124 results on '"Dermawan, Josephine K."'
Search Results
102. Neuregulin 1 (NRG1) fusion‐positive high‐grade spindle cell sarcoma: A distinct group of soft tissue tumors with metastatic potential.
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Dermawan, Josephine K., Zou, Youran, and Antonescu, Cristina R.
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- 2022
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103. Low‐grade endometrial stromal sarcoma‐like tumors in male with JAZF1 gene fusions.
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Dermawan, Josephine K., Zhang, Lei, Singer, Samuel, Chi, Ping, and Antonescu, Cristina R.
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- 2022
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104. Accurate and Reliable Diagnosis of Avascular Necrosis of the Femoral Head From Total Hip Arthroplasty Specimens Requires Pathologic Examination
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Dermawan, Josephine K, primary, Goldblum, Andrew, additional, Reith, John D, additional, and Kilpatrick, Scott E, additional
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- 2020
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105. Expanding the spectrum of chronic necrotising (semi‐invasive) aspergillosis: a series of eight cases presenting as radiologically solid lung nodules mimicking malignancy
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Dermawan, Josephine K, primary, Ghosh, Subha, additional, and Mukhopadhyay, Sanjay, additional
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- 2020
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106. Endobronchial pseudocarcinomatous hyperplasia mimicking squamous cell carcinoma associated with primary pulmonary ALK‐negative anaplastic large cell lymphoma
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Dermawan, Josephine K., primary, Hsi, Eric D., additional, Sethi, Sonali, additional, and Arrossi, Andrea V., additional
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- 2020
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107. Novel CRTC1::MRTFB(MKL2)Gene Fusion Detected in Myxoid Mesenchymal Neoplasms With Myogenic Differentiation Involving Bone and Soft Tissues
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Warmke, Laura M., Collier, Christopher D., Niziolek, Paul J., Davis, Jessica L., Zou, Ying S., Michal, Michael, Bell, Robert C., Policarpio-Nicolas, Maria Luisa C., Cheng, Yu-Wei, Duckworth, Lauren, Dermawan, Josephine K., Fritchie, Karen J., and Dehner, Carina A.
- Abstract
Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present 3 cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB(formerly MKL2) gene fusion. Three tumors occurred in 1 male and 2 female patients with a median age of 72 years (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). Although 1 tumor presented as an incidental finding, the other 2 tumors were noted, given their persistent growth. At the time of the last follow-up, 1 patient was alive with unresected disease at 6 months, 1 patient was alive without evidence of disease at 12 months after surgery, and 1 patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFBgene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFBfusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms.
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- 2024
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108. The Prognostic Significance of the 8th Edition TNM Staging of Pulmonary Carcinoid Tumors
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Dermawan, Josephine K., primary and Farver, Carol F., additional
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- 2019
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109. Molecular testing in metastatic colorectal adenocarcinoma cytology cell pellets
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McHugh, Kelsey E., primary, Dermawan, Josephine K., additional, Cheng, Yu‐Wei, additional, Cruise, Michael, additional, Sohal, Davendra P. S., additional, and Reynolds, Jordan P., additional
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- 2019
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110. Cytological findings of monophasic synovial sarcoma presenting as a lung mass: report of a case and review of the literature
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Dermawan, Josephine K. T., primary and Policarpio‐Nicolas, Maria Luisa C., additional
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- 2019
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111. Accurate and Reliable Diagnosis of Avascular Necrosis of the Femoral Head From Total Hip Arthroplasty Specimens Requires Pathologic Examination.
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Dermawan, Josephine K, Goldblum, Andrew, Reith, John D, and Kilpatrick, Scott E
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IDIOPATHIC femoral necrosis , *TOTAL hip replacement , *FEMUR head , *FEMORAL epiphysis , *ARTIFICIAL joints , *OSTEOARTHRITIS , *OLDER patients , *SURGICAL diagnosis - Abstract
Objectives: To evaluate the necessity of pathologic examination for confirming the diagnosis of avascular necrosis (AVN).Methods: We retrospectively reviewed consecutive nonfractured total hip arthroplasty cases (n = 1,722), comparing operative diagnoses and radiologic data with final histologic diagnoses, focusing specifically on AVN.Results: Among 199 histologically confirmed cases of AVN, 62 (31%) had a preoperative diagnosis of osteoarthritis/degenerative joint disease (OA/DJD); 58 of the latter patients had radiology reports, but only two (3%) documented AVN. Patients with AVN preoperatively diagnosed as OA/DJD were significantly older (mean, 65 years) than patients with AVN correctly diagnosed clinically (mean, 52 years; P < .00001). Among 163 cases with a preoperative diagnosis of AVN, 26 (16%) were confirmed as OA/DJD; the radiology report incorrectly diagnosed AVN in 17 (65%) patients. These latter patients also were significantly older (mean, 60 years) than patients with AVN correctly diagnosed clinically (P = .0008). Patients with a preoperative clinical and/or radiologic diagnosis of AVN were more likely to be younger and have known AVN risk factors.Conclusions: Accurate and reliable diagnosis of AVN requires pathologic examination, especially among older patients without known risk factors. Prompt diagnosis may lead to behavioral changes in affected patients that reduce the risk of subsequent lesions. [ABSTRACT FROM AUTHOR]- Published
- 2021
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112. Insulinoma-associated protein 1 (INSM1) differentiates carcinoid tumourlets of the lung from pulmonary meningothelial-like nodules
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Dermawan, Josephine K, primary and Mukhopadhyay, Sanjay, additional
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- 2018
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113. Novel PAX3::MAML3fusion identified in alveolar rhabdomyosarcoma, using DNA methylation profiling to expand the genetic spectrum of “fusion-positive” cases
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Dermawan, Josephine K., Malik, Faizan, Gross, John M., Baraban, Ezra, Pratilas, Christine, Mneimneh, Wadad, Trucco, Matteo, Sun, Wenyue, Barr, Frederic G., D’Almeida Costa, Felipe, and Fritchie, Karen J.
- Abstract
Alveolar rhabdomyosarcoma (ARMS) with FOXO1gene rearrangements is an aggressive pediatric rhabdomyosarcoma subtype that is prognostically distinct from embryonal rhabdomyosarcoma and fusion-negative ARMS. Herein, we report two cases of ARMS with PAX3::MAML3fusions. The tumors arose in an infant and an adolescent as stage IV metastatic disease (by Children’s Oncology Group staging system). Histologically, both cases were small round blue cell tumors arranged in vague nests and solid sheets that were diffusely positive for desmin and myogenin. By methylation profiling and unsupervised clustering analysis, the tumors clustered with ARMS with classic FOXO1rearrangements and ARMS with variant PAX3::NCOA1/INO80Dfusions, but not with biphenotypic sinonasal sarcoma (BSNS) with PAX3::MAML3/NCOA2/FOXO1/YAP1fusions, nor with other small round blue cell tumors, including embryonal rhabdomyosarcoma. The differentially methylated genes between ARMS and BSNS were highly enriched in genes involved in myogenesis, and 21% of these genes overlap with target genes of the PAX3::FOXO1 fusion transcription factor. On follow-up after initiation of vincristine/actinomycin/cyclophosphamide chemotherapy, the tumors showed partial and complete clinical response, consistent with typical upfront chemotherapy responsiveness of ARMS with the classic FOXO1rearrangement. We conclude that PAX3::MAML3is a novel variant fusion of ARMS, which displays a methylation signature distinct from BSNS despite sharing similar PAX3fusions. These findings highlight the utility of methylation profiling in classifying ARMS with non-canonical fusions.
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- 2024
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114. Nuclear DUX4 immunohistochemistry is a highly sensitive and specific marker for the presence of CIC::DUX4 fusion in CIC‐rearranged sarcomas: a study of 48 molecularly confirmed cases.
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Macedo, Rodrigo T, Baranovska‐Andrigo, Vira, Pancsa, Tamás, Klubíčková, Natálie, Rubin, Brian P, Kilpatrick, Scott E, Goldblum, John R, Fritchie, Karen J, Billings, Steven D, Michal, Michal, Švajdler, Marián, Kinkor, Zdeněk, Michal, Michael, and Dermawan, Josephine K
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EWING'S sarcoma , *SYNOVIOMA , *BIOMARKERS , *SARCOMA , *SENSITIVITY & specificity (Statistics) - Abstract
Aims Methods and results Conclusions CIC‐rearranged sarcomas (CRS) are clinically aggressive undifferentiated round cell sarcomas (URCS), commonly driven by CIC::DUX4. Due to the repetitive nature of DUX4 and the variability of the fusion breakpoints, CIC::DUX4 fusion may be missed by molecular testing. Immunohistochemical (IHC) stains have been studied as surrogates for the CIC::DUX4 fusion. We aim to assess the performance of DUX4 IHC in the work‐up of CRS and its expression in non‐CRS round cell or epithelioid neoplasms.Cases of molecularly confirmed CRS (n = 48) and non‐CRS (n = 105) were included. CRS cases consisted of 35 females and 13 males, with ages ranging from less than 1 year to 67 years (median = 41 years). Among the molecularly confirmed non‐CRS cases, C‐terminal DUX4 expression was investigated in Ewing sarcomas (38 cases), alveolar rhabdomyosarcomas (18 cases), desmoplastic small round cell tumours (12 cases) and synovial sarcomas (n = five), as well as in non‐mesenchymal neoplasms such as SMARCA4/SMARCB1‐deficient tumours (n = five), carcinomas of unknown primary (n = three) and haematolymphoid neoplasms (four cases). DUX4 IHC was considered positive when strong nuclear expression was detected in more than 50% of neoplastic cells. When used as a surrogate for the diagnosis of CRS, the sensitivity and specificity of DUX4 IHC was 98 and 100%, respectively. Only one CRS case was negative for DUX4 IHC and harboured a CIC::FOXO4 fusion.DUX4 IHC is a highly sensitive and specific surrogate marker for the presence of CIC::DUX4 fusion, demonstrating its utility in establishing a diagnosis of CRS. [ABSTRACT FROM AUTHOR]
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- 2024
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115. The Impact of Li-Fraumeni and Germline Retinoblastoma Mutations on Leiomyosarcoma Initiation, Outcomes, and Genetic Testing Recommendations.
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Dermawan JK, Abramson DH, Chiang S, Hensley ML, Tap WD, Movva S, Maki RG, Mandelker D, and Antonescu CR
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- Humans, Female, Middle Aged, Male, Adult, Aged, Genetic Predisposition to Disease, Retinoblastoma Binding Proteins genetics, High-Throughput Nucleotide Sequencing, Tumor Suppressor Protein p53 genetics, Young Adult, Aged, 80 and over, Ubiquitin-Protein Ligases, Leiomyosarcoma genetics, Leiomyosarcoma pathology, Leiomyosarcoma diagnosis, Germ-Line Mutation, Li-Fraumeni Syndrome genetics, Li-Fraumeni Syndrome diagnosis, Genetic Testing methods
- Abstract
Purpose: Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous, occurring mostly in sporadic but also syndromic settings. The role of pathogenic germline variants (PGV) as LMS drivers and their impact on outcomes remains uncertain., Experimental Design: We performed a comprehensive clinicopathologic and molecular analysis using a tumor-normal DNA next-generation sequencing assay (Memorial Sloan Kettering-Integrated Mutational Profiling of Actionable Cancer Targets) of germline-associated LMS compared with sporadic LMS., Results: Among 285 LMS [120 soft-tissue LMS (STLMS) and 165 uterine LMS (ULMS)] with germline testing, 78 (27%, 43 STLMS and 35 ULMS) cases harbored PGV, with 35/78 (45%) of PGV carriers showing biallelic inactivation of the corresponding gene in the tumor (26 STLMS and nine ULMS). The most frequent germline predispositions were TP53 (Li-Fraumeni syndrome; 17 patients, 16 in STLMS) and RB1 (retinoblastoma; 13 patients, 11 in STLMS). Germline TP53 and somatic RB1 alterations often co-occurred in the tumor andvice versa. Other biallelically inactivated PGV were enriched in DNA damage repair-related genes: CHEK2, MSH2, MSH6, RAD51D, BRCA2, and FANCA. Monoallelic PGV were mostly in ULMS and associated with co-occurring TP53 and RB1 somatic alterations. Patients with STLMS with biallelic but not monoallelic PGV were significantly younger than patients with sporadic STLMS (median ages 38 vs. 52 vs. 58 years). No differences in disease-specific or progression-free survival were observed in germline-associated versus sporadic LMS regardless of biallelic status., Conclusions: Although patients with ULMS had a relatively low proportion of PGV, a high percentage of patients with STLMS with PGV had tumor biallelic status, indicating that PGV drive tumorigenesis in these individuals. These findings have significant implications for genetic testing recommendations., (©2024 American Association for Cancer Research.)
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- 2024
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116. Botryoid-type Embryonal Rhabdomyosarcoma: A Comprehensive Clinicopathologic and Molecular Appraisal With Cross-comparison to its Conventional-type Counterpart.
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Sharma AE, Dermawan JK, Chiang S, Wexler LH, and Antonescu CR
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Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of RMS, occurring in soft tissue and visceral sites of young children, and is associated with favorable outcomes. A subset occurs in mucosal-lined luminal structures, displaying a unique grape-like growth termed as "botryoid-type." To further delineate the differences between conventional (cERMS) and botryoid-type (bERMS) RMS, we performed a comparative histologic review and comprehensive molecular profiling of 48 cases (25 bERMS and 23 cERMS). All tumors were subjected to a hybridization capture-based targeted matched tumor-normal DNA NGS assay. The mean age was 17 and 7 years for bERMS and cERMS, respectively. Most bERMS were female with a predilection for the gynecologic tract (75%), while cERMS had a slight male predominance and were preferentially located in abdominopelvic and paratesticular sites (30%, each). All bERMS exhibited an exophytic, bulbous architecture accompanied by a subepithelial "cambium layer." Distinctive germline alterations were detected, with DICER1 (18%) and FH (6%) mutations only in bERMS, and rare TP53, VHL, and APC mutations in cERMS. Similarly, contrasting somatic genomic landscapes were observed, with frequent DICER1 (52%, P**<0.0001) and TP53 (36%, P*<0.05) alterations exclusively in bERMS. Cartilaginous differentiation was only observed in DICER1-mutated bERMS. All patients had longitudinal follow-up. bERMS patients with somatic/germline DICER1 mutations showed significantly improved recurrence-free survival compared with that of DICER1-wild type patients (P*<0.05). Moreover, bERMS showed improved disease-specific survival compared with that of cERMS, with 8% versus 30% (P*<0.05) dead of disease, respectively. In summary, we compare the molecular underpinnings of the largest cohort of bERMS and cERMS with targeted DNA sequencing and long-term follow-up data. Our findings reveal divergent genomic topographies between the 2 groups, with bERMS showing unique germline and somatic abnormalities, including enrichment in DICER1 and TP53 alterations, and a trend towards improved survival., Competing Interests: Conflicts of Interest and Source of Funding: P50 CA217694 (C.R.A.), P30 CA008748 (C.R.A. and L.H.W.), Kristin Ann Carr Foundation (C.R.A.), Cycle for survival (C.R.A. and L.H.W.). For the remaining authors, none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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117. EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms.
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Rekhi B, Dermawan JK, Fritchie KJ, Zimpfer A, Mohammad TM, Ali FS, Nandy K, Zou Y, Stoehr R, and Agaimy A
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With the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20-56 years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4-7.5 cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8-21 months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma., (© 2024. The Author(s).)
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- 2024
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118. Chromoplexy Is a Frequent Early Clonal Event in EWSR1-Rearranged Round Cell Sarcomas That Can Be Detected Using Clinically Validated Targeted Sequencing Panels.
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Dermawan JK, Slotkin E, Tap WD, Meyers P, Wexler L, Healey J, Vanoli F, Vanderbilt CM, and Antonescu CR
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- Humans, Sequence Analysis, RNA, Clonal Evolution, Sarcoma, Ewing genetics, Sarcoma, Ewing pathology, Bone Neoplasms genetics, Bone Neoplasms pathology, RNA-Binding Protein EWS genetics, Chromosome Breakage
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Chromoplexy is a phenomenon defined by large-scale chromosomal chained rearrangements. A previous study observed chromoplectic events in a subset of Ewing sarcomas (ES), which was linked to an increased relapse rate. Chromoplexy analysis could potentially facilitate patient risk stratification, particularly if it could be detected with clinically applied targeted next-generation sequencing (NGS) panels. Using DELLY, a structural variant (SV) calling algorithm that is part of the MSK-IMPACT pipeline, we characterized the spectrum of SVs in EWSR1-fused round cell sarcomas, including 173 ES and 104 desmoplastic small round cell tumors (DSRCT), to detect chromoplexy and evaluate its association with clinical and genomic features. Chromoplectic events were detected in 31% of the ES cases and 19% of the DSRCT cases. EWSR1 involvement accounted for 76% to 93% of these events, being rearranged with diverse noncanonical gene partners across the genome, involving mainly translocations but also intrachromosomal deletions and inversions. A major breakpoint cluster was located on EWSR1 exons 8-13. In a subset of cases, the SVs disrupted adjacent loci, forming deletion bridges. Longitudinal sequencing and breakpoint allele fraction analysis showed that chromoplexy is an early event that remains detectable throughout disease progression and likely develops simultaneously with the driver fusion. The presence of chromoplexy was validated in an external ES patient cohort with whole exome sequencing. Chromoplexy was significantly more likely to be present in cases that were metastatic at presentation. Together, this study identifies chromoplexy as a frequent genomic alteration in diverse EWSR1-rearranged tumors that can be captured by targeted NGS panels., Significance: Chromoplexy is detectable using targeted NGS in a substantial portion of EWSR1-rearranged round cell sarcomas as an early and persistent clonal event, expanding the genomic complexity of fusion-associated sarcomas., (©2024 American Association for Cancer Research.)
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- 2024
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119. Translational Aspects of Epithelioid Sarcoma: Current Consensus.
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Grünewald TGP, Postel-Vinay S, Nakayama RT, Berlow NE, Bolzicco A, Cerullo V, Dermawan JK, Frezza AM, Italiano A, Jin JX, Le Loarer F, Martin-Broto J, Pecora A, Perez-Martinez A, Tam YB, Tirode F, Trama A, Pasquali S, Vescia M, Wortmann L, Wortmann M, Yoshida A, Webb K, Huang PH, Keller C, and Antonescu CR
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- Adolescent, Young Adult, Humans, DNA-Binding Proteins genetics, Chromosomal Proteins, Non-Histone genetics, Homozygote, Consensus, Sequence Deletion, SMARCB1 Protein genetics, SMARCB1 Protein metabolism, Transcription Factors genetics, Sarcoma diagnosis, Sarcoma genetics, Sarcoma therapy
- Abstract
Epithelioid sarcoma (EpS) is an ultra-rare malignant soft-tissue cancer mostly affecting adolescents and young adults. EpS often exhibits an unfavorable clinical course with fatal outcome in ∼50% of cases despite aggressive multimodal therapies combining surgery, chemotherapy, and irradiation. EpS is traditionally classified in a more common, less aggressive distal (classic) type and a rarer aggressive proximal type. Both subtypes are characterized by a loss of nuclear INI1 expression, most often following homozygous deletion of its encoding gene, SMARCB1-a core subunit of the SWI/SNF chromatin remodeling complex. In 2020, the EZH2 inhibitor tazemetostat was the first targeted therapy approved for EpS, raising new hopes. Still, the vast majority of patients did not benefit from this drug or relapsed rapidly. Further, other recent therapeutic modalities, including immunotherapy, are only effective in a fraction of patients. Thus, novel strategies, specifically targeted to EpS, are urgently needed. To accelerate translational research on EpS and eventually boost the discovery and development of new diagnostic tools and therapeutic options, a vibrant translational research community has formed in past years and held two international EpS digital expert meetings in 2021 and 2023. This review summarizes our current understanding of EpS from the translational research perspective and points to innovative research directions to address the most pressing questions in the field, as defined by expert consensus and patient advocacy groups., (©2023 American Association for Cancer Research.)
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- 2024
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120. Mesenchymal chondrosarcoma of the head and neck with HEY1::NCOA2 fusion: A clinicopathologic and molecular study of 13 cases with emphasis on diagnostic pitfalls.
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Xu B, Rooper LM, Dermawan JK, Zhang Y, Suurmeijer AJH, Dickson BC, Demicco EG, and Antonescu CR
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- Adult, Cell Cycle Proteins genetics, Child, Female, Humans, In Situ Hybridization, Fluorescence, Male, Young Adult, Basic Helix-Loop-Helix Transcription Factors genetics, Chondrosarcoma, Mesenchymal genetics, Chondrosarcoma, Mesenchymal pathology, Gene Fusion, Head and Neck Neoplasms genetics, Head and Neck Neoplasms pathology, Nuclear Receptor Coactivator 2 genetics
- Abstract
Background: Mesenchymal chondrosarcoma (MCS) is a rare translocation-associated sarcoma, driven by a canonical HEY1::NCOA2 fusion. The tumors typically have a biphasic phenotype of primitive small blue round cells intermixed with hyaline cartilage. The head and neck (HN) region is a common site for MCS, accounting for 12-45% of all cases reported., Aims: We assembled a relatively large cohort of 13 molecularly confirmed HN MCS for a detailed clinicopathologic analysis. The underlying fusion events were determined using fluorescence in situ hybridization and/or targeted RNA sequencing., Results: The median age of presentation was 19 years. Five MCSs (39%) had an intraosseous presentation (skull, maxilla, palate, and mandible), while the remaining eight cases occurred in the brain/meninges, orbit, and nasal cavity. Microscopically, HN MCSs were characterized by primitive round cells arranged in a distinctive nested architecture and a rich staghorn vasculature. A cartilaginous component of hyaline cartilage islands and/or single chondrocytes were present in 69% cases. A combined immunoprofile of CD99(+)/SATB2(+)/CD34(-)/STAT6(-) was typically noted. As this immunoprofile is non-specific, the referral diagnoses in cases lacking a cartilaginous component included Ewing sarcoma family and osteosarcoma. Among the seven patients with follow-up data, three developed distant metastasis and one died of disease., Conclusion: HN MCS may arise at intra- or extra-osseous sites. The HN MCS appears to have a more prolonged survival compared other MCS sites. Testing for HEY1::NCOA2 fusion is recommended in HN tumors with nested round cell morphology and staghorn vasculature that lack a distinctive cartilaginous component., (© 2022 Wiley Periodicals LLC.)
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- 2022
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121. FGFR2::TACC2 fusion as a novel KIT-independent mechanism of targeted therapy failure in a multidrug-resistant gastrointestinal stromal tumor.
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Dermawan JK, Vanderbilt CM, Chang JC, Untch BR, Singer S, Chi P, Tap WD, and Antonescu CR
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- Carrier Proteins genetics, Gene Fusion, Humans, Imatinib Mesylate, Mutation, Proto-Oncogene Proteins c-kit genetics, Receptor, Fibroblast Growth Factor, Type 2 genetics, Receptor, Platelet-Derived Growth Factor alpha genetics, Tumor Suppressor Proteins genetics, Antineoplastic Agents pharmacology, Gastrointestinal Stromal Tumors drug therapy, Gastrointestinal Stromal Tumors genetics, Gastrointestinal Stromal Tumors pathology, Liver Neoplasms drug therapy, Liver Neoplasms genetics
- Abstract
Genetic alterations in FGF/FGFR pathway are infrequent in gastrointestinal stromal tumors (GIST), with rare cases of quadruple wildtype GISTs harboring FGFR1 gene fusions and mutations. Additionally, FGF/FGFR overexpression was shown to promote drug resistance to kinase inhibitors in GISTs. However, FGFR gene fusions have not been directly implicated as a mechanism of drug resistance in GISTs. Herein, we report a patient presenting with a primary small bowel spindle cell GIST and concurrent peritoneal and liver metastases displaying an imatinib-sensitive KIT exon 11 in-frame deletion. After an initial 9-month benefit to imatinib, the patient experienced intraabdominal peritoneal recurrence owing to secondary KIT exon 13 missense mutation and FGFR4 amplification. Despite several additional rounds of tyrosine kinase inhibitors (TKI), the patient's disease progressed after 2 years and presented with multiple peritoneal and liver metastases, including one pericolonic mass harboring secondary KIT exon 18 missense mutation, and a concurrent transverse colonic mass with a FGFR2::TACC2 fusion and AKT2 amplification. All tumors, including primary and recurrent masses, harbored an MGA c.7272 T > G (p.Y2424*) nonsense mutation and CDKN2A/CDKN2B/MTAP deletions. The transcolonic mass showed elevated mitotic count (18/10 HPF), as well as significant decrease in CD117 and DOG1 expression, in contrast to all the other resistant nodules that displayed diffuse and strong CD117 and DOG1 immunostaining. The FGFR2::TACC2 fusion resulted from a 742 kb intrachromosomal inversion at the chr10q26.3 locus, leading to a fusion between exons 1-17 of FGFR2 and exons 7-17 TACC2, which preserves the extracellular and protein tyrosine kinase domains of FGFR2. We present the first report of a multidrug-resistant GIST patient who developed an FGFR2 gene fusion as a secondary genetic event to the selective pressure of various TKIs. This case also highlights the heterogeneous escape mechanisms to targeted therapy across various tumor nodules, spanning from both KIT-dependent and KIT-independent off-target activation pathways., (© 2022 Wiley Periodicals LLC.)
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- 2022
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122. Radiology-Pathology Correlation in Coatomer Subunit Alpha Syndrome With Novel Findings of Pulmonary Lymphangiectasia.
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Ghosh S, Dermawan JKT, Saeedan MB, Akindipe O, Farver CF, and Arrossi AV
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- Humans, Radiography, Lymphangiectasis diagnostic imaging, Lymphangiectasis pathology, Radiology
- Abstract
Competing Interests: The authors declare no conflicts of interest.
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- 2022
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123. The Role of Histologic Grading and Ki-67 Index in Predicting Outcomes in Pulmonary Carcinoid Tumors.
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Dermawan JKT and Farver CF
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- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoid Tumor diagnosis, Carcinoid Tumor surgery, Female, Follow-Up Studies, Humans, Lung Neoplasms diagnosis, Lung Neoplasms surgery, Male, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local pathology, Neoplasm Staging, ROC Curve, Young Adult, Carcinoid Tumor metabolism, Carcinoid Tumor pathology, Ki-67 Antigen metabolism, Lung Neoplasms metabolism, Lung Neoplasms pathology
- Abstract
Pulmonary carcinoid tumors are relatively uncommon and have an indolent clinical course. The role of histologic grading and cell proliferation as measured by a Ki-67 index in predicting long-term recurrence in carcinoid tumors of the lung is not defined. We report the largest single-institution study of carcinoid tumors and correlate histologic grade and Ki-67 index with clinical outcome. We reviewed all surgical lung resection cases from 1995 to 2016 with a diagnosis of primary carcinoid tumor. We collected clinicopathologic parameters, including tumor size, nodal status, histologic pattern, presence of lymphovascular invasion, mitotic count, %Ki-67 positive cells (Ki-67 index) using a digital algorithm, time to tumor recurrence, and staged these tumors based on the 8th edition of TNM Staging. The final cohort consists of 176 carcinoid tumor cases with complete data: 165 (94%) were typical carcinoids and 11 (6%) were atypical carcinoids. The Ki-67 index is significantly increased in atypical versus typical carcinoids and in higher stage disease. Only the Ki-67 index and not the histologic patterns or lymphovascular invasion status was a significant predictor of tumor recurrence on multivariate analysis among all pulmonary carcinoid tumors and within typical carcinoid tumors alone. A Ki-67 index cutoff of 5% offered the optimal combination of sensitivity and specificity in predicting long-term recurrence based on the receiver operating characteristic curve. In addition, stratifying pulmonary carcinoid tumors based on a 3-tier histologic grading system (grade 1: typical carcinoids with Ki-67 index ≤5%, grade 2: typical carcinoids with Ki-67 index >5%, and grade 3: atypical carcinoids regardless of Ki-67 index) significantly correlated with likelihood of tumor recurrence. Finally, we propose an integrated staging system unique to pulmonary carcinoid tumors by keeping the original TNM stage for grade 1 tumors, but upstaging grade 2 tumors to stage II, and grade 3 tumors to stage III.
- Published
- 2020
- Full Text
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124. Thickened Endometrium in Postmenopausal Women With an Initial Biopsy of Limited, Benign, Surface Endometrium: Clinical Outcome and Subsequent Pathologic Diagnosis.
- Author
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Dermawan JKT, Hur C, Uberti MG, Flyckt R, Falcone T, Brainard J, and Abdul-Karim FW
- Subjects
- Aged, Aged, 80 and over, Biopsy, Endometrium pathology, Female, Follow-Up Studies, Humans, Hysteroscopy, Middle Aged, Postmenopause, Retrospective Studies, Urogenital Abnormalities pathology, Uterine Hemorrhage pathology, Uterus pathology, Urogenital Abnormalities diagnosis, Uterine Hemorrhage diagnosis, Uterus abnormalities
- Abstract
Endometrial biopsy or curetting is indicated for postmenopausal women with abnormal uterine bleeding and/or thickened endometrium. Often, endometrial biopsy or curetting yields limited benign surface endometrium, which may indicate insufficient sampling. This study addresses the clinical outcome and subsequent pathologic diagnoses in postmenopausal women who received this initial diagnosis. Among a total of 370 endometrial biopsy or curetting between 2012 and 2015, 192 (52%) were diagnosed as limited benign surface endometrial epithelium. The women ranged in age from 55 to 91 yr old. Their clinical presentations mainly included postmenopausal bleeding, pelvic pain, and enlarged uterus. Primarily because the initial report was interpreted as "benign," 108 (57%) had no subsequent follow-up. Interestingly, women with an increased endometrial thickness were more likely to receive repeat evaluation. Among the 84 women who underwent follow-up endometrial sampling, 6 (7%) had hyperplasia with atypia or malignancy, 21 (25%) had a repeat diagnosis of limited surface sample, 4 (5%) had insufficient materials, and 53 (63%) had other benign findings. Among the subset of women who did receive subsequent follow-up, endometrial atypia or malignancies are more likely found in those with increased body mass index. In conclusion, a slight majority of women with postmenopausal bleeding and/or thickened endometrium had an initial limited surface endometrial sample. Most had no subsequent endometrial sampling. Among those with subsequent follow-up, the majority had benign findings. The study highlights the inconsistencies in adequacy criteria for endometrial sampling and the lack of standardization of subsequent management.
- Published
- 2019
- Full Text
- View/download PDF
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