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https://www.readbyqxmd.com/read/29760048/tipifarnib-inhibits-hras-driven-dedifferentiated-thyroid-cancers
#1
Brian R Untch, Vanessa Dos Anjos, Maria E R Garcia-Rendueles, Jeffrey A Knauf, Gnana P Krishnamoorthy, Mahesh Saqcena, Umeshkumar K Bhanot, Nicholas D Socci, Alan L Ho, Ronald Ghossein, James A Fagin
Of the three RAS oncoproteins, only HRAS is delocalized and inactivated by farnesyltransferase inhibitors (FTI), an approach yet to be exploited clinically. In this study, we treat mice bearing Hras-driven poorly differentiated and anaplastic thyroid cancers (Tpo-Cre/HrasG12V/p53flox/flox) with the FTI tipifarnib. Treatment caused sustained tumor regression and increased survival; however, early and late resistance was observed. Adaptive reactivation of RAS-MAPK signaling was abrogated in vitro by selective RTK (i...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29522275/patterns-of-recurrence-in-oral-tongue-cancer-with-perineural-invasion
#2
Jennifer R Cracchiolo, Bin Xu, Jocelyn C Migliacci, Nora Katabi, David G Pfister, Nancy Y Lee, Snehal G Patel, Ronald A Ghossein, Richard J Wong
BACKGROUND: Although perineural invasion (PNI) is recognized as an adverse prognostic factor in oral tongue squamous cell carcinoma (SCC), the patterns of failure are poorly defined. METHODS: Patients with oral tongue SCC who received primary surgical treatment were identified. Specimens were reviewed by head and neck pathologists. Disease-specific survival (DSS) and locoregional recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant recurrence-free survival (DRFS) were calculated...
March 9, 2018: Head & Neck
https://www.readbyqxmd.com/read/29339178/the-evolving-diagnosis-of-noninvasive-follicular-thyroid-neoplasm-with-papillary-like-nuclear-features-niftp
#3
EDITORIAL
Ricardo V Lloyd, Sylvia L Asa, Virginia A LiVolsi, Peter M Sadow, Arthur S Tischler, Ronald A Ghossein, R Michael Tuttle, Yuri E Nikiforov
No abstract text is available yet for this article.
April 2018: Human Pathology
https://www.readbyqxmd.com/read/29251736/pge-2-ep-1-receptor-inhibits-vasopressin-dependent-water-reabsorption-and-sodium-transport-in-mouse-collecting-duct
#4
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
March 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29230383/solitary-extramedullary-plasmacytoma-of-the-cricoid-cartilage-case-report
#5
Simone Krebs, Ian Ganly, Ronald Ghossein, Joanna Yang, Joachim Yahalom, Heiko Schöder
Solitary plasmacytoma (SP) is an extremely rare form of hematologic malignancy that can be classified as solitary bone plasmacytoma or solitary extramedullary plasmacytoma. Here, we report a patient who presented with progressive shortness of breath and foreign body sensation in his throat. Fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) demonstrated an abnormal FDG-avid soft tissue mass arising from the larynx involving the cricoid cartilage without additional suspicious lesions...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29204912/should-subcentimeter-non-invasive-encapsulated-follicular-variant-of-papillary-thyroid-carcinoma-be-included-in-the-noninvasive-follicular-thyroid-neoplasm-with-papillary-like-nuclear-features-category
#6
Bin Xu, Nada Farhat, Justine A Barletta, Yin P Hung, Dario de Biase, Gian Piero Casadei, Ayse Mine Onenerk, R Michael Tuttle, Benjamin R Roman, Nora Katabi, Vania Nosé, Peter Sadow, Giovanni Tallini, William C Faquin, Ronald Ghossein
OBJECTIVE: In 2016, non-invasive, well-circumscribed and encapsulated, follicular variant of papillary thyroid carcinoma (NI-EFV PTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in order to reduce overtreatment of this indolent tumor. However, the study cohort did not include subcentimeter tumors, i.e., papillary thyroid microcarcinoma (mPTC) with NI-EFV morphology, and such lesions are still regarded and staged by most pathologists as microcarcinomas...
January 2018: Endocrine
https://www.readbyqxmd.com/read/29182491/improved-lung-function-after-sinus-surgery-in-cystic-fibrosis-patients-with-moderate-obstruction
#7
Sabrina Khalfoun, Dmitry Tumin, Maroun Ghossein, Meredith Lind, Don Hayes, Stephen Kirkby
Objectives Cystic fibrosis (CF) is characterized by infection and inflammation of the sinorespiratory tract. Functional endoscopic sinus surgery (FESS) is an option for patients with severe sinusitis. We sought to evaluate pulmonary function testing after FESS in pediatric and adult patients with CF. Study Design Retrospective chart review using data from all patients with CF who underwent FESS from January 2009 to July 2014. Setting Patients were from a single institution. Subjects and Methods Data were extracted for 181 patients and 320 surgeries...
February 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29020884/pathologic-reporting-of-tall-cell-variant-of-papillary-thyroid-cancer-have-we-reached-a-consensus
#8
Juan C Hernandez-Prera, Rosalie A Machado, Sylvia L Asa, Zubair Baloch, William C Faquin, Ronald Ghossein, Virginia A LiVolsi, Ricardo V Lloyd, Ozgur Mete, Yuri E Nikiforov, Raja R Seethala, Saul Suster, Lester D Thompson, Andrew T Turk, Peter M Sadow, Mark L Urken, Bruce M Wenig
BACKGROUND: Tall-cell variant (TCV) is widely believed to be a more aggressive subtype of papillary thyroid carcinoma (PTC). Despite the significance of TCV with respect to risk stratification and therapeutic decision making, its diagnosis is subject to inter-observer variability. This study aimed to determine the level of agreement among expert pathologists in the identification and reporting of TCV. METHODS: Seventeen surgical resections for thyroid cancer containing the diagnostic term "tall cell" in their pathology reports and 22 cases diagnosed as classical PTC were selected...
December 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28947422/pd-1-expression-in-head-and-neck-squamous-cell-carcinomas-derives-primarily-from-functionally-anergic-cd4-tils-in-the-presence-of-pd-l1-tams
#9
Austin K Mattox, Jina Lee, William H Westra, Robert H Pierce, Ronald Ghossein, William C Faquin, Thomas J Diefenbach, Luc G Morris, Derrick T Lin, Lori J Wirth, Armida Lefranc-Torres, Eiichi Ishida, Patrick D Chakravarty, Lauren Johnson, Yang C Zeng, Huabiao Chen, Mark C Poznansky, Neil M Iyengar, Sara I Pai
Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cavity tumor. In this study, we examined the basis for the activity of programmed cell death protein (PD-1)-based immune checkpoint therapy that is being explored widely in head and neck cancers. Using multispectral imaging, we systematically investigated the OTSCC tumor microenvironment (TME) by evaluating the frequency of PD-1 expression in CD8+ , CD4+ , and FoxP3+ tumor-infiltrating lymphocytes (TIL). We also defined the cellular sources of PD-1 ligand (PD-L1) to evaluate the utility of PD-1:PD-L1 blocking antibody therapy in this patient population...
November 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28859191/natural-history-and-tumor-volume-kinetics-of-papillary-thyroid-cancers-during-active-surveillance
#10
R Michael Tuttle, James A Fagin, Gerald Minkowitz, Richard J Wong, Benjamin Roman, Snehal Patel, Brian Untch, Ian Ganly, Ashok R Shaha, Jatin P Shah, Mark Pace, Duan Li, Ariadne Bach, Oscar Lin, Adrian Whiting, Ronald Ghossein, Inigo Landa, Mona Sabra, Laura Boucai, Stephanie Fish, Luc G T Morris
Importance: Active surveillance of low-risk papillary thyroid cancer (PTC) is now an accepted alternative to immediate surgery, but experience with this approach outside of Japan is limited. The kinetics (probability, rate, and magnitude) of PTC tumor growth under active surveillance have not been well defined. Objective: To describe the kinetics of PTC tumor growth during active surveillance. Design, Setting, and Participants: Cohort study of 291 patients undergoing active surveillance for low-risk PTC (intrathyroidal tumors ≤1...
October 1, 2017: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28796899/plag1-immunohistochemistry-is-a-sensitive-marker-for-pleomorphic-adenoma-a-comparative-study-with-plag1-genetic-abnormalities
#11
Nora Katabi, Bin Xu, Achim A Jungbluth, Lei Zhang, Sung Y Shao, Jason Lane, Ronald Ghossein, Cristina R Antonescu
AIMS: Pleomorphic adenoma gene 1 (PLAG1) gene rearrangement is the most common genetic abnormality in pleomorphic adenoma (PA), resulting in overexpression of PLAG1 protein. PA and carcinoma ex pleomorphic adenoma (CA ex-PA) can mimic various benign and malignant salivary gland tumours. The aims of this study are to evaluate the sensitivity and specificity of PLAG1 immunohistochemistry (IHC) in the differential diagnosis of PA and CA ex-PA and to compare the PLAG1 immunohistochemical results to PLAG1 gene abnormalities as detected by fluorescence in-situ hybridisation (FISH)...
January 2018: Histopathology
https://www.readbyqxmd.com/read/28782127/crucial-parameters-in-thyroid-carcinoma-reporting-challenges-controversies-and-clinical-implications
#12
REVIEW
Bin Xu, Ronald A Ghossein
In the modern era, a pathology report of thyroid carcinoma requires the inclusion of numerous prognostically relevant histopathological features, e.g. the presence and extent of vascular and capsular invasion, extrathyroidal extension, the surgical margin status and the characteristics of nodal metastasis. These pathological features are crucial components of the initial risk stratification to determine the need for completion thyroidectomy and/or postoperative radioactive iodine ablation therapy. The current review aims to summarise the diagnostic criteria, the controversies, the prognostic impacts and the challenges of these pathological characteristics, focusing specifically on the parameters that are incorporated into the American Joint Committee on Cancer (AJCC) staging system, the College of American Pathologists (CAP) reporting template, the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) guidelines...
January 2018: Histopathology
https://www.readbyqxmd.com/read/28739497/salivary-gland-epithelial-neoplasms-in-pediatric-population-a-single-institute-experience-with-a-focus-on-the-histologic-spectrum-and-clinical-outcome
#13
Bin Xu, Amandeep Aneja, Ronald Ghossein, Nora Katabi
Salivary gland epithelial neoplasms are rare in children and adolescents, with only a handful of large series having been published. A retrospective study was conducted for 57 cases in patients 20 years or younger. The tumors were located in the parotid (n=36), submandibular gland (n=7), and minor salivary glands (n=14). Nineteen (33%) tumors were pleomorphic adenoma, whereas the remaining (67%) were malignant. The histologic types of carcinomas were mucoepidermoid carcinoma (MEC, n=19, 33%), acinic cell carcinoma (n=7, 12%), adenoid cystic carcinoma (n=6, 11%), secretory carcinoma (mammary analogue) (SC, n=4, 7%), and myoepithelial carcinoma (n=2, 4%)...
September 2017: Human Pathology
https://www.readbyqxmd.com/read/28719465/predictors-of-outcome-in-adenoid-cystic-carcinoma-of-salivary-glands-a-clinicopathologic-study-with-correlation-between-myb-fusion-and-protein-expression
#14
Bin Xu, Esther Drill, Allen Ho, Alan Ho, Lara Dunn, Carlos Nicolas Prieto-Granada, Timothy Chan, Ian Ganly, Ronald Ghossein, Nora Katabi
Adenoid cystic carcinoma (ACC) is the second most common salivary gland malignancy and it has a high rate of recurrences and a poor long-term prognosis. Our aim was to assess the prognostic factors in ACC and study MYB-NFIB fusion and MYB protein expression in a large retrospective cohort of 135 patients with a median follow-up of 6.3 years. The 5- and 10-year local recurrence-free survival (RFS) rate of 94% and 78%, 5- and 10-year distant metastasis survival rate of 77% and 58%, and 5- and 10-year RFS of 66% and 44%...
October 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28662274/phase-2-study-evaluating-the-combination-of-sorafenib-and-temsirolimus-in-the-treatment-of-radioactive-iodine-refractory-thyroid-cancer
#15
Eric J Sherman, Lara A Dunn, Alan L Ho, Shrujal S Baxi, Ronald A Ghossein, Matthew G Fury, Sofia Haque, Cami S Sima, Grace Cullen, James A Fagin, David G Pfister
BACKGROUND: Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results...
November 1, 2017: Cancer
https://www.readbyqxmd.com/read/28634282/genomic-alterations-in-fatal-forms-of-non-anaplastic-thyroid-cancer-identification-of-med12-and-rbm10-as-novel-thyroid-cancer-genes-associated-with-tumor-virulence
#16
Tihana Ibrahimpasic, Bin Xu, Iñigo Landa, Snjezana Dogan, Sumit Middha, Venkatraman Seshan, Shyam Deraje, Diane L Carlson, Jocelyn Migliacci, Jeffrey A Knauf, Brian Untch, Michael F Berger, Luc Morris, R Michael Tuttle, Timothy Chan, James A Fagin, Ronald Ghossein, Ian Ganly
Purpose: Patients with anaplastic thyroid cancer (ATC) have a very high death rate. In contrast, deaths from non-anaplastic thyroid (NAT) cancer are much less common. The genetic alterations in fatal NAT cancers have not been reported.Experimental Design: We performed next-generation sequencing of 410 cancer genes from 57 fatal NAT primary cancers. Results were compared with The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTCs) and to the genomic changes reported in ATC.Results: There was a very high prevalence of TERT promoter mutations, comparable with that of ATC, and these co-occurred with BRAF and RAS mutations...
October 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28611946/patients-with-multifocal-macroscopic-papillary-thyroid-carcinoma-have-a-low-risk-of-recurrence-at-early-follow-up-after-total-thyroidectomy-and-radioactive-iodine-treatment
#17
Amanda La Greca, Bin Xu, Ronald Ghossein, R Michael Tuttle, Mona M Sabra
BACKGROUND: Multifocal thyroid cancer involvement is a common presentation in papillary thyroid cancer. The risk of recurrence of intrathyroidal multifocal papillary microcarcinoma (<1 cm) is documented to be low. However, the risk of recurrence of multifocal macroscopic thyroid cancer is not known. Prior studies have suggested that both the number of foci and the presence of nodal involvement at diagnosis are important predictors of recurrence in multifocal papillary thyroid carcinoma (PTC)...
February 2017: European Thyroid Journal
https://www.readbyqxmd.com/read/28584132/transposon-mutagenesis-identifies-chromatin-modifiers-cooperating-with-ras-in-thyroid-tumorigenesis-and-detects-atxn7-as-a-cancer-gene
#18
Cristina Montero-Conde, Luis J Leandro-Garcia, Xu Chen, Gisele Oler, Sergio Ruiz-Llorente, Mabel Ryder, Iñigo Landa, Francisco Sanchez-Vega, Konnor La, Ronald A Ghossein, Dean F Bajorin, Jeffrey A Knauf, Jesse D Riordan, Adam J Dupuy, James A Fagin
Oncogenic RAS mutations are present in 15-30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with HrasG12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-Hras G12V mice...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28557250/decreased-endothelial-function-and-increased-subclinical-heart-failure-in-women-many-years-after-pre-eclampsia
#19
N M Breetveld, C Ghossein-Doha, J van Neer, M J J M Sengers, L Geerts, S M J van Kuijk, A P van Dijk, M J van der Vlugt, W M Heidema, H P Brunner-La Rocca, R R Scholten, M E A Spaanderman
OBJECTIVES: Pre-eclampsia (PE) is associated with both postpartum endothelial dysfunction and asymptomatic structural heart alterations consistent with heart failure stage B (HF-B). In this study we assessed the relation between endothelial function, by means of flow-mediated dilation (FMD), and HF-B at 4 years postpartum. METHODS: In 67 formerly PE women and 37 healthy parous controls, we ultrasonographically assessed cardiac function, geometry and FMD. HF-B was diagnosed as left ventricular hypertrophy (left ventricular mass index (LVMi) >95 g/m(2) ), concentric remodelling (relative wall thickness (RWT) >0...
May 27, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28554832/evolution-of-the-histologic-classification-of-thyroid-neoplasms-and-its-impact-on-clinical-management
#20
REVIEW
B Xu, R Ghossein
The vast majority of low grade follicular cell derived thyroid carcinomas follows an indolent clinical course and is associated with very low mortality. Risk stratification using multiple clinical and pathologic characteristics has become the standard of care to guide appropriate management and avoid overtreatment. Over the past few decades, the field of thyroid pathology has witnessed several major changes that significantly impacted upon patients' care. These are: 1) The reclassification of non-invasive encapsulated follicular variant of papillary thyroid carcinoma as noninvasive follicular thyroid neoplasm with papillary-like nuclear features; 2) the diagnosis of Hurthle cell carcinoma based on the presence of capsular and vascular invasion; 3) a detailed definition of poorly differentiated thyroid carcinoma, taking into consideration mitosis and necrosis; and 4) the emphasis on a detailed pathologic analysis such as the extent of vascular invasion and extrathyroidal extension...
March 2018: European Journal of Surgical Oncology
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