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Article: Giant Gastric Folds in Juvenile Polyposis.

Leonard, Nicole B / Bronner, Mary P

2021 Volume 15, Issue 3, Page(s) 985–993

Abstract: To advance the diagnostic accuracy of juvenile polyposis syndrome, an important yet often difficult diagnosis, we describe in detail a new and medically significant presentation. This hereditary and high-risk GI cancer syndrome is often associated with ... ...

Abstract	To advance the diagnostic accuracy of juvenile polyposis syndrome, an important yet often difficult diagnosis, we describe in detail a new and medically significant presentation. This hereditary and high-risk GI cancer syndrome is often associated with hereditary hemorrhagic telangiectasia, as in this 47-year-old female patient with a
Language	English
Publishing date	2021-12-23
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2440540-1
ISSN	1662-0631
ISSN	1662-0631
DOI	10.1159/000521125
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Article ; Online: Utility of frozen section analysis on follicular lesions of the thyroid.

Bronner, Mary P / Hamilton, Ralph / LiVolsi, Virginia A

Endocrine pathology

2020 Volume 5, Issue 3, Page(s) 154–161

Abstract: ... by the pathologists in the study (M.P.B., VAL.) without knowledge of the original diagnoses. Our results indicate: (1 ...

Abstract	The experience of one surgeon (R.H.) with intraoperative frozen sections (FS) performed on thyroid nodules over a 10-year period was studied to assess the utility of FS in follicular thyroid lesions. One hundred and ten patients with dominant or solitary nodules demonstrating a follicular growth pattern were evaluated. The FS slides and subsequently the permanent sections of the nodules were reviewed by the pathologists in the study (M.P.B., VAL.) without knowledge of the original diagnoses. Our results indicate: (1) if the FS was definitively benign (58 patients), the final diagnosis was benign [these lesions consisted of adenomatous nodule, nodular goiter, follicular adenoma, and Hürthle cell adenoma); (2) if an FS diagnosis of malignancy was rendered (4 patients), it was confirmed on permanent sections (follicular variant of papillary carcinoma in all 4); and (3) if the FS diagnosis was deferred (48 patients), the final diagnosis was benign in all but 10 (21 %) (of these 10, 6 had minimally invasive follicular carcinoma [2 of the Hürthle cell type], and 4 had follicular variants of papillary carcinoma). Overall, sensitivity, specificity, and accuracy rates for FS diagnoses were 29, 100, and 91%. Because unilateral lobectomy may be acceptable therapy for well-differentiated thyroid cancers, and because the efficiency of FS evaluation in diagnosing malignancy is low (only 4 malignancies of 110 total patients were diagnosed at FS, or 3.6% overall), we conclude that in this era of cost-containment, FS is not useful in the evaluation of follicular thyroid nodules identified preoperatively as follicular lesions by fine-needle aspiration cytology. Several recommendations concerning the 3 categories of FS diagnosis (i.e., definitively benign, definitively malignant-especially the follicular variant of papillary carcinoma-and deferred) are also put forward.
Language	English
Publishing date	2020-03-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1033267-4
ISSN	1559-0097 ; 1046-3976
ISSN (online)	1559-0097
ISSN	1046-3976
DOI	10.1007/BF02921471
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Article ; Online: Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas.

Underhill, Hunter R / Karsy, Michael / Davidson, Christian J / Hellwig, Sabine / Stevenson, Samuel / Goold, Eric A / Vincenti, Sydney / Sellers, Drew L / Dean, Charlie / Harrison, Brion E / Bronner, Mary P / Colman, Howard / Jensen, Randy L

Cancer research

2024 Volume 84, Issue 7, Page(s) 1149–1164

Abstract: Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, ... ...

Abstract	Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema. Here, we developed and validated True2 sequencing to reduce NGS-associated errors to <1 false positive/100 kb panel positions while detecting 97.6% of somatic mutations with an allele frequency ≥0.1%. True2 was then used to study the tumor and peritumoral edema of 22 adult diffuse gliomas including glioblastoma, astrocytoma, oligodendroglioma, and NF1-related low-grade neuroglioma. The tumor and peritumoral edema displayed a similar mutation burden, indicating that surgery debulks these cancers physically but not molecularly. Moreover, variants in the peritumoral edema included unique cancer driver mutations absent in the bulk tumor. Finally, analysis of multiple samples from each patient revealed multiple subclones with unique mutations in the same gene in 17 of 22 patients, supporting the occurrence of convergent evolution in response to patient-specific selective pressures in the tumor microenvironment that may form the molecular foundation of recurrent disease. Collectively, True2 enables the detection of ultralow frequency mutations during molecular analyses of adult diffuse gliomas, which is necessary to understand cancer evolution, recurrence, and individual response to therapy. Significance: True2 is a next-generation sequencing workflow that facilitates unbiased discovery of somatic mutations across the full range of variant allele frequencies, which could help identify residual disease vulnerabilities for targeted adjuvant therapies.
MeSH term(s)	Adult ; Humans ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Brain Edema/genetics ; Brain Edema/diagnosis ; Brain Edema/pathology ; Glioma/pathology ; Edema ; Mutation ; Tumor Microenvironment
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-23-2557
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Article ; Online: Histologic mimics and diagnostic pitfalls of gastrointestinal endoscopic lifting media, ORISE™ gel and Eleview®.

Dong, Zachary M / Fang, John / Byrne, Kathryn R / Bronner, Mary P / Hale, Gillian L

Human pathology

2021 Volume 119, Page(s) 28–40

Abstract: Synthetic lifting media, ORISE™ gel and Eleview®, are increasingly used in gastrointestinal endoscopy, but neither comparative features nor pitfalls are well-established. Media histopathology, morphologic mimics, and complications are described, along ... ...

Abstract	Synthetic lifting media, ORISE™ gel and Eleview®, are increasingly used in gastrointestinal endoscopy, but neither comparative features nor pitfalls are well-established. Media histopathology, morphologic mimics, and complications are described, along with helpful stains and endoscopist media preference. A 3-year retrospective search was performed. A total of 123 cases (108 endoscopies and 15 subsequent surgeries) were identified. ORISE gel was used in 86 (79.6%), Eleview in 20 (13.9%), and others in 7 (6.5%). ORISE gel was histologically identified in 58.1% (n = 50) of endoscopic specimens and all 15 resections. Eleview media were not detected histologically. ORISE gel mimicked mucin in hematoxylin and eosin-stained biopsies, concerning for adenocarcinoma misdiagnosis and/or upstaging, but did not stain for mucin. Acid-fast bacterial staining highlights ORISE gel for specific and definitive identification. In resections, ORISE evolves into an amorphous eosinophilic material, often with exuberant giant cell reaction and transmural bowel penetration. Polyp formation leads to polypectomy in one patient, and operative lesions concerning for adenocarcinoma resulted in frozen sections in two patients. ORISE gel mimics mucin, malignant masses, amyloid, pulse granulomata, elastofibromas, and infectious granulomata. No significant endoscopist media preference was identified. Recognition of ORISE gel in tissues eliminates multiple pitfalls. Eleview was not detectable, yielded none of the pitfalls seen with ORISE gel, and, on our survey, has equivalent endoscopist acceptance. In this largest published series to date, Eleview is clearly preferable to ORISE gel.
MeSH term(s)	Aged ; Aged, 80 and over ; Artifacts ; Biopsy ; Color ; Diagnostic Errors ; Endoscopy, Gastrointestinal/adverse effects ; Female ; Gastrointestinal Tract/pathology ; Gastrointestinal Tract/surgery ; Gels ; Humans ; Male ; Middle Aged ; Poloxamer/administration & dosage ; Poloxamer/adverse effects ; Predictive Value of Tests ; Retrospective Studies ; Unnecessary Procedures
Chemical Substances	Gels ; SIC-8000 ; Poloxamer (106392-12-5)
Language	English
Publishing date	2021-10-01
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2021.09.008
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Zs.A 722: Show issues

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Article ; Online: Three pathologic criteria for reproducible diagnosis of colonic sessile serrated lesion versus hyperplastic polyp.

Boylan, Katherine E / Kanth, Priyanka / Delker, Don / Hazel, Mark W / Boucher, Kenneth M / Affolter, Kajsa / Clayton, Fred / Evason, Kimberley J / Jedrzkiewicz, Jolanta / Pletneva, Maria / Samowitz, Wade / Swanson, Eric / Bronner, Mary P

Human pathology

2023 Volume 137, Page(s) 25–35

Abstract: ... proved superior to endoscopic size (AUC = 85.9% versus 55.2%, P = .001). Interobserver variability ...

Abstract	Colonic SSLs are thought to predispose to ∼30% of colonic adenocarcinomas. This increased risk, compared to benign HPs, makes their distinction vitally important. However, no gold standard exists to differentiate them, and wide observer variability is reported. To better distinguish these polyps, we investigated 94 serrated polyps (53 SSLs and 41 HPs) using an easy-to-apply pathologic scoring system that combines, for the first time, three established distinguishing features: polyp morphology, location, and size. As an additional novel approach, polyp size was assessed by serrated biopsy number compared to endoscopic size. RNA expression profiling served as an additional biomarker. The considerable morphologic overlap across serrated polyps was quantitated for the first time. Interobserver variability was assessed by 8 expert gastrointestinal pathologists. By ROC analysis, polyp size by biopsy number performed best, followed by polyp location and morphology (areas under the curves [AUCs] = 85.9%, 81.2%, and 65.9%, respectively). Optimal discrimination combined all 3 features (AUC = 92.9%). For polyp size, the biopsy number proved superior to endoscopic size (AUC = 85.9% versus 55.2%, P = .001). Interobserver variability analysis yielded the highest reported Fleiss and Kappa statistics (0.879) and percent agreement (96.8%), showing great promise toward improved diagnosis. The proposed 3-criteria pathologic system, combining size by biopsy number, location, and morphology, yields an improved, easy-to-use, and highly reproducible diagnostic approach for differentiating SSLs and HPs.
MeSH term(s)	Humans ; Colonic Polyps/pathology ; Adenoma/pathology ; Colonic Neoplasms/genetics ; Biopsy ; Colorectal Neoplasms/pathology
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2023.04.002
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Article ; Online: Successful lung cancer EGFR sequencing from DNA extracted from TTF-1 immunohistochemistry slides: a new means to extend insufficient tissue.

Deftereos, Georgios / Sandoval, Amy / Furtado, Larissa V / Bronner, Mary / Matynia, Anna P

Human pathology

2020 Volume 97, Page(s) 52–59

Abstract: Lung cancer biopsy material is limited and is used for morphologic diagnosis and immunohistochemical and molecular testing. This can lead to tissue exhaustion, resulting in repeat biopsies (when clinically possible), delayed testing, and increased risks. ...

Abstract	Lung cancer biopsy material is limited and is used for morphologic diagnosis and immunohistochemical and molecular testing. This can lead to tissue exhaustion, resulting in repeat biopsies (when clinically possible), delayed testing, and increased risks. Consequently, there is a need to optimize preanalytical specimen use for molecular testing. Although hematoxylin/eosin can be used for as a DNA source for molecular testing, little is known regarding the potential use of immunohistochemistry (IHC) slides, as these are subject to harsh conditions that can lead to DNA degradation. Our aim was to evaluate whether DNA extracted from TTF-1 IHC slides, a common stain for lung adenocarcinoma, can be tested for EGFR mutations. Twenty-two lung adenocarcinoma samples (11 EGFR wild type and 11 mutated) were selected. Slides were stained for TTF-1 IHC. Following TTF-1 staining, tissue underwent DNA extraction. Pyrosequencing for mutations in exons 18, 19, 20, and 21 of EGFR was performed, and results were compared to clinical EGFR testing data. All 22 TTF-1 samples produced successful results, and 21 were concordant. Of the 11 originally EGFR-mutated cases, 10 TTF-1 samples showed identical mutations in all exons of interest. One case with an L858R mutation on original testing was negative on sequencing of the TTF-1 sample, possibly due to lower tumor burden on the TTF-1 stained slide. All 11 originally EGFR wild-type cases showed identical results on the TTF-1 samples. TTF-1 IHC slides can be a viable DNA source for molecular testing, especially important in lung biopsies with insufficient material following diagnostic evaluation.
MeSH term(s)	Adenocarcinoma of Lung/chemistry ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/pathology ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Biopsy ; DNA Mutational Analysis ; ErbB Receptors/genetics ; Exons ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemistry ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Mutation ; Predictive Value of Tests ; Proof of Concept Study ; Thyroid Nuclear Factor 1/analysis
Chemical Substances	Biomarkers, Tumor ; NKX2-1 protein, human ; Thyroid Nuclear Factor 1 ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2020-01-22
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2019.12.009
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Article ; Online: Proteome heterogeneity and malignancy detection in pancreatic cyst fluids.

Pan, Sheng / Brand, Randall E / Lai, Lisa A / Dawson, David W / Donahue, Timothy R / Kim, Stephen / Khalaf, Natalia I / Othman, Mohamed O / Fisher, William E / Bronner, Mary P / Simeone, Diane M / Brentnall, Teresa A / Chen, Ru

Clinical and translational medicine

2021 Volume 11, Issue 8, Page(s) e506

MeSH term(s)	Cyst Fluid ; Humans ; Pancreatic Cyst/genetics ; Pancreatic Cyst/pathology ; Proteome/genetics
Chemical Substances	Proteome
Language	English
Publishing date	2021-08-29
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2697013-2
ISSN	2001-1326 ; 2001-1326
ISSN (online)	2001-1326
ISSN	2001-1326
DOI	10.1002/ctm2.506
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Article ; Online: Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer.

Tsai, Hong-Yuan / Bronner, Mary P / March, Jordon K / Valentine, John F / Shroyer, Noah F / Lai, Lisa A / Brentnall, Teresa A / Pan, Sheng / Chen, Ru

Cancer letters

2022 Volume 549, Page(s) 215915

Abstract: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further ... ...

Abstract	Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between the expression of TRAP1 and antioxidant genes in colon tumor tissues using the GSE106582 database. Using a luciferase reporter assay, we detected increased transcriptional activation of antioxidant response elements (AREs) in G-TPP-treated DLD1 and RKO cells but not in SW48 cells. We found that G-TPP induced upregulation of GRP78, CHOP and PARP cleavage in G-TPP-sensitive cells (SW48). In contrast, G-TPP treatment of G-TPP-resistant cells (DLD1 and RKO) resulted in excessive activation of the antioxidant gene NRF2, leading to ROS detoxification and improved cell survival. The NRF2 target genes HO1 and NQO1 were upregulated in G-TPP-treated DLD1 cells, making the cells more resistant to G-TPP treatment. Furthermore, treatment with both a NRF2 inhibitor and a TRAP1 inhibitor led to excessive ROS production and exacerbated G-TPP-induced cell death in G-TPP-resistant cells. Taken together, dual targeting of TRAP1 and NRF2 may potentially overcome colon cancer resistance by raising cellular ROS levels above the cytotoxic threshold.
MeSH term(s)	Antioxidants ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/genetics ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Macrocyclic Compounds ; NF-E2-Related Factor 2/genetics ; Poly(ADP-ribose) Polymerase Inhibitors ; Reactive Oxygen Species ; Receptors, Tumor Necrosis Factor ; Terphenyl Compounds
Chemical Substances	Antioxidants ; HSP90 Heat-Shock Proteins ; Macrocyclic Compounds ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; Poly(ADP-ribose) Polymerase Inhibitors ; Reactive Oxygen Species ; Receptors, Tumor Necrosis Factor ; TRAP1 protein, human ; Terphenyl Compounds ; gamitrinib-triphenylphosphonium
Language	English
Publishing date	2022-09-13
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2022.215915
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Zs.A 1177: Show issues

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Article: The esophageal wall.

Rice, Thomas W / Bronner, Mary P

Thoracic surgery clinics

2011 Volume 21, Issue 2, Page(s) 299–305, x

Abstract: The esophagus spans three body cavities and has no mesentery, continually borrowing or sharing vessels, lymphatics, and nerves with associated organs. However, constant along this path is an intricate mural structure. An understanding of the esophageal ... ...

Abstract	The esophagus spans three body cavities and has no mesentery, continually borrowing or sharing vessels, lymphatics, and nerves with associated organs. However, constant along this path is an intricate mural structure. An understanding of the esophageal wall, its blood supply, lymphatic drainage, and innervation is essential for successful esophageal surgery.
MeSH term(s)	Barrett Esophagus/pathology ; Basement Membrane/anatomy & histology ; Epithelium/anatomy & histology ; Esophagus/anatomy & histology ; Esophagus/blood supply ; Esophagus/pathology ; Goblet Cells/pathology ; Humans ; Hyperplasia ; Mucous Membrane/anatomy & histology
Language	English
Publishing date	2011-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2149218-9
ISSN	1558-5069 ; 1547-4127
ISSN (online)	1558-5069
ISSN	1547-4127
DOI	10.1016/j.thorsurg.2011.01.005
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Article: Granulomatous appendicitis and the appendix in idiopathic inflammatory bowel disease.

Bronner, Mary P

Seminars in diagnostic pathology

2005 Volume 21, Issue 2, Page(s) 98–107

Abstract: Granulomatous appendicitis is a rare condition, accounting for less than 2% of all cases of appendicitis. The initial belief that it represented a manifestation of Crohn's disease is incorrect in the great majority of cases, as only 5-10% of patients ... ...

Abstract	Granulomatous appendicitis is a rare condition, accounting for less than 2% of all cases of appendicitis. The initial belief that it represented a manifestation of Crohn's disease is incorrect in the great majority of cases, as only 5-10% of patients with granulomatous appendicitis develop Crohn's disease elsewhere in their gastrointestinal tract. The remaining etiologies are diverse. Unusual causes include sarcoidosis, foreign body reaction, and infection by mycobacteria, fungi, or parasites. These conditions combined explain less than 10% of cases. More recently, two etiologies have been recognized that potentially account for most of the previous "idiopathic" cases of granulomatous appendicitis. The first is infection by pathogenic Yersinia species, now demonstrated in approximately 25% of cases. The second cause may be the most common of all, namely subacute/recurrent appendicitis with interval appendectomy. This condition likely produces a granulomatous reaction in relation to a protracted secondary inflammatory response to appendicitis and temporizing measures to delay appendectomy, such as antibiotic therapy. Thus, granulomatous appendicitis only rarely represents a manifestation of Crohn's disease. Rather, the overwhelming majority of patients with this condition are cured by appendectomy alone. The appendix, however, can be involved by idiopathic inflammatory bowel disease, both Crohn's disease and ulcerative colitis. It can be involved by ulcerative colitis in patients with distal colonic involvement and sparing of the intervening colonic segment, a phenomenon known as the appendiceal "skip lesion" or "cecal patch" and this pattern of involvement does not necessarily indicate Crohn's disease. Interestingly, appendectomy has been shown to provide some protection against developing inflammatory bowel disease and in reducing its severity if performed before the onset of disease.
MeSH term(s)	Appendectomy ; Appendicitis/etiology ; Appendicitis/surgery ; Appendix/pathology ; Granuloma/complications ; Humans ; Inflammatory Bowel Diseases/complications ; Inflammatory Bowel Diseases/pathology ; Recurrence
Language	English
Publishing date	2005-03-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605834-6
ISSN	1930-1111 ; 0740-2570
ISSN (online)	1930-1111
ISSN	0740-2570
DOI	10.1053/j.semdp.2004.12.001
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