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Article ; Online: Recent advances in smooth muscle tumors with PGR and PLAG1 gene fusions and myofibroblastic uterine neoplasms.

Chiang, Sarah

2020 Volume 60, Issue 3, Page(s) 138–146

Abstract: Uterine epithelioid and myxoid leiomyosarcomas and inflammatory myofibroblastic tumors are rare mesenchymal neoplasms. Next-generation sequencing recently detected novel PGR fusions in uterine epithelioid leiomyosarcomas that demonstrate characteristic ... ...

Abstract	Uterine epithelioid and myxoid leiomyosarcomas and inflammatory myofibroblastic tumors are rare mesenchymal neoplasms. Next-generation sequencing recently detected novel PGR fusions in uterine epithelioid leiomyosarcomas that demonstrate characteristic rhabdoid and spindled morphology. PLAG1 gene fusions have also been identified in a subset of myxoid leiomyosarcomas and are associated with PLAG1 overexpression. ALK rearrangements underpin the vast majority of uterine inflammatory myofibroblastic tumors, which demonstrate morphologic, and immunohistochemical features similar to those of inflammatory myofibroblastic tumors elsewhere. This review summarizes the morphologic, immunophenotypic, and molecular genetic features of PGR fusion-positive epithelioid leiomyosarcoma, PLAG1 fusion-positive myxoid leiomyosarcoma, and inflammatory myofibroblastic tumors of the uterus.
MeSH term(s)	Adult ; Biomarkers, Tumor/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Female ; Gene Fusion ; Gene Rearrangement ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Middle Aged ; Neoplasms, Muscle Tissue/genetics ; Neoplasms, Muscle Tissue/metabolism ; Receptors, Progesterone/genetics ; Receptors, Progesterone/metabolism ; Smooth Muscle Tumor/genetics ; Smooth Muscle Tumor/metabolism ; Transcription Factors/genetics ; Uterine Neoplasms/genetics ; Uterine Neoplasms/metabolism
Chemical Substances	Biomarkers, Tumor ; DNA-Binding Proteins ; PLAG1 protein, human ; Receptors, Progesterone ; Transcription Factors ; progesterone receptor A ; progesterone receptor B
Language	English
Publishing date	2020-12-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.22920
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Zs.A 2966: Show issues

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Article ; Online: S100 and Pan-Trk Staining to Report NTRK Fusion-Positive Uterine Sarcoma: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting.

Chiang, Sarah

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists

2020 Volume 40, Issue 1, Page(s) 24–27

Abstract: NTRK fusion-positive uterine sarcoma is a recently recognized mesenchymal tumor that is defined by its morphologic resemblance to soft tissue fibrosarcoma, NTRK gene rearrangements, and potential response to Trk inhibition. Reported lesions affect ... ...

Abstract	NTRK fusion-positive uterine sarcoma is a recently recognized mesenchymal tumor that is defined by its morphologic resemblance to soft tissue fibrosarcoma, NTRK gene rearrangements, and potential response to Trk inhibition. Reported lesions affect premenopausal women with a median age of 32 yr, and most arise in the uterine cervix. Haphazard, storiform, or herringbone patterns of spindle cells with mild to moderate nuclear atypia are characteristic. SMA, CD34, and S100 are variably positive, but tumors are negative for desmin, ER, PR, and SOX10 and retain H3K27me3 expression. While pan-Trk immunohistochemistry is positive in these tumors, it has decreased sensitivity and specificity in the evaluation of sarcomas in general and the detection of NTRK3 rearrangements. A variety of molecular methods such as fluorescence in situ hybridization and next-generation sequencing may be useful in confirming NTRK fusion in fibrosarcoma-like uterine sarcomas.
MeSH term(s)	Adult ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cervix Uteri/pathology ; Female ; Gene Fusion ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Middle Aged ; Premenopause ; Receptor, trkA/genetics ; Receptor, trkA/metabolism ; Receptor, trkC/genetics ; Receptor, trkC/metabolism ; S100 Proteins/genetics ; S100 Proteins/metabolism ; Sarcoma/diagnosis ; Sarcoma/genetics ; Sarcoma/pathology ; Sensitivity and Specificity ; Uterine Neoplasms/diagnosis ; Uterine Neoplasms/genetics ; Uterine Neoplasms/pathology
Chemical Substances	Biomarkers, Tumor ; NTRK1 protein, human ; NTRK3 protein, human ; S100 Proteins ; Receptor, trkA (EC 2.7.10.1) ; Receptor, trkC (EC 2.7.10.1)
Language	English
Publishing date	2020-12-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604859-6
ISSN	1538-7151 ; 0277-1691
ISSN (online)	1538-7151
ISSN	0277-1691
DOI	10.1097/PGP.0000000000000702
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Zs.A 1814: Show issues

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Article ; Online: Etiologies of Brain Arteriovenous Malformation Recurrence: A Focus on Pediatric Disease.

Lauzier, David C / Chiang, Sarah N / Moran, Christopher J

Pediatric neurology

2023 Volume 148, Page(s) 94–100

Abstract: Pediatric brain arteriovenous malformations are a major cause of morbidity and mortality, with the harmful effects of this disease compounded by the additional disability-years experienced by children with ruptured or other symptomatic arteriovenous ... ...

Abstract	Pediatric brain arteriovenous malformations are a major cause of morbidity and mortality, with the harmful effects of this disease compounded by the additional disability-years experienced by children with ruptured or other symptomatic arteriovenous malformations. In addition to the risks shared with their adult counterparts, pediatric patients frequently experience recurrence following radiographic cure, which presents an additional source of morbidity and mortality. Therefore, there is a need to synthesize potential mechanisms contributing to the elevated recurrence risk in the pediatric population and discuss how these translate to practical considerations for managing these patients.
Language	English
Publishing date	2023-08-22
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639164-3
ISSN	1873-5150 ; 0887-8994
ISSN (online)	1873-5150
ISSN	0887-8994
DOI	10.1016/j.pediatrneurol.2023.08.022
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Zs.A 2260: Show issues

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Article ; Online: What do patients want to know about gender-affirming surgery? Analysis of common patient concerns and online health materials.

Fotouhi, Annahita R / Chiang, Sarah N / Said, Abdullah M / Skolnick, Gary B / Snyder-Warwick, Alison K

Journal of plastic, reconstructive & aesthetic surgery : JPRAS

2023 Volume 85, Page(s) 55–58

Abstract: Purpose: Patients considering gender-affirming surgery often utilize online health materials to obtain information about procedures. However, the distribution of patient concerns and content of online resources for gender-affirming surgery have not been ...

Abstract	Purpose: Patients considering gender-affirming surgery often utilize online health materials to obtain information about procedures. However, the distribution of patient concerns and content of online resources for gender-affirming surgery have not been examined. We aimed to quantify and comprehensively analyze the most searched questions of patients seeking gender-affirming surgery and to examine the quality and readability of associated websites providing the answers. Methods: Questions were extracted from Google using the search phrases "gender-affirming surgery," "transgender surgery," "top surgery," and "bottom surgery." Questions were categorized by topic and average search volume per month was determined. Websites linked to questions were categorized by type, and quality of the health information was evaluated utilizing the DISCERN instrument (16-80). Readability was assessed with the Flesch Reading Ease Score and Flesch-Kincaid Grade Level. Results: Ninety questions and associated websites were analyzed. Common questions were most frequently answered by academic websites (30%). Topics included cost (27%), technical details of surgery (23%), and preoperative considerations (11%). Median (interquartile range) DISCERN score across all website categories was 42 (18). The mean readability was of a 12th-grade level, well above the grade six reading level recommended by the American Medical Association. Conclusions: Online gender-affirming surgery materials are difficult to comprehend and of poor quality. To enhance patient knowledge, informed consent, and shared decision-making, there is a substantial need to create understandable and high-quality online health information for those seeking gender-affirming surgery.
MeSH term(s)	United States ; Humans ; Sex Reassignment Surgery ; Comprehension ; Internet
Language	English
Publishing date	2023-06-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2217750-4
ISSN	1878-0539 ; 1748-6815 ; 0007-1226
ISSN (online)	1878-0539
ISSN	1748-6815 ; 0007-1226
DOI	10.1016/j.bjps.2023.06.060
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Article: Investigating Weekend Effect in the Management of Upper and Lower Extremity Degloving Injuries.

Varagur, Kaamya / Sullivan, Janessa / Chiang, Sarah N / Skolnick, Gary B / Sacks, Justin M / Christensen, Joani M

Plastic and reconstructive surgery. Global open

2023 Volume 11, Issue 10, Page(s) e5345

Abstract: Background: Weekend presentation has been associated with adverse outcomes in emergent conditions, including stroke, myocardial infarction, and critical limb ischemia. We examine whether a weekend effect exists in the management of and outcomes after ... ...

Abstract	Background: Weekend presentation has been associated with adverse outcomes in emergent conditions, including stroke, myocardial infarction, and critical limb ischemia. We examine whether a weekend effect exists in the management of and outcomes after extremity degloving injuries. Methods: The cohort included adults presenting with open extremity degloving injuries to a tertiary level one trauma center between June 2018 and May 2022. We collected demographics, comorbidities, injury information, interventions, and complications. Propensity score weighting was used to minimize confounding differences between those presenting on weekends (Sat-Sun) versus weekdays (Mon-Fri). Weighted regressions were used to examine differences in interventions by day of presentation. Multivariable weighted regressions accounting for differences in interventions received were used to examine whether weekend presentation was associated with amputation risk, complications, or functional deficits. Results: Ninety-five patients with 100 open extremity degloving injuries were included. In total, 39% of injuries were weekend-presenting. There was a higher rate of noninsulin-dependent diabetes among patients presenting on weekends ( Conclusion: Weekend presentation may impact interventions received and amputation risk in patients presenting with open extremity degloving injuries.
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2851682-5
ISSN	2169-7574 ; 2169-7574
ISSN (online)	2169-7574
ISSN	2169-7574
DOI	10.1097/GOX.0000000000005345
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Zs.A 7091: Show issues

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Article ; Online: High-Grade Sarcomas with Myogenic Differentiation Harboring Hotspot PDGFRB Mutations.

Dermawan, Josephine K / Chiang, Sarah / Hensley, Martee L / Tap, William D / Antonescu, Cristina R

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2023 Volume 36, Issue 5, Page(s) 100104

Abstract: PDGFRB-activating mutations have been reported in pediatric myofibroma and myofibromatosis. However, recurrent gain-of-function PDGFRB mutations have not been documented in sarcomas with myogenic differentiation. Driven by occasional sarcomas harboring ... ...

Abstract	PDGFRB-activating mutations have been reported in pediatric myofibroma and myofibromatosis. However, recurrent gain-of-function PDGFRB mutations have not been documented in sarcomas with myogenic differentiation. Driven by occasional sarcomas harboring PDGFRB mutations, we investigated their prevalence and clinicopathologic and genomic features in a large cohort of sarcomas. An institutional targeted DNA next-generation sequencing database was searched for sarcomas with myogenic differentiation harboring hotspot PDGFRB gene alterations. Among 3300 patients with sarcomas, 21 (0.6%) patients were identified (17 women, 4 men) with an age range of 35 to 88 years. The site distribution included 13 gynecologic tract (12 uteri, 1 vagina), 4 bone and soft tissue, and 4 viscera. All except 1 were high grade. Most patients were diagnosed as sarcomas with myogenic differentiation based on partial staining for 1 or more muscle markers, whereas 6 were labeled as leiomyosarcoma (LMS). Most tumors showed monomorphic spindle morphology, with either heterogeneous features of myofibroblastic and smooth muscle differentiation or an undifferentiated phenotype. Hormone receptors were negative in all uterine cases. PDGFRB immunostaining in all cases tested was strong and diffuse, whereas PDGFRA was negative/focal. The most frequent PDGFRB mutations were exon 12 (43%), exon 14 (N666K/S/T) (38%), and exon 18 (D850Y/H/V or insertion/deletion) (19%). The most frequent co-existing genetic alterations (26% to 37%) occurred in CDKN2A/B, TP53, TERT, and MED12. Moreover, PDGFRB-mutant sarcomas had an overall distinct genomic landscape compared with both uterine and soft tissue LMS control groups. These tumors were associated with a highly aggressive clinical course, with frequent distant metastases (81%) and death (76%), regardless of anatomic location, and worse overall survival compared with the 2 LMS control groups. This is the first study documenting recurrent hotspot PDGFRB alterations in high-grade sarcomas, which show a predilection for uterine location and myogenic differentiation that fall short of the diagnostic criteria for LMS. Further studies are needed to investigate the therapeutic potential of kinase inhibitors in this group of tumors.
MeSH term(s)	Humans ; Female ; Receptor, Platelet-Derived Growth Factor beta/genetics ; Sarcoma/genetics ; Sarcoma/pathology ; Leiomyosarcoma/genetics ; Mutation ; Soft Tissue Neoplasms/genetics ; Soft Tissue Neoplasms/pathology
Chemical Substances	Receptor, Platelet-Derived Growth Factor beta (EC 2.7.10.1) ; PDGFRB protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2023.100104
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Zs.A 2450: Show issues

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Article: Unilateral Cleft Lip Repair: Technical Maneuvers to Achieve Vermilion and Mucosal Height.

Chiang, Sarah N / Zubovic, Ema / Skolnick, Gary B / Patel, Kamlesh B

Plastic and reconstructive surgery. Global open

2022 Volume 10, Issue 2, Page(s) e4125

Abstract: Patients with unilateral cleft lip often require secondary procedures due to asymmetric fullness or deficiencies along the mucosal free margin of the upper lip. Here, we describe our technique for mucosal advancement and repair to attain symmetry.: ... ...

Abstract	Patients with unilateral cleft lip often require secondary procedures due to asymmetric fullness or deficiencies along the mucosal free margin of the upper lip. Here, we describe our technique for mucosal advancement and repair to attain symmetry. Methods: Maneuvers to obtain vermilion and mucosal height include (1) use of a tailored vermilion flap; (2) supraperiosteal release of the lesser segment; (3) backcut "poker incision" to mobilize the mucosal flap on the lesser segment; (4) transverse release of mucosa across the greater segment; (5) accurate reduction along vermilion-mucosal junction; and (6) bilateral medial mucosal advancement. To examine postoperative outcomes, photographic data were available for 14 patients with unilateral complete cleft lip. The Cleft Lip Component Symmetry Index was then calculated as a ratio of upper lip height on cleft to noncleft sides, where an index of 1 indicates symmetry. Results: Sixteen consecutive patients underwent unilateral cleft lip repair with this technique over a 3-year period, none of whom have required secondary operations. The symmetry index for 14 of 16 patients was 1.02 ± 0.11 (95% confidence interval [0.96, 1.08], Conclusions: Postoperative asymmetry after unilateral cleft lip repair, particularly along the free margin, continues to be a common problem, necessitating secondary procedures. The technique of mucosal repair merits more careful attention than it has previously received, and here we describe in detail a method that has allowed for improved symmetry.
Language	English
Publishing date	2022-02-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2851682-5
ISSN	2169-7574 ; 2169-7574
ISSN (online)	2169-7574
ISSN	2169-7574
DOI	10.1097/GOX.0000000000004125
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Zs.A 7091: Show issues

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Article ; Online: Idiopathic Intracranial Hypertension and Vascular Anomalies in Chiari I Malformation.

Lauzier, David C / Chiang, Sarah N / Chatterjee, Arindam R / Osbun, Joshua W

Neurosurgery clinics of North America

2022 Volume 34, Issue 1, Page(s) 175–183

Abstract: Mounting evidence has suggested a relationship between Chiari I malformation and idiopathic intracranial hypertension, with some studies implicating anomalies of the cerebral venous system in the development of these conditions. However, precise ... ...

Abstract	Mounting evidence has suggested a relationship between Chiari I malformation and idiopathic intracranial hypertension, with some studies implicating anomalies of the cerebral venous system in the development of these conditions. However, precise mechanisms explaining these associations are not well described. There is a clear need to clarify the interplay between these conditions to guide further study in this area. In tandem with these efforts, it is necessary to review proper diagnosis and management to improve outcomes in patients suffering from these diseases.
MeSH term(s)	Humans ; Pseudotumor Cerebri/complications ; Pseudotumor Cerebri/diagnosis ; Arnold-Chiari Malformation/complications ; Arnold-Chiari Malformation/diagnosis ; Arnold-Chiari Malformation/surgery
Language	English
Publishing date	2022-11-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1196855-2
ISSN	1558-1349 ; 1042-3680
ISSN (online)	1558-1349
ISSN	1042-3680
DOI	10.1016/j.nec.2022.09.008
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Se 1200: Show issues

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Article ; Online: Uterine mesenchymal tumours: recent advances.

Momeni-Boroujeni, Amir / Chiang, Sarah

Histopathology

2019 Volume 76, Issue 1, Page(s) 64–75

Abstract: Almost all uterine mesenchymal tumours have been historically classified as either smooth muscle or endometrial stromal neoplasms. Recent application of molecular techniques has identified numerous lesions with distinctive genetic abnormalities and ... ...

Abstract	Almost all uterine mesenchymal tumours have been historically classified as either smooth muscle or endometrial stromal neoplasms. Recent application of molecular techniques has identified numerous lesions with distinctive genetic abnormalities and clinicopathological characteristics. Newly discovered uterine sarcoma subtypes include high-grade endometrial stromal sarcomas with BCOR genetic abnormalities, fibrosarcoma-like uterine sarcomas with NTRK rearrangements and COL1A-PDGFRB fusions, as well as undifferentiated uterine sarcomas with SMARCA4 mutations. Novel PLAG1 and PGR fusions have been identified in subsets of myxoid and epithelioid leiomyosarcomas. Some uterine tumours resembling ovarian sex-cord tumour harbour GREB1 and ESR1 rearrangements. Histological and immunophenotypical features as well as underlying genetic abnormalities defining these lesions are discussed.
MeSH term(s)	Female ; Gene Rearrangement ; Humans ; Leiomyosarcoma/genetics ; Leiomyosarcoma/pathology ; Oncogene Fusion ; Sarcoma, Endometrial Stromal/genetics ; Sarcoma, Endometrial Stromal/pathology ; Uterine Neoplasms/genetics ; Uterine Neoplasms/pathology ; Uterus/pathology
Language	English
Publishing date	2019-12-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14008
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Zs.A 1328: Show issues

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Article ; Online: Establishing guidelines for sentinel lymph node ultrastaging in endometrial cancer.

Chiang, Sarah / Tessier-Cloutier, Basile / Klein, Eric / Ardon, Orly / Mueller, Jennifer J / Leitao, Mario M / Abu-Rustum, Nadeem R / Ellenson, Lora H

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

2024

Abstract: Background: Many sentinel lymph node (SLN) ultrastaging protocols for endometrial cancer exist, but there is no consensus method.: Objective: This study aims to develop guidelines for size criteria in SLN evaluation for endometrial cancer, to ... ...

Abstract	Background: Many sentinel lymph node (SLN) ultrastaging protocols for endometrial cancer exist, but there is no consensus method. Objective: This study aims to develop guidelines for size criteria in SLN evaluation for endometrial cancer, to determine whether a single cytokeratin AE1:AE3 immunohistochemical slide provides sufficient data for diagnosis, and to compare cost efficiency between current and limited ultrastaging protocols at a large tertiary care institution. Methods: Our current SLN ultrastaging protocol consists of cutting two adjacent paraffin block sections at two levels (L1 and L2), 50 μm apart, with two slides at each level stained with hematoxylin and eosin and cytokeratin AE1:AE3 immunohistochemistry. We retrospectively reviewed digitized L1 and L2 slides of all positive ultrastaged SLNs from patients treated for endometrial cancer between January 2013 and January 2020. SLN diagnosis was defined by measuring the largest cluster of contiguous tumor cells in a single cross section: macrometastasis (>2.0 mm), micrometastasis (>0.2 to ≤2.0 mm or >200 cells), or isolated tumor cells (≤0.2 mm or ≤200 cells). Concordance between L1 and L2 results was evaluated. Cost efficiency between current (two immunohistochemical slides per block) and proposed limited (one immunohistochemical slide per block) protocols was compared. Results: Digitized slides of 147 positive SLNs from 109 patients were reviewed; 4.1% of SLNs were reclassified based on refined size criteria. Complete concordance between L1 and L2 interpretations was seen in 91.8% of SLNs. A false-negative rate of 0%-0.9% in detecting micrometastasis and macrometastasis using a limited protocol was observed. Estimated charge-level savings of a limited protocol were 50% per patient. Conclusion: High diagnostic accuracy in SLN interpretation may be achieved using a limited ultrastaging protocol of one immunohistochemical slide per block and linear measurement of the largest cluster of contiguous tumor cells. Implementation of the proposed limited ultrastaging protocol may result in laboratory cost savings with minimal impact on health outcomes.
Language	English
Publishing date	2024-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1070385-8
ISSN	1525-1438 ; 1048-891X
ISSN (online)	1525-1438
ISSN	1048-891X
DOI	10.1136/ijgc-2023-005157
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