every aspect of cellular physiology including signal transduction, metabolism and transcription. Much has been revealed about the molecular mechanisms that control organelle dynamics and membrane traffic and how these processes are regulated by metabolic, physical, and chemical cues. From this emerges the understanding of the integration of specific organellar phenomena within complex, multiscale, and non-linear regulatory networks...
June 2, 2017: Traffic
https://www.readbyqxmd.com/read/28551330/histopathologic-evaluation-of-atypical-neurofibromatous-tumors-and-their-transformation-into-malignant-peripheral-nerve-sheath-tumor-in-neurofibromatosis-1-patients-a-consensus-overview
#5
Markku M Miettinen, Cristina R Antonescu, Christopher D M Fletcher, Aerang Kim, Alexander J Lazar, Martha M Quezado, Karlyne M Reilly, Anat Stemmer-Rachamimov, Douglas R Stewart, David Viskochil, Brigitte Widemann, Arie Perry
Neurofibromatosis 1 (NF1) patients develop multiple neurofibromas, with 8-15% of patients experiencing malignant peripheral nerve sheath tumor (MPNST) during their lifetime. Prediction of transformation, typically from plexiform neurofibroma, is clinically and histologically challenging. In this overview, following a consensus meeting in October 2016, we outline the histopathologic features and molecular mechanisms involved in the malignant trans-formation of neurofibromas. Nuclear atypia alone is generally insignificant...
May 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28539323/etv1-positive-cells-give-rise-to-brafv600e-mutant-gastrointestinal-stromal-tumors
#6
Leili Ran, Devan Murphy, Jessica Sher, Zhen Cao, Shangqian Wang, Edward Walczak, Youxin Guan, Yuanyuan Xie, Shipra Shukla, Yu Zhan, Cristina R Antonescu, Yu Chen, Ping Chi
Gastrointestinal Stromal Tumor (GIST) is the most common subtype of sarcoma. Despite clinical advances in the treatment of KIT/PDGFRA-mutant GIST, similar progress against KIT/PDGFRA-wild type GIST, including mutant BRAF-driven tumors, have been limited by a lack of model systems. ETV1 is a master regulator in the intestinal cells of Cajal (ICC), thought to be the cells of origin of GIST. Here we present a model in which the ETV1 promoter is used to specifically and inducibly drive Cre recombinase in ICC as a strategy to study GIST pathogenesis...
May 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28521780/ultrasound-and-microbubble-induced-release-from-intracellular-compartments
#7
Farah Hussein, Costin Antonescu, Raffi Karshafian
BACKGROUND: Ultrasound and microbubbles (USMB) have been shown to enhance the intracellular uptake of molecules, generally thought to occur as a result of sonoporation. The underlying mechanism associated with USMB-enhanced intracellular uptake such as membrane disruption and endocytosis may also be associated with USMB-induced release of cellular materials to the extracellular milieu. This study investigates USMB effects on the molecular release from cells through membrane-disruption and exocytosis...
May 18, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28510278/tfg-met-fusion-in-an-infantile-spindle-cell-sarcoma-with-neural-features
#8
Uta Flucke, Max M van Noesel, Marc Wijnen, Lei Zhang, Chun-Liang Chen, Yun-Shao Sung, Cristina R Antonescu
An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression...
May 16, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28505004/a-subset-of-malignant-mesotheliomas-in-young-adults-are-associated-with-recurrent-ewsr1-fus-atf1-fusions
#9
Patrice Desmeules, Philippe Joubert, Lei Zhang, Hikmat A Al-Ahmadie, Christopher D Fletcher, Efsevia Vakiani, Deborah F Delair, Natasha Rekhtman, Marc Ladanyi, William D Travis, Cristina R Antonescu
Malignant mesothelioma (MM) is a rare, aggressive tumor often associated with asbestos exposure and characterized by complex genetic abnormalities, including deletions of chromosome 22. A gene fusion involving EWSR1 and YY1 gene on 14q32 has been reported in 2 patients over the age of 60 with peritoneal MM. However, the incidence of EWSR1 rearrangements in MM and the spectrum of its fusion partners remain unknown. We recently encountered 2 MM cases with EWSR1-ATF1 fusions and sought to investigate the prevalence and clinicopathologic features associated with this abnormality...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28504702/pgbd5-promotes-site-specific-oncogenic-mutations-in-human-tumors
#10
Anton G Henssen, Richard Koche, Jiali Zhuang, Eileen Jiang, Casie Reed, Amy Eisenberg, Eric Still, Ian C MacArthur, Elias Rodríguez-Fos, Santiago Gonzalez, Montserrat Puiggròs, Andrew N Blackford, Christopher E Mason, Elisa de Stanchina, Mithat Gönen, Anne-Katrin Emde, Minita Shah, Kanika Arora, Catherine Reeves, Nicholas D Socci, Elizabeth Perlman, Cristina R Antonescu, Charles W M Roberts, Hanno Steen, Elizabeth Mullen, Stephen P Jackson, David Torrents, Zhiping Weng, Scott A Armstrong, Alex Kentsis
Genomic rearrangements are a hallmark of human cancers. Here, we identify the piggyBac transposable element derived 5 (PGBD5) gene as encoding an active DNA transposase expressed in the majority of childhood solid tumors, including lethal rhabdoid tumors. Using assembly-based whole-genome DNA sequencing, we found previously undefined genomic rearrangements in human rhabdoid tumors. These rearrangements involved PGBD5-specific signal (PSS) sequences at their breakpoints and recurrently inactivated tumor-suppressor genes...
May 15, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28449608/primary-pulmonary-myxoid-sarcoma-a-newly-described-entity-report-of-a-case-and-review-of-the-literature
#11
Carlos N Prieto-Granada, Rose B Ganim, Lei Zhang, Cristina Antonescu, James Mueller
Primary pulmonary myxoid sarcoma (PPMS) is a recently described, exceedingly rare low-grade lung sarcoma that tends to present in young females as an endobronchial mass and shows evidence of an EWSR1- CREB1 fusion. Herein, we present a case of PPMS with fluorescence in situ hybridization (FISH) analysis for EWSR1 and CREB1 rearrangements. An 80-year-old woman presented with an endobronchial, multinodular tumor exhibiting spindle, ovoid and epithelioid cells arranged in reticular/lattice-like and alveolar-like patterns in a myxoid background...
April 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28448384/cytoreductive-surgery-for-metastatic-gastrointestinal-stromal-tumors-treated-with-tyrosine-kinase-inhibitors-a-2-institutional-analysis
#12
Mark Fairweather, Vinod P Balachandran, George Z Li, Monica M Bertagnolli, Cristina Antonescu, William Tap, Samuel Singer, Ronald P DeMatteo, Chandrajit P Raut
OBJECTIVE: To refine treatment recommendations for patients with metastatic gastrointestinal stromal tumors (GISTs) treated with tyrosine kinase inhibitors (TKIs) and surgery. BACKGROUND: Early reports suggested that patients with metastatic GIST responding to TKIs treated with surgery may have favorable outcomes. However, identification of prognostic factors was limited by small cohorts. METHODS: Progression-free survival (PFS) and overall survival (OS) from time of surgery and from start of initial TKI was determined...
April 26, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28404587/cic-dux4-induces-small-round-cell-sarcomas-distinct-from-ewing-sarcoma
#13
Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R Antonescu, Takuro Nakamura
CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). However, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here, we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA...
April 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/28346326/sarcomas-with-cic-rearrangements-are-a-distinct-pathologic-entity-with-aggressive-outcome-a-clinicopathologic-and-molecular-study-of-115-cases
#14
Cristina R Antonescu, Adepitan A Owosho, Lei Zhang, Sonja Chen, Kemal Deniz, Joseph M Huryn, Yu-Chien Kao, Shih-Chiang Huang, Samuel Singer, William Tap, Inga-Marie Schaefer, Christopher D Fletcher
CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors. Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (ie, atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available...
July 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28337592/head-and-neck-round-cell-sarcomas-a-comparative-clinicopathologic-analysis-of-2-molecular-subsets-ewing-and-cic-rearranged-sarcomas
#15
Adepitan A Owosho, Cherry L Estilo, Joseph M Huryn, Lei Zhang, Christopher D M Fletcher, Cristina R Antonescu
CIC-rearranged sarcoma (CRS) is a relatively new entity defined by its pathognomonic genetic signature and undifferentiated round cell phenotype, initially grouped together with the 'Ewing sarcoma-like tumors'. However, increasing data suggest that these tumors should be regarded as a stand-alone pathologic entity. We conducted a clinicopathologic analysis on molecularly conformed Ewing sarcoma (ES) and CRS arising in the head and neck (HN) and compared to a well characterized cohort of ES and CRS from other locations...
March 23, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28296677/rbm10-tfe3-renal-cell-carcinoma-a-potential-diagnostic-pitfall-due-to-cryptic-intrachromosomal-xp11-2-inversion-resulting-in-false-negative-tfe3-fish
#16
MULTICENTER STUDY
Pedram Argani, Lei Zhang, Victor E Reuter, Satish K Tickoo, Cristina R Antonescu
Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in archival material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion...
May 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28291122/smarcb1-ini-1-deficient-sinonasal-carcinoma-a-series-of-39-cases-expanding-the-morphologic-and-clinicopathologic-spectrum-of-a-recently-described-entity
#17
Abbas Agaimy, Arndt Hartmann, Cristina R Antonescu, Simion I Chiosea, Samir K El-Mofty, Helene Geddert, Heinrich Iro, James S Lewis, Bruno Märkl, Stacey E Mills, Marc-Oliver Riener, Thomas Robertson, Ann Sandison, Sabine Semrau, Roderick H W Simpson, Edward Stelow, William H Westra, Justin A Bishop
To more fully characterize the clinical and pathologic spectrum of a recently described tumor entity of the sinonasal tract characterized by loss of nuclear expression of SMARCB1 (INI1), we analyzed 39 SMARCB1-deficient sinonasal carcinomas collected from multiple medical centers. The tumors affected 23 males and 16 females with an age range of 19 to 89 years (median, 52). All patients presented with locally advanced disease (T3, n=5; T4, n=27) involving the sinuses (mainly ethmoid) with variable involvement of the nasal cavity...
April 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28270683/max-inactivation-is-an-early-event-in-gist-development-that-regulates-p16-and-cell-proliferation
#18
Inga-Marie Schaefer, Yuexiang Wang, Cher-Wei Liang, Nacef Bahri, Anna Quattrone, Leona Doyle, Adrian Mariño-Enríquez, Alexandra Lauria, Meijun Zhu, Maria Debiec-Rychter, Susanne Grunewald, Jaclyn F Hechtman, Armelle Dufresne, Cristina R Antonescu, Carol Beadling, Ewa T Sicinska, Matt van de Rijn, George D Demetri, Marc Ladanyi, Christopher L Corless, Michael C Heinrich, Chandrajit P Raut, Sebastian Bauer, Jonathan A Fletcher
KIT, PDGFRA, NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), and additional genetic alterations are required for progression to malignancy. The most frequent secondary alteration, demonstrated in ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating mutations of the chromosome 14q MAX gene in 16 of 76 GISTs (21%). We find MAX mutations in 17% and 50% of sporadic and NF1-syndromic GISTs, respectively, and we find loss of MAX protein expression in 48% and 90% of sporadic and NF1-syndromic GISTs, respectively, and in three of eight micro-GISTs, which are early GISTs...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28249647/a-clinicopathologic-study-on-ss18-fusion-positive-head-and-neck-synovial-sarcomas
#19
Adepitan A Owosho, Cherry L Estilo, Evan B Rosen, SaeHee K Yom, Joseph M Huryn, Cristina R Antonescu
OBJECTIVE: To determine clinicopathologic factors on survival in patients with head and neck synovial sarcoma. PATIENTS AND METHODS: We retrospectively identified patients with molecularly confirmed synovial sarcomas of the head and neck (SS-HN), either by the presence of SS18-SSX fusion transcript by RT-PCR or SS18 gene rearrangement by FISH, who were managed at our institution over a 20-year period (1996-2015). Kaplan-Meier survival analysis and log-rank test were performed to evaluate variables related to disease specific survival (DSS)...
March 2017: Oral Oncology
https://www.readbyqxmd.com/read/28248815/recurrent-srf-rela-fusions-define-a-novel-subset-of-cellular-myofibroma-myopericytoma-a-potential-diagnostic-pitfall-with-sarcomas-with-myogenic-differentiation
#20
Cristina R Antonescu, Yun-Shao Sung, Lei Zhang, Narasimhan P Agaram, Christopher D Fletcher
Cellular myofibroblastic tumors other than desmoid-type fibromatosis are often diagnostically challenging due to their relative rarity, lack of known genetic abnormalities, and expression of muscle markers which may be confused with sarcomas with myogenic differentiation. In this study we investigate the molecular alterations of a group of cellular myofibroblastic lesions with in the myofibroma and myopericytoma spectrum for better subclassification. Two index cases were studied by paired-end RNA sequencing for potential fusion gene discovery...
May 2017: American Journal of Surgical Pathology
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